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Youths with ADHD are at higher risk of suicide, burn injuries, road injuries, and more generally all-cause mortality than normally developing children. Methylphenidate (MPH) is known to be effective in reducing ADHD symptoms. Can it also reduce the risk of all-cause mortality? A team of Taiwanese researchers, collaborating with two British researchers, explored that question by looking at a nationwide population cohort.

Taiwan has a single-payer national health insurance system that includes the entire population (99.6 percent coverage). Using the National Health Insurance Research Database (NHIRD), the team identified over 183,000 youths under 18 with an ADHD diagnosis. Of these, just over 68,000 had been prescribed to MPH. The team matched them with an equal number of ADHD youths who were not prescribed MPH. All records were anonymized and checked against the National Mortality Register.

All-cause mortality was split into two subcategories. Unnatural-cause mortality consisted of homicide, suicide, and motor vehicle fatalities. Natural-cause mortality encompassed all other premature deaths. In the raw data, ADHD youths on MPH had half the all-cause mortality of those not on MPH. Natural-cause mortality was down about 40 percent and unnatural-cause mortality was by almost two-thirds. In the non-MPH group, 32 committed suicide in the follow-up year, versus only a single individual in the MPH group. There were seven homicide victims in the non-MPH group, versus none at all in the MPH group.

These staggering reductions, however, were almost exclusively among males. The team then adjusted for potential confounding variables - gender, age, residence, insurance premium, out-patient visits, and pre-existing diagnoses. In the adjusted model, the risk for all-cause mortality was still reduced - by about 20 percent - for those on MPH and remained statistically significant. Virtually identical reductions were found for males and for children first diagnosed with ADHD between 4 and 7 years old. But all other risk estimates became statistically non-significant, due in large measure to the rarity of mortality events.

The authors concluded, "This is the first study reporting that a longer interval between first ADHD diagnosis and first prescription of MPH is associated with a higher risk of all-cause mortality. In addition, we also found that participants receiving longer-duration MPH treatment had a lower risk of all-cause mortality. ... an implication is that receiving a diagnosis earlier and receiving medication earlier may reduce the risk of later adverse consequences."

They nevertheless cautioned, "although we adjusted for multiple covariant, information lacking in the database precluded the measurement of other possible confounders, such as family history, psychosocial stressors, the effect of behavioral therapy or severity of comorbidities. Therefore, as with all observational data, it is not possible to be conclusive about whether the association with lower mortality is related to an effect of MPH treatment itself or whether other characteristics of the children receiving MPH may account for the lower risk (i.e. confounding by indication).

Finally, although the cohort sizes were large, the number of deaths was small, and this limited statistical power, particularly for the investigation of cause-specific mortality and of subgroup differences. Because of the relatively low number of deaths and limited follow-up duration, longer-term studies with larger samples are warranted ..."

Children with ADHD are at higher risk of getting severe burns than normally-developing children. Burn injuries can be traumatic, imposing physical, psychological, and economic burdens on children, their families, and society. Methylphenidate is known to be effective in reducing ADHD symptoms. Can it also reduce the risk of burn injuries?

A team of Taiwanese researchers collaborating with two British researchers explored that question by looking at a nationwide population cohort. Taiwan has a single-payer national health insurance system that includes the entire population (99.6 percent coverage). Using Taiwan's National Health Insurance Research Database(NHIRD), they identified over 90,000 youths under 18 years old with a diagnosis of ADHD. Youths who had burned injuries before diagnosis were excluded. ADHD youths were further divided into three groups: those not prescribed methylphenidate (over 22,000), those prescribed methylphenidate for less than 90 days (over 17,500), and those prescribed methylphenidates for 90 days or more(over 50,000).

Because methylphenidate is the only approved stimulant in Taiwan, it was the only stimulant analyzed in this study. Atomoxetine, a non-stimulant, is also approved in Taiwan, but only for those whose, outcomes with methylphenidate are suboptimal. It was only used by 4 percent of those on ADHD medication, and generally after prior use of methylphenidate, so there was no way to evaluate its effectiveness. Among ADHD youths not on methylphenidate, the proportion who got burn injuries was 6.7 percent. That dropped to 4.5 percent for those medicated for under 90 days, and to 2.9 percent for those on longer-term medication.

Calculations indicated that half of all burn injuries could have been prevented if all youths had been on methylphenidate. After adjusting for multiple confounders - seizure, intellectual disability, autism, conduct disorder, opposition defiant disorder, anxiety, depression, and psychotropic use (benzodiazepine, Z-drugs, antipsychotics, and antidepressants) that taking methylphenidate for any length of time was 38 percent less likely to suffer burn injuries. Moreover, longer-term medication had a greater beneficial effect. Those taking methylphenidate for under 90 days were 30 percent less likely to get burn injuries, whereas those taking it for 90 or more days were less than half as likely to get burn injuries as those not on methylphenidate.

