Israel has a military draft that applies to males and females alike, except orthodox women and orthodox male seminary(yeshiva) students, who are exempt. Upon turning 17 every Israeli undergoes a medical review, including both a physical and psychiatric assessment, in preparation for the draft. The Draft Board Registry maintains comprehensive health information on all unselected Israelis until they turn 21. The registry also tracks all family members of draft registrants, including full siblings.

An Israeli study team used registry records from 1998 through2014 to obtain data for a total of over a million individuals (1,085,388). Because of the exemption for orthodox women, 59% were male.

The team identified 903,690 full siblings in the study population (58% males), including 166,359 male-male sibling pairs, 104,494 female-female sibling pairs, and 197,571 opposite-sex sibling pairs.

Next, the team identified all cases in the study population with a diagnosis of a psychiatric disorder, low IQ (≥2 standard deviations below the population mean), Type-1 diabetes, hernia, or hematological malignancies. It matched each case with ten age- and sex-matched controls selected at random from the study population. Then, for each case and case-matched controls, it identified all siblings.

There were 3,272 cases receiving treatment for ADHD, 2,128 with autistic spectrum disorder, 9,572 with severe/profound intellectual disability, 7,902 with psychotic disorders, 9,704 with mood disorders, 10,606with anxiety disorders, 24,815 with personality disorders, 791 with substance abuse disorders, 31,186 with low IQ, 2,770 with Type-1 diabetes, 30,199 with a hernia, and 931 with hematological malignancies.

Draftees with ADHD were five and a half times more likely to have a sibling with ADHD than controls.

There were no significant associations between ADHD and any of the somatic disorders - Type-1 diabetes, hernia, or hematological malignancies - nor between ADHD and low IQ.

There were also no significant associations between ADHD and autism spectrum disorder, severe/profound intellectual disability, mood disorders, and substance use disorders.

On the other hand, draftees with ADHD were more than 40% more likely to have siblings with anxiety or personality disorders than controls.

Surprisingly, draftees with ADHD were less than half as likely to have siblings with psychotic disorders than controls.

There were some limitations. The psychiatric classification system used by the Israeli military did not permit assessing the risk of bipolar disorder and depression separately. That meant having to use a broader category of mood disorders, including both disorders. In addition, the military diagnostic system does not allow diagnosis of comorbid psychiatric disorders in the same individual, instead of assigning only the most severe diagnosis.

Taiwan has a single-payer healthcare system that covers virtually every inhabitant (99.5%). That makes it relatively easy to track healthcare issues using its comprehensive National Health Insurance Research Database.

This database maintains a subset, the Longitudinal Health Insurance Database (LHID), consisting of a million persons, with no significant differences in sex, age, or healthcare use from the parent database.

A Taiwanese research team used the LHID to identify 114,486 individuals diagnosed with ADHD from 1997 to 2013. It then compared their motor vehicle (including motorcycles, which are extremely common in Taiwan) crash patterns with 338,261 normally developing controls from the same database.

Adjusting for sex, age, and psychiatric comorbidities, persons with ADHD were about a fifth (19%)more likely to be in traffic crashes. Breaking it down further by sex, women with ADHD were no more likely to be in crashes, but men with ADHD were about a quarter (24%) more likely than their healthy counterparts.

Since the database also tracks pharmaceutical prescriptions, the team also looked into the effect of methylphenidate (MPH), the medication that is the first-line treatment for ADHD under Taiwanese guidelines, and the only approved stimulant. Atomoxetine, a non-stimulant, is used where MPH is either ineffective or not indicated for any other reason and is only used in 4% of all cases.

Of the 114,486 persons diagnosed with ADHD, 89,826 used MPH, and 24,660 did not.

Compared with persons with ADHD who were not on methylphenidate, those with ADHD who were on MPH for 180 days (roughly half a year) or less had 77% fewer accidents, and those on MPH for over 180 days had 93% fewer accidents. This strong dose-response relationship is suggestive of a causal relationship, with MPH perhaps reducing impulsive behavior, particularly among young men with ADHD.

The team also conducted within-person analyses, comparing times when persons with ADHD were taking MPH with periods when they were not. These showed no effect within 30 days of use, rising to a 65%reduction in crashes within 60 to 90 days of use, which was barely outside the 95% confidence interval (p = .07), very likely because of "the extremely low incidence of transport accidence (i.e. 0.6%)enlarged the confidence interval."

