Gender differences in psychiatric comorbidity: a population‐based study of 40 000 adults with attention deficit hyperactivity disorder

Objective

We aimed at determining whether gender modified associations between ADHD and psychiatric comorbidities in adults.

Method

We identified adults with ADHD by linking Norwegian national registries and compared them with the remaining adult population (born 1967–1997, ADHD and bipolar during 2004–2015, other psychiatric disorders 2008–2015). Prevalence differences (PDs) and prevalence ratios (PRs) of psychiatric disorders were determined by Poisson regression. Interaction by gender was evaluated on additive (PDs) and multiplicative (PRs) scales. Proportions of psychiatric disorders attributable to ADHD were calculated.

Results

We identified 40 103 adults with ADHD (44% women) and 1 661 103 adults (49% women) in the remaining population. PDs associated with ADHD were significantly larger in women than in men for anxiety, depression, bipolar and personality disorders, for example depression in women: 24.4 (95% CI, 23.8–24.9) vs. in men: 13.1 (12.8–13.4). PDs were significantly larger in men for schizophrenia and substance use disorder (SUD), for example SUD in men: 23.0 (22.5–23.5) vs. in women: 13.7 (13.3–14.0). Between 5.6 and 16.5% of psychiatric disorders in the population were attributable to ADHD.

Conclusion

The association between ADHD and psychiatric comorbidities differed significantly among men and women. Clinicians treating adults with ADHD should be aware of these frequent and gender‐specific comorbidities, such that early treatment can be offered.     

Epilepsy in a large cohort of children diagnosed with attention deficit/hyperactivity disorders (ADHD)

PurposeThe knowledge about possible relationships between ADHD and epilepsy is largely based on small samples of ADHD patients and on cohorts with epilepsy. There is insufficient information about the clinical characteristics of epilepsy among children diagnosed with ADHD. The aim of this study was to investigate the prevalence and characteristics of epilepsy in a large, unselected cohort of children with ADHD.MethodsWe conducted a retrospective chart-review of children with ADHD who were evaluated in our clinic between the years 2000 and 2005. We compared age, sex, disorders of psychological development, cognitive level, pharmacological treatment for ADHD, initial response to treatment and ADHD subtype with and without epilepsy. In addition, we compared our data with data from a Norwegian study in a large general pediatric population.ResultsOf 607 children with ADHD (age 6–14 years; 82.4% males); 14 (2.3%) had a history of epilepsy, and 13 of these had active epilepsy. This is a higher occurrence than expected in the general pediatric population (0.5%). The majority of our patients had mild (an easily treated) epilepsy and they were more likely to be seizure free (79%) compared to the patients with epilepsy in general pediatric population. The ADHD patients with and without epilepsy did not differ regarding age, gender, disorders of psychological development, IQ level < 85 or ADHD subtype. The patients had been diagnosed with epilepsy on average 1.8 years before the ADHD assessment. All patients with epilepsy were treated with methylphenidate (MPH), and initial response to MPH was achieved in 85.7%.ConclusionThe epilepsy diagnosis preceded the ADHD diagnosis, and was found in a significantly higher rate than would be expected in the general pediatric population. The majority of patients had mild epilepsy and ADHD-Combined Inattentive/Hyperactive-Impulsive Subtype. All cases with epilepsy and ADHD were treated with MPH, with initial response achieved in 86%.     

The cognitive genetics of attention deficit hyperactivity disorder (ADHD): sustained attention as a candidate phenotype

Here we describe the application of cognitive genetics to the study of attention deficit hyperactivity disorder (ADHD). Cognitive genetics owes much to the pioneering work of cognitive neuropsychologists such as John Marshall, whose careful observations of cognitive dissociations between brain-lesioned patients greatly advanced the theoretical understanding of normal cognitive function. These theories have in turn helped to constrain linkages between candidate genes and cognitive processes and thus help to drive the relatively new field of cognitive genetics in a hypothesis-driven fashion. We examined the relationship between sustained attention deficits in ADHD and genetic variation in a catecholamine-related gene, dopamine beta hydroxylase (DbetaH). DBH encodes the enzyme that converts dopamine to noradrenaline and is crucial to catecholamine regulation. A polymorphism with the DBH gene has been associated with ADHD. In fifty-two children with ADHD, we examined whether variation in the Taq I DBH gene polymorphism was related to sustained attention performance. Participants performed the Sustained Attention to Response Test (SART). Performance on the SART discriminates ADHD from control children, and in imaging work, is associated with right frontoparietal activation. A significant effect of DBH genotype was found on SART performance measures. Children possessing two copies of the ADHD-associated risk allele (A2) had significantly poorer sustained attention than those ADHD children who did not possess this allele or a non-genotyped control group. The DBH gene may contribute to the susceptibility for ADHD, in part because of its varying effects on the development of brain mechanisms mediating sustained attention.     