The authors emphasized, "This nationwide population-based study has several strengths. First, the nationally representative sample was substantial and minimized selection bias. Second, patients with ADHD were identified through physician-based diagnoses. Third, all MPH [methylphenidate] prescriptions are recorded in the NHIRD, avoiding misclassification bias. Also, by excluding burn injuries before ADHD diagnosis, the reverse causal relationship between ADHD and burn injury was eliminated."

To what extent does sex matter in the expression of ADHD symptoms and associated cognitive deficits among youths with ADHD?

A recently published meta-analysis of 54 studies by a Canadian team of researchers at the University of Quebec at Montreal suggests it makes little to no difference. A meta-analysis of 26 studies with over 5,900 youths found no significant difference in inattention symptoms, and a meta-analysis of 24 studies with over 5,500 youths likewise found no difference in hyperactivity-impulsivity symptoms. Separating out hyperactivity and impulsivity made no difference.

Given these results, it's no surprise that a meta-analysis of 15 studies with over 3,500 youths again found no significant divergence between the sexes for total ADHD symptoms. Parents and teachers differed, however, in their ratings of symptoms. Whereas parents observed no differences, teachers reported boys had slightly more inattention and hyperactive-impulsive behaviors than girls. Turning to cognitive functions, a series of meta-analyses found no significant sex differences for interference control, working memory, and planning scores. But boys performed slightly worse on inhibition and motor response inhibition. While the raw data also showed boys slightly under-performing girls on cognitive flexibility, strong evidence of publication bias made this unreliable.

The team also compared youths with ADHD and youths without ADHD. Both for females and for males, those differences in ADHD symptoms were - as would be expected - extremely large, whether for total symptoms, inattention, or hyperactivity-impulsivity. All cognitive function scores were moderately better for normally developing boys compared with boys with ADHD, and for normally developing girls compared with girls with ADHD. Yet once again, when comparing these effect sizes between girls and boys, there were no significant differences for any of the symptom and cognitive function effects.

"In other words," the authors wrote, "boys and girls with ADHD presented significantly more primary symptoms and executive and attention deficits than did their peers without ADHD, and effect sizes were not significantly different between the sexes." They concluded, "girls with ADHD do not differ from boys with ADHD in many domains of cognitive functioning, and they have significantly more severe difficulties across the executive and attentional functions measured relative to girls without ADHD. This meta-analysis is the first to examine sex differences in cognitive flexibility, working memory, and planning."

Two new studies, examining entire nationwide populations on opposite sides of the world, have just reported findings on the association between hypertensive disorders of pregnancy (HDP) and subsequent ADHD in off spring. HDP includes chronic hypertension, pre-eclampsia, pre-eclampsia superimposed on chronic hypertension, and gestational hypertension.

According to the Mayo Clinic, Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, most often the liver and kidneys. Preeclampsia usually begins after 20 weeks of pregnancy in women whose blood pressure had been normal. Left untreated, it can lead to serious complications for both mother and baby and can be fatal. This range of conditions affects more than one in twenty pregnancies worldwide. HDP hampers permeability of the placenta, which may reduce delivery of blood-borne oxygen and nutrients to the fetus, potentially affecting brain development. ADHD could thus theoretically emerge as a neurodevelopmental outcome.

To what extent is this borne out in national-wide population studies? Both Taiwan and Sweden have single-payer national health insurance systems that systematically track virtually every resident. One study team used the Taiwan National Health Insurance research database to examine a cohort of 877,233 children born between 2004 and 2008. The other study team used the Swedish national registers to explore a cohort of 1,085,024 individuals born between 1987 and 1996.

The Taiwanese study adjusted for the following covariate/confounders: year of birth, fetal sex, paternal age, maternal age, family income, urbanization level, maternal diabetes diagnosis, preterm birth, small for gestational age, and parental psychiatric disorders. The Swedish study adjusted for the calendar year of birth, offspring sex, maternal age, parity, height, body mass index, smoking, presentational diabetes, parental educational level, occupation, and marital status. In the Taiwanese population, children of mothers with hypertensive disorders during pregnancy were about 20% more likely to develop ADHD than those of mothers without such disorders. There was no significant difference between chronic hypertension and pregnancy-induced hypertension/pre-eclampsia.

