A recent study from Istanbul sheds light on how psychiatric admissions and diagnoses changed during the first few months of the pandemic compared to previous periods, offering critical insights for parents, clinicians, and policymakers.
This study, conducted by a team of researchers led by Ozalp Ekinci, examined psychiatric admissions among children and adolescents during 2019 and 2020.
By looking at diagnosis rates for various psychiatric conditions, the researchers aimed to pinpoint shifts in the mental health landscape as a direct response to the pandemic.
The analysis revealed several notable trends in psychiatric diagnoses among children and adolescents:
This study’s findings highlight some key takeaways that can guide mental health support efforts for children and adolescents:
As we continue to see the effects of the COVID-19 pandemic on mental health, studies like this one serve as important reminders of the unique mental health needs of young people. Supporting children and adolescents through proactive and targeted mental health services—especially during times of crisis—will be crucial to fostering resilience and well-being in future generations.
Adult ADHD has long been a subject of debate in the field of mental health, with previous estimates of its prevalence varying widely. To achieve a more precise understanding, an international team of researchers conducted a new umbrella review and meta-analysis, offering an updated estimate of adult ADHD rates worldwide.
This large-scale analysis combined five systematic reviews and meta-analyses, incorporating data from 57 unique primary studies. Altogether, the research synthesized findings from a pooled total of over 21 million participants. This comprehensive approach provided a more accurate estimate of the global prevalence of ADHD in adults.
The study concluded that the worldwide prevalence of adult ADHD is 3.1%, with a 95% confidence interval ranging from 2.6% to 3.6%. This estimate falls within the range of earlier reports but provides a more targeted understanding of the rate at which ADHD affects adults globally.
The researchers described this prevalence rate as “relatively high.” They noted that it is only slightly lower than the estimated prevalence of major mental health conditions like schizophrenia (4%) and major depressive disorder (5%)—disorders that have historically received significant attention and resources worldwide.
Moreover, the prevalence of adult ADHD is higher than that of several other well-known mental health conditions, including bipolar disorder (1%), as well as anxiety disorders such as PTSD (Post-Traumatic Stress Disorder), OCD (Obsessive-Compulsive Disorder), GAD (Generalized Anxiety Disorder), and panic disorders.
This updated estimate emphasizes that ADHD is a significant global mental health concern in adults, comparable to or exceeding the prevalence of other disorders that are often more widely recognized. These findings underscore the need for greater awareness, research, and treatment options for adult ADHD, which is still frequently misunderstood or overlooked in the broader discourse of mental health.
By providing a clearer picture of how prevalent ADHD is in adult populations around the world, this study contributes valuable data that could shape future research, policy, and clinical approaches.
A large international research team has just released a detailed analysis of studies looking at the connection between parents' mental health conditions and their children's mental health, particularly focusing on ADHD (Attention Deficit Hyperactivity Disorder). This analysis, called a meta-analysis, involved carefully examining previous studies on the subject. By September 2022, they had found 211 studies, involving more than 23 million people, that could be combined for their analysis.
Most of the studies focused on mental disorders other than ADHD. However, when they specifically looked at ADHD, they found five studies with over 6.7 million participants. These studies showed that children of parents with ADHD were more than eight times as likely to have ADHD compared to children whose parents did not have ADHD. The likelihood of this result happening by chance was extremely low, meaning the connection between parental ADHD and child ADHD is strong.
The researchers wanted to figure out how common ADHD is among children of parents both with and without ADHD. To do this, they first analyzed 65 studies with about 2.9 million participants, focusing on children whose parents did not have ADHD. They found that around 3% of these children had ADHD.
Next, they analyzed five studies with over 44,000 cases where the parents did have ADHD. In this group, they found that 32% of the children also had ADHD, meaning about one in three. This is a significant difference—children of parents with ADHD are about ten times more likely to have the condition than children whose parents who do not have ADHD.
The researchers also wanted to see if other mental health issues in parents, besides ADHD, were linked to ADHD in their children. They analyzed four studies involving 1.5 million participants and found that if a parent had any mental health disorder (like anxiety, depression, or substance use issues), the child’s chances of having ADHD increased by 80%. However, this is far less than the 840% increase seen in children whose parents specifically had ADHD. In other words, ADHD is much more likely to be passed down in families compared to other mental disorders.
The study had a lot of strengths, mainly due to the large number of participants involved, which helps make the findings more reliable. However, there were also some limitations:
Despite these limitations, the research team concluded that their analysis provides strong evidence that children of parents with ADHD or other serious mental health disorders are at a higher risk of developing mental disorders themselves. While more research is needed to fill in the gaps, the findings suggest that it would be wise to carefully monitor the mental health of children whose parents have these conditions to provide support and early intervention if needed
Congenital heart disease (CHD) is a common birth defect where the heart’s blood vessels don’t develop normally before birth. This condition affects about 9% of all births worldwide, meaning about one in eleven babies is born with CHD. A recent analysis found that children with CHD have three times the risk of developing ADHD compared to children without CHD. However, that study only included five smaller studies, and almost 90% of the results varied between studies, making the findings less reliable. To improve on this, a team of researchers conducted a new, more thorough analysis.
The updated analysis combined eleven studies, involving nearly 300,000 people. This larger study also confirmed that children with CHD are three times more likely to develop ADHD than those without CHD. Importantly, there was no evidence that the results were biased by only including studies that showed stronger results ("publication bias"). The variation between the studies (heterogeneity) was lower in this new analysis, down to a more manageable 60%.
The researchers looked at two types of studies: cohort studies and cross-sectional studies, and found different levels of risk:
While both types of studies suggest a strong link between CHD and ADHD, cohort studies are more reliable because they track children over time, which helps researchers establish that CHD occurred before ADHD, suggesting a stronger cause-and-effect relationship. Both types of studies are observational. In any observational study, researchers look at data without actively changing or controlling anything in the study environment. Because they aren't conducting controlled experiments, it's possible that some important factors, known as "confounding factors," aren't being measured or accounted for. These factors can influence both the exposure (what the study is investigating, like CHD) and the outcome (ADHD) in a way that creates an association that is apparent but not rea.
Nine of the studies, which included almost 300,000 participants, adjusted their findings to account for "confounding factors"—things like age, gender, or other health conditions that could also influence whether a child develops ADHD. Even after making these adjustments, the risk of ADHD in children with CHD was still three times higher.
The researchers also found that the way ADHD was diagnosed—whether through clinical assessments or standardized symptom checklists—didn’t change the results much. Additionally, there was no major difference between studies done in the U.S. and those conducted in other countries, or between higher- and lower-quality studies.
The research team concluded that children born with congenital heart disease are at a much higher risk of developing ADHD than children without CHD. They suggested that children with CHD should be monitored more closely for ADHD as they grow up to ensure early intervention if needed.
Potentially traumatic experiences (PTEs) refer to events where someone is exposed to situations that involve threats to life, serious injury, or danger to themselves or others. These events can include things like accidents, violence, or the death of someone close. PTEs are significant because they can have lasting effects on a person's mental health.
A research team from Norway, working with a collaborator from the U.S., used their country’s universal health care system to study how PTEs affect the mental health of children and adolescents in Hordaland County, which includes the city of Bergen. They wanted to see how experiencing PTEs influenced the likelihood of these young people seeking help from child and adolescent mental health services (CAMHS) or being diagnosed with psychiatric disorders, including ADHD.
In 2012, the study invited all 19,439 teenagers born between 1993 and 1995 in Hordaland County to participate. These teens were 16 to 19 years old at the time. Out of this group, 9,555 teens agreed to let the researchers link their personal data with the National Patient Registry (NPR), which keeps track of health records. There was no significant difference in the types or number of PTEs between those who agreed to this data sharing and those who did not.
After removing participants with incomplete information, the researchers were left with 8,755 teens. These teens’ psychiatric diagnoses, including ADHD, were taken from the NPR. The researchers asked the participants if they had ever experienced specific traumatic events, such as:
If a participant reported experiencing the death of someone close, they were asked to specify who it was (a parent, sibling, grandparent, other family member, close friend, or romantic partner). One limitation of the study was that it did not ask about bullying, which could also be a traumatic experience.
The researchers divided the teens into three trauma groups based on their experiences:
Teens in the situational and interpersonal trauma groups were more likely to see their economic situation as worse than those in the low trauma group. For example, 11% of the situational trauma group and 17% of the interpersonal trauma group considered themselves economically worse off, compared to just 6.1% of the low trauma group. Also, fewer parents of teens in the two higher trauma groups had higher levels of education, which can impact family support and resources.
After adjusting for gender and parental education, the researchers found that:
The effect was even stronger when comparing the interpersonal trauma group to the low trauma group. Teens in the interpersonal trauma group were almost five times more likely to be diagnosed with ADHD than those in the low trauma group.
One limitation of the study is that while the researchers acknowledged that sex and socioeconomic status (SES) are important factors in the relationship between trauma and psychiatric disorders, they did not directly adjust for SES. However, they did indirectly account for it by considering the education levels of the parents, which is closely related to SES.
The study showed that adolescents who experience more interpersonal trauma (like violence or sexual abuse) are at a significantly higher risk of being diagnosed with ADHD. The findings suggest that it’s important to pay special attention to teens who experience both situational and interpersonal traumas, especially those exposed to interpersonal violence. Early intervention and support could be key to helping these adolescents manage their mental health.
A meta-analysis of short-term, placebo-controlled, randomized clinical trials (Cortese et al. 2018), looking at both efficacy and safety, supported prescribing stimulants – methylphenidate use in children and adolescents and amphetamine use in adults – as first-choice medications.
However, these were short-term studies, and they focused on relieving ADHD symptoms. What about longer-term outcomes, especially looking more broadly at functional impairment and overall quality of life?
Sweden has a single-payer health insurance system that encompasses virtually every resident and is linked to national registers that enable researchers to conduct nationwide population studies.
A joint Finnish-Swedish research team used Sweden’s registers to study outcomes for all individuals of working age, 16 to 65 years old, living in Sweden who had received a diagnosis of ADHD from 2006 through 2021. The resulting study cohort encompassed 221,714 persons with ADHD.
The team adjusted for the following confounding variables: Genetics, baseline severity of symptoms, baseline comorbidities, temporal order of treatments (which medication was used as first, second, third, and so forth, including also nonuse of ADHD medications), time since cohort entry, and time-varying use of psychotropic drugs, including antidepressants, anxiolytics, hypnotics, mood stabilizers (carbamazepine, valproic acid, and lamotrigine), lithium, antipsychotics, and drugs for addictive disorders.
With these adjustments, they discovered that amphetamine treatment was associated with a roughly 25% reduction in psychiatric hospitalization relative to unmedicated ADHD. Lisdexamphetamine was associated with a roughly 20% reduction, dexamphetamine with a 12% reduction, and methylphenidate with a 7% reduction. All four medications are stimulants.
None of the non-stimulant medications – atomoxetine, guanfacine, clonidine – had any significant effect on psychiatric hospitalization. Nor did modafinil a drug that is not FDA approved for ADHD but is sometimes used when other drugs fail.
Amphetamine was also associated with the greatest reduction in suicide attempts or deaths, with a roughly 40% decline relative to unmedicated ADHD. Dexamphetamine was associated with a roughly 30% decline and lisdexamphetamine with a roughly 25% decline. The stimulant methylphenidate was only associated with an 8% reduction, and modafinil had no significant effect.
Surprisingly, non-stimulant medications were associated with significant increases in suicide attempts or deaths: 20% for atomoxetine, 65% for guanfacine, and almost double for clonidine.
Amphetamine and lisdexamphetamine also reduced the risk of nonpsychiatric hospitalization by more than a third compared to unmedicated ADHD. Dexamphetamine was associated with a risk reduction of more than 25%, methylphenidate with 20% lesser risk.
The non-stimulant atomoxetine was associated with a roughly 15% reduction in risk of nonpsychiatric hospitalization. But neither guanfacine nor clonidine had any significant effect.
Turning to work disability, atomoxetine was the only ADHD medication associated with a reduction – a roughly 10% improvement. All other medications had no significant effect.
The team concluded, “In this cohort study of adolescents and adults with ADHD, the use of medications for ADHD, especially lisdexamphetamine and other stimulants, was associated with decreased risk of psychiatric hospitalizations, suicidal behavior, and nonpsychiatric hospitalizations during periods when they were used compared with periods when ADHD medication was not used. Non-stimulant atomoxetine use was associated with decreased risk of work disability.”
Inflammatory bowel disease (IBD) consists of 2 main subtypes: Crohn’s disease and ulcerative colitis. Typical symptoms include abdominal pain, diarrhea, and rectal bleeding. Both are incurable, increase the risk of colorectal cancer, and often affect other organs as well.
A single earlier study suggested a weak link between childhood-onset IBD and ADHD.
A Danish research team used its country’s national registers – based on a single-payer national health insurance system that encompasses virtually the entire population – to include all 3,559 patients diagnosed with pediatric-onset IBD from 1998 through 2018.
The team then matched these individuals five-to-one on age, age of diagnosis, year of diagnosis, sex, municipality of residence, and time period, with 17,795 individuals from the same pool who were free of IBD.
ADHD was identified based on two criteria: clinical diagnoses in patient records, and methylphenidate stimulant prescriptions in the medications register.
Overall, the team found no significant association between pediatric-onset IBD and ADHD. The same was true for both Crohn’s disease and ulcerative colitis.
There were no differences in outcomes for boys or girls.
There was also no significant association found using only ADHD diagnoses or only methylphenidate prescriptions.
Among children and adolescents with IBD onset under age 14, there was a borderline significant association, but it was a negative one: They were less likely to subsequently be clinically diagnosed with ADHD or to receive prescriptions for methylphenidate.
The team concluded, “Remarkably, we found a reduced risk of receiving methylphenidate and being diagnosed with ADHD, which merits further investigation.”
NEW STUDY: The cumulative impact of attention deficit hyperactivity disorder, autism and intellectual disability for young people
Neurodevelopmental conditions often coexist, creating a complex web of challenges for affected individuals. A recent study by Hollingdale et al. delves into the cumulative effects of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID) on young people’s behavioral and socio-emotional well-being, as well as their overall functioning as rated by clinicians.
The researchers conducted a cross-sectional analysis of 2768 young individuals aged 3-17 years, with a mean age of approximately 11.5 years. Diagnostic information along with caregiver-rated behavioral and socio-emotional data, and clinician-rated functioning scores, were collected from electronic patient records at the point of initial diagnosis.
The study aimed to understand whether the number of neurodevelopmental conditions—ranging from one to three—correlates with more pronounced behavioral and socio-emotional issues, and lower levels of clinician-rated functioning. The behavioral and socio-emotional aspects were assessed using the Strengths and Difficulties Questionnaire, while the Children's Global Assessment Scale was used to evaluate clinician-rated functioning.
The findings revealed that young people with multiple neurodevelopmental conditions tend to exhibit higher levels of inattention and hyperactivity, greater peer-related problems, reduced prosocial behaviors, and poorer overall functioning. Interestingly, this cumulative impact was more evident in males compared to females, with females only showing significant cumulative effects in clinician-rated functioning.
This research underscores the importance of recognizing the compounded difficulties faced by young people with multiple neurodevelopmental conditions. It highlights the need for tailored interventions that address the unique and overlapping challenges presented by ADHD, ASD, and ID. For practitioners, understanding these cumulative effects is crucial for developing effective treatment plans that can better support the holistic development and well-being of these young individuals.