Excessive daytime sleepiness in adults with possible attention deficit/hyperactivity disorder (ADHD): a web-based cross-sectional study

ObjectivesArousal dysregulation has been speculated to be involved in the pathological mechanism of attention deficit/hyperactivity disorder (ADHD). However, there has been no epidemiological study assessing the real condition of excessive daytime sleepiness (EDS) in adults with ADHD. This study investigated the prevalence of EDS and the relationship between sleepiness and ADHD symptoms in adults with possible ADHD.MethodsAn observational, cross-sectional, web-based study was performed. Participants were 9822 Japanese adults aged 20–69 years who completed an Internet-based questionnaire that assessed ADHD symptoms, autistic traits, depressive symptoms, chronotype, sleepiness, and sleep disturbances.ResultsParticipants with possible ADHD were more likely than non-ADHD participants to have an evening chronotype and experience depressive symptoms, sleepiness, and sleep disturbances. The rates of having moderate and severe sleepiness in the possible ADHD group were higher than those in the non-ADHD group. Hierarchical logistic regression analyses revealed that the presence of ADHD symptoms was independently associated with EDS even after adjusting for factors related to the presence of sleepiness. When examining inattention and hyperactivity scores among participants with possible ADHD, the inattention score was significantly higher in the severe EDS group compared with the moderate and non-EDS groups.ConclusionsEDS was relatively common in adults with possible ADHD. ADHD symptoms, especially inattentiveness, were associated with the formation of EDS in this population.     

Sleep quality in adult patients with attention deficit hyperactivity disorder (ADHD)

Sleep disorders are common in adults with attention deficit/hyperactivity disorder (ADHD). Two sleep questionnaires; the Brown ADD Scale, the Symptom-Checklist-90-R, and a self-developed symptom questionnaire were administered in this study. In a sample of 61 patients without comorbidity, current substance abuse and medication intake, sleep problems were reported more often than in healthy controls. A lack of being refreshed in the morning was very closely associated with ADHD symptomatology whereas insomnia was related to the presence of comorbidity and depressive symptoms. In the total sample (N = 120), medication intake (mainly stimulants) was not related to any of the sleep parameters. It seems important to screen adult patients with ADHD for the presence of sleep disorders, especially insomnia, restless legs syndrome, and sleep-related breathing disorders (the last in conjunction with the body mass index). Since primary sleep disorders are associated with cognitive impairment, one might expect that ADHD symptomatology may improve if comorbid sleep disorders are adequately treated in addition to the specific ADHD treatment.     

Risk of accidents and unintentional injuries in men and women with attention deficit hyperactivity disorder across the adult lifespan

Introduction

Attention deficit hyperactivity disorder (ADHD) is associated with risk-taking behavior, leading to accidents and unintentional injuries (summarized here as incidents). Main aim of this study is to determine if men and women with and without ADHD differ in the risk of mild (treated outpatient) and severe (treated inpatient) incidents across the adult lifespan (age groups: 18–29; 30–59, and ≥60 years). Secondary aim: investigate the role of comorbid mental disorders and drugs for the treatment of these comorbidities, and ADHD-medication.

Methods

Using anonymized German claims data (N = 4,575,027), adults with ADHD diagnosis during 2016–2019 (N = 17,041) were compared with a 1:4 age and sex-matched group without ADHD diagnosis. Regression analyses statistically tested group differences.

Results

Incidents occur in a U-shaped form across the adult lifespan. Individuals with ADHD show the same pattern but at a substantially increased risk of both mild and severe incidents throughout the lifespan. Women without ADHD are at lower risk in young adulthood than men but at higher risk in older adulthood. Women with ADHD show the same pattern for severe incidents, but for mild incidents they have the highest risk throughout the lifespan. Co-occurring anxiety disorder and the use of psycholeptics and ADHD-medication decreased the incident risk.

Conclusion

We extend available knowledge which has hitherto focused on young adult males and traffic accidents. ADHD is associated with increased incidents across the adult lifespan, with distinct patterns regarding age, sex, and incident severity. An accurate diagnosis of ADHD in adulthood provides the first step towards prevention of accidents and unintentional injuries.     

