Altered single‐subject gray matter structural networks in drug‐naïve attention deficit hyperactivity disorder children

Altered topological organization of brain structural covariance networks has been observed in attention deficit hyperactivity disorder (ADHD). However, results have been inconsistent, potentially related to confounding medication effects. In addition, since structural networks are traditionally constructed at the group level, variabilities in individual structural features remain to be well characterized. Structural brain imaging with MRI was performed on 84 drug‐naïve children with ADHD and 83 age‐matched healthy controls. Single‐subject gray matter (GM) networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared using nonparametric permutation testing. Compared with healthy subjects, GM networks in ADHD patients demonstrated significantly altered topological characteristics, including higher global and local efficiency and clustering coefficient, and shorter path length. In addition, ADHD patients exhibited abnormal centrality in corticostriatal circuitry including the superior frontal gyrus, orbitofrontal gyrus, medial superior frontal gyrus, precentral gyrus, middle temporal gyrus, and pallidum (all p < .05, false discovery rate [FDR] corrected). Altered global and nodal topological efficiencies were associated with the severity of hyperactivity symptoms and the performance on the Stroop and Wisconsin Card Sorting Test tests (all p < .05, FDR corrected). ADHD combined and inattention subtypes were differentiated by nodal attributes of amygdala (p < .05, FDR corrected). Alterations in GM network topologies were observed in drug‐naïve ADHD patients, in particular in frontostriatal loops and amygdala. These alterations may contribute to impaired cognitive functioning and impulsive behavior in ADHD.     

Quantitative susceptibility mapping shows lower brain iron content in children with attention‐deficit hyperactivity disorder

To investigate the feasibility of quantitative susceptibility mapping in children with attention‐deficit hyperactivity disorder (ADHD), 53 children with ADHD aged 5–16 years were prospectively selected as the study group and 49 healthy children matched with age and gender were selected as the control group. All children underwent magnetic resonance imaging conventional sequence, 3D‐T1, and enhanced T2*‐weighted magnetic resonance angiography (ESWAN) sequence scanning. The iron content of brain regions was obtained through software postprocessing, and the iron content of brain regions of children with ADHD and healthy children was compared and analyzed to find out the characteristics of the iron content of brain regions of children with ADHD. The iron content in frontal lobe, globus pallidus, caudate nucleus, substantia nigra, putamen, and hippocampus of children with ADHD was lower than that of healthy children (p < .05). There was no significant difference in the content of iron in the left and right brain regions of children with ADHD (p > .05). The volume of frontal lobe and hippocampus of children with ADHD was lower than that of healthy children (p < .05). Iron content in brain areas such as globus pallidus, caudate nucleus, hippocampus, and putamen could distinguish children with ADHD (Area under curve [AUC] > 0.5, p < .05). Quantitative susceptibility mapping showed decreased iron content in some brain regions of children with ADHD.     

Examining the nature of the comorbidity between pediatric attention deficit/hyperactivity disorder and post‐traumatic stress disorder