In conclusion, the presence of multiple neurodevelopmental conditions can significantly affect various domains of a young person’s life, with notable differences between males and females. This study provides a critical insight into the intricate nature of these conditions and calls for a more nuanced approach in both research and clinical practice.
In the field of mental health, professionals often use a variety of tools to diagnose and understand neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). One such tool is the Autism Diagnostic Observation Schedule (ADOS), which is specifically designed to help diagnose autism. However, the ADOS wasn't originally intended for children who have both autism and ADHD, though this comorbidity is not uncommon.
A recent study aimed to explore how children with ADHD, autism, or both, pay attention to social images, such as faces. The study focused on using eye-tracking technology to measure where children direct their gaze when viewing pictures, and how long they look at certain parts of the image. This is important because differences in visual attention can provide insights into the nature of these disorders.
The researchers included 84 children in their study, categorized into four groups: those with ASD, those with ADHD, those with both ASD and ADHD, and neurotypical (NT) children without these conditions. During the study, children were shown social scenes from the ADOS, and their eye movements were recorded. The ADOS assessment was administered afterward. To ensure that the results were not influenced by medications, children who were on stimulant medications for ADHD were asked to pause their medication temporarily.
The results of the study showed that children with ASD, whether they also had ADHD or not, tended to spend less time looking at faces compared to children with just ADHD or NT children. The severity of autism symptoms, measured by the Social Communication Questionnaire (SCQ), was associated with reduced attention to faces. Interestingly, ADHD symptom severity, measured by Conners' Rating Scales (CRS-3), did not correlate with how children looked at faces.
These findings suggest that measuring visual attention might be a valuable addition to the assessment process for ASD, especially in cases where ADHD is also present. The study indicates that if a child with ADHD shows reduced attention to faces, it might point to additional challenges related to autism. The researchers noted that more studies with larger groups of children are needed to confirm these findings, but the results are promising. They hope that such measures could eventually enhance diagnostic processes and help in managing the complexities of cases involving comorbidity of ADHD and ASD.
This research opens up the possibility of using eye-tracking as a supplementary diagnostic tool in the assessment of autism, providing a more nuanced understanding of how attentional differences in social settings are linked to ASD and ADHD.
Using Statistics New Zealand’s Integrated Data Infrastructure (IDI), a large database of linked de-identified administrative and survey data about people and households, a local study team examined a three-year birth cohort (mid-1992 through mid-1995) totaling 149,076 persons.
Using Statistics New Zealand’s Integrated Data Infrastructure (IDI), a large database of linked de-identified administrative and survey data about people and households, a local study team examined a three-year birth cohort (mid-1992 through mid-1995) totaling 149,076 persons.
The team assessed the presence of ADHD within this cohort through diagnosis codes and inference from medication dispensing, where there was at least one code relating to an ADHD diagnosis in the medication datasets. This subgroup consisted of 3,975 persons.
Next, they related this information to criminal justice system interactions of increasing severity, starting with police proceedings, and continuing with court charges, court convictions, and incarcerations. These interactions were tracked during an eight-year period from participants’ 17th birthday through their 25th birthday.
In this same period the team also tracked types of offenses: against people; against property; against organizations, government, and community; and violent offenses.
In all cases, the study team adjusted for gender, ethnicity, deprivation, and area of residence as potential confounders.
With these adjustments, young adults with ADHD were over twice as likely as their typically developing peers to be proceeded against by police, to be charged with an offense, and to be convicted. They were almost five times as likely to be incarcerated.
With the same adjustments, young adults with ADHD were over twice as likely as their typically developing peers to be convicted of offenses against organizations, government, and community. They were almost three times as likely to be convicted of crimes against persons, and over three and a half times more likely to be convicted of either violent offenses or offenses against property.
The authors noted, “The greater effect size for incarceration observed in our study may be due to the lack of control for comorbid conditions such as CD [conduct disorder], which are known criminogenic risk factors.”
They also noted, “The sharp increase in the risk of incarceration observed may also signal differences in the NZ justice system’s approach to ADHD, which may be less responsive to the condition than other nations, particularly the steps in the justice system between conviction and sentence. This would suggest that the UNCRPD [United Nations Convention on the Rights of Persons with Disabilities] obligations of equal recognition before the law and the elimination of discrimination on the basis of disability are not being met for individuals with ADHD in NZ.”
They concluded, “Our findings revealed that not only were individuals with ADHD overrepresented at all stages of the CJS [criminal justice system] and offense types examined, there was also a pattern of increasing risk for CJS interactions as these individuals moved through the system. These results highlight the importance of early identification and responsivity to ADHD within the CJS and suggest that the NZ justice system may require changes to both of these areas to ensure that young individuals with ADHD receive equitable access to, and treatment within, the CJS.”
Recognizing whether your ADHD is being managed appropriately requires an understanding of what constitutes effective treatment. Here are some indicators of proper ADHD treatment:
Recognizing whether your ADHD is being managed appropriately requires an understanding of what constitutes effective treatment. Here are some indicators of proper ADHD treatment:
Comprehensive Evaluation: An appropriate diagnosis of ADHD involves a comprehensive evaluation, including medical history, clinical interviews, and assessment tools. It should also exclude other conditions that may mimic ADHD.
Clear Communication: Your doctor should provide a clear explanation of ADHD, its symptoms, treatment options, potential side effects, and expected outcomes. They should answer your questions patiently and help dispel any misconceptions.
Individualized Treatment Plan: ADHD treatment often involves a combination of medication, psychotherapy, and lifestyle changes. Your doctor should tailor the treatment plan to your specific needs, symptoms, and life circumstances.
Medication Management: If medication is part of your treatment plan, your doctor should monitor its effects and side effects closely, adjusting the dosage as necessary. Remember, the aim is to maximize benefits and minimize side effects. Much research shows that it is usually best to start treatment with an FDA approved medication. If your doctor decides otherwise, you should ask why.
Psychotherapy and Coaching: Pills don’t provide skills. Many adults with ADHD never acquired life skills due to untreated ADHD. Cognitive-behavioral therapy (CBT) is beneficial for managing ADHD. Your doctor might recommend this and refer you to a psychologist, or they might provide some elements of these services themselves.
Regular Follow-Ups: Regular follow-ups are critical to assess the effectiveness of the treatment plan and to make necessary adjustments. Your doctor should be tracking your progress and adapting your treatment as needed.
Empowering You: A good doctor will support you in managing your ADHD, providing education, resources, and tools that empower you to lead a healthy, fulfilling life.
Focus on Strengths: ADHD can come with strengths, such as creativity, dynamism, and the ability to think outside the box. An effective healthcare provider will help you leverage these strengths.
Involvement of Loved Ones: Depending on your circumstances, involving your loved ones in your treatment process can be beneficial. They can provide additional support and understanding.
Co-ordinating with Other Healthcare Providers: If you have other healthcare providers involved in your care, your doctor should communicate and coordinate with them to ensure consistent and comprehensive care.
Remember, you have the right to seek a second opinion if you feel your ADHD is not being appropriately managed. Trust your instincts and advocate for your health. It may also be helpful to join ADHD support groups (online or offline) to connect with others who share similar experiences. Their insights and recommendations could be beneficial. Also keep in mind that achieving an optimal outcome for one’s ADHD often requires the doctor to try a few different medications as it is not currently possible to predict which patients do best on which medications.
Noting that “evidence on the association between ADHD and a physical condition associated with obesity, namely type 2 diabetes mellitus (T2D), is sparse and has not been meta-analysed yet,” a European study team performed a systematic search of the peer-reviewed medical literature followed by a meta-analysis, and then a nationwide population study.
Noting that “evidence on the association between ADHD and a physical condition associated with obesity, namely type 2 diabetes mellitus (T2D), is sparse and has not been meta-analysed yet,” a European study team performed a systematic search of the peer-reviewed medical literature followed by a meta-analysis, and then a nationwide population study.
Unlike type 1 diabetes, which is an auto-immune disease, type 2 diabetes is believed to be primarily related to lifestyle, associated with insufficient exercise, overconsumption of highly processed foods, and especially with large amounts of refined sugar. This leads to insulin resistance and excessively high blood glucose levels that damage the body and greatly lower life expectancy.
Because difficulty with impulse control is a symptom of ADHD, one might hypothesize that individuals with ADHD would be more likely to develop type-2 diabetes.
The meta-analysis of four cohort studies encompassing more than 5.7 million persons of all ages spread over three continents (in the U.S., Taiwan, and Sweden) seemed to point in that direction. It found that individuals with ADHD had more than twice the odds of developing type 2 diabetes than normally developing peers. There was no sign of publication bias, but between-study variability (heterogeneity) was moderately high.
The nationwide population study of over 4.2 million Swedish adults came up with the same result when adjusting only for sex and birth year.
Within the Swedish cohort there were 1.3 million families with at least two full siblings. Comparisons among siblings with and without ADHD again showed those with ADHD having more than twice the odds of developing type 2 diabetes. That indicated there was little in the way of familial confounding.
However, further adjusting for education, psychiatric comorbidity, and antipsychotic drugs dropped those higher odds among those with ADHD in the overall population to negligible (13% higher) and barely significant levels.
The drops were particularly pronounced for psychiatric comorbidities, especially anxiety, depression, and substance use disorders, all of which had equal impacts.
The authors concluded, “This study revealed a significant association between ADHD and T2D [type 2 diabetes] that was largely due to psychiatric comorbidities, in particular SUD [substance use disorders], depression, and anxiety. Our findings suggest that clinicians need to be aware of the increased risk of developing T2D in individuals with ADHD and that psychiatric comorbidities may be the main driver of this association. Appropriate identification and treatment of these psychiatric comorbidities may reduce the risk for developing T2D in ADHD, together with efforts to intervene on other modifiable T2D risk factors (e.g., unhealthy lifestyle habits and use of antipsychotics, which are common in ADHD), and to devise individual programs to increase physical activity. Considering the significant economic burden of ADHD and T2D, a better understanding of this relationship is essential for targeted interventions or prevention programs with the potential for a positive impact on both public health and the lives of persons living with ADHD.”
Thanks to improvements in cancer treatment, there is a growing population of childhood and adolescent cancer survivors (CACSs). CACSs are at an increased risk of chronic physical, psychological, and social problems because of their cancer experiences and intensive cancer treatments.
Thanks to improvements in cancer treatment, there is a growing population of childhood and adolescent cancer survivors (CACSs). CACSs are at an increased risk of chronic physical, psychological, and social problems because of their cancer experiences and intensive cancer treatments. These include depression, anxiety, suicidal ideation, and post-traumatic stress disorder (PTSD).
To what extent, if at all, does this also apply to ADHD? Noting that “previous studies … have reported inconsistent findings,” a local research team took advantage of Taiwan’s mandatory single-payer National Health Insurance that covers over 99% of the island’s population. More specifically, the National Health Insurance Research Database (NHIRD) maintains data on the insured population available on formal request for study purposes.
Linking the catastrophic illness database, mental disorders database, and longitudinal health insurance database, they tracked children age younger than 10 years and adolescents aged 11-17 years who were diagnosed with any malignancy (cancer) between 2002 and 2011 with no history of major psychiatric disorders (including ADHD). Parental history of major psychiatric disorders was likewise controlled as a potential confounder.
The team identified 5,121 CACSs, which they matched one to ten with 51,210 age-, sex-, income-, and residence-matched cancer-free controls.
ADHD diagnoses were made by board-certified psychiatrists during the study follow-up period (from enrollment through 2011) based on a comprehensive clinical interview and clinical judgment.
Cancer survivors were diagnosed with ADHD at more than six times the rate of matched controls. Survival duration made no significant difference in this outcome.
Cancers of bone, connective tissue, skin, and breast were associated with a more than threefold increase in risk of an ADHD diagnosis. For cancers of the circulatory system, there was a more than sixfold increased risk of ADHD, and for those of the genitourinary organs, more than sevenfold increased risk.
For brain cancer survivors, the increased risk of ADHD was more than twelvefold. That may be at least in part because the brain itself was targeted for treatment in these instances, which plausibly could cause damage resulting in psychiatric disorders.
The team concluded, “we observed a comparatively higher risk of MPDs [major psychiatric disorders] among CACSs than among controls and likewise found that such risks varied across different cancer types. Survivors of both CNS [central nervous system] and non-CNS cancers have increased risks of MPD diagnoses. Among the enrolled CACSs, ASD [autism spectrum disorder] and ADHD were associated with most types/categories of cancers. Long-term care of this vulnerable population must include psychosocial interventions for patients and their families. Physicians need to be aware of early signs of mental health problems in this high-risk subpopulation and arrange early interventions accordingly.”
An international study team has just reported findings from a series of meta-analyses exploring associations between ADHD medications and headaches in children and adolescents.
An international study team has just reported findings from a series of meta-analyses exploring associations between ADHD medications and headaches in children and adolescents.
First, to compare headache occurrence in individuals with ADHD to those without ADHD, the team performed a very large meta-analysis of twelve studies with over 2.7 million children and adolescents. Those with ADHD had twice the rate of headaches.
There was no indication of publication bias, but there was considerable variation (heterogeneity) among studies, with crude odds ratios spanning from 0.9 to 3.37. Nevertheless, ten of the twelve studies pointed to higher odds among children and adolescents with ADHD. The four studies that controlled for age, sex, race, and other socioeconomic status variables reaffirmed the finding of a doubling of headache risk, this time with acceptable heterogeneity.
Three studies with a combined 7,755 participants found no difference in tension headaches, but five studies with over a quarter million persons found more than a doubling of the rate of migraine in children and adolescents with ADHD.
Next, the team performed meta-analyses of 58 randomized controlled trials (RCTs) of specific ADHD medications that met eligibility criteria for their systematic review. Because only a single eligible RCT apiece looked at bupropion and clonidine, these ADHD medications could not be included in the meta-analyses.
A meta-analysis of ten RCTs with a total of 2,672 participants found absolutely no association between use of amphetamines (including lisdexamphetamine) and headaches. Variation (heterogeneity) between studies was minimal, and there was no sign of publication bias.
A smaller meta-analysis of six RCTs with a combined 818 participants found a 24% increase in headaches among modafinil users, but it was not statistically significant, perhaps because of the much smaller combined sample size.
A meta-analysis of 17 RCTs with a total of 3,371 participants found a 33% increase in headache occurrence among methylphenidate users over placebo. Between-study variation (heterogeneity) was negligible, and there was absolutely no sign of publication bias.
Similarly, a meta-analysis of 22 RCTs with a combined 3,857 participants reported a 29% increase in headache occurrence among atomoxetine users over placebo. Again, heterogeneity between studies was negligible, with absolutely no indication of publication bias.
Finally, a meta-analysis of eight RCTs with 1,956 participants found a 43% increase in headache occurrence among guanfacine users over placebo. Once again, with negligible heterogeneity and no indication of publication bias.
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental condition that is typically diagnosed in childhood but can persist into adulthood. Its symptoms include inattention, hyperactivity, and impulsivity, and it can significantly affect daily life, academic achievement, and professional success.
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental condition that is typically diagnosed in childhood but can persist into adulthood. Its symptoms include inattention, hyperactivity, and impulsivity, and it can significantly affect daily life, academic achievement, and professional success. As scientific understanding of the condition continues to evolve, new research is revealing more insights into the prevalence, comorbidity, treatment, and physiological aspects of ADHD in adults. Here's a roundup of some recent findings:
A recent study assessing the prevalence of treatment for ADHD among US college students found that the location of mental health care significantly affects treatment outcomes. Specifically, students receiving mental healthcare on campus were less likely to receive any medication or therapy for ADHD, suggesting the need to evaluate the quality of mental health services available on college campuses and their effectiveness in treating ADHD.
