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There has been much interest in omega-3 Polyunsaturated fatty acids (PUFAs) as treatments for ADHD. Humans are unable to synthesize the omega-3 PUFA alpha-linolenic acid (ALA)and the omega-6 PUFA linoleic acid (LA), and must therefore obtain these through food, which is why they are known as essential fatty acids.  Because cells in the brain need omega-3 PUFAs, they have been studied as a treatment for ADHD by many researchers.  Several meta-analyses are available.

A 2014 meta-analysis by Elizabeth Haw key and Joel Niggcombined nine studies involving 586 participants. It found mean blood levels of omega-3 PUFAs in persons with ADHD to be lower than in controls. The standardized mean difference (SMD) effect size was medium (SMD = .42, 95% CI = .26-.59), with less than a one in one thousand probability of such a result being obtained by chance alone. Adjusting for publication bias reduced the effect size slightly to .36 with a 95% CI of .21-.51, in the small-to-medium range. The authors then examined whether omega-3 supplementation could help alleviate ADHD symptoms. Combining 16 studies with 1,408 participants, they found improvements, but this time with a small effect size (SMD = .26, 95% CI =.15-.37), again with less than a one in a thousand probability of such a result being observed by chance. Adjusting for publication bias reduced the effect size to .16 with a 95% CI of .03-.28.  For comparison, the SMD for stimulants is about 0.9.

Another meta-analysis conducted in the same year by BasantPuri and Julian Martins combined 18 PUFA supplementation studies involving1,640 participants. They also found a small effect size for reduced ADHD symptoms (SMD = .19, 95% CI = .09-.30, p<.001). Adjusting for publication bias further reduced the effect size to a paltry and statistically insignificant level (SMD = .12, 95% CI = -.01-.25). It should be noted that while16 of the studies involved omega-3 supplementation, two involved only omega-6supplementation. Yet the results for the latter did not differ noticeably from the former. When the authors limited the analysis to the 11 studies specifically including both the omega-6GLAand the omega-3 EPA, the effect size for reducing inattention symptoms was a bit higher(SMD = .31, 95% CI = .16-.46, p<.0001). But the results were not significantly different from those for the studies without the GLA+ALA combination (.012; 95% CI: .161-.137; p=.875). Publication bias was not addressed, and the hunt for a highly specific subset with positive results may have produced a false-positive finding.  The authors conceded, "Weaknesses of this study include the following: although the pooled effect was statistically significant, only two studies showed a significant effect by themselves; the funnel plot showed evidence of publication bias; there was evidence of reporting bias; few studies were formally registered; study methodological quality was variable, and the placebo used across studies varied."

A 2016 meta-analysis by Laura Lachance et al. tried looking for differences in the ratio of omega-6 to omega-3 PUFAs, and more specifically, AA to EPA, in the blood of persons with ADHD versus normally developing persons. Pooling five studies with485 participants, it found the omega-6 to omega-3 ratio to be significantly higher in persons with ADHD, and pooling three studies with 279 participants, it likewise found the AA to EPA ratio significantly higher.

A 2017 meta-analysis by Jane Pei-Chen Chang et al. Reexamined comparative levels of omega-3 PUFAs in ADHD patients versus normally developing controls. Combining six studies with 396 participants, ADHD patients had lower levels in blood and mouth tissue, with a medium effect size (SMD =.38) that was not statistically significant (p=.14).  Omega-6 levels were indistinguishable (SMD =.03) in the two groups. AA (SMD = .18, p=.33) and EPA (SMD = .25, p=.17) levels were slightly lower, but once again statistically not significant. DHA levels were lower as well, this time with a medium effect size (SMD = .56), but at the outer margin of significance (p=.05). Only by dropping one study were the authors able to claim significance for EPA, AA, and omega-3 differences.