Biederman J, Petty CR, Spencer TJ, Woodworth KY, Bhide P, Zhu J, Faraone SV. Examining the nature of the comorbidity between pediatric attention deficit/hyperactivity disorder and post‐traumatic stress disorder. Objective: This study sought to address the link between attention deficit/hyperactivity disorder (ADHD) and post‐traumatic stress disorder (PTSD) in youth by providing a comprehensive comparison of clinical correlates of ADHD subjects with and without PTSD across multiple non‐overlapping domains of functioning and familial patterns of transmission. Method: Participants were 271 youths with ADHD and 230 controls without ADHD of both sexes along with their siblings. Participants completed a large battery of measures designed to assess psychiatric comorbidity, psychosocial, educational, and cognitive parameters. Results: Post‐traumatic stress disorder was significantly higher in ADHD probands vs. controls (5.2% vs. 1.7%, χ²₍₁₎ = 4.36, P = 0.04). Irrespective of the comorbidity with PTSD, ADHD subjects had similar ages at onset of ADHD, similar type and mean number of ADHD symptoms, and similar ADHD‐associated impairments. PTSD in ADHD probands was significantly associated with a higher risk of psychiatric hospitalization, school impairment, poorer social functioning and higher prevalences of mood, conduct disorder, and anxiety disorders. The mean onset of PTSD (12.6 years) was significantly later than that of ADHD and comorbid disorders (all P < 0.05). Siblings of ADHD and ADHD + PTSD probands had higher prevalences of ADHD vs. siblings of controls (35% vs. 18%, z = 4.00, P < 0.001 and 67% vs. 18%, z = 4.02, P < 0.001 respectively) and siblings of ADHD+PTSD probands had a significantly higher prevalence of PTSD compared with the siblings of ADHD and control probands (20% vs. 3% and 3%, z = 2.99, P = 0.003 and z = 2.07, P = 0.04 respectively). Conclusion: Findings indicate that the comorbidity with PTSD in ADHD leads to greater clinical severity as regards psychiatric comorbidity and psychosocial dysfunction. ADHD is equally familial in the presence of PTSD in the proband indicating that their co‐occurrence is not owing to diagnostic error.     

Gestational and postnatal tobacco smoke exposure as predictor of ADHD, comorbid ODD/CD, and treatment response in the MTA

Objective: To examine relationships among early smoke exposure (ESE), attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant or conduct disorder (ODD/CD), and whether ESE affects symptom severity, comorbidity, and later treatment response. Study design: The Multimodal Treatment Study of Children with ADHD (MTA) had 468 children with ADHD and 279 others from the same classrooms (local normative comparison group, LNCG) with smoke-exposure data. We compared ESE as ‘gestational’ or ‘postnatal’ (ambient house smoke only, without gestational) between ADHD and LNCG, and tested its association with ADHD severity, comorbid ODD/CD, methylphenidate response, and differential treatment response to four randomly assigned treatments. Results: About 1/3 more ADHD than LNCG children had ESE (both types), but association with gestational smoke attenuated from P=0.024 to 0.094 when subjects with comorbid ODD/CD were excluded, although total smoke exposure retained significance (P=0.006). In the MTA/ADHD participants, comorbid ODD/CD, and parent/teacher-rated ADHD and ODD symptom severity were not associated with gestational smoking, but severity of ODD was associated with postnatal smoke, and for boys only, ADHD severity at 14 months associated with postnatal smoke. When ODD and CD were ‘unbundled’, CD was associated (P=0.005) with gestational smoke. Neither ESE moderated response to methylphenidate, optimal dose, 2-year growth slowing, or differential ODD symptom response to 14-months of 4 randomly assigned treatments. However, for ADHD symptoms, postnatal smoke moderated (P=0.008) the 14-month advantage of behavioral treatment (Beh) over community-treated comparison (CC): postnatally exposed boys benefited relatively more from Beh (d>0.5). ADHD symptom improvement also showed significant interaction of sex with gestational (P=0.015) and postnatal (P=0.044) smoke moderator effect for the contrast of MTA medication algorithm vs. Beh and CC: smoke-exposed girls did not show the usual algorithm superiority. Conclusions: These findings suggest possible moderating effects of postnatal ESE on the advantage of intensive behavioral treatment and sex-differential moderating effects of ESE on the advantage of intensive medication over behavioral treatment. This exploratory result requires replication. The findings do not convincingly support the hypothesis that the association of gestational smoking with offspring ADHD is accounted for by comorbid ODD/CD.     