Neural correlates of performance monitoring in adult patients with attention deficit hyperactivity disorder (ADHD)

Introduction. In this study, the neural correlates of error processing in adult patients with attention deficit hyperactivity disorder (ADHD) are to be investigated for the first time. Recent studies in children with ADHD suggested, with some inconsistencies, deficits in error processing. Based on an analogue study with students, we hypothesized that ADHD patients show reduced amplitudes in the event-related potential (ERP) of the Pe (error positivity) but normal amplitudes of the ERN (error-related negativity) after incorrect responses. Method. In this study we investigated 34 adult ADHD patients and 34 healthy controls with a modified version of the Eriksen flanker task while recording the neural activity with 26 scalp EEG electrodes. Patients discontinued all medication at least 3 days prior to investigation. Age was included as a control variable for the statistical analyses. Results and conclusion. As hypothesized, we found reduced Pe amplitudes, but also reduced ERN values, in ADHD patients. Importantly, theses differences as well as the deficits in behavioural performance were mainly detectable in the younger subsample, but not in the elderly subsample. Our results indicate that adult ADHD patients are characterized by deficits in error processing, which vanish with age.     

Psychodramatic group psychotherapy as a parental intervention in attention deficit hyperactivity disorder: A preliminary study

It is already known that clinical attention deficit hyperactivity disorder (ADHD) is affected by some negative parenting variables. The aim of this study was to investigate the effects of psychodramatic group psychotherapy (PGP) on parenting variables. The study group included seven mothers whose children had been diagnosed with ADHD and were attending a special education and rehabilitation center. Twelve PGP sessions, one per week, were conducted with these mothers. Participants’ statements were recorded at each session, and these statements were evaluated to indicate basic parental variables, namely: parental psychopathology, negative parental cognitions, negative parental attitudes, family functionality–marital conflict, and parental stress. The statistical study revealed that statements indicating parental psychopathology and negative parental attitudes showed a statistically significant negative correlation with time. Qualitative data indicate mothers stigmatization, self-stigmatization and harsh punishment toward the children. Parental psychopathology and negative parental attitudes are two parental factors that are known to have a negative impact on the clinical status of ADHD, and PGP might be effective in improving these two factors.     

Investigation of attention deficit hyperactivity disorder (ADHD) sub-types in children via EEG frequency domain analysis

Aim of the study: To investigate the frequency domain effects and changes in electroencephalography (EEG) signals in children diagnosed with attention deficit hyperactivity disorder (ADHD).

Patients and methods: The study contains 40 children. All children were between the ages of 7 and 12 years. Participants were classified into four groups which were ADHD (n=20), ADHD-I (ADHD-Inattentive type) (n=10), ADHD-C (ADHD-Combined type) (n=10), and control (n=20) groups. In this study, the frequency domain of EEG signals for ADHD, subtypes and control groups were analyzed and compared using Matlab software. The mean age of the ADHD children's group was 8.7 years and the control group 9.1 years.

Results: Spectral analysis of mean power (μV²) and relative-mean power (%) was carried out for four different frequency bands: delta (0--4 Hz), theta (4--8 Hz), alpha (8--13 Hz) and beta (13--32 Hz). The ADHD and subtypes of ADHD-I, and ADHD-C groups had higher average power value of delta and theta band than that of control group. However, this is not the case for alpha and beta bands. Increases in delta/beta ratio and statistical significance were found only between ADHD-I and control group, and in delta/beta, theta/delta ratio statistical significance values were found to exist between ADHD-C and control group.

Conclusion: EEG analyzes can be used as an alternative method when ADHD subgroups are identified.     

Evaluation of sleep organization in patients with attention deficit hyperactivity disorder (ADHD) and ADHD as a comorbidity of epilepsy

Objective/backgroundEpilepsy or attention deficit hyperactivity disorder (ADHD) can influence sleep organization in different ways. The aim of this study was to evaluate sleep organization in children and adolescents with ADHD and epilepsy, and to analyze the influence of methylphenidate.MethodsThis was an observational, cross-sectional study of children and adolescents with epilepsy, who were seizure free for at least three months, and were also diagnosed with ADHD. They were selected from the epilepsy and child neurology outpatient clinic of a university hospital in Brazil. After sample size calculation, patients were consecutively included into four different groups, with 21 patients each: epilepsy + ADHD using methylphenidate, epilepsy + ADHD not using methylphenidate, only ADHD, and a healthy control group. All participants were evaluated with the Sleep Disturbance Scale for Children (SDSC) and monitored with actigraphy for five nights/days.ResultsActigraphic analysis showed a higher number of night awakenings in the epilepsy + ADHD groups; they were most prominent in the group without methylphenidate (p = 0.001). Parental reports demonstrated a higher risk for sleep disturbances in the epilepsy + ADHD without methylphenidate and the ADHD groups (p < 0.001).ConclusionPrimary ADHD as a comorbidity of epilepsy impairs sleep organization in children, and the use of short-acting methylphenidate seems to improve it. Both objective (actigraphic) and subjective (SDSC) measures showed significant sleep alterations between primary ADHD and ADHD as a comorbidity of epilepsy; this was most prominent in the group without methylphenidate.     