Chang et al. also performed a meta-analysis of supplementation studies. Combining seven studies with 534 participants, they found a small to medium reduction in ADHD symptoms with omega-3 supplementation(SMD = .38, 95% CI = .2-.56, p<.0001). Corrections for publication bias were not reported. The authors also reported large reductions in both omission errors (SMD = 1.09, 95% CI = .43-.1.75, p<.001) and commission errors (SMD =2.14, 95% CI = 1.24-3.03, p<.00001) on a neuropsychological test of attention. But the former involved only 3 studies with 214 participants, and the latter only two studies with 85 participants.

Also in 2017, Pelsser et al. published a systematic review that identified only two meta-analyses of double-blind, placebo-controlled trials of PUFA supplementation. One of those, a 2012meta-analysis by Gillies et al., found no statistically significant declines in either parent-rated ADHD symptoms (five trials, 413 participants, SMD = -.17,95% CI = -.38-.03) or teacher-rated ADHD symptoms (four trials, 324participants, SMD = .05, 95% CI = -.18-.27). The other, a 2013 meta-analysis by Sonuga-Barke et al., found only a slight and barely statistically significant reduction in symptoms (11 trials, 827 participants, SMD = .16, 95% CI =.01-.31). Pelsser et al. concluded, "Considering the small average ESs [effect sizes] PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment."

Putting all of this together, there are indications that individuals with ADHD may have lower levels of omega-3 PUFAs, and that omega-3 supplementation may slightly reduce symptoms of ADHD, but the evidence remains inconclusive, with at best small effect sizes. It is possible, but not yet demonstrated, that omega-3 PUFAs might produce good outcomes in a small subset of patients.

A Danish team recruited 29,489 participants from voluntary blood donors between the ages of 17 and 67, ensuring a large sample size. Participants were asked to complete two simple questionnaires on digital tablets. One asked two questions: "Have you ever had a migraine?" and "Have you ever had visual disturbances lasting 5-60 min followed by a headache?" A yes to either was considered positive for migraine. The other used the ADHD Self-Report Scale, with 18 ADHD symptoms evaluated on a five-point scale.

Excluding those who did not answer all questions left 26,456 participants. The risk for migraines among those with ADHD was near twice the risk for others. The (odds)'s ratio (OR) was 1.8, with a 95 percent confidence interval from 1.53 to 2.12 (p < 0.001). The OR was higher among females (2.01) than males (1.64). For those with visual disturbances, the OR was higher (1.98) than for those without (1.52). The association disappeared in those over 60, with an OR essentially equal to one(0.98, 95% CI = 0.84 - 1.15, p = 0.8).

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Although the authors concluded, "We demonstrate a significant comorbidity between migraine and ADHD in adults, and this is most prominent for participants with migraine with visual disturbances," the significance to which they refer is of the p-values, and should not be misinterpreted as an indication of a strong association, as the odds ratios point variably tweak, and weak-to-moderate associations, depending on subpopulations.  The work is, however, important as it points to another somatic comorbidity of ADHD. That list is growing and now includes obesity, eczema, and asthma.

An international team of researchers recently published a meta-analysis of randomized controlled trials examining the efficacy of meditation-based therapies. Thirteen randomized controlled clinical trials(RCTs) were included: seven, with 270 participants, focused on children and adolescents; the other six, with 339 participants, were on adults. Because only one of the RCTs was appropriately blinded, the results discussed below, although promising, must be considered preliminary.

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Among children and adolescents, the meta-analysis revealed a significant, medium effect size (SMD = -0.44, 95% CI -0.69 to -0.19)on ADHD symptoms for meditation therapy versus no treatment. There were virtually no heterogeneity among studies and no sign of publication bias. Improvements in inattention and hyperactivity/impulsivity had similar effect sizes. Neuropsychological measures of inhibition and attention indicated small-to-medium effect sizes but failed to achieve statistical significance, perhaps due to the small numbers of trials and participants (159 and 179, respectively).