Autism spectrum disorder symptoms in children with ADHD: A community-based study

This study examined the prevalence of autism spectrum disorder (ASD) symptoms in a community-based sample of children with attention-deficit/hyperactivity disorder (ADHD) and non-ADHD controls. We also examined the relationship between ASD symptoms and ADHD subtype, ADHD symptom severity and child gender. Participants were 6–10-year-old children (164 ADHD; 198 non-ADHD control) attending 43 schools in Melbourne, Australia, who were participating in the Children's Attention Project. ADHD was assessed in two stages using the parent and teacher Conners’ 3 ADHD index and the Diagnostic Interview Schedule for Children IV (DISC-IV). ASD symptoms were identified using the Social Communication Questionnaire (SCQ). Unadjusted and adjusted linear and logistic regression examined continuous and categorical outcomes, respectively. Children with ADHD had more ASD symptoms than non-ADHD controls (adjusted mean difference = 4.0, 95% confidence interval (CI) 2.8; 5.3, p < 0.001, effect size = 0.7). Boys with ADHD had greater ASD symptom severity than girls with ADHD (adjusted mean difference = 2.9, 95% CI 0.8; 5.2, p = 0.01, effect size = 0.4). Greater ADHD symptom severity was associated with greater ASD symptom severity (regression co-efficient = 1.6, 95% CI 1.2; 2.0, p < 0.001). No differences were observed by ADHD subtype. Greater hyperactive/impulsive symptoms were associated with greater ASD symptoms (regression coefficient = 1.0; 95% CI 0.0; 2.0, p = 0.04) however, this finding attenuated in adjusted analyses (p = 0.45). ASD symptoms are common in children with ADHD. It is important for clinicians to assess for ASD symptoms to ensure appropriate intervention.     

The presentation of depression symptoms in attention‐deficit/hyperactivity disorder: comparing child and parent reports

Background

Attention‐deficit/hyperactivity disorder (ADHD) frequently co‐occurs with depression, and outcomes are poor when both are present. Little is known about whether depression symptoms present differently in ADHD compared to the general population, or how reliable young people with ADHD are at reporting these symptoms. This study aimed to describe depression symptoms in a clinical ADHD sample compared to a population sample, and compare self‐reports of depression symptoms with parent‐reports.

Methods

Two hundred and forty‐nine children with ADHD and their parents completed follow‐up questionnaires around 5 years after taking part in a Cardiff University ADHD study. Child depression symptoms were measured using parent‐ and child‐reported Mood and Feelings Questionnaires (MFQ) and compared to a population sample with MFQ data (n = 1460). Within both samples, child‐ and parent‐reported depression symptoms were compared.

Results

Although the profile of depression symptoms was similar between young people with ADHD and those in the general population, depression symptoms were much more common in the ADHD sample (parent‐rated MFQ score = 24.52 vs. 9.39; child‐rated = 21.02 vs. 11.86). The most common symptoms in both samples included irritability, restlessness and concentration difficulties, with core depression symptoms such as feeling miserable/unhappy also prominent. Within the ADHD sample, but not the population sample, children reported depression symptoms less frequently than their parents.

Conclusions

Young people with ADHD are at high risk of experiencing symptoms of depression but may under‐report the severity of their symptoms. Obtaining parent reports of depression symptoms in this group may be important to avoid missing key indicators of risk.     

Baduk (the Game of Go) Improved Cognitive Function and Brain Activity in Children with Attention Deficit Hyperactivity Disorder

Objective

Attention deficit hyperactivity disorder (ADHD) symptoms are associated with the deficit in executive functions. Playing Go involves many aspect of cognitive function and we hypothesized that it would be effective for children with ADHD.

Methods

Seventeen drug naïve children with ADHD and seventeen age and sex matched comparison subjects were participated. Participants played Go under the instructor''s education for 2 hours/day, 5 days/week. Before and at the end of Go period, clinical symptoms, cognitive functions, and brain EEG were assessed with Dupaul''s ADHD scale (ARS), Child depression inventory (CDI), digit span, the Children''s Color Trails Test (CCTT), and 8-channel QEEG system (LXE3208, Laxtha Inc., Daejeon, Korea).

