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Conduct disorder (CD) is characterised by persistent antisocial and aggressive behaviour and typically emerges in childhood or adolescence. Although several authors have proposed that CD is a neurodevelopmental disorder, very little evidence is available about brain development in this condition. Structural brain alterations have been observed in CD, and some indirect evidence for delayed brain maturation has been reported. However, no detailed analysis of age-related changes in brain structure in youth with CD has been conducted. Using cross-sectional MRI data, this study aimed to explore differences in brain maturation in youth with CD versus healthy controls to provide further understanding of the neurodevelopmental processes underlying CD. 291 CD cases (153 males) and 379 healthy controls (160 males) aged 9–18 years (Mage = 14.4) were selected from the European multisite FemNAT-CD study. Structural MRI scans were analysed using surface-based morphometry followed by application of the ENIGMA quality control protocols. An atlas-based approach was used to investigate group differences and test for group-by-age and group-by-age-by-sex interactions in cortical thickness, surface area and subcortical volumes. Relative to healthy controls, the CD group showed lower surface area across frontal, temporal and parietal regions as well as lower total surface area. No significant group-by-age or group-by-age-by-sex interactions were observed on any brain structure measure. These findings suggest that CD is associated with lower surface area across multiple cortical regions, but do not support the idea that CD is associated with delayed brain maturation, at least within the age bracket considered here. [ABSTRACT FROM AUTHOR]

Previous work has shown divergent pupil dilation (PD) and gaze behavior in individuals with autism spectrum disorder (ASD), which may relate to the development of social difficulties in early life. Here, we investigated temporal dynamics of both phenotypes during naturalistic videos of a person displaying facial emotion expressions in 61 autistic and 61 non-autistic preschoolers. PD was segmented into three serial time components derived from a principal component analysis. Growth curve analysis was applied to analyze changes in looking time on eye and mouth regions over time. Groups did not differ in PD time components. Growth curve analysis revealed initially shorter looking times on the eyes and longer looking times on the mouth in autistic versus non-autistic preschoolers. However, a reversion of this pattern was observed over time, suggesting a delayed compensatory increase in eye attention during prolonged viewing periods in autistic children. Positive and negative associations of PD components and gaze behavior over time indicated a dynamic temporal relationship during emotion viewing. Our findings emphasize the need to apply time-sensitive measures in ecologically valid research, which may index etiological mechanisms of social difficulties in ASD. [ABSTRACT FROM AUTHOR]

Evidence of alterations in emotion processing in maltreated youth has been hypothesized to reflect latent vulnerability for psychopathology. However, previous studies have not systematically examined the influence of psychopathology on the results. Here, we examined emotion recognition and learning in youth who differed in terms of presence vs. absence of maltreatment and psychopathology and tested for potential sex effects. Maltreatment and psychopathology were assessed in 828 youth (514 females) aged 9–18 years using diagnostic interviews and self- and parent-report questionnaires. Emotion recognition was assessed via identification of morphed facial expressions of six universal emotions. For emotion learning, reward and punishment values were assigned to novel stimuli and participants had to learn to correctly respond/withhold response to stimuli to maximize points. A three-way interaction of maltreatment by psychopathology by emotion indicated that when psychopathology was low, maltreated youth were less accurate than non-maltreated youth for happy, fear and disgust. A three-way interaction of sex, maltreatment and emotion indicated that maltreated girls and boys were impaired for fear, but girls showed an impairment for happy, while boys for disgust. There were no effects of maltreatment, psychopathology, or sex on reward learning. However, a two-way interaction between sex and maltreatment showed that maltreated girls were worse at learning from punishment relative to non-maltreated girls, while maltreated boys were better than non-maltreated boys. The study provides the first clear evidence of latent-vulnerability in emotion recognition in maltreated youth and suggests that girls and boys might be characterized by distinct profiles of emotion recognition and learning following maltreatment. [ABSTRACT FROM AUTHOR]

An editorial is presented on the 2023 ESCAP Research Academy workshop held in Copenhagen, emphasizing Attention Deficit Hyperactivity Disorder (ADHD) and emotional dysregulation. Topics discussed include presentations by experts on theoretical concepts, clinical assessment, and treatment strategies for emotional dysregulation in ADHD, as well as collaborative projects aimed at assessing prescribing habits across ESCAP member countries.