EEG characteristics and visual cognitive function of children with attention deficit hyperactivity disorder (ADHD)

Using visual and auditory continuous performance tests (CPT) and EEG, cognitive function and EEG power were investigated in patients with attention deficit hyperactivity disorder (ADHD). CPT and EEG were conducted for 44 ADHD children and 44 healthy controls of comparable age and sex. The EEG power tests include relative power of theta, alpha, and beta, and theta/beta and theta/alpha ratios. ADHD patients showed significantly higher theta relative power, lower beta relative power, and higher theta/beta ratio (p < 0.05). ADHD patients showed a significantly lower score of auditory CPT (p < 0.05). The EEG power characteristics were correlated significantly with the visual attention function in ADHD children (p < 0.01). Higher-order level cognitive dysfunction affects ADHD pathogenesis. Cortical hypoarousal effects on several mechanisms including the fronto-striatal circuitry may be implicated in the inhibition of prepotent and premature responses.     

A psycho-genetic study of associations between the symptoms of binge eating disorder and those of attention deficit (hyperactivity) disorder

Objective

Some recent studies have reported intriguingly strong correlations between ADHD and obesity. This study examined whether ADHD symptoms were more pronounced in adults with symptoms of binge eating disorder (BE) than in their non-binging obese counterparts, and whether the links were stronger with inattentive vs impulsive/hyperactive symptoms. We also assessed the role of the dopamine D3 receptor in ADHD symptoms since the DRD3 gene has been associated with impulsivity and drug addiction - both relevant features of ADHD.

Methods

A case (BE: n = 60) double-control (normal weight: n = 61 and obese: n = 60) design was employed. Assessments of both childhood and adults ADHD symptoms were made, as well as genotyping of seven markers of DRD3 including the functional Ser9Gly polymorphism.

Results

Three DRD3 genotypes, including Ser/Ser, had significantly elevated scores on the hyperactive/impulsive symptom scale. In turn, the four ADHD symptom scales were all significantly elevated in the BE and obese groups, who did not differ from each other, compared to those with normal weight.

Conclusions

Results indicated a role for the D3 receptor in the manifestation of the hyperactive/impulsive symptoms of ADHD, and that symptoms of ADHD are significantly, but not differentially, elevated in obese adults with and without binge eating. Our findings suggest that ADHD screening in adults seeking treatment for obesity, including those with BE, may be warranted as methods used to treat ADHD may help some to better manage overeating and other factors contributing to weight gain.     

White‐matter abnormalities in attention deficit hyperactivity disorder: A diffusion tensor imaging study

Current evidence suggests that attention deficit hyperactivity disorder (ADHD) involves dysfunction in wide functional networks of brain areas associated with attention and cognition. This study examines the structural integrity of white‐matter neural pathways, which underpin these functional networks, connecting fronto‐striatal and fronto‐parietal circuits, in children with ADHD. Fifteen right‐handed 8 to 18‐year‐old males with ADHD‐combined type and 15 right‐handed, age, verbal, and performance IQ‐matched, healthy males underwent diffusion tensor imaging. A recent method of tract‐based spatial statistics was used to examine fractional anisotropy (FA) and mean diffusivity within major white‐matter pathways throughout the whole‐brain. White‐matter abnormalities were found in several distinct clusters within left fronto‐temporal regions and right parietal‐occipital regions. Specifically, participants with ADHD showed greater FA in white‐matter regions underlying inferior parietal, occipito‐parietal, inferior frontal, and inferior temporal cortex. Secondly, eigenvalue analysis suggests that the difference in FA in ADHD may relate to a lesser degree of neural branching within key white‐matter pathways. Tractography methods showed these regions to generally form part of white‐matter pathways connecting prefrontal and parieto‐occipital areas with the striatum and the cerebellum. Our findings demonstrate anomalous white‐matter development in ADHD in distinct cortical regions that have previously been shown to be dysfunctional or hypoactive in fMRI studies of ADHD. These data add to an emerging picture of abnormal development within fronto‐parietal cortical networks that may underpin the cognitive and attentional disturbances associated with ADHD. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Transitioning from child and adolescent mental health services with attention‐deficit hyperactivity disorder in Ireland: Case note review