Another study found a correlation between ADHD and the l-Arginine/Nitric oxide (Arg/NO) pathway, a physiological process linked to dopamine release and cardiovascular functioning. The study found that adults with ADHD who were not treated with methylphenidate (a common ADHD medication) showed variations in the Arg/NO pathway. This could have implications for monitoring potential cardiovascular side effects of ADHD medications, as well as for understanding the biochemical changes that occur in ADHD.
ADHD and chronic pain appear to be related, according to a comparative study of clinical and general population samples. Particularly in females with ADHD, the prevalence of chronic and multisite pain was found to be high. This calls for longitudinal studies to understand the complex sex differences of comorbid chronic pain and ADHD in adolescents and the potential impacts of stimulant use on pain.
Finally, a study investigated the comorbidity of ADHD and bipolar disorder (BD) and its potential link to violent behavior. The research revealed a positive effect of ADHD symptoms on violence tendency and aggression scores. Moreover, male gender and young age were also found to have significant positive effects on violence and aggression scores, suggesting an association between these disorders and violent behavior.
Noting that the degree comorbidity (co-occurrence) of epilepsy and ADHD “has never been quantified based on a systematic review with meta-analysis,” a Chinese study team based at Wuhan university has just reported findings based on doing just that.
Noting that the degree of comorbidity (co-occurrence) between epilepsy and ADHD “has never been quantified based on a systematic review with meta-analysis,” a Chinese study team based at Wuhan university has just reported findings based on doing just that.
Their systematic search of the peer-reviewed medical literature yielded 17 studies examining the prevalence of epilepsy among persons with ADHD, and 49 studies measuring the prevalence of ADHD among persons with epilepsy.
According to the Apple dictionary app, epilepsy is “a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, associated with abnormal electrical activity in the brain.” Its lifetime prevalence in the general population is about 0.76%, or about one in every 130 persons.
Meta-analysis of 17 studies with a combined total of over 900,000 participants spread over twelve countries on five continents yielded an epilepsy prevalence estimate of 3.4% among individuals with ADHD, or well over four times the prevalence in the general population. There was no sign of publication bias, but variability (heterogeneity) among studies was extremely high.
The worldwide prevalence of ADHD in children, on the other hand, is about 7.2%, affecting roughly one in fourteen.
Meta-analysis of 49 studies with a combined total of 172,206 persons from 16 countries on five continents reported an ADHD prevalence of just over 22% among persons with epilepsy. However, heterogeneity among studies was extremely high, and there was very strong evidence of publication bias.
Using the trim-and-fill correction for publication bias yielded a reduced estimate of 16%, which is still over twice the prevalence in the general population.
Furthermore, the authors noted, “Given that the large sample studies in this study are basically population-based studies and the small sample studies are hospital-based studies, there is also the possibility of Berkson’s bias. Specifically, patients with comorbidities are more likely to need help or seek medical advice. This possibility would yield a higher comorbidity rate in hospital-based studies.”
And that is exactly what emerged from subgroup analysis. The prevalence of ADHD in epilepsy among the hospital-based studies was 27.1%, over twice the 13.2% prevalence reported from the 13 population-based studies. The largest population-based study, a U.S. study with over 114,000 participants, yielded a prevalence of only 3.5%.
The authors cautioned that the very high degree of heterogeneity between studies indicates “it is inappropriate to consider the summary effect as representative of the real effect.”
Noting “the incidence of parental obesity has been rising together with the prevalence of mental illness, suggesting a possible link between the two phenomena,” a Chinese study team performed a systematic search of the peer-reviewed literature on that topic.
Noting “the incidence of parental obesity has been rising together with the prevalence of mental illness, suggesting a possible link between the two phenomena,” a Chinese study team performed a systematic search of the peer-reviewed literature on that topic.
Further noting that previous meta-analyses have suggested a link between maternal obesity and increased risk of ADHD in offspring, they set out to also look at paternal obesity.
Only two studies, however, probed the relationship between paternal overweight and obesity and offspring ADHD, making that meta-analysis impractical. A meta-analysis of six studies with a combined total of over a hundred thousand participants found no significant association between overweight or obsess fathers and offspring mental disease of any kind (with all such disorders lumped together). There was no indication of publication bias and little variability (heterogeneity) between studies.
Ten studies with a combined total of over 800,000 participants, however, examined the relationship between overweight and obese mothers and offspring ADHD. Overweight mothers were twenty percent more likely to have offspring with ADHD. Obese mothers were more than fifty percent more likely to have offspring with ADHD. There was absolutely no sign of publication bias in either case. Inter-study heterogeneity was negligible for overweight, and moderate for obesity.
The team concluded, “We found that the most recent evidence indicates the detrimental connections between parental pre-pregnancy overweight/obesity and offspring mental health.” That is perhaps a bit overstated, as the only clear sign was with maternal overweight or obesity.
Parkinson’s disease is a chronic, progressive neurological disease, characterized by the drastic reduction of dopamine transporters and the dopaminergic neurons upon which they are expressed.
Parkinson’s disease is a chronic, progressive neurological disease, characterized by the drastic reduction of dopamine transporters and the dopaminergic neurons upon which they are expressed. The resulting symptoms include bradykinesia (slowness of initiation of voluntary movements), tremors, rigidity, and postural instability.
Taiwan’s National Health Service covers about 99 percent of its 24 million inhabitants and maintains complete records in its National Health Insurance Research Database. The Longitudinal Health Insurance Database2000 (LHID 2000) is a nationally representative subset of the latter.
Using the LHID 2000, a Taiwanese research team identified 10,726 patients with Parkinson’s disease. It paired them with an identical number of randomly selected non-Parkinson’s controls, matched by age, gender, and index date (first date of diagnosis of Parkinson’s disease).
The team then looked retroactively through the database to determine which of the 21,452 individuals had previously been diagnosed with ADHD. Fourteen of the 10,726 Parkinson’s patients had been diagnosed with ADHD, versus five of the 10,726 in the control group.
Parkinson’s patients were thus 2.8 times as likely to have had a previous diagnosis of ADHD as the controls. When adjusted for age, gender, and Carlson Comorbidity Index scores, they were 3.6 times as likely to have had a previous ADHD diagnosis.
The authors cautioned that this association between prior ADHD diagnosis and subsequent Parkinson’s diagnosis is not causal.
Only one in 766 of Parkinson’s patients (a seventh of one percent) had previously been diagnosed with ADHD. So even if there were any causal relationship, it would be extremely weak.
After adjusting for age, sex, race/ethnicity, education level, family income to poverty ratio, and geographic region, youths with food allergies were found to be over 70% more likely to be diagnosed with ADHD than those without food allergies. After further mutual adjustment for other allergic conditions, they were still well over 40% more likely to be diagnosed with ADHD than their non-allergic peers.
A growing body of studies suggests a link between inflammation and autoimmune diseases on the one hand and ADHD on the other. It has been hypothesized that excessive release of cytokines (small signaling proteins that regulate immune response and inflammation and repair) and keratinocytes (skin cells) under allergic conditions may cause structural and functional changes to the nervous system and brain, which can contribute to psychiatric disorders, including ADHD.
Noting that previous studies have focused primarily on associations between ADHD and respiratory allergies(asthma) and skin allergies, a joint Chinese and American study team set out to see what, if any, association there might be with food allergies.
To this end, they turned to the national health Interview Survey (NHIS), conducted annually by the National Center for Health Statistics at the Centers for Disease Control and Prevention. This survey relies on a very large, nationally representative sample of the U.S. population.
The study encompassed 192,573 youths aged 4 through 17 years old. Of these, 15,376 had an ADHD diagnosis, 8,603 had food allergies, 24,218 had respiratory allergies, and 18,703 had skin allergies.
After adjusting for age, sex, race/ethnicity, education level, family income to poverty ratio, and geographic region, youths with food allergies were found to be over 70% more likely to be diagnosed with ADHD than those without food allergies. After further mutual adjustment for other allergic conditions, they were still well over 40% more likely to be diagnosed with ADHD than their non-allergic peers.
How did that compare with respiratory and skin allergies? In the same study population, making identical adjustments for potential confounders, youths with respiratory allergies were 50% more likely to be diagnosed with ADHD than those without such allergies. Those with skin allergies were 65% more likely to be diagnosed with ADHD. After further mutual adjustment for other allergic conditions, those with respiratory allergies were still over a third more likely to be diagnosed with ADHD, and those with skin allergies were 50% more likely to be diagnosed with ADHD.
The authors concluded, "The current study found a significant and positive association between common allergic conditions, including food allergy, respiratory allergy, skin allergy, and ADHD in children. Although the detailed mechanisms linking food allergy and other allergic conditions to ADHD remain to be understood, physicians should be aware of the increased risk of ADHD as a comorbidity of children with allergic conditions".
Persons with type 1 diabetes were found to be eight times more likely to be diagnosed with ADHD than those who were not diabetic.
Taiwan has a mandatory single-payer universal health insurance system, the National Health Insurance (NHI), that records diagnoses and prescriptions across virtually the entire resident population. Out of the roughly 28 million residents covered by NHI, a randomly assigned sample of 3 million is tracked in the Taiwan National Health Insurance Research Database(NHIRD).
Expert panels have to confirm all diagnoses of severe systemic autoimmune diseases, ensuring a high level of accuracy.
A Taiwanese study team availed itself of these records to explore the link between type 1 diabetes mellitus (T1DM) and ADHD. ADHD diagnoses were made by board-certified psychiatrists, based on comprehensive interviews and clinical judgment.
The team found a total of 6,226 cases diagnosed with T1DM in the decade from 2001 through 2010 and followed them through the end of 2001. It matched each case with ten age- and sex-matched non-T1DM controls from the same database, for a total of 62,260 controls.
Persons with type 1 diabetes were found to be eight times more likely to be diagnosed with ADHD than those who were not diabetic. There was no difference in the risk ratio between youth and adults. The risk of ADHD among females with T1DM was only slightly lower than among males: sevenfold greater, rather than 8.5 times greater.
The authors concluded, "Our findings indicate the importance of the close monitoring of the mental health condition of patients with T1DM by clinicians ... The exact path of mechanisms between T1DM and major psychiatric disorders should be elucidated in future studies."
Meta-analysis discovers clear link between mothers with PCOS and children with ADHD.
Polycystic ovary syndrome (PCOS) affects somewhere between 6 and 20% of women of reproductive age. Typical effects include:
· failure to ovulate;
· high levels of male hormones (androgens), which can lead to acne, seborrhea, hair loss on the scalp, increased body or facial hair, and infrequent or absent menstruation;
· metabolic disruption, including obesity and insulin resistance.
In pregnancy, PCOS is also known to increase the chances of birth complications.
Previous studies have suggested a link between maternal PCOS and ADHD.
A team of Arabian (Saudi and United Arab Emirates) researchers conducted a systematic review of the peer-reviewed medical literature and were able to identify four studies with a total of 1,354,182 participants that could be combined into a meta-analysis.
The meta-analysis found that children born to mothers with PCOS were 43% more likely to develop ADHD. The 95% confidence interval stretched from 35% to 51%, indicating a highly reliable finding.
Moreover, there was between-study variation: They all produced essentially identical results. There was also no sign of publication bias.
"However,"the authors noted, "the reported results do not necessarily provide definitive findings of a causal inference due to the randomized study design. All the included studies were observational in design." With this caution, they could only conclude that "the results of this meta-analysis showed that there might be a link between maternal PCOS and the risk of developing ASD and ADHD in the offspring."
ADHD aggregates with Alzheimer's disease and any dementia within families
Alzheimer's disease is characterized by an aging-related progressive deterioration in cognition and ability for independent living. It is the most common form of dementia. Few studies, with limited sample sizes, have probed the relationship between ADHD and dementia, with conflicting results.
A Swedish study team used the country's universal system of population and health registers' linked through unique personal identification numbers - to examine patterns among the more than 2.1 million Swedes born between 1980 and 2001.
Each of these individuals was then linked to their biological relatives, parents, grandparents, uncles, and aunts through the Medical Birth Register and Multi-generation Register.
This generated three cohorts of relatives representing different levels of genetic relatedness: parents sharing half of their genes; grandparents sharing a quarter of their genes; and uncles and aunts who also share a quarter of their genes with index persons. After linking index persons to their biological relatives, the study cohorts contained more than 2.2 million parents, over 2.5 million grandparents, and almost a million uncles/aunts.
By the end of follow-up, 3,042 (0.13%) parents, 171,732 (6.82%) grandparents, and 1,369 (0.15%) uncles/aunts had a diagnosis of Alzheimer's. The numbers for any dementia were 3,792 (0.17%) for parents, 197,843 (7.86%) for grandparents, and 1,697 (0.18%) for uncles/aunts.
Parents of persons with ADHD were 34% more likely to have any dementia, and 55% more likely to have Alzheimer's. Among grandparents of persons with ADHD, the association dropped to 10-11% more likely for any kind of dementia. Among aunts and uncles, it dropped to a 14% greater likelihood of Alzheimer's(similar to grandparents) and a 4% greater chance of any dementia. In this case, however, the results were not statistically significant, probably due in part to the much smaller sample size
Both with parents and grandparents of persons with ADHD, the risk of early onset of any kind of dementia was well over twice as high as the risk of late-onset.
"We found that ADHD aggregated with AD [Alzheimer's disease] and any dementia within families, and the strength of association attenuated with decreasing degree of genetic relatedness," the authors concluded, and called for further studies to identify genetic variants and family-wide environmental risk factors contributing to both conditions. If verified by such studies, that would indicate a need for "investigation of early-life psychiatric prevention on the development of neurodegenerative diseases in older age."
Individuals who are prescribed ADHD medications are much more likely to also be prescribed other medications both for psychiatric and non-psychiatric disorders.
Persons with ADHD have known to have high rates of psychiatric comorbidities. There is also growing evidence of somatic (non-psychiatric) comorbid disorders among youths with ADHD, such as metabolic syndrome (which can lead to type 2 diabetes) and chronic inflammation (such as asthma and allergic rhinitis). Much less is known, however, about comorbid conditions in adults with ADHD.
An international team of researchers looked for indicators of comorbid conditions in a nationwide cohort study using Swedish national registers. The target population was Swedish residents between the ages of 18 and 64 in 2013 and more specifically those who had been prescribed ADHD medication. They identified over 41,000 individuals who met these criteria, including over twenty thousand young adults aged 18-29 years, over sixteen thousand middle-aged adults aged 30-49 years, and over four thousand older adults aged 50-64. The remainder of the overall cohort were used as controls.
Young adults receiving ADHD medications were four times as likely to also be receiving somatic medications, and older adults were seven times as likely. The highest rate of co-medication -roughly five times more frequent than among controls - was for respiratory system medications. The second most common was for alimentary tract and metabolic system medications, with odds over four times higher than for controls. Cardiovascular system medications were the next most common, with odds among young adults receiving ADHD medications over four times those of controls, though reducing with age to being twice as common in older adults with ADHD. Patterns were similar among men and women.
Adults receiving ADHD medications were far more likely to also be receiving other psychotropic medications. Middle-aged adults were 21 times as likely to be dispensed such medications as controls, older adults eighteen times more likely, and younger adults fifteen times more likely.
For young adults prescribed ADHD medications, the most prevalent co-prescriptions were for addictive disorders, which were dispensed at over 26 times the rate for controls. For middle-aged and older adults, on the other hand, the most prevalent co-prescriptions were for antipsychotics, which were likewise dispensed at over 26 times the rate for controls. Results remained consistent for individuals who had an ADHD diagnosis in addition to an ADHD prescription.