The ability to infer intentions from observed behavior and predict actions based on this inference, known as intention attribution (IA), has been hypothesized to be impaired in individuals with autism spectrum disorder (ASD). The underlying neural processes, however, have not been conclusively determined. The aim of this study was to examine the neural signature of IA in children and adolescents with ASD, and to elucidate potential links to contextual updating processes using electroencephalography. Results did not indicate that IA or early contextual updating was impaired in ASD. However, there was evidence of aberrant processing of expectation violations in ASD, particularly if the expectation was based on IA. Results are discussed within the context of impaired predictive coding in ASD. [ABSTRACT FROM AUTHOR]

Interpretation bias and dysfunctional social assumptions are proposed to play a pivotal role in the development and maintenance of social phobia (SP), especially in youth. In this study, we aimed to investigate disorder-specific implicit assumptions of rejection and implicit interpretation bias in youth with severe, chronic SP and healthy controls (CG). Twenty-seven youth with SP in inpatient/day-care treatment (M age = 15.6 years, 74% female) and 24 healthy controls (M age = 15.7 years, 54% female) were included. The Implicit Association Test (IAT) and the Affect Misattribution Procedure (AMP) were completed to assess implicit assumptions and interpretation bias related to the processing of social and affective stimuli. No group differences were observed for the IAT controlling for depressive symptoms in the analyses. However, group differences were found regarding interpretation bias (p =.017, η2p =.137). Correlations between implicit scores and explicit questionnaire results were medium to large in the SP group (r =|.28| to |.54|, pall ≤.05), but lower in the control group (r =|.04| to |.46|, pall ≤.05). Our results confirm the finding of an interpretation bias in youth SP, especially regarding the implicit processing of faces, whereas implicit dysfunctional social assumptions of being rejected do not seem to be specific for SP. Future research should investigate the causal relationship of assumptions/interpretation bias and SP. [ABSTRACT FROM AUTHOR]

The consequences of the current COVID-19 pandemic for mental health remain unclear, especially regarding the effects on suicidal behaviors. To assess changes in the pattern of suicide attempt (SA) admissions and completed suicides (CS) in association with the COVID-19 pandemic. As part of a longitudinal study, SA admissions and CS are systematically documented and analyzed in all psychiatric hospitals in Frankfurt/Main (765.000 inhabitants). Number, sociodemographic factors, diagnoses and methods of SA and CS were compared between the periods of March–December 2019 and March–December 2020. The number of CS did not change, while the number of SA significantly decreased. Age, sex, occupational status, and psychiatric diagnoses did not change in SA, whereas the percentage of patients living alone while attempting suicide increased. The rate and number of intoxications as a SA method increased and more people attempted suicide in their own home, which was not observed in CS. Such a shift from public places to home is supported by the weekday of SA, as the rate of SA on weekends was significantly lower during the pandemic, likely because of lockdown measures. Only admissions to psychiatric hospitals were recorded, but not to other institutions. As it seems unlikely that the number of SA decreased while the number of CS remained unchanged, it is conceivable that the number of unreported SA cases increased during the pandemic. Our data suggest that a higher number of SA remained unnoticed during the pandemic because of their location and the use of methods associated with lower lethality. [ABSTRACT FROM AUTHOR]

Youth with attention-deficit/hyperactivity disorder (ADHD) are at increased risk to develop co-morbid depression. Identifying factors that contribute to depression risk may allow early intervention and prevention. Poor emotion regulation, which is common in adolescents, is a candidate risk factor. Impaired cognitive emotion regulation is a fundamental characteristic of depression and depression risk in the general population. However, little is known about cognitive emotion regulation in youth with ADHD and its link to depression and depression risk. Using explicit and implicit measures, this study assessed cognitive emotion regulation in youth with ADHD (N = 40) compared to demographically matched healthy controls (N = 40) and determined the association with depressive symptomatology. As explicit measure, we assessed the use of cognitive emotion regulation strategies via self-report. As implicit measure, performance in an ambiguous cue-conditioning task was assessed as indicator of affective bias in the processing of information. Compared to controls, patients reported more frequent use of maladaptive (i.e., self-blame, catastrophizing, and rumination) and less frequent use of adaptive (i.e., positive reappraisal) emotion regulation strategies. This pattern was associated with the severity of current depressive symptoms in patients. In the implicit measure of cognitive bias, there was no significant difference in response of patients and controls and no association with depression. Our findings point to depression-related alterations in the use of cognitive emotion regulation strategies in youth with ADHD. The study suggests those alterations as a candidate risk factor for ADHD-depression comorbidity that may be used for risk assessment and prevention strategies. [ABSTRACT FROM AUTHOR]

