Symptoms in individuals with adult-onset ADHD are masked during childhood

The limitations associated with measuring cannabis dependence, a response to Budney and colleagues

Corticosteroid-induced psychiatric disorders: genetic studies are needed

Attention as neurocognitive endophenotype of ADHD across the life span: a family study Abstract Endophenotypes mediate pathways between genetic variations and the psychiatric phenotype, or share genetic risk with the psychiatric phenotype. Identifying endophenotypes is an important step to unravel disease pathways underlying complex psychiatric phenotypes such as ADHD. Potential viable endophenotypes for ADHD across the lifespan are neurocognitive measures of basic attention functions, such as sustained attention, and executive attention functions (EF), such as inhibition. The present study evaluated the endophenotype criteria of familiality and state-independency for measures of basic attention and EF in affected- and unaffected parents of children with ADHD (N = 139), and typically developing children (N = 60). In addition, the added value of neurocognitive measures relative to questionnaire data in genetically informed designs was explored by comparing the intergenerational transmission of neurocognitive measures to those of ADHD symptom scores. Results revealed small-to-medium-sized familial effects of ADHD for reaction time measures of EF components and state-independency given familial effects. Parent–child correlations as estimates of intergenerational transmission of those neurocognitive measures were not higher than those of behavioral ADHD symptom ratings. Taken together, our results argue against neurocognitive measures as pivotal endophenotypes for ADHD across the lifespan. If studied as neurocognitive endophenotypes of ADHD in adults, reaction time measures of executive—rather than basic attention function—seem to be more sensitive.

STX1A gene variations contribute to the susceptibility of children attention-deficit/hyperactivity disorder: a case–control association study Abstract It was presumed syntaxin-1A (STX1A) might relate to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), but the results were inconsistent. The present study aims to confirm whether the STX1A gene is involved in the susceptibility of children ADHD. We genotyped three single nucleotide polymorphisms (SNPs) of STX1A gene using Sequenom MassARRAY technology. A case–control study was performed among Chinese Han population including 754 cases and 772 controls from two different provinces. The Conners Parent Symptom Questionnaire and Integrated Visual and Auditory Continuous Performance Test were used to assess ADHD clinical symptoms. We found for the first time that rs3793243 GG genotype carriers had a lower risk of ADHD compared with AA genotype (OR 0.564, 95% confidence interval (CI) 0.406–0.692, P = 0.001), and rs875342 was also associated with children ADHD (OR 1.806, 95% CI 1.349–2.591, P = 0.001). In addition, the two positive SNPs were also significantly associated with the clinical characteristics of ADHD. Expression quantitative trait loci analysis indicated that rs3793243 might mediate STX1A gene expression. Using a case–control study to explore the association between STX1A gene and children ADHD in Chinese Han population, our results suggest STX1A genetic variants might contribute to the susceptibility of children ADHD.

Interplay between genome-wide implicated genetic variants and environmental factors related to childhood antisocial behavior in the UK ALSPAC cohort Abstract We investigated gene–environment (G × E) interactions related to childhood antisocial behavior between polymorphisms implicated by recent genome-wide association studies (GWASs) and two key environmental adversities (maltreatment and smoking during pregnancy) in a large population cohort (ALSPAC). We also studied the MAOA candidate gene and addressed comorbid attention-deficit/hyperactivity disorder (ADHD). ALSPAC is a large, prospective, ethnically homogeneous British cohort. Our outcome consisted of mother-rated conduct disorder symptom scores at age 7;9 years. G × E interactions were tested in a sex-stratified way (α = 0.0031) for four GWAS-implicated variants (for males, rs4714329 and rs9471290; for females, rs2764450 and rs11215217), and a length polymorphism near the MAOA-promoter region. We found that males with rs4714329-GG (P = 0.0015) and rs9471290-AA (P = 0.0001) genotypes were significantly more susceptible to effects of smoking during pregnancy in relation to childhood antisocial behavior. Females with the rs11215217-TC genotype (P = 0.0018) were significantly less susceptible to effects of maltreatment, whereas females with the MAOA-HL genotype (P = 0.0002) were more susceptible to maltreatment effects related to antisocial behavior. After adjustment for comorbid ADHD symptomatology, aforementioned G × E’s remained significant, except for rs11215217 × maltreatment, which retained only nominal significance. Genetic variants implicated by recent GWASs of antisocial behavior moderated associations of smoking during pregnancy and maltreatment with childhood antisocial behavior in the general population. While we also found a G × E interaction between the candidate gene MAOA and maltreatment, we were mostly unable to replicate the previous results regarding MAOA–G × E’s. Future studies should, in addition to genome-wide implicated variants, consider polygenic and/or multimarker analyses and take into account potential sex stratification.