In addition, individuals receiving ADHD medications were also on average taking more types of prescriptions, rising from 2.5 classes of medications at age 18 to five classes at age 64. For controls, the equivalent numbers were 0.9 types of medications at age 18, rising to 2.7 at age 64.
Looking at specific somatic medications prescribed, those for respiratory conditions were ones typically prescribed for asthma and allergic reactions, reinforcing a previously known association. Insulin preparations also had high rates of co-prescription, again further confirming the known association with obesity and diabetes.
On the other hand, the most commonly dispensed alimentary tract and metabolic system medications included proton pump inhibitors, typically prescribed for gastric/duodenal ulcers and gastroesophageal reflux disease. Sodium fluoride, prescribed to prevent dental caries, was also prominent. Neither of these is an established association and warrants further exploration.
Turning to psychotropic medications, the most frequent prescriptions were with drugs used to treat addictive disorders and with antipsychotics. Rates of opioid co-prescription were also notably high, a source of concern given the higher proclivity of persons with ADHD to substance use disorders.
Despite roughly 1 in 5 patients in opioid recovery having ADHD, less than 1 in 20 of those patients will be treated with ADHD medication.
A key aspect of ADHD is greater difficulty controlling urges, so it is no surprise that there is a strong association between ADHD and substance use disorders, and opioid addiction in particular. It's also known that stimulants are effective in reducing ADHD symptoms. That would suggest that ADHD patients being treated for opioid addiction should also be treated for ADHD.
How extensive is such complementary treatment? A Norwegian research team used national register data from the Norwegian Prescription Database to find out. They began by identifying all 9,235 individuals who were dispensed at least one opioid agonist prescription from 2015 through 2017.
Opioid agonists, such as methadone and buprenorphine (Suboxone), while opioids have properties that prevent withdrawal and reduce cravings. They can do this precisely by substituting a less dangerous slow-acting opioid for a more dangerous rapid-acting one. They are also less addictive because they do not generate the intense highs of fast-acting opioids. That greatly reduces the risk of overdose, and risk of relapse to more hazardous opioid use, and promotes connections with the professional healthcare sector.
About 7,500 Norwegians are undergoing opioid agonist therapy at any given time. During the three-year study period, roughly three out of four were dispensed buprenorphine and the remainder methadone.
Although somewhere around one in five patients on opioid agonist therapy have ADHD (estimates range from11 to 33%), the team found that less than one in twenty were also dispensed ADHD medication. In 2015, only 3.5 percent received ADHD medication, rising slightly to 4.6 percent in 2017. In 2017, 62 percent received methylphenidate, 42 percent received various amphetamines, and only five percent received non-stimulant atomoxetine (there was some overlap).
Patients on buprenorphine were 60 percent more likely to be dispensed ADHD medications than those on methadone.
The authors concluded, "Co-prescribing of CAS [centrally acting stimulant] and atomoxetine was low in the OAT [opioid agonist therapy] population in Norway, relative to the expected prevalence of ADHD in this patient group. Considering that up to a third of the OAT population is estimated to have ADHD, only 3.5 to 4.6% of patients received both ADHD medication and OAT opioids in Norway in the period from 2015 to 2017. Randomized-controlled trials evaluating ADHD medication in different doses are needed to improve the treatment of ADHD in the OAT population."
ADHD patients were found to be seven times more likely than controls to have first-degree relatives with ADHD.
Taiwan's National Health Insurance program is a single-payer system that covers 99.6% of the island's 23 million residents. It includes family relationships.
This enabled a Taiwanese study team to examine the comorbidity of psychiatric disorders among close relatives in the entire population over eleven years, beginning at the start of 2001 and concluding at the end of2011.
For greater certainty of diagnosis, only persons twice diagnosed with the same psychiatric disorder were included as index individuals. There were 431,887 index patients, 152,443 of whom were ADHD index patients.
These index patients were then compared with all of their first-degree relatives (FDRs): parents, children, siblings, and twins. This produced 1,017,430 patient-FDR pairs, of which 401,301 were ADHD patient-FDR pairs.
Next, four controls were matched by age, gender, and type relative to each case, resulting in 4,069,720 control pairs.
After adjusting for age, gender, urbanization, and income level, ADHD patients were seven times more likely than controls to have first-degree relatives with ADHD. They were also seven times more likely to have FDRs with major depressive disorder, four times more likely to have FDRs with autism spectrum disorder, twice as likely to have FDRs with bipolar disorder, and 80%more likely to have FDRs with schizophrenia.
German researchers study how useful EEG markers may or may not be in the treatment of full-spectrum ADHD as compared to sub-threshold ADHD.
Noting that to date, no study investigated potential behavioral and neural markers in adults with subthreshold ADHD as compared to adults with full syndrome ADHD and healthy controls, the German team of researchers at the University of Tübingen out to do just that, recruiting volunteers through flyers and advertisements.
Their ADHD sample consisted of 113 adults between 18 and 60 years of age (mean age 38) who fulfilled the DSM-IV-TR criteria of ADHD and were either not on medication or a steady dose of medication over the prior two months.
Another 46 participants (also mean age 38), whose symptoms did not reach the DSM-IV-TR criteria, were assigned to the group with subthreshold ADHD.
The control sample was comprised of 42 healthy participants (mean age 37).
Individuals with schizophrenia, bipolar disorder, borderline personality disorder, epilepsy, or traumatic brain injury were excluded from the sample, as were those with current substance abuse or dependence.
All participants were German-speaking Caucasians. There were no significant differences in gender, age, education, or verbal/nonverbal intelligence among the three groups.
Participants first completed an online pre-screening, which was followed up with an interview to confirm the ADHD diagnosis.
ADHD impairs executive functions, "defined as the 'top-down' cognitive abilities for maintaining problem-solving skills to achieve future goals." The researchers explored three categories of executive functioning: 1) capacity for inhibition, "the ability to inhibit dominant, automatic, or prepotent responses when necessary- 2) ability to shift, enabling smooth switching between tasks or mental sets; and 3) ability to update, "updating and monitoring of working memory representations." Participants took a battery of neuropsychological tests to assess performance in each category.
Significant differences emerged between the group with ADHD and healthy controls in all measures except one: the STROOP Reading test. But there were no significant differences between participants suffering from subthreshold and full-syndrome ADHD. Nor were there any significant differences between those with subthreshold ADHD and healthy controls.
The researchers also recorded electroencephalograms(EEGs) for each participant. In healthy individuals, there is little to no association between resting-state EEG spectral power measures and executive functions. In individuals with ADHD, some studies have indicated increased theta-to-beta ratios, while others have found no significant differences. This study found no significant differences between the three groups.
The authors concluded, "The main results of the study can be summarized as follows: First, increased executive function deficits (in updating, inhibition, and shifting functions) could be observed in the full syndrome ADHD as compared to the healthy control group while, on the electrophysiological level, no differences in the theta to the beta ratio between these groups were found. Second, we observed only slightly impaired neuropsychological functions and no abnormal electrophysiological activity in the subthreshold ADHD sample. Taken together, our data suggest some practical uses of the assessment of objective cognitive markers but no additional value of examining electrophysiological characteristics in the diagnosis of subthreshold and full syndrome ADHD in adulthood."
They added, "These findings deeply question the value of including resting EEG markers into the diagnostic procedure and also have implications for standard neurofeedback protocols frequently used in the treatment of ADHD, where patients are trained to reduce their theta power while simultaneously increasing beta activity."
After noting that the association between ADHD and obesity has been called into question because of small sample sizes, wide age ranges, self-reported assessments, and inadequate attention to potential confounders, an Israeli study team set out "to assess the association between board-certified psychiatrist diagnoses of ADHD and measured adolescent BMI [body mass index] in a nationally represented sample of over one million adolescents who were medically evaluated before mandatory military service."
The team distinguished between severe and mild ADHD. It also focused on a single age group.
All Israelis are subject to compulsory military service. In preparation for that service, military physicians perform a thorough medical evaluation. Trained paramedics recorded every conscript's height and weight.
The study cohort was divided into five BMI percentile groups according to the U.S. Centers for Disease Control and Prevention's BMI percentiles for 17-year-olds, and further divided by sex: <5th percentile (underweight), 5th-49th percentile (low-normal), 50th-84th percentile (high normal), 85th-94th percentile (overweight) and ≥95th (obese). Low-normal was used as the reference group.
Adjustments were made for sex, birth year, age at examination, height, country of birth (Israeli or other), socioeconomic status, and education level.
In the fully adjusted results, those with severe ADHD were 32% more likely to be overweight and 84% more likely to be obese than their typically developing peers. Limiting results to Israeli-born conscripts made a no difference.
Male adolescents with mild ADHD were 24% more likely to be overweight, and 42% more likely to be obese. Females with mild ADHD are 33% more likely to be overweight, and 42% more likely to be obese. Again, the country of birth made no difference.
The authors concluded, that both severe and mild ADHD was associated with an increased risk for obesity in adolescents at the age of 17 years. The increasing recognition of the persistence of ADHD into adulthood suggests that this dual morbidity may have a significant impact on the long-term health of individuals with ADHD, thus early preventive measures should be taken.
A French team of physicians conducted a systematic search of peer-reviewed literature to conduct a meta-analysis to examine the relationship between childhood ADHD and subsequent psychotic disorders.
What relationship, if any, might there be between childhood ADHD and subsequent psychotic disorders? Previous epidemiological studies have produced conflicting results.
A French team of physicians conducted a systematic search of the peer-reviewed literature to conduct a meta-analysis to examine this question in greater depth.
They pooled twelve studies with a combined total of 1.85 million participants, consisting of 124,095 with ADHD and just over 1.72 million controls.
The psychotic disorders analyzed included schizophrenia, schizophreniform disorder, schizotypal personality disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, and psychotic disorder not otherwise specified. These disorders had to be diagnosed after the diagnosis of ADHD in children and adolescents under 18 years old.
The meta-analysis found that persons diagnosed in childhood or adolescence with ADHD were well over four times more likely to have subsequent diagnoses of psychotic disorders than those without a diagnosis of ADHD. Limiting the meta-analysis to the six studies that were adjusted for confounders produced an identical result.
There were no statistically significant between-group differences for subgroup analyses comparing psychotic disorder or schizophrenia outcomes, cohort or case-control study design, and adjusted or unadjusted estimates. There were no significant differences between males and females.
Heterogeneity among studies was moderate (43%), and there was no sign of publication bias. Removing one study reduced heterogeneity to low levels (18%), while very slightly raising the odds of subsequent diagnosis of psychotic disorder. Looking only at the more restrictive diagnosis of schizophrenia also made no difference in the odds.
No matter how the data were analyzed, in all instances, the odds of subsequent diagnosis of psychotic disorder rose well over fourfold for those diagnosed with ADHD in their youth.
The authors concluded, "To improve our knowledge, further cohort studies should be conducted. Ideally, these studies would ensure a sufficiently long follow-up to account for the mean age at which P [psychotic disorders] develop. Such studies should consider the use of psychostimulants and the role of SUD [substance use disorder] in the causal path between ADHD and PD."
Meta-analysis shows clear correlation between maternal PCOS and offspring ADHD.
Polycystic ovary syndrome (PCOS) is a disorder affecting women of reproductive age, characterized by elevated levels of male hormones (androgens). The name is derived from the presence of cysts surrounding the ovum, which cause enlargement of the ovaries. Its cause remains unknown. There is speculation that high androgen levels could affect brain development in the fetus.
A team of Iranian researchers (Maleki et al.) published a twofold meta-analysis earlier this year exploring the relationship between PCOS and offspring ADHD. A systematic search of the peer-reviewed medical literature came up with six studies, consisting of three cohort studies, and three case-control studies.
A meta-analysis of the three case-control studies with a combined total of 79,978 participants found that children of mothers with PCOS were 42 percent more likely to develop ADHD.
A separate meta-analysis of the three cohort studies with a combined total of 325,435 participants produced essentially identical outcomes: children of mothers with PCOS were 43 percent more likely to develop ADHD.
There was no indication of publication bias in either meta-analysis and virtually no heterogeneity. Except for one case-control study, all studies were considered to be of high quality.
The authors concluded, "Our study showed that maternal PCOS is a risk factor for ADHD. Therefore, Screening for ADHD among children of these women should be considered as part of the comprehensive clinical care for women with PCOS."
More recently, a second-team (Dubey et al.), based in Texas, published a meta-analysis on the same subject. Their systematic search produced the same studies, but classified one study described as case-control by Malekiet al. as a cohort study.
Their meta-analysis of four cohort studies with a combined total of over two million participants (they counted participants differently than Maleki et al.) found that children of mothers with PCOS were 43 percent more likely to develop ADHD. Adjusting for confounders made no difference.
Again, there was no indication of publication bias, and between-study heterogeneity was virtually nil.
Considering they relied on the same studies, the fact that both teams reported identical outcomes is unsurprising, confirming there's a clear association between maternal PCOS and ADHD in offspring.
It is difficult enough for a typical child to manage type-1 diabetes. For a child that also has ADHD, with learning difficulties, attention and memory problems, and limitations in social communication, it can be all the more challenging to carry out the complex tasks necessary to maintain glycemic control (control of blood sugar levels) and avoid diabetic harm.
To explore the additional risk associated with ADHD among children with type-1 diabetes, an international research team used the Swedish national registers to conduct a nationwide population study. Sweden has a single-payer national health insurance system, and assigns unique personal identification numbers to all residents, making it easy to cross-reference through various population and health registers.
The team used the Swedish Diabetes Register to identify all individuals born in Sweden from 1973 onwards with childhood-onset type 1 diabetes diagnosed before age 18. They then restricted the cohort to those who had no diabetic complications at diagnosis and whose HbA1c values had been recorded within 5 years of diagnosis.
Also known as the glycated hemoglobin test, HbA1c is an indicator of the average blood sugar (glucose) level over the past three months. When glucose builds up in the blood, it binds to the hemoglobin in red blood cells. The HbA1ctest measures bound glucose. Since red blood cells live for about 3 months, the test shows the average blood glucose over that period.
The team also searched for records of diabetes-related kidney damage (nephropathy) and damage to the retina (retinopathy). Diabetic retinopathy is the leading cause of blindness among working-age adults.
The nationwide cohort consisted of 11,326 Swedish youths diagnosed with type-1 diabetes, of whom 415 (3.7%) were also diagnosed with ADHD.
Poor glycemic control, defined as mean HbA1c greater than 8.5%, was found in 38% of those with ADHD, twice the 19% found in those without neurodevelopmental disorders. After adjusting for confounders(sex, age at diabetes diagnosis, year of birth and year of diabetes diagnosis, another psychiatric morbidity, parental highest education level, parental psychiatric morbidity, smoking status, mean BMI [body mass index], and mean systolic and diastolic blood pressure), those with ADHD were 2.3 times as likely to have poor glycemic control.
Patients with ADHD were also almost twice as likely to suffer kidney damage, after adjusting for sex, age at diabetes diagnosis, year of birth, year of diabetes diagnosis, another psychiatric morbidity, parental highest education level, parental psychiatric morbidity, mean HbA1c levels, mean BMI, systolic and diastolic blood pressure, and smoking status.
After the same adjustments, patients with ADHD were found to be a third (33%) more likely to suffer retinal damage.
The team concluded, "childhood-onset type 1 diabetes patients with neurodevelopmental disorders, especially those with ADHD or intellectual disability, are more prone to poor glycemic control and a higher risk of chronic diabetic complications compared with those without neurodevelopmental disorders.