Among youths with conduct disorder, those with callous-unemotional traits are at increased risk for persistent antisocial behaviour. Although callous-unemotional traits have been found to be associated with white-matter brain abnormalities, previous diffusion imaging studies were conducted in small samples, preventing examination of potential sex by callous-unemotional traits interaction effects on white matter. Here, we used tract-based spatial statistics at a whole-brain level and within regions of interest to compare the white matter correlates of callous-unemotional traits in female vs. male youths with conduct disorder, in a sample (n = 124) recruited through a multi-site protocol. A sex-specific association between callous-unemotional traits and white matter was found in the left uncinate fasciculus, where callous-unemotional traits were positively associated with axial diffusivity in males, while an opposite pattern was found in females. These findings are in line with previous studies suggesting that the uncinate fasciculus is a key tract implicated in the development of psychopathy, but also add to recent evidence showing that sexual dimorphism needs to be taken into account when examining the structural correlates of mental disorders in general, and callous-unemotional traits in conduct disorder in particular. [ABSTRACT FROM AUTHOR]

Restricted repetitive behaviors (RRBs) are a core feature of autism spectrum disorders (ASD) and further occur in intellectual disability (ID), mental disorders (MD), and in typically developed people (TD). There is a need of a valid and reliable measure to record RRBs as transdiagnostic symptom, which captures RRBs heterogeneity and evaluates severity. The Repetitive Behavior Scale-Revised (RBS-R) is an established screening instrument for RRBs, but was predominantly limited to ASD samples. We examined the psychometric properties of the German version of the RBS-R in 948 participants with ASD, ID, MD and TD aged 4 to 17 years. The suitability was proofed delivering a four-factor solution, good internal consistency, external validity as well as group, age, and sex effects. [ABSTRACT FROM AUTHOR]

In Autism Spectrum Disorders (ASD), impaired response inhibition and lack of adaptation are hypothesized to underlie core ASD symptoms, such as social communication and repetitive, stereotyped behavior. Thus, the aim of the present study was to compare neural correlates of inhibition, post-error adaptation, and reaction time variability in ASD and neuro-typical control (NTC) participants by investigating possible differences in error-related changes of oscillatory MEG activity. Twelve male NTC (mean age 20.3 ± 3.7) and fourteen male patients with ASD (mean age 17.8 ± 2.9) were included in the analysis. Subjects with ASD showed increased error-related reaction time variability. MEG analysis revealed decreased beta power in the ASD group in comparison to the NTC group over the centro-parietal channels in both, the pre-stimulus and post-response interval. In the ASD group, mean centro-parietal beta power negatively correlated with dimensional autism symptoms. In both groups, false alarms were followed by an early increase in temporo-frontal theta to alpha power; and by a later decrease in alpha to beta power at central and posterior sensors. Single trial correlations were additionally studied in the ASD group, who showed a positive correlation of pre-stimulus beta power with post-response theta, alpha, and beta power, particularly after hit trials. On a broader scale, the results deliver important insights into top-down control deficits that may relate to core symptoms observed in ASD. [ABSTRACT FROM AUTHOR]