The authors concluded, "All registration medical claim data came from the nationally-representative sample of NHI, minimizing the selection and recall bias. By excluding transport accidents before ADHD diagnosis, we have precluded the reverse association between ADHD and road traffic accidents as much as possible. The advantage of the between-subjects comparison was that we were able to examine the MPH effect in different dose groups. However, confounding by indication cannot be eliminated. For example, those with a severe degree of ADHD symptoms, an exhibition of risky behaviors, or comorbid with other psychiatric illnesses were more likely to be prescribed medication. Hence, we also performed within-subject comparisons to adjust for time-invariant factors."

Transport safety thus offers another compelling reason to treat ADHD symptoms. Methylphenidate in particular seems to be especially effective in reducing traffic fatalities and injuries.

A Swedish-Danish-Dutch team used the Swedish Medical Birth Register to identify the almost 1.7 million individuals born in the country between 1980 and 1995. Then, using the Multi-Generation Register, they identified 341,066 pairs of full siblings and 46,142 pairs of maternal half-siblings, totaling 774,416 individuals.

The team used the National Patient Register to identify diagnoses of ADHD, as well as neurodevelopmental disorders (autism spectrum disorder, developmental disorders, intellectual disability, motor disorders), externalizing psychiatric disorders (oppositional defiant and related disorders, alcohol misuse, drug misuse), and internalizing psychiatric disorders (depression, anxiety disorder, phobias, stress disorders, obsessive-compulsive disorder).

The team found that ADHD was strongly correlated with general psychopathology overall (r =0.67), as well as with the neurodevelopmental (r = 0.75), externalizing (r =0.67), and internalizing (r = 0.67) sub factors.

To tease out the effects of heredity, shared environment, and non-shared environment, a multivariate correlation model was used. Genetic variables were estimated by fixing them to correlate between siblings at their expected average gene sharing (0.5for full siblings, 0.25 for half-siblings). Non-genetic environmental components shared by siblings (such as growing up in the same family) were estimated by fixing them to correlate at 1 across full and half-siblings. Finally, non-shared environmental variables were estimated by fixing them to correlate at zero across all siblings.

This model estimated the heritability of the general psychopathology factor at 49%, with the contribution of the shared environment at 7 percent and the non-shared environment at 44%. After adjusting for the general psychopathology factor, ADHD showed a significant and moderately strong phenotypic correlation with the neurodevelopmental-specific factor (r = 0.43), and a significantly smaller correlation with the externalizing-specific factor (r = 0.25).

For phenotypic correlation between ADHD and the general psychopathology factor, genetics explained 52% of the total correlation, the non-shared environment 39%, and the shared familial environment only 9%. For the phenotypic correlation between ADHD and the neurodevelopmental-specific factor, genetics explained the entire correlation because the other two factors had competing effects that canceled each other out. For the phenotypic correlation between ADHD and the externalizing-specific factor, genetics explained 23% of the correlation, shared environment 22%, and non-shared environment 55%.

The authors concluded that "ADHD is more phenotypically and genetically linked to neurodevelopmental disorders than to externalizing and internalizing disorders, after accounting for a general psychopathology factor. ... After accounting for the general psychopathology factor, the correlation between ADHD and the neurodevelopmental-specific factor remained moderately strong, and was largely genetic in origin, suggesting substantial unique sharing of biological mechanisms among disorders. In contrast, the correlation between ADHD and the externalizing-specific factor was much smaller and was largely explained by-shared environmental effects. Lastly, the correlation between ADHD and the internalizing subfactor was almost entirely explained by the general psychopathology factor. This finding suggests that the comorbidity of ADHD and internalizing disorders are largely due to shared genetic effects and non-shared environmental influences that have effects on general psychopathology."

Many college students truly have ADHD and deserve to be treated, but some attempt to fake ADHD symptoms to get stimulant medications for nonmedical uses, such as studying and getting high.  Some students who fake ADHD also seek to gain accommodations that would give them additional time to complete exams. To address this issue, two psychologists examined data from 514 university students being assessed for ADHD to evaluate the ability of assessment tools to detect students who fake ADHD symptoms.

All participants had asked to be assessed to determine whether they could qualify for disability services. This was therefore by no means a random sample of university students, and could be expected to include some non-ADHD individuals seeking the benefits of an ADHD diagnosis. But this offered a good opportunity to explore which combination of tools would yield the best accuracy, and be best at excluding malingerers.

That was achieved by using both multiple informants and multiple assessment tools and comparing results. Self-assessment was supplemented by assessment by other informants (e.g. parent, partner, friend, or another relative). These were supplemented with symptom validity tests to check for telltale highly inconsistent symptom reporting, or symptom exaggeration, which could signal false positives.