Further longitudinal studies with a more comprehensive evaluation of diabetes management and molecular data are needed to provide insight into potential mediators in the association between comorbid neurodevelopmental disorder and diabetes complications in type 1 diabetes."
Youths with ADHD are known to be more prone to language problems when compared with typically developing peers. To what extent does that affect their ability to share a narrative with others?
A Danish research team conducted a systematic review and meta-analysis of the peer-reviewed medical literature to explore this question. They stressed that this ability is important because "a narrative is a genre of discourse - a form of social communication used to derive meaning from experiences and to construct a shared understanding of events. In other words, it is the fundamental ability of orally producing a coherent story." They focused on the production of narratives rather than comprehension.
Studies had to have a minimum of 10 participants. They had to compare aspects of oral narrative production in children and adolescents with either a formal ADHD diagnosis or a score above a clinical cut-off on a validated ADHD rating scale to a control group of typically developing youths. Youths with confirmed autism spectrum disorder (ASD) or language impairment diagnoses were excluded. There were no constraints on IQ.
The team found sixteen studies with a combined total of 1,015 youths that met these criteria and were suitable for meta-analysis.
They examined seven aspects of oral narrative production:
· Coherence: A story structure that is logical and easy to follow in cause and sequence. There is a clear beginning, middle, and end. There are goals, attempts, and outcomes. A meta-analysis of nine studies with a combined total of 750 participants found youths with ADHD less coherent than their typically developing peers, with a medium effect size. There was virtually no between-study heterogeneity and no sign of publication bias.
· Cohesion: This ensures referencing of events and characters in a manner that enables the listener to grasp how characters, events, and ideas in a story are related. Ambiguous or contradictory references get in the way of this. A meta-analysis of eight studies with a combined total of 501 participants found youths with ADHD showed less cohesion than their typically developing peers, with a medium effect size. Again, with virtually no between-study heterogeneity, and no sign of publication bias.
· Disruptions: These can be sequence errors, misinterpretations, embellishments, or confabulations - fabricating imaginary experiences as compensation for loss of memory. A meta-analysis of six studies with 389 participants found youths with ADHD had more disruptions than their typically developing peers, with a small-to-medium effect size. There was virtually no between-study heterogeneity and no sign of publication bias.
· Fluency: Best explained in terms of errors that interfere with this quality, such as false starts, repeating words or sentences, and abandoning sentences without completing them. A meta-analysis of four studies with 220 participants found no difference in fluency between youths with ADHD and their typically developing peers.
· Production: This is a measure of output -overall length of the story, number of sentences, number of words. After adjusting for evidence of publication bias, a meta-analysis of twelve studies with 645 participants found no difference here.
· Syntactic complexity: This includes the extent of vocabulary and the use of proper grammar. A meta-analysis of six studies with 272 participants found youths with ADHD displayed less syntactic complexity than their typically developing peers, with a small-to-medium effect size. There was virtually no between-study heterogeneity and no sign of publication bi
· Internal state language: References to perceptions, thoughts, beliefs, and feelings. There were only two studies with 130 participants, so no meta-analysis was performed.
The authors concluded, "the results from the current meta-analysis suggest that children with ADHD have impairments in their narrative language. In particular, children with ADHD produce narratives that are less coherent, less cohesive, less syntactically complex, and include more disruptive errors than typically developing children do."
Both Taiwan and Sweden have universal single-payer health insurance systems that in effect track their entire national populations. With detailed health and other records on millions of individuals, with no significant exclusions, one can essentially eliminate sampling error, and also explore how associations vary by degree of familial/genetic relationship.
A Taiwanese research team used the Taiwan National Health Insurance Research Database to follow 708,517 family triads (father-mother-child) from 2001 through 2011. That's a total of over 2.1 million persons. The database covers over 99% of Taiwan's population.
Noting that previous studies had found links between maternal autoimmune diseases and ADHD in their offspring and that research on associations with paternal autoimmune diseases had been inconclusive, they were particularly interested in exploring the latter.
Children born from 2001 through 2008 were enrolled in the study. The investigators then noted the presence or absence of any autoimmune disease in their parents from 1996 through childbirth.
In Taiwan, expert panels review diagnostic information of severe systemic autoimmune diseases to confirm the diagnosis. Once confirmed, patient co-payments are waived. ADHD diagnoses are by board-certified psychiatrists.
To reduce the effect of confounding variables, adjustments were made for family demographic data (income level and residence), parental ages, parental mental disorders, and sex of children.
The presence of any maternal autoimmune diseases was associated with a 60% greater risk of ADHD in offspring. The risk was especially elevated for inflammatory bowel diseases (2.4 times the risk) and ankylosing spondylitis (twice the risk).
The presence of any paternal autoimmune diseases was also associated with an elevated risk of ADHD in offspring, although only about half as much as for maternal autoimmune diseases, with a 33% greater risk overall. The association was especially pronounced for psoriasis and ankylosing spondylitis, both doubling the risk of ADHD in offspring.
Meanwhile, half a world away, a joint Swedish, Norwegian, and U.S. team used the Swedish national registries to dig further into these associations. They did this by examining data not only from mothers and fathers, but from full siblings, aunts, uncles, and cousins as well, to probe genetic links.
The team used the Swedish registers to identify 5,178,225 individuals born in Sweden between 1960 and 2010 for whom the identity of the biological mother was known, excluding all who died or emigrated before age 10. They then used the registers to identify the aforementioned relatives.
The researchers only included autoimmune diseases with at least two thousand diagnosed individuals in the cohort, to avoid small sample effects.
They adjusted for sex and year of birth, but not "for another covariate that is often adjusted for (e.g. maternal education, family income, parental psychiatric disorder, parental AD [autoimmune disease] as these are likely not true confounders of the association between ADHD and ADD, but may rather represent either mediator between ADHD and AD's, or proxies of ADHD and/or AD risk or alternatively proxies for the associations we aim to measure."
The team found statistically significant associations between ADHD and autoimmune diseases in all categories of relatives. Mothers of children with ADHD were 29% more likely to have an autoimmune disease than those of typically developing children; fathers were 14% more likely to have an autoimmune disease; full siblings 19% more likely; aunts 12% more likely; uncles 7% more likely; and cousins 4% more likely.
Quantitative genetic modeling produced a significant genetic correlation, but no significant environmental correlation. Genetic correlation explained most, if not all, the covariance between ADHD and any autoimmune disease.
The authors concluded, "ADHD was to some degree more strongly associated with maternal than paternal AD's, but by using aunts and uncles in a genetically informative study design, we demonstrate that this difference cannot be readily explained by AD-mediated maternal effects. Quantitative genetic modeling further indicates that the familial co-aggregation of ADHD and ADs is partly due to shared genetic factors. In addition, biological aunts, uncles, and cousins must be assumed to share the little environment with the index individuals, in further support of shared genetic factors underlying the familial co-aggregation. Moreover, both epidemiological and molecular genetics studies have demonstrated positive genetic correlations between ADHD and ADs, in agreement with our findings."
The authors emphasize that these results do not warrant screening for autoimmune diseases among asymptomatic individuals with ADHD.
Hyperthyroidism, an overactive thyroid gland, occurs in about one in five hundred women. It has been tied to adverse effects in both mother and fetus, including pre-eclampsia (a condition in pregnancy characterized by high blood pressure, sometimes with fluid retention and excessive protein in the urine, which can indicate kidney damage), preterm delivery, heart failure, and in uteri retardation of growth.
In hypothyroidism, on the other hand, thyroid activity is abnormally low, which retards growth and mental development. It is particularly common in regions with widespread iodine deficiency. Depending on the region, it affects one in three hundred to one in thirty women. Maternal hypothyroidism is associated with an increased risk of pre-eclampsia, premature separation of the placenta from the wall of the uterus, miscarriage, in uteri growth retardation, and fetal death.
The fetus relies on maternal thyroid hormones until its own thyroid function initiates halfway through pregnancy. As we have just seen, this direct link in the early stages of pregnancy has serious consequences described above. Does it also affect the risk of developing ADHD in offspring?
A team of researchers based in Hong Kong reformed a comprehensive search of the peer-reviewed medical literature on this subject. It then conducted two meta-analyses, one examining maternal hyperthyroidism during pregnancy, the other on maternal hypothyroidism.
The meta-analysis for maternal hyperthyroidism during pregnancy combined two nationwide cohort studies with a total of over 3.1 million persons, using the Danish and Norwegian medical registries. It found a slight but significant association with ADHD in offspring.
The meta-analysis for maternal hypothyroidism during pregnancy included the same two nationwide cohort studies, plus an Israeli nationwide cohort study (along with a tiny U.S. cohort study), with a total of over 3.4 million persons. It likewise found a slight but significant association with ADHD in offspring.
Though the component studies did some assessment of confounders, the authors of the meta-analyses noted, "By including a more comprehensive range of confounding factors and biologically relevant covariate (e.g. thyroxine treatment), future studies are warranted to re-visit the association between maternal thyroid dysfunction and various health outcomes in offspring."
The mechanisms underlying the association between ADHD symptoms and suicidal ideation are poorly understood. A team of researchers from France and Montreal set out to explore this relationship with 2,331 French college students.
The students were participants in the internet-based student Health Research Enterprise project, a prospective population-based cohort study of students in higher education institutions in France. The i-Share study includes a longitudinal collection of data on childhood and family history, lifestyle, health information, and psychosocial examinations during the college years and beyond. 15,528 participants were included in the initial cohort, of which 2,331 completed all the questionnaires and did not have any missing data at the one-year follow-up. The mean age was 21, and four out of five were women. ADHD symptoms were assessed at the initiation of the study. Suicidal ideation was evaluated through a questionnaire completed a year later. Before that, three months after initiation, participants filled out a mental health survey that inquired about two potential mediators of suicidal ideation: depressive symptoms and self-esteem.
After adjusting for potential confounding factors (e.g., sex, childhood adversity, living conditions, and substance use) and taking into account the role of the mediators, the effect of ADHD symptoms on suicidal ideation (i.e., the direct effect) was no longer statistically significant, whereas pathways through depressive symptoms and self-esteem were both statistically significant. The pathway through depressive symptoms accounted for 25% of the total effect, while the pathway through self-esteem accounted for 64% of the total effect. Most of this indirect effect of self-esteem was in turn explained by the unique effect of self-esteem (not explained by depression), which accounted for 45% of the association, whereas a smaller part was explained by the effect of self-esteem through depression (accounting for 19% of the total effect). Ultimately, both mediators had the same effect (45% vs. 44%). Patterns were similar for males and females.
The authors caution that the study sample was not representative of the population of college students. It relied on volunteers, females were overrepresented, and the dropout ratio was very high. Participants in the final sample were more satisfied with their financial resources during their college years and during childhood, and less frequently consumed tobacco, than those in the initial cohort. The researchers recommend that ADHD patients be screened for self-esteem, and point out that other studies have indicated that exercise, Internet support groups, and interpersonal group therapy can build self-esteem in young people.
Comorbidities contribute substantially to premature mortality risks in ADHD patients, but even those with ADHD alone are at a 40% greater risk.
The Nordic countries maintain detailed registers of their inhabitants. This enables researchers to examine patterns over entire nations. An international research team used the Swedish national registers for a prospective cohort study of 2,675,615 persons in the Medical Birth Register born in Sweden over 27 years from January 1, 1983, through December 31, 2009. Follow-up was completed in December 2013, with the oldest cohort member aged 31. The mean age at study entry was 6, and the mean at follow-up was 11.
Using personal identification numbers, researchers were able to cross-reference with the National Patient Register and the National Drug Register. From this, they determined that 86,670 members of the cohort (3.2 percent) had ADHD, based either on records of clinical diagnosis or of prescription of ADHD drugs. Psychiatric comorbidities were likewise identified in the National Patient Register.
These comorbidities were significantly more prevalent in the ADHD population than in the rest of the cohort. For example, whereas only 2.2% of the non-ADHD group was diagnosed with substance use disorder (SUD), 13.3% of the ADHD group also had SUD, a six-fold difference. For depression, it was a seven-fold difference; for schizophrenia a nine-fold difference.
The ADHD group had a significantly higher risk of premature death from all causes than the non-ADHD group, with an adjusted hazard ratio(HR) of 3.94 (95% CI 3.51-4.43). Unintentional injury (36%) and suicide (31%)were the leading causes of death in the ADHD group. Those with ADHD were more than eight times more likely to die by suicide than non-ADHD individuals and roughly four times more likely to die from unintentional injury.
The vast majority of the increased risk appears to be associated with comorbid psychiatric conditions. Those with ADHD but no diagnosed comorbidities had an adjusted HR of 1.41 (95% CI 1.01-1.97). With a single comorbidity, the HR more than doubled to 3.71 (95% CI 2.88-4.78). With four or more comorbidities, it rose to a staggering 25.22 (95% CI 19.6-32.46).
The comorbid condition with the greatest impact was SUD, which increased the risk eight-fold by comparison with those with only ADHD (HR= 8.01, 95% CI 6.16-10.41). Anxiety disorder, schizophrenia, and personality disorder increased the risk about fourfold. Bipolar disorder, depression, and eating disorders increased risk by roughly two and a half times.
The co-variate analysis helped tease out what portion of the risk was associated with ADHD alone versus comorbid conditions. Adjusting for the year of birth, sex, birth weight, maternal age at birth, parental educational level, and parental employment status, those with ADHD (including comorbid conditions)were 2.7 times more likely to prematurely die of natural causes than those without. Adjusting for comorbid psychiatric conditions completely eliminated the risk from ADHD alone (HR = 1.01, 95% CI.72-1.42).
Likewise, those with ADHD (including comorbid conditions)were six times as likely to die of unnatural causes. Adjusting for early-onset comorbid disorders (such as conduct disorders, autism spectrum disorder, and intellectual disability) only modestly reduced the HR to 5.3, but further adjusting for later-onset comorbid disorders(including substance use disorder, depressive disorder, bipolar disorder, anxiety disorder, schizophrenia, personality disorder, and eating disorders)reduced the HR to 1.57 (95% CI 1.35-1.83), and reduced it to insignificance in the case of suicide (HR = 1.13, 95% CI .88-1.45).
Summing up, the lion's share of the greater risk of premature death in persons with ADHD is attributable to psychiatric comorbidities. Nevertheless, those with ADHD alone still face a 40 percent greater risk than those without ADHD.
The study did not examine the effects of ADHD medication, which the authors state should be analyzed because of documented potential benefits on ADHD symptoms and comorbid disorders.
The authors concluded, Among adults, early-onset psychiatric comorbidity contributed substantially to the premature mortality risks due to natural causes. On the other hand, later-onset psychiatric comorbidity, especially SUD, explained a substantial part of the risk for unnatural deaths, including all the risk of suicide deaths and most of the deaths due to unintentional injuries. These results suggest that overall health conditions and risk of psychiatric comorbidity should be evaluated clinically to identify high-risk groups among individuals with ADHD.
A newly published meta-analysis of 57 studies encompassing almost a third of a million participants has uncovered a very strong association between ADHD and suicide, a strong association with suicidal ideation, and a small-to-medium association with suicide attempts.
The population examined included children, adolescents, and adults. Only persons formally diagnosed were considered to have ADHD. Studies that included self-injuries without suicidal intent were excluded. Most of the studies focused on European and American populations, with one in six from other locations, mostly Asian.