Functional and effective connectivity measures for tracking brain region interactions that have been investigated using both electroencephalography (EEG) and magnetoencephalography (MEG) bringing up new insights into clinical research. However, the differences between these connectivity methods, especially at the source level, have not yet been systematically studied. The dynamic characterization of coherent sources and temporal partial directed coherence, as measures of functional and effective connectivity, were applied to multimodal resting EEG and MEG data obtained from 11 young patients (mean age 13.2 ± 1.5 years) with attention-deficit/hyperactivity disorder (ADHD) and age-matched healthy subjects. Additionally, machine-learning algorithms were applied to the extracted connectivity features to identify biomarkers differentiating the two groups. An altered thalamo-cortical connectivity profile was attested in patients with ADHD who showed solely information outflow from cortical regions in comparison to healthy controls who exhibited bidirectional interregional connectivity in alpha, beta, and gamma frequency bands. We achieved an accuracy of 98% by combining features from all five studied frequency bands. Our findings suggest that both types of connectivity as extracted from EEG or MEG are sensitive methods to investigate neuronal network features in neuropsychiatric disorders. The connectivity features investigated here can be further tested as biomarkers of ADHD. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is determined by genetic and environmental factors, and shares genetic risk with ASD. Functional single-nucleotide polymorphisms of the metabotropic glutamatergic signaling pathway are reported to increase the risk for ASD. The aim of this pilot study was to explore the main effects of respective ASD variants as well as their interaction effects with well-replicated ADHD environmental risk factors on the risk for ADHD, ADHD symptom severities, and comorbidities. We included 318 children with ADHD, aged 5–13 years, and their parents (N = 164 trios, N = 113 duos, N = 41 singletons). Interaction of ASD risk variants CYFIP1-rs7170637, CYFIP1-rs3693, CAMK4-rs25925, and GRM1-rs6923492 with prenatal biological and lifetime psychosocial risk factors was explored in a subsample with complete environmental risk factors (N = 139 trios, N = 83 duos, two singletons) by transmission disequilibrium test and stepwise regression analyses. We identified nominally significant (alpha < 0.05) GxE interactions of acute life events with CYFIP1-rs3693 on ADHD diagnosis (p = 0.004; fdr = 0.096) but no significant association of any single marker. Further results suggest that the risk for comorbid disruptive disorders was significantly modulated by GxE interactions between familial risk factors and CAMK4-rs25925 (p = 0.001; fdr = 0.018) and prenatal alcohol exposure with CYFIP1-rs3693 (p = 0.003; fdr = 0.027); both findings survived correction for multiple testing (fdr value < 0.05). Nominal significant GxE interactions moderating the risk for anxiety disorders have also been identified, but did not pass multiple testing corrections. This pilot study suggests that common ASD variants of the glutamatergic system interact with prenatal and lifetime psychosocial risk factors influencing the risk for ADHD common comorbidities and thus warrants replication in larger samples. [ABSTRACT FROM AUTHOR]

Youth with disruptive behavior disorders (DBD; Oppositional defiant disorder and/or conduct disorder) are known to show impaired social relationships. Little is known about positive (PFQ) and negative best friendship quality (NFQ) in youth with DBD, and their relations with DBD specific symptoms such as aggression subtypes, empathic abilities, and callous unemotional (CU)-traits. The current study includes N = 115 youth with and N = 146 without DBD (Mage = 13.98, SD = 2.2). A diagnostic interview and self-rating questionnaires assessed ODD/CD diagnosis, friendship quality, aggression, empathy, and CU-traits. When examined on a categorical level, youth with and without DBD did not differ in friendship quality. On a dimensional level across groups, perspective taking was positively associated with PFQ. Proactive aggression was positively associated with NFQ. CU-traits in females were positively, while CU-traits in males were negatively, associated with NFQ. Results highlight that behavioral and cognitive symptoms, rather than clinical categories, are important to consider when discussing friendship qualities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of the present study was to establish diagnostic validity of the new algorithm of the Autism Diagnostic Observation Scale, the ADOS-2, to differentiate between ASD and other clinically relevant psychiatric and developmental disorders in a large German sample. Validity of ADOS and ADOS-2 diagnostic algorithms was established in 826 individuals (n = 455 autism, n = 216 autism spectrum, n = 155 non-ASD patients) by receiver operating curves. Confidence intervals overlapped largely for ADOS and ADOS-2 algorithms, confirming diagnostic validity of both algorithms. Adding information of the Social Communication Questionnaire and the Social Responsiveness Scale resulted in slightly improved classification rates for autism in Module 4. We thus replicated previous findings of the diagnostic validity of the ADOS-2 algorithms. [ABSTRACT FROM AUTHOR]