On the other hand, some individuals with ADHD have executive functioning problems that may make it difficult for them to reliably appraise their symptoms on self-assessment tests, which can lead to false negatives. Performance validity tests were therefore also administered, to detect poor effort during evaluation, which could lead to false negatives.

Observer reporting was found to be more reliable than self-reporting, with significantly lower inconsistency scores (p < .001), and significantly higher exaggeration scores (p < .001). More than twice as many self-reports showed evidence of symptom exaggeration as did observer reports. This probably understates the problem when one considers that the observer reports were performed not by clinicians but by parents and partners who may themselves have had reasons to game the tests in favor of an ADHD diagnosis.

Even so, the authors noted, "External incentives such as procurement of a desired controlled substance or eligibility for the desired disability accommodation are likely to be of more perceived value to those who directly obtain them." They suggested compensating for this by making ADHD diagnoses only based on positive observer tests in addition to self-reports: "Applying an 'and' rule-one where both self-and observers reports were required to meet the diagnostic threshold-generally cut the proportions meeting various thresholds at least in half and washed out the differences between the adequate and inadequate symptom validity groups."

They also recommended including formal tests of response validity, using both symptom validity tests and performance validity tests. Overall, they found that just over half of the sub-sample of 410 students administered performance validity tests demonstrated either inadequate symptom or performance validity.

Finally, they recommended "that clinicians give considerable weight to direct, objective evidence of functional impairment when making decisions about the presence of ADHD in adults. The degree to which symptoms cause significant difficulty functioning in day-to-day life is a core element of the ADHD diagnostic criteria (American Psychiatric Association,2013), and it cannot be assumed that significant symptoms cause such difficulty, as symptoms are only moderately associated with such functional impairment. ... we urge clinicians to procure objective records (e.g., grade transcripts, work performance evaluations, disciplinary and legal records) to aid in determining functional impairment in adults assessed for ADHD."

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.

An international group of twelve experts recently published a consensus report examining the state of the evidence and offering recommendations to guide the screening, diagnosis, and treatment of individuals with ADHD-SUD comorbidity.[1]

In a clear sign that we are still in the early stages of understanding this relationship, five of the thirteen recommendations received the lowest recommendation grade (D), eight received the next-lowest (C), and none received the highest (A and B). The lower grades reflected the absence of the highest level of evidence, obtained from meta-analyses or systematic reviews of relevant randomized controlled trials (RCTs).

Nevertheless, with these limitations in mind, the experts agreed on the following points:

Diagnosis

•  The strongest recommendation, the only one based on a 2+ level of evidence (well-conducted case-control or cohort studies with allowing risk of confounding or bias and a moderate probability that the relationship is causal) is that the "Short Version of the Adult ADHD Self-Report Scale (ASRS-SV) screener is currently the most widely used and investigated screening tool in individuals with ADHD and comorbid SUD, with good sensitivity and specificity across studies."
• Two other recommendations were graded C: The diagnostic process should include current and past substance abuse, and seek to involve partners and relatives in evaluating symptoms and functional impairments.
• Four recommendations got the lowest grade, D. The experts suggested starting the diagnostic process as soon as possible and focusing on drug- and alcohol-free periods in the patient's life during history taking. They also recommended that physicians and clinical psychologists should only make diagnoses if they have extensive training in diagnosing ADHD, as well as experience with adults with ADHD and with addiction care, and that they should consider treating adults with sufficiently severe ADHD symptoms.
  

Treatmen

•  In general, evidence was stronger in this area, and only one of the six recommendations was graded D. The other five recommendations were graded C, with the highest level of evidence being 2(cohort or case and control studies with undetermined risk of bias), although in three cases it was level 3 (non-analytical studies, such as case reports and case series).
• The grade D recommendation was to always consider a combination of psychotherapy and pharmacotherapy.

The grade C recommendations included considering adequate medical treatment of both ADHD and SUD; integrating ADHD treatment with SUD treatment as soon as possible;

Myth: ADHD is caused by poor parenting or teaching.
Parents and teachers are popular targets for those who misunderstand ADHD.  This myth posits that ADHD would not exist if parents and teachers were more effective at disciplining and teaching children.  From this perspective, ADHD is a failure of society, not a brain disease.