Results

There were significant improvements of ARS total score (z=2.93, p<0.01) and inattentive score (z=2.94, p<0.01) in children with ADHD. However, there was no significant change in hyperactivity score (z=1.33, p=0.18). There were improvement of digit total score (z=2.60, p<0.01; z=2.06, p=0.03), digit forward score (z=2.21, p=0.02; z=2.02, p=0.04) in both ADHD and healthy comparisons. In addition, ADHD children showed decreased time of CCTT-2 (z=2.21, p=0.03). The change of theta/beta right of prefrontal cortex during 16 weeks was greater in children with ADHD than in healthy comparisons (F=4.45, p=0.04). The change of right theta/beta in prefrontal cortex has a positive correlation with ARS-inattention score in children with ADHD (r=0.44, p=0.03).

Conclusion

We suggest that playing Go would be effective for children with ADHD by activating hypoarousal prefrontal function and enhancing executive function.     

ADHD,circadian rhythms and seasonality

ObjectiveWe evaluated whether the association between Adult Attention-Deficit/Hyperactivity Disorder (ADHD) and Seasonal Affective Disorder (SAD) was mediated by the circadian rhythm.MethodData of 2239 persons from the Netherlands Study of Depression and Anxiety (NESDA) were used. Two groups were compared: with clinically significant ADHD symptoms (N = 175) and with No ADHD symptoms (N = 2064). Sleep parameters were sleep-onset and offset times, mid sleep and sleep duration from the Munich Chronotype Questionnaire. We identified the prevalence of probable SAD and subsyndromal SAD using the Seasonal Pattern Assessment Questionnaire (SPAQ). Clinically significant ADHD symptoms were identified by using a T score>65 on the Conners Adult ADHD Rating Scale.ResultsThe prevalence of probable SAD was estimated at 9.9% in the ADHD group (vs. 3.3% in the No ADHD group) and of probable s-SAD at 12.5% in the ADHD group (vs 4.6% in the No ADHD group). Regression analyses showed consistently significant associations between ADHD symptoms and probable SAD, even after adjustment for current depression and anxiety, age, sex, education, use of antidepressants and benzodiazepines (B = 1.81, p < 0.001). Late self-reported sleep onset was an important mediator in the significant relationship between ADHD symptoms and probable SAD, even after correction for confounders (total model effects: B = 0.14, p ≤ 0.001).ConclusionBoth seasonal and circadian rhythm disturbances are significantly associated with ADHD symptoms. Delayed sleep onset time in ADHD may explain the increase in SAD symptoms. Treating patients with SAD for possible ADHD and delayed sleep onset time may reduce symptom severity in these complex patients.     

Prediction of childhood ADHD symptoms to quality of life in young adults: Adult ADHD and anxiety/depression as mediators

Childhood attention-deficit/hyperactivity disorder (ADHD) symptoms may persist, co-occur with anxiety and depression (ANX/DEP), and influence quality of life (QoL) in later life. However, the information about whether these persistent ADHD and ANX/DEP mediate the influence of childhood ADHD on adverse QoL in adulthood is lacking. This study aimed to determine whether adult ADHD symptoms and/or ANX/DEP mediated the association between childhood ADHD and QoL. We assessed 1382 young men aged 19–30 years in Taiwan using self-administered questionnaires for retrospective recall of ADHD symptoms at ages 6–12, and assessment of current ADHD and ANX/DEP symptoms, and QoL. We conducted mediation analyses and compared the values of mediation ratio (P_M) by adding mediators (adult ADHD and ANX/DEP), individually and simultaneously into a regression model with childhood ADHD as an independent variable and QoL as a dependent variable. Our results showed that both adult ADHD and ANX/DEP symptoms significantly mediated the association between childhood ADHD and QoL (P_M = 0.71 for ANX/DEP, P_M = 0.78 for adult ADHD symptoms, and P_M = 0.91 for both). The significance of negative correlations between childhood ADHD and four domains of adult QoL disappeared after adding these two mediators in the model. Our findings suggested that the strong relationship between childhood ADHD and adult life quality can be explained by the presence of persistent ADHD symptoms and co-occurring ANX/DEP. These two mediators are recommended to be included in the assessment and intervention for ADHD to offset the potential adverse life quality outcome in ADHD.     