Attention problems are observed in attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Most neuropsychological studies that compared both disorders focused on complex executive functions (EF), but missed to contrast basic attention functions, as well as ASD- and ADHD subtypes. The present study compared EF as well as basic attention functioning of children with the combined subtype (ADHD-C), the predominantly inattentive subtype (ADHD-I), and autism spectrum disorder without ADHD (ASD-) with typically developing controls (TD). Basic attention functions and EF profiles were analysed by testing the comprehensive attention function model of van Zomeren and Brouwer using profile analysis. Additionally, neurocognitive impairments in ASD- and ADHD were regressed on dimensional measures of attention- and hyperactive-impulsive symptoms across and within groups. ADHD-C revealed a strong impairment across measures of EF compared to ASD- and TD. The ADHD-C profile furthermore showed disorder specific impairments in interference control, whereas the ASD- profile showed a disorder specific impairment in basic attention component divided attention. Attention- and hyperactive-impulsive symptom severity did not predict neurocognitive impairments across- or within groups. Study findings thus support disorder and subtype specific attention/EF profiles, which refute the idea of a continuum of ADHD-I, ADHD-C, and ASD with increasing neurocognitive impairments. [ABSTRACT FROM AUTHOR]

Conduct disorder (CD) is a common and highly impairing psychiatric disorder of childhood and adolescence that frequently leads to poor physical and mental health outcomes in adulthood. The prevalence of CD is substantially higher in males than females, and partly due to this, most research on this condition has used all-male or predominantly male samples. Although the number of females exhibiting CD has increased in recent decades, the majority of studies on neurobiological measures, neurocognitive phenotypes, and treatments for CD have focused on male subjects only, despite strong evidence for sex differences in the aetiology and neurobiology of CD. Here, we selectively review the existing literature on CD and related phenotypes in females, focusing in particular on sex differences in CD symptoms, patterns of psychiatric comorbidity, and callous-unemotional personality traits. We also consider studies investigating the neurobiology of CD in females, with a focus on studies using genetic, structural and functional neuroimaging, psychophysiological, and neuroendocrinological methods. We end the article by providing an overview of the study design of the FemNAT-CD consortium, an interdisciplinary, multi-level and multi-site study that explicitly focuses on CD in females, but which is also investigating sex differences in the causes, developmental course, and neurobiological correlates of CD. [ABSTRACT FROM AUTHOR]

The genetic architecture underlying Autism spectrum disorder (ASD) has been suggested to differ between individuals with lower (IQ ≤ 70; LIQ) and higher intellectual abilities (IQ > 70; HIQ). Among the identified pathomechanisms, the glutamatergic signalling pathway is of specific interest in ASD. We investigated 187 common functional variants of this neurotransmitter system for association with ASD and with symptom severity in two independent samples, a German (German-ALL: N = 583 families) and the Autism Genome Project cohort (AGP-ALL: N = 2001 families), split into HIQ, and LIQ subgroups. We did not identify any association withstanding correction for multiple testing. However, we report a replicated nominal significant under-transmission (OR < 0.79, p < 0.04) of the AKAP13 rs745191-T allele in both LIQ cohorts, but not in the much larger HIQ cohorts. At the phenotypic level, we nominally replicated associations of CAMK2A-rs2241694 with non-verbal communication in both combined LIQ and HIQ ASD cohorts. Variants PLD1-rs2124147 and ADCY1-rs2461127 were nominally associated with impaired non-verbal abilities and AKAP2-rs3739456 with repetitive behaviour in both LIQ cohorts. All four LIQ-associated genes are involved in G-protein coupled signal transduction, a downstream pathway of metabotropic glutamate receptor activation. We conclude that functional common variants of glutamatergic genes do not have a strong impact on ASD, but seem to moderately affect ASD risk and phenotypic expression. Since most of our nominally replicated hits were identified in the LIQ cohort, further investigation of the glutamatergic system in this subpopulation might be warranted. [ABSTRACT FROM AUTHOR]