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For adults, the significant effect size on ADHD symptoms was medium-to-large (SMD = -.66, 95% CI -1.21 to -0.11). Once again, there was little sign of publication bias. But in this case, there was great heterogeneity among the studies. Improvements in inattention and hyperactivity/impulsivity were again comparable, although they fell just short of statistical significance for the latter. Neuropsychological measures of the efficacy of medication therapy produced statistically significant medium effect sizes for inhibition (SMD = -0.54) and working memory (SMD = - 0.42), with virtually no heterogeneity or sign of publication bias.

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Although these results are promising, the authors of the meta-analysis concluded, "Despite statistically significant effects on ADHD combined core symptoms, due to paucity of RCTs, heterogeneity across studies, and lack of studies at low risk of bias, there is insufficient methodologically sound evidence to support meditation-based therapies for ADHD."

A systematic review of the literature found seven studies examining this question. Significantly, six were large cohort studies with a combined total of almost three million individuals. The other was a large case-control study with 7,874 participants.
The largest cohort study, with more than a million and a half children, found that prenatal antidepressant exposure increased the risk for ADHD.  The adjusted odds ratio was 1.6forany antidepressant and for selective serotonin reuptake inhibitors (SSRI). But sibling comparison models, which better adjust for confounds shared by siblings(e.g., poverty, stress in the home), this study found no increased risk of ADHD.
The second-largest cohort study, with over 875 thousand children, found a small adjusted risk of 1.2 for all antidepressants, with little variation by class of antidepressant. The fourth-largest study, with over 140 thousand children, likewise found a small adjusted risk of 1.2, which barely achieved statistical significance (95% CI 1.0-1.4).
The third-largest study, with over 190 thousand children, obtained an adjusted risk of 1.4 for all antidepressants. But it also pointed to a possible explanation for the small association found in this and other studies, suggesting that the apparent association with antidepressant use was due to ADHD's known genetic association with psychiatric conditions treated by antidepressants.
The fifth-largest study, with more than 55 thousand children, similarly found an adjusted risk of 1.7 for SSRIs and an adjusted risk of 1.7 for an unmediated maternal psychiatric disorder. Again, the underlying psychiatric disorder appears to be confounding the effect of antidepressants.
The sixth-largest study, with over 38 thousand children, found no evidence of any effect from SSRIs. Yet it found evidence of a large effect from bupropion, with an odds ratio of 3.6, and only one in 50 odds of obtaining such a result by chance (p = 0.02). However, it offered no comparison with untreated depression and made no adjustments for potential confounders.
The case-control study found an odds ratio of 2.3 for maternal use of any antidepressant, which dropped to a statistically non-significant 1.6 when adjusted for a maternal psychiatric disorder (95% CI0.66-3.71).

Few studies have examined the safety and tolerability of ADHD medications (stimulants and atomoxetine) extending beyond six months, and none beyond a few years. A pair of Swedish neuroscientists at Uppsala University Hospital set out to explore longer-term outcomes. They conducted a six-year prospective study of 112 adults diagnosed with ADHD who were being treated with ADHD medications (primarily MPH, but also dexamphetamine and atomoxetine).

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They found that at the end of that period, roughly half were still on medication, and half had discontinued treatment. There were no significant differences between the two groups in age, sex, ADHD severity, or comorbidity. The average ADHD score for the entire cohort declined to vary significantly, from a mean of 37 to a mean of 26, with less than one in a thousand odds of that being due to chance. There was also no sign of drug tolerance or a need to increase the dosage over time.
All 55 adults who discontinued treatment had taken MPH for at least part of the time. Eleven had also been treated with dexamphetamine(DEX) and 15 with atomoxetine (ATX). The average time on treatment was just under two years. Almost a third quit MPH because they perceived no beneficial effect. Since they were on average taking higher doses at discontinuation than initiation, that is unlikely to have been due to suboptimal dosage. Almost another third was discontinued for various adverse mental effects, including hyperactivity, elation, depressive moods, aggression, insomnia, fatigue, and lethargy. Another one in eleven quit when they lost contact with the prescribing physician. In the case of ATX, almost half quit because of what they perceived as adverse mental effects.