Neuropsychological studies of late onset and subthreshold diagnoses of adult attention-deficit/hyperactivity disorder.

BACKGROUND: Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is difficult when the diagnostician cannot establish an onset prior to the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve the DSM-IV threshold for diagnosis. Because neuropsychological deficits are associated with ADHD, we addressed the validity of the DSM-IV age at onset and symptom threshold criteria by using neuropsychological test scores as external validators. METHODS: We compared four groups of adults: 1) full ADHD subjects met all DSM-IV criteria for childhood-onset ADHD; 2) late-onset ADHD subjects met all criteria except the age at onset criterion; 3) subthreshold ADHD subjects did not meet full symptom criteria; and 4) non-ADHD subjects did not meet any of the above criteria. RESULTS: Late-onset and full ADHD subjects had similar patterns of neuropsychological dysfunction. By comparison, subthreshold ADHD subjects showed few neuropsychological differences with non-ADHD subjects. CONCLUSIONS: Our results showing similar neuropsychological underpinning in subjects with late-onset ADHD suggest that the DSM-IV age at onset criterion may be too stringent. Our data also suggest that ADHD subjects who failed to ever meet the DSM-IV threshold for diagnosis have a milder form of the disorder.     

A longitudinal study of post-traumatic stress,depressive, and anxiety symptoms trajectories in subjects with bipolar disorder during the COVID-19 pandemic

BackgroundBipolar disorder (BD) is recognized to be at high risk for developing negative psychopathological sequelae to potentially traumatic events. Nevertheless, scant data are still available about the effects of the COVID-19 emergency on the clinical course of BD. The present study examined prospectively the development and trajectories of post-traumatic stress, depressive, and anxiety symptoms among subjects with BD that were followed in an outpatient psychiatric clinic at the time of pandemic onset.MethodsA cohort of 89 subjects with BD was enrolled during the first wave of the COVID-19 pandemic, and assessed at baseline (T0), 2-months (T1), and 6-months (T2) follow-up. A K-means cluster analysis was used to identify distinct trajectories of depressive, anxiety, and post-traumatic stress symptoms during the three time points.ResultsWe identified three trajectories: the Acute reaction (13.5%); the Increasing severity (23.6%); and the Low symptoms (62.9%) groups, respectively. In the Acute reaction group a significant prevalence of female gender was reported with respect to the Low symptoms one. Subjects in the Increasing severity group reported significantly lower employment rate, and higher rate of relatives at risk for COVID-19 medical complications. Subjects in the Increasing Severity group reported higher rates of previous hospitalization and manic symptoms at baseline than those included in the Low symptoms one.ConclusionsOur results describe three distinct symptom trajectories during the COVID-19 emergency in a cohort of subjects suffering from BD, suggesting the need of a long-term follow-up for detecting the impact of the COVID-19 pandemic in this vulnerable population.     

Prevalence of attention deficit hyperactivity disorder symptoms in narcolepsy: a systematic review

ObjectiveNarcolepsy is characterized by excessive daytime sleepiness and cataplexy. Attention deficit hyperactivity disorder (ADHD) is characterized by hyperactivity, inattention, and impulsivity. However, despite their differences, both narcolepsy and ADHD share the symptoms of sleep disturbance and excessive daytime sleepiness. Recent studies have suggested a link between the two disorders. The objective of systematic review was to assess the prevalence of ADHD symptoms in narcolepsy.MethodsWe performed a systematic search of MEDLINE (inception to December 2018) and EMBASE (inception to December 2018) for English publications of human studies using the keywords “narcolepsy” and “ADHD”.ResultsFive studies examining a total of 328 patients met the eligibility criteria for this study examining the prevalence of ADHD symptoms in narcolepsy. The pooled prevalence of ADHD symptoms in narcolepsy was 33.0%. Two studies using the international classification of sleep disorders, second edition (ICSD-2) observed a pooled prevalence of ADHD symptoms in narcolepsy of 25.0%, while two other studies that relied on the ICSD-3 criteria observed a pooled prevalence of ADHD symptoms in narcolepsy of 36.4%.ConclusionsThe prevalence of ADHD symptoms was >30%, making it an important comorbidity of narcolepsy. Future studies should be performed to better assess the relationship between ADHD and narcolepsy.     