Recent findings revealed rare copy number variants and missense changes in the X-linked gene PTCHD1 in autism spectrum disorder (ASD) and intellectual disability (ID). Here, we aim to explore the contribution of common PTCHD1 variants in ASD and gain additional evidence for the role of rare variants of this gene in ASD and ID. A two-stage case-control association study investigated 28 tag single nucleotide polymorphisms (SNPs) in 994 ASD cases and 1035 controls from four European populations. Mutation screening was performed in 673 individuals who included 240 ASD cases, 183 ID patients and 250 controls. The case-control association study showed a significant association with rs7052177 (P=6.13E-4) in the ASD discovery sample that was replicated in an independent sample (P=0.03). A Mantel-Haenszel meta-analysis for rs7052177T considering the four European populations showed an odds ratio of 0.58 (P=7E-05). This SNP is predicted to be located in a transcription factor binding site. No rare missense PTCHD1 variants were found in our ASD cohort and only one was identified in the ID sample. A duplication (27 bp) in the promoter region, absent from 590 controls, was found in three ASD patients (Fisher exact test, P=0.024). A gene reporter assay showed a significant decrease in the transcriptional activity (26%) driven by this variant. Moreover, we found that the longest allele of a trinucleotide repeat located upstream from PTCHD1 was associated with ASD (P=0.003, permP=0.0186). Our results further support the involvement of PTCHD1 in ASD, suggesting that both common and rare variants contribute to the disorder. [ABSTRACT FROM AUTHOR]

Several linkage analyses implicated the chromosome 9q22 region in attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disease with remarkable persistence into adulthood. This locus contains the brain-expressed GTP-binding RAS-like 2 gene (DIRAS2) thought to regulate neurogenesis. As DIRAS2 is a positional and functional ADHD candidate gene, we conducted an association study in 600 patients suffering from adult ADHD (aADHD) and 420 controls. Replication samples consisted of 1035 aADHD patients and 1381 controls, as well as 166 families with a child affected from childhood ADHD. Given the high degree of co-morbidity with ADHD, we also investigated patients suffering from bipolar disorder (BD) (n=336) or personality disorders (PDs) (n=622). Twelve single-nucleotide polymorphisms (SNPs) covering the structural gene and the transcriptional control region of DIRAS2 were analyzed. Four SNPs and two haplotype blocks showed evidence of association with ADHD, with nominal p-values ranging from p=0.006 to p=0.05. In the adult replication samples, we obtained a consistent effect of rs1412005 and of a risk haplotype containing the promoter region (p=0.026). Meta-analysis resulted in a significant common OR of 1.12 (p=0.04) for rs1412005 and confirmed association with the promoter risk haplotype (OR=1.45, p=0.0003). Subsequent analysis in nuclear families with childhood ADHD again showed an association of the promoter haplotype block (p=0.02). rs1412005 also increased risk toward BD (p=0.026) and cluster B PD (p=0.031). Additional SNPs showed association with personality scores (p=0.008-0.048). Converging lines of evidence implicate genetic variance in the promoter region of DIRAS2 in the etiology of ADHD and co-morbid impulsive disorders. [ABSTRACT FROM AUTHOR]

Twin and family studies in autistic disorders (AD) have elucidated a high heritability of AD. In this literature review, we will present an overview on molecular genetic studies in AD and highlight the most recent findings of an increased rate of copy number variations in AD. An extensive literature search in the PubMed database was performed to obtain English published articles on genetic findings in autism. Results of linkage, (genome wide) association and cytogenetic studies are presented, and putative aetiopathological pathways are discussed. Implications of the different genetic findings for genetic counselling and genetic testing at present will be described. The article ends with a prospectus on future directions. [ABSTRACT FROM AUTHOR]

Twin studies described a strongly heritable component of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. However, findings varied considerably between studies. In addition, ADHD presents with a high rate of comorbid disorders and associated psychopathology. Therefore, this literature review reports findings from population-based twin studies regarding the influence of subtypes, assessment instruments, rater effects, sex differences, and comorbidity rates on ADHD heritability estimates. In addition, genetic effects on the persistence of ADHD are discussed. By reviewing relevant factors influencing heritability estimates more homogeneous subtypes relevant for molecular genetic studies can be elicited. A systematic search of population-based twin studies in ADHD was performed, using the databases PubMed and PsycInfo. Results of family studies were added in case insufficient or contradictory findings were obtained in twin studies. Heritability estimates were strongly influenced by rater effects and assessment instruments. Inattentive and hyperactive–impulsive symptoms were likely influenced by common as well as specific genetic risk factors. Besides persistent ADHD, ADHD accompanied by symptoms of conduct or antisocial personality disorder might be another strongly genetically determined subtype, however, family environmental risk factors have also been established for this pattern of comorbidity. [ABSTRACT FROM AUTHOR]