The most striking result was for actual suicides. The odds ratio (OR) for four datasets encompassing roughly one hundred forty thousand participants was 6.69 (95% CI 3.24 to 17.39, p <.0001). As a frame of reference, an OR of 1.5 is a small effect size, 2.5 is a medium one, and 4.3 is a large one. That means the effect size, in this case, is very large.
For suicidal ideation, 23 datasets with a combined total of just over 73,000 participants produced a medium-to-large OR of 3.5 (95% CI 2.94 to 4.25, p < .0001). In three datasets with more than nine thousand participants that adjusted for confounders, the adjusted OR was 4.5 (95% CI 1.72 to 11.63, p < .0001), indicating a large effect size.
For suicide attempts, 44 datasets encompassing over 228,000 participants produced an OR of 2.4 (95% CI1.64 to 3.43, p < .0001). In six datasets with over 65,000 participants that adjusted for confounders, the adjusted OR dropped to 2.1 (95% CI 1.27 to 3.47,p = .005).
There was no evidence of publication bias for studies on suicides or suicidal ideation, but significant evidence of bias for studies on suicide attempts (Eager's p = .03). This means that studies with positive findings were more likely to be published than negative studies.
There was, however, strong statistical evidence for differences between studies in the size of their ORS. This indicates that the pooled OR cannot summarize results from all datasets, and more work is needed to clarify why the ORS differs among studies.
The authors appropriately caution that their meta-analysis is not informative on cause-effect relationships, but offer as a hypothesis that ADHD contributes to suicidal spectrum behaviors (SSBs) through Impulsivity, a core symptom of ADHD, along with impaired decision-making and risk-taking, that characterize several individuals with ADHD Additionally, a sizeable portion of individuals with ADHD present with deficits in executive functions. As executive functions are implicated in the regulation of impulse control and emotions, executive dysfunctions may contribute to SSBs.
Given the large to very large effect sizes for suicide and suicidal ideation, the authors advise: Awareness of this association should prompt practitioners to systematically screen for SSBs in patients with ADHD at the first assessment and at each follow-up, which in turn should contribute to decreasing the risk of SSB's. This is particularly noteworthy considering that questionnaires/scales commonly used to screen/assess ADHD symptoms generally do not include suicide-related items.
Treating ADHD With Methylphenidate in Adults With Autism
A team from Harvard Medical School and Massachusetts General Hospital conducted a six-week open-label trial of liquid-formulation extended-release methylphenidate (MPH-ER) to treat ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). ASD is a lifelong disorder with deficits in social communication and interaction and restricted, repetitive behaviors. Roughly half of those diagnosed with ASD also are diagnosed with ADHD.
This was the first stimulant trial in adults with both ASD and ADHD. There were twelve males and three female participants, all with moderate to severe ADHD, and in their twenties, with IQ scores of at least 85.
The use of a liquid formulation enabled doses to be raised very gradually, starting with a daily dose of 5 mg(1mL) and titrating up to 60 mg over the first three weeks, then maintaining that level through the sixth week. Participants were reevaluated for ADHD symptoms every week during the six-week trial. The severity of ASD was assessed at the start, midpoint, and conclusion of the trial, as were other psychiatric symptoms.
Before the trial, researchers agreed on a combination of targets on two clinician-rated scoring systems that would have to be reached for treatment to be considered successful. One is a score of 2 or less on the CGI-S, a measure of illness severity, with scores ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The other is a reduction of at least 30 percent in the AIS RS score, which combines each of 18 symptoms of ADHD on a severity grid (0=not present; 3=severe; overall minimum score: 0; overall maximum score: 54).
After the trial, twelve of the fifteen patients (80 percent) met the preset conditions for success. Fully fourteen (93 percent) saw a ≥ 30 percent reduction in their AISRS score, while twelve scored ≤ 2 on illness severity.
However, when using the patient-rated ASRS scoring system, only five (33 percent) saw a ≥ 30 percent reduction in ADHD severity.
Thirteen participants (87percent) reported at least one adverse event, and nine (60 percent) reported two or more. One reported a serious adverse event (attempted suicide) in a patient with multiple prior attempts. Because the attempt was not deemed due to medication, they continued and completed the trial. Seven participants experienced titration-limiting adverse events (headaches, palpitations, jaw pain, and insomnia). Headache was most frequent (53%), followed by insomnia and anxiety(33% each), and decreased appetite (27%).
During the trial, weight significantly decreased, while pulse significantly increased. There were no significant differences in other vital and cardiovascular measurements.
The authors concluded, "this OLT of short-term MPH-ER therapy documents that acute treatment with MPH-ER in young adults with ASD was associated with significant improvement in ADHD symptoms, mirroring the typically-expected magnitude of response observed in adults with only ADHD. Treatment with MPH-ER was well-tolerated, though associated with a higher than expected frequency of adverse events."
They also cautioned, "The results of this study need to be considered in light of some methodological limitations. This was an open-label study; therefore, assessments were not blind to treatment. We did not employ a placebo control group and, therefore, cannot separate the effects of treatment from time or placebo effects. ... firmer conclusions regarding the safety and efficacy of MPH-ER for the treatment of ADHD in HF-ASD populations await results from larger, randomized, placebo-controlled clinical trials."
ADHD is far more prevalent among persons with AUD (roughly20 percent) than it is in the general population. The most accurate way of identifying ADHD is through structured clinical interviews. Given that this is not feasible in routine clinical settings, ADHD self-report scales offer a less reliable but much less resource-intensive alternative. Could the latter be calibrated in a way that would yield diagnoses that better correspond with the former?
A German team compared the outcomes of both methods on 404 adults undergoing residential treatment for AUD. All were abstinent while undergoing evaluations. First, to obtain reliable ADHD diagnoses, each underwent the Diagnostic Interview for ADHD in Adults, DIVA. If DIVA indicated probable ADHD, two expert clinicians conducted successive follow-up interviews. ADHD was only diagnosed when both experts concurred with the DIVA outcome.
Participants were then asked to use two adult ADHD self-report scales, the six-item Adult ADHD Self Report Scale v1.1 (ASRS) and the 30-item Conner's Adult ADHD Rating Scale (CAARS-S-SR). The outcomes were then compared with the expert interview diagnoses.
Using established cut-off values for the ASRS, less than two-thirds of patients known to have ADHD were scored as having ADHD by the test. In other words, there was a very high rate of false negatives. Lowering the cut-off to a sum score ≥ 11 resulted in an incorrect diagnosis of more than seven out of eight. But the rate of false positives shared to almost two in five. Similarly, the CAARS-S-SR had its greatest sensitivity (ability to accurately identify those with ADHD) at the lowest threshold of ≥ 60, but at a similarly high cost in false positives (more than a third).
The authors found it was impossible to come anywhere near the precision of the expert clinical interviews. Nevertheless, they judged the best compromise to be to use the lowest thresholds on both tests and then require positive determinations from both. That led to successfully diagnosing more than three out of four individuals known to have ADHD, with a false positive rate of just over one in five.
Using this combination of the two self-reporting questionnaires with lower thresholds, they suggest, could substantially reduce the under-diagnosis of ADHD in alcohol-dependent patients.
Autism spectrum disorder (ASD) is frequently comorbid with ADHD. Among adults with ADHD, as many as half are reported to also have ASD.
A Dutch team set out to answer two questions:
1) Do adults with ADHD and comorbid ASD experience less effectiveness in pharmacological treatment for ADHD than adults with only ADHD
2) Do adults with ADHD and comorbid ASD experience different or more severe side effects of pharmacological treatment for ADHD than adults with only ADHD, as measured in side effect scores, blood pressure, heart rate, and weight?
This was a retrospective study, using well-documented medical records, of the effects of drug treatment with methylphenidate (MPH), dexamphetamine (DEX), atomoxetine (ATX), bupropion, or modafinil.
The researchers compared 60 adults with comorbid ASD and ADHD to 226 adults with only ADHD. ADHD symptoms were scored using the Conner's ADHD Rating Scale: Self Report-Short Version (CAA RS: S-S). Side effects of ADHD medication were measured using either a 13-item or 20-item checklist with 4-point scales for item response. Researchers also tracked changes in body weight, blood pressure, and heart rate.
Following treatment, ADHD symptoms among the comorbid group declined by a quarter, and among the ADHD-only group by almost a third. There was no significant difference between men and women. Controlling for age, gender, and ADHD subtype, a comorbid diagnosis of ASD also did not significantly affect ADHD symptom reduction.
Turning to side effects, in the ADHD+ASD group, there were significant increases in decreased appetite and weight loss, and decreases in agitation, anxiety, and sadness/unhappiness. In the ADHD-only group, there were significant increases in decreased appetite, weight loss, and dry mouth, and decreases in sleeping disorder, nervousness, agitation, anxiety, and sadness/unhappiness. Yet there were no significant differences between the two groups. Side effects increased and decreased similarly in both. Likewise, there were no significant differences between the groups in changes in heart rate and blood pressure. The only significant difference in medication dosage was for bupropion, which was higher in the ADHD+ASD group, though without any sign of the difference in side effects.
The authors concluded that this retrospective study "showed pharmacological treatment of adults with diagnoses of ADHD and ASD to be just as successful as the pharmacological treatment of adults with only ADHD," but cautioned that "randomized controlled trial should be conducted to evaluate the effectiveness and possible side effects of pharmacological treatment for ADHD in patients with ASD more reliably."
An Israeli team compared eating habits and body mass index(BMI) in adults with and without ADHD. They recruited 60 students from Hebrew University in Jerusalem between 20 and 30 years old. To avoid bias due to particular diets, the authors excluded vegetarians and vegans, as well as persons with chronic diseases that require altered diets, such as diabetes, inflammatory bowel diseases, and chronic kidney disease. Twenty-nine of the participants had been diagnosed with ADHD.
All participants filled out the Food Frequency Questionnaire, a semi-quantitative scale querying about 119 food items. Based on World Health Organization guidelines, it distinguished between "healthy" items (such as vegetables, fruits, whole grains, and minimally processed foods)and "unhealthy" ones (such as cookies, processed meats, and other processed foods). The data obtained from the questionnaires were linked to a nutrient database to estimate daily nutrient intake. BMI was calculated from heights and weights reported by the students.
No significant differences were found between the two groups for servings, calories, fats, carbohydrates, and proteins. Yet, the ratio of healthy to unhealthy portions was significantly higher among controls than among those with ADHD. Those without ADHD consumed about a quarter more servings of healthy food and about a quarter fewer servings of unhealthy food.
On average, BMI levels were about 13 percent higher in participants with ADHD than among those without, meaning they were significantly more likely to be overweight. This finding is consistent with many prior studies.
The authors concluded, "Although participants in both groups consumed similar amounts of servings, calories, and nutrients, students with ADHD reported eating lower amounts of healthy food and higher amounts of unhealthy food. The results suggest that ADHD is not associated with general overeating, but with a biased proportion of unhealthy versus healthy food consumption."
They also recognized limitations to their study. One was a relatively small sample size and the fact that all participants were recruited from a single university. Another is that they did not try to fully evaluate the effects of medication, other than to note the absence of significant differences in food choices between those who used medication regularly and those who used it only occasionally. An unrecognized limitation was the exclusive reliance on self-reporting, both for food consumption, weight, and height.
Despite these limitations, this study is an important first step toward understanding the eating habits of people with ADHD. It suggests to me that those treating ADHD should promote healthy lifestyles, as that should reduce ADHD's known risks of obesity and adverse medical outcomes.
All Swedish residents have their health records tracked through unique personal identity numbers. That makes it possible to identify psychiatric and medical disorders with great accuracy across an entire population, in this case encompassing more than five and a half million adults aged 18 to 64. A subgroup of more than 1.6 million persons between the ages of 50 and 64 enabled a separate examination of disorders in older adults.
Slightly over one percent of the entire population (about 61,000) was diagnosed with ADHD at some point as an adult. Individuals with ADHD were nine times as likely to suffer from depression as were adults not diagnosed with ADHD. They were also more than nine times as likely to suffer from anxiety or a substance use disorder, and twenty times as likely to be diagnosed with bipolar disorder. These findings are very consistent with reports from clinical samples in the USA and Europe.
Adults with ADHD also had elevated levels of metabolic disorders, being almost twice as likely to have high blood pressure, and more than twice as likely to have type 2 diabetes. Persons with ADHD but without psychiatric comorbidities were also almost twice as likely to have high blood pressure, and more than twice as likely to have type2 diabetes.
Similar patterns were found in men and women with ADHD, although comorbid depression, bipolar disorder, and anxiety were moderately more prevalent in females than in males, whereas substance use disorder, type 2 diabetes, and hypertension were more prevalent in males than in females.
ADHD was less than a third as prevalent in the over-50 population as in the general adult population. Nevertheless, individuals in this older group with ADHD were twelve times as likely to suffer from depression, anxiety, or substance use disorders, and more than 23 times as likely to be diagnosed with bipolar disorder as their non-ADHD peers. They were also 63% more likely to have high blood pressure, and 72% more likely to have type 2 diabetes.
The authors noted, "Although the mechanisms underlying these associations are not well understood, we know from both epidemiologic and molecular genetic studies that a shared genetic predisposition might account for the coexistence of two or more psychiatric conditions. In addition, individuals with ADHD may experience increased difficulties as the demands of life increase, which may contribute to the development of depression and anxiety." As for associations with hypertension and type 2 diabetes, these "might reflect health risk behaviors among adult patients with comorbid ADHD in addition to a shared biological substrate. As others have noted, inattention, disinhibition, and disorganization associated with ADHD could make it difficult for patients to adhere to treatment regimens for metabolic disorders." They concluded that "Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes."
A Norwegian team based at the University of Bergen recently performed a population study using the country's detailed national health registries. With records from more than two and a half million Norwegians, the team examined what, if any, associations could be found between ADHD and nine autoimmune diseases: ankylosing spondylitis, Crohn's disease, iridocyclitis, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and ulcerative colitis.
After adjusting for age and maternal education, the team found no association between ADHD and five of the nine autoimmune disorders: type 1 diabetes, rheumatoid arthritis, iridocyclitis, systemic lupus erythematosus, and multiple sclerosis. In the case of ankylosing spondylitis, it found no association with males with ADHD, but a negative association with females. Females with ADHD were less likely to have ankylosing spondylitis. The adjusted odds ratio (AOR) was 0.56 (95% CI 0.32-0.96).
Positive associations were found for only three autoimmune diseases. The strongest was for psoriasis, with adjusted odds ratios of 1.6(95% CI 1.5-1.7) for females and 1.3 (95% CI 1.2-1.4) for males. When further adjusted for education, smoking, and body mass index (BMI), however, the adjusted odds ratio for females with ADHD dropped to 1.3 (95% CI 1.0-1.6).
The second-strongest association was with Crohn's disease. But here it was only among women. The odds ratio, in this case, was 1.4 (95% CI 1.2-1.8). Males with ADHD were less likely to have Crohn's disease, with an odds ratio of 0.71 (95% CI 0.54-0.92).
Finally, females with ADHD were slightly more likely to have ulcerative colitis, with a barely significant odds ratio of 1.3 (95% CI 1.1-1.5), while no such association was found for males with ADHD, whose odds ratio was a statistically non-significant 0.9.
Given the large sample size of over two and a half million, this is no underpowered study. It found no association between ADHD and the generic category of autoimmune disorders. Furthermore, it is a stretch to argue that there are any clear and clinically meaningful links between ADHD and any of the specific disorders that were analyzed in this study. The small and often opposite effect sizes may simply reflect limitations with the data (presumed autoimmune disorders were identified based on drugs prescribed), or other unidentified confounding factors.