In the Swedish population, children of mothers with hypertensive disorders during pregnancy were about 10% more likely to develop ADHD than those of mothers without such disorders. But the Swedish study also went a step further. It is incredibly difficult to identify all significant confounding variables. But if you have a large enough study population, one can examine the effect of restricting the analysis to siblings within the same families. In that way, one can control in large measure for familial confounding “ shared environment and heredity. In the subsample of siblings “ 1,279 exposed to HDP versus 1,607 not exposed “ those exposed to outerwear were 9% more likely to develop ADHD, but this outcome was not statistically significant.

Noting the reduced statistical power of the subsample, the authors nonetheless concluded, the magnitude of these associations might be too weak(for ADHD in particular) to be considered an important risk factor at the level of the general population  Moreover, in a separate cohort of 285,901 Swedish men born between 1982 and 1992 who attended assessments for military conscription, mildly lower cognitive scores among those exposed to HDP in uteri vanished altogether (mean difference = 0) when limited to comparisons between full siblings (1,917 exposed versus 2,044 not exposed).

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.

ADHD continues to be a significant and difficult challenge in the collegiate world.

The symptoms of the disorder directly impact a person’s ability to manage the demands of college. Matriculating students are expected to rapidly obtain and deploy many self-management skills. Increased academic expectations demand a greater capacity for sustained attention. And the evolving social milieu can tax the emotion-regulation and social cognition of those with ADHD.

Having seen our patients struggle, the Association for Collegiate Psychiatry decided to submit a workshop for presentation at the 2019 APA meeting in San Francisco. While developing the presentation, we discovered a wealth of recent ‘young adult’ follow-up data from longitudinal studies.

Without exception, the study's findings reflected a significant decrease in functional outcomes across multiple domains of adult life. Further, we discovered that the new work coming from the TRAC observational study of college students has found troublesome rates of psychiatric comorbidity after the first year. This epidemiologic evidence supports devoting resources to the care of this cohort.

However, it appears that this has not penetrated the world of campus mental health treatment. At present, most post-secondary schools (to our knowledge, data is quite limited) lean toward policies that make it difficult for students with ADHD to be diagnosed or treated on campus. One obstacle is requiring evidence of a childhood diagnosis, which many children with high-IQ compensated ADHD may not have received. Another can be the demand for expensive and comprehensive neuropsychological testing even though the diagnostic value of that testing remains unclear.

Some student health centers ask students to obtain prescriptions from the treaters they saw before coming to campus, even if those prescribers are out of state. Though these policies may be deployed to decrease the diversion of stimulant medication, such hurdles may be difficult for the 18-year-old ADHD student to navigate. The result is that many students with this predictably destructive condition go untreated.

The good news is this subject interests the collegiate community. Among other things, our APA workshop was selected to be the APA’s ‘Member’s of the Month’ for January 2020. Much work remains in developing and deploying diagnostic policies and treatment strategies that colleges and universities feel comfortable supporting. We mentioned the APSARD community during the workshop as a resource for professionals interested in ADHD. And we hope the wider ADHD research and treatment communities will join us in focusing our energy on this underserved and sometimes maligned group of students who need our help.

The study team began with a representative sample of 69,972U. S. adults aged 18 years or older who completed the 2012 and 2013 U.S. National Health and Wellness Survey. These adults were invited to complete the Validate Attitudes and Lifestyle Issues in Depression, ADHD, and Troubles with Eating(VALIDATE) study, which included 1) a customized questionnaire designed to collect data on sociodemographic and clinical characteristics and lifestyle, and2) several validated work productivity, daily functioning, self-esteem, and health-related quality of life (HRQoL) questionnaires. Of the 22,937 respondents, 444 had been previously diagnosed with ADHD, and 1,055 reported ADHD-like symptoms but had no previous clinical diagnosis.

There were no significant differences between the two groups in terms of age, education, income, health insurance, and most comorbid disorders. But those who had not been previously diagnosed were significantly more likely to be first-generation Americans (p<.001), nonwhite (p<.001), unemployed (p=.024), or suffer from depression, insomnia, or hypertension.

After matching the two groups for sociodemographic characteristics and comorbid conditions, covariate comparisons were made between 436 respondents diagnosed with ADHD and 867 previously undiagnosed respondents. Among respondents who were employed, diagnosed individuals registered a mean work productivity loss of 29% as opposed to 49% for the previously undiagnosed (p<.001). They also registered a 37% level of activity impairment versus a 53% level among the undiagnosed(p<.001). On the Sheehan Disability Scale, which ranges from 0 (no impairment) to 30 (highly impaired), the diagnosed group had a mean of 10, as opposed to a mean of 15 for the undiagnosed (p<.001). Diagnosed respondents also significantly outperformed undiagnosed ones on the Rosenberg Self-Esteem Scale (19 versus 15, on a scale of 0 to 30, p<.001), and on two quality-of-life scales (p<.001).