Retinal Nerve Fiber Layer Thickness and Its Relationship With Executive Functions in Adult Attention Deficit Hyperactivity Disorder Patients

ObjectiveThe aim of this study was to compare the thickness of the retinal nerve fiber layer (RNFL) with controls in individuals with attention deficit hyperactivity disorder (ADHD) and to examine the relationship between RNFL thickness and the level of performance in disease severity and executive function tests in ADHD cases. MethodsThe study included 38 volunteer patients diagnosed with ADHD and 30 healthy volunteers. Adult ADHD self-report scale was used for ADHD symptom severity. Executive functions were evaluated by Digit Span Test, Verbal Fluency Test, Stroop Test, and Trail Making Test. RNFL thickness of all participants was evaluated using optical coherence tomography (OCT). ResultsIn the comparison of RNFL values, it was found that right mean, right temporal, right temporal inferior, left mean, left nasal, and left nasal inferior quadrant values were statistically thinner in ADHD cases compared to the control group (p<0.05). There was no statistically significant correlation between the mean RNFL thickness values of the right and left eyes of ADHD cases and the symptom severity and performance levels in executive function tests. ConclusionThis study is a guide in terms of being the first study investigating the relationship between RNFL thickness, symptom severity, and various neuropsychological tests in adults with ADHD.     

Do child psychiatrists in Germany diagnose bipolar disorders in children and adolescents? Results from a survey

OBJECTIVES: There is a controversy about the prevalence of childhood bipolar disorders (BD). Based on discrepant results, we studied if German psychiatrists in outpatient settings diagnose BD in children and adolescents at all, and if there are possible correlates of the diagnoses of pediatric BD. We also asked how often typical manic symptoms (e.g. elated mood) are actually seen in attention deficit hyperactivity disorder (ADHD) patients. METHODS: Provided by the medical register we had a complete list of all 251 psychiatrists in the area. Using a questionnaire we asked if and how often they diagnose BD among children and adolescents and how often they observe manic-like symptoms in children with ADHD (response rate 61%). RESULTS: While 63% of all psychiatrists have diagnosed BD in adolescents, only 7.8% did so in children. Age and therapeutic approach of the psychiatrists were associated with the likelihood of having diagnosed BD in children. Furthermore some typical bipolar symptoms were also present in ADHD patients. CONCLUSIONS: Our study only relied on self-reports of the psychiatrists about the diagnoses and number of cases, but BD in children seems to be rarely diagnosed in outpatient settings in Germany. The design of our study, however, cannot resolve the questions what the reasons are for this low rate of BD diagnoses, e.g. misdiagnoses, overlooking comorbidity or referral strategies. Epidemiological studies are needed and should consider multiple follow-ups.     

Prevalence of childhood attention deficit hyperactivity disorder in opiate-dependent adults

Background. There is a clear association between childhood attention deficit hyperactivity disorder and substance use disorders in adulthood. Symptoms of attention deficit disorder may also persist into adulthood. The study aimed to determine the prevalence of childhood ADHD in a sample of treatment seeking opiate-dependent adults. Methods. Treatment-seeking opiate-dependent subjects completed the Utah adult ADHD screening test and the self-report early delinquency scale. Results. A total of 15% were “likely” and 49 were “highly likely” to have suffered ADHD in childhood. The averages scores for the delinquency scales were over 6 times those reported from population norms. Conclusion. Symptoms of childhood ADHD is common in adults with opiate dependence. The residual symptoms in adults should be investigated as may be amenable to newer treatments for adult attention deficit disorder.     