In a context of international concern about early adult mental health service provision, this study identifies characteristics and service outcomes of young people with attention‐deficit hyperactivity disorder (ADHD) reaching the child and adolescent mental health service (CAMHS) transition boundary (TB) in Ireland. The iTRACK study invited all 60 CAMHS teams in Ireland to participate; 8 teams retrospectively identified clinical case files for 62 eligible young people reaching the CAMHS TB in all 4 Health Service Executive Regions. A secondary case note analysis identified characteristics, co‐morbidities, referral and service outcomes for iTRACK cases with ADHD (n = 20). Two‐thirds of young people with ADHD were on psychotropic medication and half had mental health co‐morbidities, yet none was directly transferred to public adult mental health services (AMHS) at the TB. Nearly half were retained in CAMHS, for an average of over a year; most either disengaged from services (40%) and/or actively refused transfer to AMHS (35%) at or after the TB. There was a perception by CAMHS clinicians that adult services did not accept ADHD cases or lacked relevant service/expertise. Despite high rates of medication use and co‐morbid mental health difficulties, there appears to be a complete absence of referral to publicly available AMHS for ADHD youth transitioning from CAMHS in Ireland. More understanding of obstacles and optimum service configuration is essential to ensure that care is both available and accessible to young people with ADHD.     

The dopamine transporter: relevance to attention deficit hyperactivity disorder (ADHD)

The dopamine transporter is elevated in adults with attention deficit hyperactivity disorder (ADHD) compared with healthy controls [Lancet 354 (1999) 2132]. The findings have been confirmed by others in a different population using a different probe for the dopamine transporter. Notwithstanding the need to confirm these findings in a multi-center trial, several hypotheses are presented to account for these observations. A premise that elevated transporter levels result from medication is not supported by current data. Other possibilities, including hypertrophy of dopamine neuronal terminals in the striatum, dysfunctional regulation of dopamine or dopamine receptors, or anomalies in the dopamine transporter gene are presented as hypotheses. The feasibility of exploring these mechanisms in animal models or in human subjects is explored.     

A drosophila model for attention deficit hyperactivity disorder (ADHD): No evidence of association with PRKG1 gene

Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric condition in children and follow up studies have indicated that 22–33% of patients continue to suffer from ADHD during late adolescence and adulthood. The action of psychostimulant drugs may be determined by additional mechanisms beyond the dopamine transporter and receptors. We are exploring new methodology for discovering these mechanisms. For example, in Drosophila, such an additional determinant of psychostimulant action could be protein kinase G (PKG) that affects food-search behavior. Here we initiated studies with the human homologue of PKG, the PRKG1 gene. The aim of this study was to investigate for the presence of linkage disequilibrium between the protein kinase G gene (PRKG1) and adult ADHD in a sample of nuclear families. Genotyping data for the C2276T polymorphism were analyzed using the Transmission Disequilibrium Test (TDT). Sixty three nuclear families were informative for the TDT on C2276T polymorphism, which showed no preferential transmission of either allele (chi-square=0.778, df=1, p=0.316). These findings exclude a direct involvement of this genetic marker of the Protein kinase G gene in the pathogenesis of ADHD.     

Childhood mania,attention deficit hyperactivity disorder and conduct disorder: a critical review of diagnostic dilemmas

Objectives:  Significant debate exists on whether early onset bipolar disorder is mistakenly attributed to attention deficit hyperactivity disorder (ADHD) or conduct disorder (CD), or whether ADHD and CD are frequently misdiagnosed as mania. We review the literature on the extent to which these disorders can be reliably differentiated, and describe the diagnostic confusion that may be the result of features common to both classes of disorders.
Methods:  The review focuses on research studies that have examined whether overlapping symptoms of bipolar disorder, ADHD, and CD contribute to misdiagnosis of the two classes of disorders, the prevalence of early onset bipolar disorder with comorbid ADHD or CD, and theories regarding the origins of this comorbidity.
Results:  Reliable and accurate diagnoses can be made despite the symptom overlap of bipolar disorder with ADHD and CD. Children with bipolar disorder and ADHD may have a distinct familial subtype of bipolar disorder. Some findings suggest that manic symptoms may represent `noise' that indicates the general severity of psychopathology in a child or adolescent.
Conclusions:  Further prospective studies may confirm whether early onset bipolarity can be successfully differentiated from ADHD or CD, whether all three types of disorders can be recognized in comorbid cases, or whether comorbid cases represent a distinct subtype of bipolar disorder.