Visual and auditory steady-state responses in attention-deficit/hyperactivity disorder Abstract We designed a study to investigate the patterns of the steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) in adolescents with attention-deficit/hyperactivity disorder (ADHD) when performing a motor response inhibition task. Thirty 12- to 18-year-old adolescents with ADHD and 30 healthy control adolescents underwent an electroencephalogram (EEG) examination during steady-state stimuli when performing a stop-signal task. Then, we calculated the amplitude and phase of the steady-state responses in both visual and auditory modalities. Results showed that adolescents with ADHD had a significantly poorer performance in the stop-signal task during both visual and auditory stimuli. The SSVEP amplitude of the ADHD group was larger than that of the healthy control group in most regions of the brain, whereas the ASSR amplitude of the ADHD group was smaller than that of the healthy control group in some brain regions (e.g., right hemisphere). In conclusion, poorer task performance (especially inattention) and neurophysiological results in ADHD demonstrate a possible impairment in the interconnection of the association cortices in the parietal and temporal lobes and the prefrontal cortex. Also, the motor control problems in ADHD may arise from neural deficits in the frontoparietal and occipitoparietal systems and other brain structures such as cerebellum.

Adult attention-deficit/hyperactivity disorder, risky substance use and substance use disorders: a follow-up study among young men Abstract We investigated whether adult attention-deficit/hyperactivity disorder (ADHD) predicts risky substance use and substance use disorders (SUDs), and its impact on the course of these problematic substance use patterns. Our sample included 4975 Swiss men (mean age 20 ± 1.2 years) who participated in the baseline and 15-month follow-up assessments of the Cohort Study on Substance Use Risk Factors. We examined: (1) the contribution of ADHD, as assessed at baseline, on the risky use of alcohol, nicotine and cannabis, and their corresponding use disorders (AUD, NUD, CUD) at follow-up; and (2) the association between ADHD and the course of outcomes (i.e., absence, initiation, maturing out, persistence) over 15 months. All analyses were adjusted for socio-demographics and co-morbidity. Men with ADHD were more likely to exhibit persistent risky alcohol and nicotine use, and to mature out of risky cannabis use. ADHD at baseline was positively linked to AUD and negatively to CUD at follow-up, but not to NUD. For all SUDs, ADHD had a positive association with use persistence and maturing out. Comparing these two trajectories revealed that early age of alcohol use initiation distinguished between persistence and maturing out of AUD, while the course of NUD and CUD was related to ADHD symptoms and SUD severity at baseline. Already in their early twenties, men with ADHD are especially likely to exhibit persistent problematic substance use patterns. Substance-specific prevention strategies, particularly implemented before early adulthood, may be crucial to reducing the development and persistence of pathological patterns in such individuals.

Behavioral and electrophysiological responses to fairness norm violations in antisocial offenders Abstract Antisocial personality disorder is characterized by a stable, lifelong pattern of disregard for and violation of others’ rights. Disruptions in the representation of fairness norms may represent a key mechanism in the development and maintenance of this disorder. Here, we investigated fairness norm considerations and reactions to their violations. To examine electrophysiological correlates, we assessed the medial frontal negativity (MFN), an event-related potential previously linked to violations of social expectancy and norms. Incarcerated antisocial violent offenders (AVOs, n = 25) and healthy controls (CTLs, n = 24) acted as proposers in the dictator game (DG) and ultimatum game (UG) and received fair vs. unfair UG offers from either another human (social context) or a computer (non-social context). Results showed that AVOs made lower offers in the DG but not the UG, indicating more rational and strategic behavior. Most importantly, when acting as recipients in the UG, acceptance rates were modulated by social context in CTLs, while AVOs generally accepted more offers. Correspondingly, ERP data indicated pronounced MFN amplitudes following human offers in CTLs, whereas MFN amplitudes in AVOs were generally reduced. The current data suggest intact fairness norm representations but altered reactions to their violation in antisocial personality disorder.

Prenatal alcohol use as a risk for attention-deficit/hyperactivity disorder Abstract The objective of the study was to investigate the association between alcohol use during pregnancy and mental disorders in childhood, controlling for confounding risk factors by a longitudinal study of pregnant women and their offspring. The initial cohort comprised pregnant women attending an obstetric service. From the initial sample of 449 pregnant women, 81 mother–child pairs agreed to participate. After 12 years, mother–child pairs were assessed through self-administered questionnaires and semi-structured interviews. The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version (K-SADS-PL) was used to assess the presence of any mental disorders in the children. The mothers were assessed by the Self-Reporting Questionnaire (SRQ) and the Alcohol Use Disorders Identification Test (AUDIT). Furthermore, data on the mother’s alcohol use collected during pregnancy were analysed. A logistic regression tested the influence of alcohol consumption in all trimesters and binge drinking on the occurrence of attention-deficit/hyperactivity disorder (ADHD), controlling for covariates. Binge drinking at any time during pregnancy or low–moderate alcohol consumption in all trimesters of pregnancy was associated with a fivefold increased odds of child ADHD. The combination of both patterns of alcohol use added an increase of 19% in the variance of ADHD’s occurrence. The episodic use of at least four drinks or the regular use of low–moderate alcohol doses during pregnancy was associated with significantly increased odds of subsequent child ADHD. Reducing binge drinking and regular alcohol use of pregnant women may lead to a significant decrease in their children developing ADHD.