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Among the 57 adults who remained on medication, four out of five reported a strong beneficial effect. Only two reported minimal or no effect. Compared with the group that discontinued, the group that remained on medication was far more likely to agree with the statements, "My quality of life has improved," and "My level of functioning has improved." Yet, as the authors caution, it is possible "that the subjects' subjective ratings contained a placebo-related mechanism in those who are compliant with the medication and pursue treatment over time." The authors reported that there were no significant differences in ADHD scores or ADHD severity between the group that quit and the group that remained on medication, even though, on average, the group that quit had been off medication for four years at follow-up.

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We cannot explain why the patients who quit treatment showed similar levels of ADHD symptoms to those who continued treatment.  It is possible that some patients remit symptoms over time and do not require sustained treatment.  But we must keep in mind that there was a wide range of outcomes in both groups. Future work needs to find predictors of those who will do well after treatment withdrawal and those who do not.

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Any decision on whether to maintain a course of medication should always weigh expected gains against adverse side effects. Short of hard evidence of continuing efficacy beyond two years, adverse events gain in relative importance. With that in mind, it is worth noting that this study reports that among those who remained on MPH, many reported side effects. More than a quarter complained of decreased appetite, one in four of dry mouth, one in five of anxiousness and increased heart rate, one in six of decreased sexual desire, one in nine of depressed mood, and one in eleven of insomnia.

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This study breaks important ground in looking at the long-term effects of medication. It reaffirms findings elsewhere of the efficacy of ADHD medications. But contrary to the authors' conclusion, the data they present suggests the possibility that permanently medicating ADHD patients may not be more efficacious than discontinuation beyond a certain point, especially when balanced against adverse side effects.
But this is just one study with a relatively small sample size. This suggests a need for additional studies with larger sample sizes to pursue these questions with greater statistical reliability.

An international team of researchers sets out to measure the association between ADHD symptoms and self-evaluations of happiness among adults in the general population of the U.K. A nationally representative sample of 7,274 adults was asked to rate their happiness on a three-point scale. They also used the Adult ADHD Self-Report Scale (ASRS) Screener to assess ADHD symptom levels.
Higher ADHD symptom levels were found to be inversely associated with self-assessments of happiness. Adults with the lowest ADHD symptoms (0-9 on theaters) were roughly twice as likely to report being happy as those scoring10-13, five times as happy as those scoring 14-17, and ten times as happy as those with the highest ADHD symptom scores (18-24). These results were highly significant.
That did not mean that most adults with high ADHD symptom scores were unhappy. Even among those with the highest ADHD symptom scores (18-24), a majority (58 percent) reported being either "fairly happy" or "very happy." Butonly11 a percent of that group reported being "very happy," as opposed to 44 percent of those scoring the lowest on ADHD symptoms.
While the association is clear and strong, establishing causation is trickier. As the authors acknowledge, "as the symptoms associated with ADHD are similar to, and sometimes overlap, with those that are commonly observed in individuals with other psychiatric disorders ... a screening instrument to identify ADHD symptoms may have had limited power to distinguish 'pure' ADHD and cases with ADHD symptoms related to other psychiatric disorders." Emotional instability and anxiety disorder each mediated more than a third of the association between ADHD and unhappiness, and depression almost a third. These could have been brought about by ADHD and could also have been produced by other psychiatric disorders.  Because the ASRS is not a diagnostic instrument, the authors concluded that "the results of this study should be considered provisional, until if, and when, they are replicated in those with a clinical diagnosis of ADHD with and without comorbid disorders."