A working group of the International League Against Epilepsy(ILAE), consisting of twenty experts spanning the globe (U.S., U.K., France, Germany, Japan, India, South Africa, Kenya, Brazil), recently published "consensus paper" summarizing and evaluating what is currently known about comorbid epilepsy with ADHD, and best practices.
ADHD is two to five times more prevalent among children with epilepsy. The authors suggest that ADHD is underdiagnosed in children with epilepsy because its symptoms are often attributed either to epilepsy itself or to the effects of antiepileptic drugs (AEDs).
The working group did a systematic search of the English-language research literature. It then reached a consensus on practice recommendations, graded on the strength of the evidence.
Three recommendations were graded A, indicating they are well-established by evidence:
· Children with epilepsy with comorbid intellectual and developmental disabilities are at increased risk of ADHD.
· There is no increased risk of ADHD in boys with epilepsy compared to girls with epilepsy.
· The anticonvulsant valproate can exacerbate attentional issues in children with childhood absence epilepsy (absence seizures look like staring spells during which the child is not aware or responsive). Moreover, a single high-quality population-based study indicates that valproate use during pregnancy is associated with inattentiveness and hyperactivity in offspring.
Four more were graded B, meaning they are probably useful/predictive:
· Poor seizure control is associated with an increased risk of ADHD.
· Data support the ability of the Strengths and difficulties questionnaire (SDQ) to predict ADHD diagnosis in children with epilepsy: "Borderline or abnormal SDQ total scores are highly correlated with the presence of a validated psychiatric diagnosis (93.6%), of which ADHD is the most common (31.7%)." The SDQ can therefore be useful as a screening tool.
· Evidence supports the efficacy of methylphenidate in children with epilepsy and comorbid ADHD.
· Methylphenidate is tolerated in children with epilepsy.
At the C level of being possibly useful, there is limited evidence that supports that atomoxetine is tolerated in children with ADHD and epilepsy and that the combined use of drugs for ADHD and epilepsy (polytherapy) is more likely to be associated with behavioral problems than monotherapy. In the latter instance, "Studies are needed to elucidate whether the polytherapy itself has resulted in the behavioral problems, or the combination of polytherapy and the underlying brain problem reflects difficult-to-control epilepsy, which, in turn, has resulted in the prescription of polytherapy."
All other recommendations were graded U (for Unproven), "Data inadequate or conflicting; treatment, test or predictor unproven." These included three where the evidence is ambiguous or insufficient:
· Evidence is conflicted on the impact of early seizure onset on the development of ADHD in children with epilepsy.
· Tolerability for amphetamine in children with epilepsy is not defined.
· Limited evidence exists for the efficacy of atomoxetine and amphetamines in children with epilepsy and ADHD.
There were also nine U-graded recommendations based solely on expert opinion. Most notable among these:
· Screening of children with epilepsy for ADHD beginning at age 6.
· Reevaluation of attention function after any change in antiepileptic drug.
· Screening should not be done within 48 hours following a seizure.
· ADHD should be distinguished from childhood absence epilepsy based on history and an EEG with hyperventilation.
· Multidisciplinary involvement in transition and adult ADHD clinics is essential as many patients experience challenges with housing, employment, relationships, and psychosocial wellbeing.
An international team of researchers has carefully examined the best current evidence and found strong evidence for an association between asthma and ADHD by combining a meta-analysis of prior data with a new analysis of the Swedish population.
The meta-analysis identified 46 datasets with a total of more than 3.3 million persons. It computed an unadjusted (odds)'s ratio (OR) of 1.7, which indicates that ADHD patients have about twice the risk of developing asthma compared with people without ADHD. Limiting the meta-analysis to studies that adjusted for confounding factors, 30 datasets with more than a third of a million participants still led to an adjusted (odds)' ratio of 1.5 (95% CI 1.4 - 1.7). The likelihood of obtaining this result by chance in such a large sample would be less than one in ten thousand.
When the team further checked this result against the results for the Swedish population of more than one and a half million persons, the (odds) ratio was almost identical to 1.6. Adjusting for confounding factors reduced it to 1.5 (95% CI 1.41 - 1.48). That means the findings are very robust: asthma and ADHD are associated, with an (odds)'ratio of 1.5, after adjusting for confounding factors.
What does this small but statistically very reliable association between asthma and ADHD mean? For researchers, it suggests that the two disorders may have common risk factors and that the search for these shared risk factors might lead to improved treatments. These risk factors might also be shared with two other somatic conditions for which ADHD patients are at increased risk: obesity and eczema. Common inflammatory processes may account for this overlap among disorders. Clinicians should be aware that children with asthma have an increased risk for ADHD, although, given the small association, systematic screening may not be warranted. But given that ADHD might interfere with asthma medication compliance, the disorder should be considered among noncompliant youth, especially among those who show other evidence of inattention, poor memory, or disorganization.
There is a growing interest (and controversy) in 'adult-onset ADHD. No current diagnostic system allows for the diagnosis of ADHD in adulthood, yet clinicians sometimes face adults who meet all criteria for ADHD, except for age at onset. Although many of these clinically referred adult-onset cases may reflect poor recall, several recent longitudinal population studies have claimed to detect cases of adult-onset ADHD that showed no signs of ADHD as a youth (Agnew-Blais, Polanczyk et al. 2016, Caye, Rocha, et al. 2016). They conclude, not only that ADHD can onset in adulthood, but that childhood-onset and adult-onset ADHD may be distinct syndromes(Moffitt, Houts, et al. 2015)
In each study, the prevalence of adult-onset ADHD was much larger than the prevalence of childhood-onset adult ADHD). These estimates should be viewed with caution. The adults in two of the studies were 18-19 years old. That is too small a slice of adulthood to draw firm conclusions. As discussed elsewhere (Faraone and Biederman 2016), the claims for adult-onset ADHD are all based on population as opposed to clinical studies.
Population studies are plagued by the "false positive paradox", which states that, even when false positive rates are low, many or even most diagnoses in a population study can be false.
Another problem is that the false positive rate is sensitive to the method of diagnosis. The child diagnoses in the studies claiming the existence of adult-onset ADHDused reports from parents and/or teachers but the adult diagnoses were based on self-report. Self-reports of ADHD in adults are less reliable than informant reports, which raises concerns about measurement error. Another longitudinal study found that current symptoms of ADHD were under-reported by adults who had had ADHD in childhood and over-reported by adults who did not have ADHD in childhood(Sibley, Pelham, et al. 2012). These issues strongly suggest that the studies claiming the existence of adult-onset ADHD underestimated the prevalence of persistent ADHD and overestimated the prevalence of adult-onset ADHD. Thus, we cannot yet accept the conclusion that most adults referred to clinicians with ADHD symptoms will not have a history of ADHD in youth.
The new papers conclude that child and adult ADHD are "distinct syndromes", "that adult ADHD is more complex than a straightforward continuation of the childhood disorder" and that adult ADHD is "not a neurodevelopmental disorder". These conclusions are provocative, suggesting a paradigm shift in how we view adulthood and childhood ADHD. Yet they seem premature. In these studies, people were categorized as adult-onset ADHD if full-threshold add had not been diagnosed in childhood. Yet, in all of these population studies, there was substantial evidence that the adult-onset cases were not neurotypical in adulthood (Faraone and Biederman 2016). Notably, in a study of referred cases, one-third of late adolescent and adult-onset cases had childhood histories of ODD, CD, and school failure(Chandra, Biederman, et al. 2016). Thus, many of the "adult onsets" of ADHD appear to have had neurodevelopmental roots.
Looking through a more parsimonious lens, Faraone and Biederman(2016)proposed that the putative cases of adult-onset ADHD reflect the existence of subthreshold childhood ADHD that emerges with full threshold diagnostic criteria in adulthood. Other work shows that subthreshold ADHD in childhood predicts onsets of full-threshold ADHD in adolescence(Lecendreux, Konofal, et al. 2015). Why is onset delayed in subthreshold cases? One possibility is that intellectual and social supports help subthreshold ADHD youth compensate in early life, with decompensation occurring when supports are removed in adulthood or the challenges of life increase. A related possibility is that the subthreshold cases are at the lower end of a dimensional liability spectrum that indexes risk for onset of ADHD symptoms and impairments. This is consistent with the idea that ADHD is an extreme form of a dimensional trait, which is supported by twin and molecular genetic studies(Larsson, Anckarsater, et al. 2012, Lee, Ripke, et al. 2013). These data suggest that disorders emerge when risk factors accumulate over time to exceed a threshold. Those with lower levels of risk at birth will take longer to accumulate sufficient risk factors and longer to onset.
In conclusion, it is premature to accept the idea that there exists an adult-onset form of ADHD that does not have its roots in neurodevelopment and is not expressed in childhood. It is, however, the right time to carefully study apparent cases of adult-onset ADHD to test the idea that they are late manifestations of a subthreshold childhood condition.
If you've ever wondered how experts make treatment recommendations for patients with ADHD, take a look at this ADHD treatment decision tree that my colleagues and I constructed for our "Primer" about ADHD,http://rdcu.be/gYyV.
Although a picture is worth a thousand words, keep in mind that this infographic only gives the bare bones of a complex process. That said, it is telling that one of the first questions an expert asks is if the patient has a comorbid condition that is more severe than ADHD. The general rule is to treat the more severe disorder first and after that condition has been stabilized plan a treatment approach for the other condition. Stimulants are typically the first-line treatment due to their greater efficacy compared with non-stimulants.
When considering any medication treatment for ADHD safety is the first concern, which is why medical contraindications to stimulants, such as cardiovascular issues or concerns about substance abuse, must be considered. For very young children (preschoolers) family behavior therapy is typically used before medication. Clinicians also must deal with personal preferences. Some parents and some adolescents and adults with ADHD simply don't want to take stimulant medications for the disorder. When that happens, clinicians should do their best to educate them about the costs and benefits of stimulant treatment.
If, as is the case for most patients, the doctor takes the stimulant arm of the decision tree, he or she must next decide if methylphenidate or amphetamine is more appropriate. Here there is very little guidance for doctors. Amphetamine compounds are a bit more effective, but can lead to greater side effects. Genetic studies suggest that a person's genetic background provides some information about who will respond well to methylphenidate, but we are not yet able to make very accurate predictions. After choosing the type of stimulant, the doctor must next consider what duration of action is appropriate for each patient.
There is no simple rule here; the choice will depend upon the specific needs of each patient. Many children benefit from longer-acting medications to get them through school, homework, and late afternoon/evening social activities. Likewise for adults. But many patients prefer shorter-acting medications, especially as these can be used to target specific times of day and can also lower the burden of side effects.
For patients taking down the non-stimulant arm of the decision tree, duration is not an issue but the patient and doctor must choose from among two classes of medications norepinephrine reuptake inhibitors or alpha-2-agonists. There are not a lot of good data to guide this decision but, again, genetics can be useful in some cases. Regardless of whether the first treatment is a stimulant or a non-stimulant, the patient's response must be closely monitored as there is no guarantee that the first choice of medication will work out well. In some cases, efficacy is low, or adverse events are high. Sometimes this can be fixed by changing the dose, and sometimes a trial of a new medication is indicated.
If you are a parent of a child with ADHD or an adult with ADHD, this trial-and-error approach can be frustrating. But don't lose hope. In the end, most ADHD patients find a dose and a medication that works for them. Last but not least, when medication leads to a partial response, even after adjusting doses and trying different medication types, doctors should consider referring the patient for a non-pharmacologic ADHD treatment.
You can read details about these in my other blogs, but here the main point is to find an evidence-based treatment. For children, the biggest evidence base is for behavioral family therapy. For adults, cognitive behavior therapy (CBT) is the best choice. Except for preschoolers, the experts I worked with on this infographic did not recommend these therapies before medication treatment. The reason is that the medications are much more effective, and many non-pharmacologic treatments (such as CBT) have no data indicating they work well in the absence of medication.
You've heard all sorts of misinformation about Attention-Deficit/Hyperactivity Disorder(ADHD), whether from friends, the internet, or uninformed press articles:
"ADHD is not real."
"Pharmaceutical companies invented ADHD to make money."
"I'm just a little ADD."
"Natural solutions are the best for ADHD treatment."
ADHD symptoms were first described in the late 1700s, primarily among hyperactive boys. It was described variously over 200 years as "fidgeting," "defects of moral control," "hyperkinetic reaction," "minimal brain damage" and eventually ADD (Attention Deficit Disorder) in the 1980s and ADHD today.
Because the natural tendency toward hyperactivity decreased with age, ADHD was originally thought to be a developmental disorder that disappeared in mid-to-late adolescence. When medicines were developed and used in ADHD treatment for young boys, physicians stopped prescribing them around mid-adolescence, because it was presumed the condition had been remediated. They were wrong. We know now that ADHD persists into adulthood for about two-thirds of ADHD youth.
ADHD was not widely recognized in girls until the mid-1990s when it became clear that girls with ADHD were less disruptive than boys with ADHD and were not being appropriately diagnosed. Girls with ADHD show less of the physical hyperactivity of boys, but suffer from "dreaminess," "lack of focus" and "lack of follow-through."
It was also in the 1990s that ADHD' pervasive comorbidity with depression, anxiety, mood, and autism spectrum disorders was established. At the same time, researchers were beginning to describe deficits in executive functioning and emotional dysregulation that became targets of substantial research in the 21st century.
Even with the 1990s recognition that ADHD is a lifetime disorder, equally present (in different forms) in both men and women, medical schools and continuing medical education courses (required for realizing sure of health professionals) have only begun to teach the most up-to-date evidence-based knowledge to the medical community. There still is much misinformation and a lack of knowledge among primary care professionals and the public.
ADHD Throughout the Lifespan
Most cases of ADHD start in Otero before the child is born. As a fetus, the future ADHD person carries versions of genes that increase the risk for the disorder. At the same time, they are exposed to toxic environments. These genetic and environmental risks change the developing brain, setting the foundation for the future emergence of ADHD.
In preschool, early signs of ADHD are seen in emotional lability, hyperactivity, disinhibited behavior and speech, and language and coordination problems. The full-blown ADHD syndrome typically occurs in early childhood, but can be delayed until adolescence. In some cases, the future ADHD person is temporarily protected from the emergence of ADHD due to factors such as high intelligence or especially supportive family and/or school environments. But, as the challenges of life increase, this social, emotional, and intellectual scaffolding is no longer sufficient to control the emergence of disabling ADHD symptoms.
Throughout childhood and adolescence, the emergence and persistence of the disorder are regulated by additional environmental risk factors such as family chaos, as well as the age-dependent expression of risk genes that exert different effects at different stages of development. During adolescence, most cases of ADHD persist and by the teenage years, many youths with ADHD have onset with a mood, anxiety, or substance use disorder. Indeed, parents and clinicians need to monitor ADHD youth for early signs of these disorders. Prompt treatment can prevent years of distress and disability.
By adulthood, the number of comorbid conditions increases, including obesity, which likely impacts future medical outcomes. Emerging data shows people with ADHD to be at increased risk for hypertension and diabetes. ADHD adults tend to be very inattentive but show fewer symptoms of hyperactivity and impulsivity. They remain at risk for substance abuse, low self-esteem, injuries due to accidents, occupational failure, and social disability, especially if they are not treated for the disorder.
Seven Important Concepts About ADHD
There are approximately 10 million U.S. adults with ADHD, 9 million of whom are undiagnosed. But with diligent research by the medical profession, we have learned seven important concepts about ADHD:
1. ADHD has been documented worldwide in 5% of the population.
2. Sixty-seven percent of ADHD children grow into ADHD adults and seniors. ADHD is heritable, runs in families, and is impacted by the physical environment and familial lifestyle.
