Reduced NoGo-anteriorisation during continuous performance test in deletion syndrome 22q11.2

Deletion syndrome 22q11.2 (DS22q11.2) is a high-risk factor for psychiatric disorders. Alterations in brain morphology and function including the anterior cingulate cortex (ACC) are suggested to underlie the increased psychiatric disposition. We assessed response-inhibition in patients with DS22q11.2 (n=13) and healthy controls (n=13) matched for age, sex, and handedness by means of a Go-NoGo-Task during recording of a multi-channel electroencephalography (EEG). Analysis of event-related potentials (P300) resulted in an aberrant topographical pattern and NoGo-anteriorisation (NGA) as a parameter of medial prefrontal function was significantly reduced in patients with DS22q11.2 compared to controls. Differences in IQ between groups did not account for the findings. Source localization analysis (LORETA) revealed diminished left temporal brain activation during the Go-condition, but no altered ACC activation in DS22q11 during the NoGo-condition. Despite recent reports of structural alterations of the ACC in DS22q11.2 our findings suggest that response-inhibition mediated by the ACC is not impaired in DS22q11.2

Dopamine Transporter (SLC6A3) Genotype Impacts Neurophysiological Correlates of Cognitive Response Control in an Adult Sample of Patients with ADHD

Studies provide ample evidence for a dysfunction in dopaminergic neurotransmission in Attention-Deficit/Hyperactivity Disorder (ADHD). In that respect, a common variable number of tandem repeats (VNTR) polymorphism in the 3′ untranslated region (UTR) of the dopamine transporter gene (SLC6A3) has been repeatedly associated with the disorder. Here, we examined the influence of the common 9- and 10-repeat alleles of SLC6A3 on prefrontal brain functioning and cognitive response control in a large sample of adult ADHD patients (n=161) and healthy controls (n=109). To this end, we inspected a neurophysiological marker of cognitive response control (NoGo anteriorization, NGA) elicited by means of a Go-NoGo task (continuous performance test, CPT). Within the group of ADHD patients, nine-repeat allele carriers showed significantly reduced NGA, whereas no influence of SLC6A3 genotype was observed in the control group. In contrast to previous association studies of children, the nine-repeat—not the 10-repeat—allele was associated with functional impairments in our sample of adult ADHD patients. Our findings confirm a significant effect of the SLC6A3 genotype on the neurophysiological correlates of cognitive response control in ADHD, and indicate that still to-be-identified age-related factors are important variables modulating the effect of genetic factors on endophenotypes

Gene-environment interactions in the etiology of human violence

This chapter reviews the current research on gene-environment interactions (G × E) with regard to human violence. Findings are summarized from both behavioral and molecular genetic studies that have investigated the interplay of genetic and environmental factors in terms of influencing violence-related behavior. Together, these studies reveal promising evidence that genetic factors combine with environmental influences to impact on the development of violent behavior and related phenotypes. G × E have been identified for a number of candidate genes implicated in violence. Moreover, the reviewed G × E were found to extend to a broad range of environmental characteristics, including both adverse and favorable conditions. As has been the case with other G × E research, findings have been mixed, with considerable heterogeneity between studies. Lack of replication together with serious methodological limitations remains a major challenge for drawing definitive conclusions about the nature of violence-related G × E. In order to fulfill its potential, it is recommended that future G × E research needs to shift its focus to dissecting the neural mechanisms and the underlying pathophysiological pathways by which genetic variation may influence differential susceptibility to environmental exposures

The genetics of attention deficit/hyperactivity disorder in adults, a review

Item does not contain fulltextThe adult form of attention deficit/hyperactivity disorder (aADHD) has a prevalence of up to 5% and is the most severe long-term outcome of this common neurodevelopmental disorder. Family studies in clinical samples suggest an increased familial liability for aADHD compared with childhood ADHD (cADHD), whereas twin studies based on self-rated symptoms in adult population samples show moderate heritability estimates of 30-40%. However, using multiple sources of information, the heritability of clinically diagnosed aADHD and cADHD is very similar. Results of candidate gene as well as genome-wide molecular genetic studies in aADHD samples implicate some of the same genes involved in ADHD in children, although in some cases different alleles and different genes may be responsible for adult versus childhood ADHD. Linkage studies have been successful in identifying loci for aADHD and led to the identification of LPHN3 and CDH13 as novel genes associated with ADHD across the lifespan. In addition, studies of rare genetic variants have identified probable causative mutations for aADHD. Use of endophenotypes based on neuropsychology and neuroimaging, as well as next-generation genome analysis and improved statistical and bioinformatic analysis methods hold the promise of identifying additional genetic variants involved in disease etiology. Large, international collaborations have paved the way for well-powered studies. Progress in identifying aADHD risk genes may provide us with tools for the prediction of disease progression in the clinic and better treatment, and ultimately may help to prevent persistence of ADHD into adulthood