Attention‐deficit/hyperactivity disorder symptoms and suicidal behavior in adult psychiatric outpatients

Aim

We aimed to examine the association between attention‐deficit/hyperactivity disorder (ADHD) symptoms and suicidal behavior in psychiatric outpatients and whether this association differs among patients with different psychiatric disorders.

Methods

Cross‐sectional data came from the Japan Prevalence Study of Adult ADHD at Psychiatric Outpatient Care, which included psychiatric outpatients aged 18–65 years recruited from one university hospital and three general psychiatric outpatient clinics in Kitakyushu City, Fukuoka, Japan from April 2014 to January 2015 (N = 864). The Adult ADHD Self‐Report Scale (ASRS) Screener was used to collect information on ADHD symptoms. Reports of current and lifetime suicidal behavior were also obtained. A multivariable Poisson regression analysis was used to examine the association between ADHD symptoms and suicidal behavior.

Results

After adjusting for covariates there was a strong association between possible ADHD (ASRS ≥14) and suicidal behavior with prevalence ratios ranging from 1.17 (lifetime suicidal ideation) to 1.59 (lifetime suicide attempt) and 2.36 (current suicidal ideation). When ASRS strata were used, there was a dose–response association between increasing ADHD symptoms and suicidal ideation and suicide attempts. Analyses of individual ICD‐10 psychiatric disorders showed that associations varied across disorders and that for anxiety disorder, ADHD symptoms were significantly linked to all forms of suicidal behavior.

Conclusion

ADHD symptom severity is associated with an increased risk for suicidal behavior in general psychiatric outpatients. As ADHD symptoms are common among adult psychiatric outpatients, detecting and treating ADHD in this population may be important for preventing suicidal behavior.     

On the prevalence of bipolar disorder in epilepsy

Although mood disorders represent a frequent psychiatric comorbidity in epilepsy, data on bipolar disorder (BD) are still limited, and the role of possible specific confounding variables (seizures and antiepileptic drug therapy) has never been considered. Data for 143 adult outpatients with epilepsy assessed with the Mini International Neuropsychiatric Interview Plus Version 5.0.0 using the Epilepsy Addendum for Psychiatric Assessment, the Mood Disorder Questionnaire, and the Interictal Dysphoric Disorder Inventory revealed that 11.8% had the Diagnostic and Statistical Manual of Mental Disorders-based diagnosis of BD, only 1.4% of whom could be considered as having “pure” BD, because in all other cases BD symptoms were related to phenotype copies of BD such as interictal dysphoric disorder of epilepsy, postictal manic or hypomanic states, and preictal dysphoria.     

Genome-wide significant association between a ‘negative mood delusions' dimension in bipolar disorder and genetic variation on chromosome 3q26.1

Research suggests that clinical symptom dimensions may be more useful in delineating the genetics of bipolar disorder (BD) than standard diagnostic models. To date, no study has applied this concept to data from genome-wide association studies (GWAS). We performed a GWAS of factor dimensions in 927 clinically well-characterized BD patients of German ancestry. Rs9875793, which is located in an intergenic region of 3q26.1 and in the vicinity of the solute carrier family 2 (facilitated glucose transporter), member 2 gene (SLC2A2), was significantly associated with the factor analysis-derived dimension ‘negative mood delusions'' (n=927; P=4.65 × 10⁻⁸, odds ratio (OR)=2.66). This dimension was comprised of the symptoms delusions of poverty, delusions of guilt and nihilistic delusions. In case–control analyses, significant association with the G allele of rs9875793 was only observed in the subgroup of BD patients who displayed symptoms of ‘negative mood delusions'' (allelic χ² model: P_G=0.0001, OR=1.92; item present, n=89). Further support for the hypothesis that rs9875793 is associated with BD in patients displaying ‘negative mood delusions'' symptom, such as delusions of guilt, was obtained from an European American sample (GAIN/TGEN), which included 1247 BD patients and 1434 controls (P_EA=0.028, OR=1.27).