Fact: ADHD occurs when genes and toxic environments harm the brain.
Blaming parents and teachers for ADHD is wrong.  We know from research studies that many parents of ADHD children have normal parenting skills and even when we train parents to be better parents, ADHD does not disappear.  Many parents of ADHD children have an anon-ADHD child that they raised with the same discipline methods.  If bad parenting causes ADHD, all the children in the family should have ADHD. Equally important, decades of research studies have shown that genes and toxic environments cause ADHD by harming the brain.  I'm not saying that all parents and teachers are perfect.  Teaching parents and teachers, special methods for dealing with ADHD can help children with ADHD.  

Myth: Watching Television causes ADHD.
This myth hit the media in 2004 when a research group published a paper suggesting that toddlers who watched too much TV were at risk for attentional problems later in life.

Fact: The study was wrong.
Sometimes researchers get it wrong. But fortunately, science is self-correcting; if an incorrect result is published, subsequent studies will show that it is wrong. That's what happened with the ADHD television study.  After the first study made such a media splash, several other researchers did similar studies.  They found out that the original study had errors and that watching too much TV does not cause ADHD.  But, because the popular media did not pick up the later studies, the myth persists. I'm not recommending that toddlers watch a lot of television, but rest assured that, if they do, it will not cause ADHD.

Myth: Too much sugar causes ADHD.
This idea is based on common sense.  Many parents know that when their children and their friends have too much sugary food, they can get very active and out of control.

Fact: Sometimes, common sense is wrong.
As a parent, I thought there was some truth to the sugar myth.   But when a colleague, Dr. Wolraich, reviewed the world literature on the topic, he found that there have been many studies on the effect of sugar on children.  These studies show that sugar does not affect either the behavior or the thinking patterns of children.  Having too much sugar is bad for other reasons, but it does not cause ADHD.

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.

Many college students truly have ADHD and deserve to be treated but some attempt to fake ADHD symptoms with the goal of getting stimulant medications for non-medical uses such as studying and getting high.  Some students who fake ADHD also seek to gain accommodations that would give them additional time to complete exams. To address this issue, two psychologists examined data from 514 university students being assessed for ADHD to evaluate the ability of assessment tools to detect students who fake ADHD symptoms.

All participants had asked to be assessed to determine whether they could qualify for disability services. This was therefore by no means a random sample of university students, and could be expected to include some non-ADHD individuals seeking the benefits of an ADHD diagnosis.; however, this offered a good opportunity to explore which combination of tools would yield the best accuracy, and be best at excluding malingerers.

That was achieved by using both multiple informants and multiple assessment tools, and comparing results. Self-assessment was supplemented by assessment by other informants (e.g. parent, partner, friend, or other relative). These were supplemented with symptom validity tests to check for telltale highly inconsistent symptom reporting, or symptom exaggeration, which could signal false positives.

On the other hand, some individuals with ADHD have executive functioning problems that may make it difficult for them to reliably appraise their own symptoms on self-assessment tests, which can lead to false negatives. Performance validity tests were therefore also administered, in order to detect poor effort during evaluation, which could lead to false negatives.

Observer reporting was found to be more reliable than self-reporting, with significantly lower inconsistency scores (p< .001), and significantly higher exaggeration scores (p < .001). More than twice as many self-reports showed evidence of symptom exaggeration as did observer reports. This probably understates the problem when one considers that the observer reports were performed not by clinicians but by parents and partners who may themselves have had reasons to game the tests in favor of an ADHD diagnosis.

Even so, the authors noted, “External incentives such as procurement of a desired controlled substance or eligibility for a desired disability accommodation are likely to be of more perceived value to those who directly obtain them.” They suggested compensating for this by making ADHD diagnoses only on the basis of positive observer tests in addition to self-reports: “Applying an ‘and’ rule—one where both self- and observer reports were required to meet the diagnostic threshold— generally cut the proportions meeting various thresholds at least in half and washed out the differences between the adequate and inadequate symptom validity groups.”

They also recommended including formal tests of response validity, using both symptom validity tests and performance validity tests. Overall, they found that just over half the subsample of 410 students administered performance validity tests demonstrated either inadequate symptom or performance validity.

Finally, they recommended “that clinicians give considerable weight to direct, objective evidence of functional impairment when making decisions about the presence of ADHD in adults. The degree to which symptoms cause significant difficulty functioning in day-to-day life is a core element of the ADHD diagnostic criteria (American Psychiatric Association,2013), and it cannot be assumed that significant symptoms cause such difficulty, as symptoms are only moderately associated with functional impairment. we urge clinicians to procure objective records (e.g., grade transcripts, work performance evaluations, disciplinary and legal records) to aid in determining functional impairment in adults assessed for ADHD.”

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.

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