Our genes are very important for the development of mental disorders-including ADHD, where genetic factors capture up to 75% of the risk. Until now, the search for these genes had yet to deliver clear results.   In the 1990s, many of us were searching for genes that increased the risk for ADHD because we know from twin studies that ADHD had a robust genetic component.  Because I realized that solving this problem required many DNA samples from people with and without ADHD, I created the ADHD Molecular Genetics Network, funded by the US NIMH.  We later joined forces with the Psychiatric Genomics Consortium (PTC) and the Danish psych group, which had access to many samples.  
The result is a study of over 20,000 people with ADHD and 35,000 who do not suffer from it - finding twelve locations (loci) where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant.  The results of the study have just been published in the scientific journal Nature Genetics, https://www.nature.com/articles/s41588-018-0269-7.
These genetic discoveries provide new insights into the biology behind developing ADHD. For example, some genes have significance for how brain cells communicate with each other, while others are important for cognitive functions such as language and learning.
Our study used the genome-wide association study (GWAS)methodology because it allowed us to discover genetic loci anywhere on the genome.  The method assays DNA variants throughout the genome and determines which variants are more common among ADHDvs. control participants.  It also allowed for the discovery of loci having very small effects.  That feature was essential because prior work suggested that, except for very rare cases, ADHD risk loci would individually have small effects.
The main findings are:

A) we found 12 loci on the genome that we can be certain harbor DNA risk variants for ADHD.  None of these loci were traditional candidate genes' for ADHD, i.e., genes involved in regulating neurotransmission systems that are affected by ADHD medications.  Instead, these genes seem to be involved in the development of brain circuits.  
B) we found a significant polygenic etiology in our data, which means that there must be many loci(perhaps thousands) having variants that increase the risk for ADHD.  We will need to collect a much larger sample to find out which specific loci are involved;

We also compared the new results with those from a genetic study of continuous measures of ADHD symptoms in the general population. We found that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population.  This supports prior clinical research suggesting that, like hypertension and hypercholesteremia, ADHD is a continuous trait in the population.  These genetic data now show that the genetic susceptibility to ADHD is also a quantitative trait comprised of many, perhaps thousands, of DNA variants
The study also examined the genetic overlap with other disorders and traits in analyses that ask the questions: Do genetic risk variants for ADHD increase or decrease the likelihood a person will express other traits and disorders.   These analyses found a strong negative genetic correlation between ADHD and education. This tells us that many of the genetic variants which increase the risk for ADHD also make it more likely that a person will perform poorly in educational settings. The study also found a positive correlation between ADHD and obesity, increased BMI, and type-2 diabetes, which is to say that variants that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population. This work has laid the foundation for future work that will clarify how genetic risks combine with environmental risks to cause ADHD.  When the pieces of that puzzle come together, researchers will be able to improve the diagnosis and treatment of ADHD.

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."

The CDC recently reported that ADHD medication use in women ages 15 to 44 increased from 0.9 percent to 4 percent from 2003 to 2015.  The most commonly used medications were formulations of amphetamine or methylphenidate.  

This increase in treatment for ADHD suggests that educational programs such as adhdinadults.com have been effective in teaching clinicians how to identify and treat the disorder.   The 4 percent rate reported by the CDC is encouraging because it is close to what Ron Kessler and colleagues reported as the prevalence of adult ADHD in the population.   CDC correctly points out that little is known about the effects of ADHD medications on pregnancies. Thus, caution is warranted.

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Oei et al.'s review of amphetamines concluded: "There is little evidence of amphetamine-induced neurotoxicity and long-term neurodevelopmental impact, as data is scarce and difficult to extricate from the influence of other factors associated with children living in households where one or more parent uses drugs in terms of poverty and neglect. ... We suggest that exposed children may be at risk of ongoing developmental and behavioral impediment, and recommend that efforts be made to improve early detection of perinatal exposure and to increase the provision of early intervention services for affected children and their families"

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Bolea-Alamanac et al.'s review of methylphenidate effects concluded: "There is a paucity of data regarding the use of methylphenidate in pregnancy and further studies are required. Although the default medical position is to interrupt any non-essential pharmacological treatment during pregnancy and lactation, in ADHD this may present a significant risk. Doctors need to evaluate each case carefully before interrupting treatment." These words of caution should be heeded by clinicians caring for women of reproductive age.