Applying a linear regression mixed model to the matched sets, the diagnosed still scored 16 points better than the undiagnosed on the WPA I: GH Productivity Loss scale (p<.001), 14 points better on the WPA I: GH Activity Impairment scale (p<.001), 4.5 points better on the Sheehan Disability Scale(p<.001), almost 4 points on the Rosenberg Self-Esteem Scale (p<.0001), with comparable gains on the two quality-of-life scales (p<.001 and p<.0001).

The authors concluded, This comparison revealed that individuals who had been diagnosed with ADHD were more likely to experience better functioning, HRQoL [health related quality-of-life], and self-esteem than those with symptomatic ADHD. This result appears to be robust, withstanding several levels of increasingly rigorous statistical adjustment. That points to substantial benefits from the treatment that follows a diagnosis of adult ADHD.

There is a well-documented gap between the known prevalence of adult ADHD and rates of diagnosis and treatment. In Germany, epidemiological studies of nationally representative community samples have found prevalence rates ranging from 3.1% to 4.7%. Yet, studies of publicly insured individuals aged 18 to 69 years old report rates of diagnosed ADHD between 0.04% and 0.4%. So, even in a country with universal health insurance, more than nine out of ten adults with ADHD go undiagnosed.

Many factors contribute to under-diagnosis: stigma, culturally influenced perceptions, and lack of motivation by those affected. Another crucial factor is the lack of recognition of ADHD symptoms by clinicians.

A research team surveyed 144 psychologists, 32 physicians, and two occupational therapists. Almost three in five participants were psychotherapists, a quarter were neuropsychologists, and one in seven were psychiatrists.

Four out of five clinicians stated they had received only a few hours of ADHD-specific training. One in four stated they had not examined guidelines for diagnosing ADHD. A lack of formal training among the vast majority, and unfamiliarity with current diagnostic guidelines in a significant minority, were surprising findings among clinicians who regularly work with adults with ADHD.

Many clinicians had difficulty identifying core features of adult ADHD as defined by the DSM-5 and International Classification of Diseases, Tenth Revision (ICD-10). Roughly one in five stated that hyperactivity had little relevance to adult ADHD. The only core feature correctly identified by more than half the respondents was having difficulties concentrating. Impairments in social behavior or aggression and memory impairment were not identified as being clearly relevant or irrelevant to adult ADHD.

The authors concluded that these findings appear to indicate some uncertainty or at least a lack of consensus among clinicians about what symptoms are relevant to ADHD in adulthood, and it is likely that this uncertainty contributes to diagnostic inaccuracy.

Most respondents reported using self-report scales of ADHD symptoms and using unstructured interviews. While slightly more than half agreed that collateral reports are important to diagnosis, only about a third reported regularly using them. This is a problem given the limited accuracy of self-reported childhood symptoms for documenting the childhood-onset of the disorder. Semi-structured interviews are also known to improve the accuracy of diagnosis, but are rarely used in clinical practice.

Over half of psychologists and a quarter of physicians reported using cognitive or neuropsychological testing, even though this is at variance with German (and other) guidelines, which specify that such testing is suitable for clarifying strengths and weaknesses, but not for ruling out or confirming a diagnosis of ADHD. The European Consensus Statement also states that cognitive/neuropsychological testing should only be used as a secondary or supplementary assessment tool.

While three out of four clinicians recommended stimulant drug treatment, psychologists tended to be more hesitant to do so. This is likely because German psychologists receive little training in pharmacotherapy, and do not have prescription privileges. Given the demonstrated efficacy of stimulant treatment, this points to a need to better educate psychologists in this regard.

Almost three in four respondents cited a lack of clinician knowledge and experience as a barrier to ADHD diagnosis. Most clinicians also stated they were either uncertain or only somewhat certain of their ability to diagnose ADHD. That suggests that more extensive ADHD-specific training is needed.

A limitation of the survey was the relatively low participation by physicians. It is also likely that the findings are not reflective of practices in ADHD specialty clinics.

The authors concluded, Further training is needed to improve clinicians' understanding of ADHD in adulthood and to align diagnostic practices with guideline recommendations. Whereas discrepancies between respondents regarding the relative importance of peripheral symptoms (e.g., memory problems) were most common, a lack of consensus was found even for core symptoms listed by diagnostic criteria. Particularly among psychologists improved awareness regarding the benefits of stimulant medications is needed to bring their treatment recommendations in line with evidence-based guidelines.