3. In youth, rates of ADHD are higher in males than females as males, but these rates even out by adulthood.
4. ADHD coexists and is often masked by several other disorders: anxiety, depression, spectrum bipolar and autism disorder, substance abuse, alcoholism, obesity, risky behaviors, disorganized lives, working memory deficits, and significant executive dysfunctions that affect personal, social, and work success.
5. ADHD medications(stimulants and non-stimulants) are the most effective treatments for ADHD symptoms. Psychological support/training designed for ADHD, and lifestyle modifications, are important adjuncts to medicine.
6. ADHD costs the U.S. economy more than $100 million annually in lost productivity, accidents, hospitalizations with comorbidities, and family and professional support for ADHD patients.
7. ADHD is diagnosable and safely treatable in trained primary care practices.
How do you know if you or someone you love has ADHD? Evaluate your life against the seven concepts above. Then get screened and diagnosed by a health care professional. The diagnosis of ADHD should be done only by a licensed clinician who has been trained in ADHD. That clinician should have one goal in mind: to plan a safe and effective course of evidence-based treatment.
When diagnosing adults, it is also useful to collect information from a significant other, which can be a parent for young adults or a spouse for older adults. But when such individuals are not available, diagnosing ADHD based on the patient's self-report is valid. Just remember that personal, work, and family lives are improved with treatment. Research and technology related to ADHD improve all the time.
ADHD in Adults is a great resource for anyone interested in learning more about ADHD, with evidence-based information and education for both healthcare professionals and the public. The website also features a new ADHD screener for predicting the presence of ADHD in adults.
Stephen V. Faraone, Ph.D., is a Distinguished Professor of Psychiatry and Neuroscience & Physiology at SUNY Update Medical University and a global expert on Adult ADHD.
The Nordic countries maintain detailed registers of their inhabitants. This enables researchers to examine patterns over entire nations. An international research team used the Swedish national registers for a prospective cohort study of 2,675,615 persons in the Medical Birth Register born in Sweden over a 27-year period from January 1, 1983, through December 31, 2009. Follow-up was completed in December 2013, with the oldest cohort member aged 31. The mean age at study entry was 6, and the mean at follow-up was 11.
Using personal identification numbers, researchers were able to cross-reference with the National Patient Register and the National Drug Register. From this, they determined that 86,670 members of the cohort (3.2 percent) had ADHD, based either on records of clinical diagnosis or of prescription of ADHD drugs. Psychiatric comorbidities were likewise identified in the National Patient Register.
These comorbidities were significantly more prevalent in the ADHD population than in the rest of the cohort. For example, whereas only 2.2% of the non-ADHD group was diagnosed with substance use disorder (SUD), 13.3% of the ADHD group also had SUD, a six-fold difference. For depression, it was a seven-fold difference, for schizophrenia a nine-fold difference.
The ADHD group had a significantly higher risk of premature death from all causes than the non-ADHD group, with an adjusted hazard ratio (HR) of 3.94 (95% CI 3.51-4.43). Unintentional injury(36%) and suicide (31%) were the leading causes of death in the ADHD group. Those with ADHD were more than eight times more likely to die by suicide than non-ADHD individuals, and roughly four times more likely to die from unintentional injury.
The vast majority of the increased risk appears to be associated with comorbid psychiatric conditions. Those with ADHD but no diagnosed comorbidities had an adjusted HR of 1.41 (95% CI 1.01-1.97). With a single comorbidity, the HR more than doubled to 3.71 (95% CI 2.88-4.78). With four or more comorbidities, it rose to a staggering 25.22 (95% CI 19.6-32.46).
The comorbid condition with the greatest impact was SUD, which increased the risk eight-fold by comparison with those with only ADHD (HR = 8.01, 95% CI 6.16-10.41). Anxiety disorder, schizophrenia, and personality disorder increased the risk about fourfold. Bipolar disorder, depression, and eating disorder increased risk by roughly two and a half times.
Co variate analysis helped tease out what portion of the risk was associated with ADHD alone versus comorbid conditions. Adjusting for the year of birth, sex, birth weight, maternal age at birth, parental educational level, and parental employment status, those with ADHD (including comorbid conditions) were 2.7 times more likely to prematurely die of natural causes than those without. Adjusting for comorbid psychiatric conditions completely eliminated the risk from ADHD alone (HR = 1.01, 95% CI .72-1.42).
Likewise, those with ADHD (including comorbid conditions) were six times as likely to die of unnatural causes. Adjusting for early-onset comorbid disorders(such as conduct disorders, autism spectrum disorder, and intellectual disability) only modestly reduced the HR to 5.3, but further adjusting for later-onset comorbid disorders (including substance use disorder, depressive disorder, bipolar disorder, anxiety disorder, schizophrenia, personality disorder, and eating disorders) reduced the HR to 1.57 (95% CI 1.35-1.83), and reduced it to insignificance in the case of suicide (HR = 1.13, 95% CI.88-1.45).
Summing up, the lion’s share of the greater risk of premature death in persons with ADHD is attributable to psychiatric comorbidities. Nevertheless, those with ADHD alone still face a 40 percent greater risk than those without ADHD.
The study did not examine effects of ADHD medication, which the authors state “should be analyzed because of documented potential benefits on ADHD symptoms and comorbid disorders.”
The authors concluded, “Among adults, early-onset psychiatric comorbidity contributed substantially to the premature mortality risks due to natural causes. On the other hand, later-onset psychiatric comorbidity, especially SUD, explained a substantial part of the risk for unnatural deaths, including all the risk of suicide deaths and most of the deaths due to unintentional injuries. These results suggest that overall health conditions and risk of psychiatric comorbidity should be evaluated clinically to identify high-risk groups among individuals with ADHD.”
A cohort study looked at over five million adults, and over 850,000 children between the ages of five and eleven, who received care at Kaiser Permanente Northern California during the ten-year period from the beginning of 2007 through the end of 2016. At any given time, KPNC serves roughly four million persons. It is representative of the population of the region, except for the highest and lowest income strata.
Among adults rates of ADHD diagnosis rose from 0.43% to 0.96%. Among children the diagnosis rates rose from 2.96% to 3.74%, ending up almost four times as high as for adults.
Non-Hispanic whites had the highest adult rates throughout, increasing from 0.67% in 2007 to 1.42% in 2016. American Indian or Alaska Native (AIAN) had the second highest rates, rising from 0.56% to 1.14%. Blacks and Hispanics had roughly comparable rates of diagnosis, the former rising from 0.22% to 0.69%, the latter from 0.25% to 0.65%. The lowest rates were among Asians (rising from 0.11% to 0.35%) and Native Hawaiian or other Pacific Islanders (increasing from 0.11% to 0.39%).
Odds of diagnosis dropped steeply with age among adults. Relative to 18-24-year-olds, 25-34-year-olds were 1/6th less likely to be diagnosed with ADHD, 35-44-year-olds 1/3rd less likely, 45-54-year-olds less than half as likely, 55-64-year-olds less than a quarter as likely, and those over 65 about a twentieth as likely. This is consistent with other studies reporting and age dependent decline in the diagnosis.
Adults with the highest levels of education were twice as likely to be diagnosed as those with the lowest levels. But variations in median household income had almost no effect. Women were marginally less likely to be diagnosed than men.
ADHD is associated with some other psychiatric disorders. Compared with normally developing adults, and adjusted for confounders, those with ADHD were five times as likely to have an eating disorder, over four times as likely to be diagnosed with bipolar disorder or depression, more than twice as likely to suffer from anxiety, but only slightly more likely to abuse drugs or alcohol.
The authors speculate that rising rates of diagnosis could reflect increasing recognition of ADHD in adults by physicians and other clinicians as well as growing public awareness of ADHD during the decade under study. Turning to the strong differences among ethnicities, they note, Racial/ethnic differences could also reflect differential rates of treatment seeking or access to care. Racial/ethnic background is known to play an important role in opinions on mental health services, health care utilization, and physician preferences. In addition, rates of diagnosis- seeking to obtain stimulant medication for nonmedical use may be more common among white vs nonwhite patients. They conclude, greater consideration must be placed on cultural influences on health care seeking and delivery, along with an increased understanding of the various social, psychological, and biological differences among races/ethnicities as well as culturally sensitive approaches to identify and treat ADHD in the total population.
But the main take home message of this work is that most cases of ADHD in adults are not being diagnosed by clinicians. We know from population studies, worldwide, that about three percent of adults suffer from the disorder. This study found that less than 1 percent are diagnosed by their doctors. Clearly, more education is needed to teach clinicians how to identify, diagnose and treat ADHD in adults.
A team from Harvard Medical School and Massachusetts General Hospital conducted a six-week open-label trial of liquid-formulation extended-release methylphenidate (MPH-ER) to treat ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). ASD is a lifelong disorder with deficits in social communication and interaction and restricted, repetitive behaviors. Roughly half of those diagnosed with ASD also are diagnosed with ADHD.
This was the first stimulant trial in adults with both ASD and ADHD. There were twelve male and three female participants, all with moderate to severe ADHD, and in their twenties, with IQ scores of at least 85.
Use of a liquid formulation enabled doses to be raised very gradually, starting with a daily dose of 5mg (1mL) and titrating up to 60mg over the first three weeks, then maintaining that level through the sixth week. Participants were reevaluated for ADHD symptoms every week during the six-week trial. Severity of ASD was assessed at the start, midpoint, and conclusion of the trial, as were other psychiatric symptoms.
Prior to the trial, researchers agreed on a combination of targets on two clinician-rated scoring systems that would have to be reached for treatment to be considered successful. One is a score of 2 or less on the CGI-S, a measure of illness severity, with scores ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The other, a reduction of at least 30 percent in the AISRS score, which combines each of 18 symptoms of ADHD on a severity grid (0=not present; 3=severe; overall minimum score: 0; overall maximum score: 54).
At the conclusion of the trial, twelve of the fifteen patients (80 percent) met the preset conditions for success. Fully fourteen (93 percent) saw a ≥ 30 percent reduction in their AISRS score, while twelve scored ≤ 2 on illness severity.
However, when using the patient-rated ASRS scoring system, only five (33 percent) saw a ≥ 30 percent reduction in ADHD severity.
Thirteen participants (87 percent) reported at least one adverse event, and nine (60 percent) reported two or more. One reported a serious adverse event (attempted suicide) in a patient with multiple prior attempts. Because the attempt was not deemed due to medication they continued in and completed the trial. Seven participants experienced titration-limiting adverse events (headaches, palpitations, jaw pain, and insomnia). Headache was most frequent (53%), followed by insomnia and anxiety (33% each), and decreased appetite (27%).
During the trial, weight significantly decreased, while pulse significantly increased. There were no significant differences in other vital and cardiovascular measurements.
The authors concluded, “this OLT of short-term MPH-ER therapy documents that acute treatment with MPH-ER in young adults with ASD was associated with significant improvement in ADHD symptoms, mirroring the typically-expected magnitude of response observed in adults with only ADHD. Treatment with MPH-ER was well-tolerated, though associated with a higher than expected frequency of adverse events.”
They also cautioned, “The results of this study need to be considered in light of some methodological limitations. This was an open-label study; therefore, assessments were not blind to treatment. We did not employ a placebo control group and, therefore, cannot separate the effects of treatment from time or placebo effects. … firmer conclusions regarding the safety and efficacy of MPH-ER for the treatment of ADHD in HF-ASD populations await results from larger, randomized, placebo-controlled clinical trials.”
ADHD is far more prevalent among persons with AUD (roughly 20 percent) than it is in the general population. The most accurate way of identifying ADHD is through structured clinical interviews. Given that this is not feasible in routine clinical settings, ADHD self-report scales offer a less reliable but much less resource-intensive alternative. Could the latter be calibrated in a way that would yield diagnoses that better correspond with the former?
A German team compared the outcomes of both methods on 404 adults undergoing residential treatment for AUD. All were abstinent while undergoing evaluations. First, to obtain reliable ADHD diagnoses, each underwent the Diagnostic Interview for ADHD in Adults, DIVA. If DIVA indicated probable ADHD, two expert clinicians conducted successive follow-up interviews. ADHD was only diagnosed when both experts concurred with the DIVA outcome.
Participants were then asked to use two adult ADHD self-report scales, the six-item Adult ADHD Self Report Scale v1.1 (ASRS) and the 30-item Conners’ Adult ADHD Rating Scale (CAARS-S-SR). The outcomes were then compared with the expert interview diagnoses.
Using established cut-off values for the ASRS, less than two-thirds of patients known to have ADHD were scored as having ADHD by the test. In other words, there was a very high rate of false negatives. Lowering the cut-off to a sum score ≥ 11 resulted in a correct diagnosis of more than seven out of eight. But the rate of false positives soared to almost two in five. Similarly, the CAARS-S-SR had its greatest sensitivity (ability to accurately identify those with ADHD) at the lowest threshold of ≥ 60, but at a similarly high cost in false positives (more than a third).
The authors found it was impossible to come anywhere near the precision of the expert clinical interviews. Nevertheless, they judged the best compromise to be to use the lowest thresholds on both tests and then require positive determinations from both. That led to successfully diagnosing more than three out of four individuals known to have ADHD, with a false positive rate of just over one in five.
Using this combination of the two self-reporting questionnaires with lower thresholds, they suggest, could substantially reduce the under-diagnosis of ADHD in alcohol-dependent patients.
The team of researchers found that pharmacological treatment of adults with diagnoses of ADHD and ASD seem to be just as successful as the pharmacological treatment of adults with only ADHD.
Autism spectrum disorder (ASD) is frequently comorbid with ADHD. Among adults with ADHD, as many as half are reported to also have ASD.
A Dutch team set out to answer two questions:
This was a retrospective study, using well-documented medical records, of the effects of drug treatment with methylphenidate (MPH), dexamphetamine (DEX), atomoxetine (ATX), bupropion, or modafinil.
The researchers compared 60 adults with comorbid ASD and ADHD to 226 adults with only ADHD. ADHD symptoms were scored using the Conner's ADHD Rating Scale: Self Report-Short Version (CAARS: S-S). Side effects of ADHD medication were measured using either a 13-item or 20-item checklist with 4-point scales for item response. Researchers also tracked changes in body weight, blood pressure, and heart rate.
Following treatment, ADHD symptoms among the comorbid group declined by a quarter, and among the ADHD-only group by almost a third. There was no significant difference between men and women. Controlling for age, gender, and ADHD subtype, a comorbid diagnosis of ASD also did not significantly affect ADHD symptom reduction.
Turning to side effects, in the ADHD+ASD group, there were significant increases in decreased appetite and weight loss, and decreases in agitation, anxiety, and sadness/unhappiness. In the ADHD-only group, there were significant increases in decreased appetite, weight loss, and dry mouth, and decreases in sleeping disorder, nervousness, agitation, anxiety, and sadness/unhappiness. Yet there were no significant differences between the two groups. Side effects increased and decreased similarly in both. Likewise, there were no significant differences between the groups in changes in heart rate and blood pressure. The only significant difference in medication dosage was for bupropion, which was higher in the ADHD+ASD group, though without any sign of difference in side effects.
The authors concluded that this retrospective study showed pharmacological treatment of adults with diagnoses of ADHD and ASD to be just as successful as the pharmacological treatment of adults with only ADHD, but cautioned that a randomized controlled trial should be conducted to evaluate the effectiveness and possible side effects of pharmacological treatment for ADHD in patients with ASD more reliably.
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