It has been shown that a functional promoter dinucleotide repeat length variation of the neuronal nitric oxide synthase gene ( NOS1 Ex1f-VNTR) is associated with impulsivity-related behavioral phenotypes. In this study, the Eysenck Impulsivity Questionnaire (IVE-7) was administered to 182 male offenders to prove the hypothesis that NOS1 Ex1f-VNTR is associated with self-reported impulsiveness, venturesomeness and empathy. Multivariate analysis of variance (MANCOVA) revealed a significant multivariate effect of NOS1 Ex1f-VNTR genotype on IVE-7 measures ( P = 0.0006). The effect was more pronounced regarding impulsiveness and empathy ( P = 0.0052 and P = 0.0036, respectively) as compared with venturesomeness, which was only of borderline significance. The findings give additional evidence that NOS-I is involved in the regulation of impulsive personality traits and support the notion that the NOS1 gene takes part in the regulation of social behavior. [ABSTRACT FROM AUTHOR]

Aggressive behavior is influenced by variation in genes of the serotonergic circuitry and early-life experience alike. The present study aimed at investigating the contribution of polymorphisms shown to moderate transcription of two genes involved in serotonergic neurotransmission (serotonin transporter, 5HTT, and monoamine oxidase A, MAOA) to the development of violence and to test for gene–environment interactions relating to adverse childhood environment. A cohort of 184 adult male volunteers referred for forensic assessment participated in the study. Each individual was assigned to either a violent or a nonviolent group. Logistic regression was performed and the best-fitting model, with a predictive power of 74%, revealed independent effects of adverse childhood environment and MAOA genotype. High environmental adversity during childhood was associated significantly with violent behavior. Forty-five percent of violent, but only 30% of nonviolent individuals carried the low-activity, short MAOA allele. Most interestingly, an interaction effect between childhood environment and 5HTT genotype on violent behavior was found in that high adversity during childhood impacted only the later-life violence if the short promoter alleles were present. These findings indicate complex interactions between genetic variation of the serotonergic circuitry and environmental factors arguing against simplistic, mono-causal explanations of violent behavior.Neuropsychopharmacology (2007) 32, 2375–2383; doi:10.1038/sj.npp.1301359; published online 7 March 2007 [ABSTRACT FROM AUTHOR]

Motor impairment in children with Asperger Syndrome (AS) or High functioning autism (HFA) has been reported previously. This study presents results of a quantitative assessment of neuromotor skills in 14–22 year old HFA/AS. 16 HFA/AS and 16 IQ-matched controls were assessed by the Zurich Neuromotor Assessment (ZNA). The HFA/AS group showed strongest impairments of dynamic balance skills and diadochokinesis. Motor abilities were associated with degree of social withdrawal in the full sample and severity of current autistic symptoms in the HFA/AS group. Similar motor patterns as in younger children were found in the older adolescents. The association of autistic symptoms with motor performance points towards an essential role of motor impairment in autism spectrum disorders. [ABSTRACT FROM AUTHOR]

DTNBP1 (dysbindin) is one of the several putative schizophrenia genes supported by association, neuroanatomical, and cellular studies. These suggest an involvement of DTNBP1 in the prefrontal cortex and cognitive functions mediated by interaction with neurotransmitter systems, in particular glutamate. The influence of DTNBP1 gene variation on prefrontal brain function at the systemic neurophysiological level, though, has not been characterized. The NoGo-anteriorization (NGA) as an event-related potential (ERP) measure elicited during the continuous performance test (CPT) has been established as a valid neurophysiological parameter for prefrontal brain function in healthy individuals and patients with schizophrenias. In the present study, we therefore investigated the influence of eight dysbindin gene variants on the NGA as a marker of prefrontal brain function in 48 healthy individuals. Two DTNBP1 polymorphisms previously linked to schizophrenia (P1765 and P1320) were found associated with changes in the NGA. Post hoc analysis showing an influence of genetic variation at these loci on the Go centroid and frontal amplitudes suggest that this might be due to modification of the execution of motor processes by the prefrontal cortex. This is the first report on a role of DTNBP1 gene variation for prefrontal brain function at a systemic neurophysiological level in healthy humans. Future studies will have to address the relevance of this observation for patients with schizophrenias.Neuropsychopharmacology (2006) 31, 2002–2010. doi:10.1038/sj.npp.1301003; published online 11 January 2006 [ABSTRACT FROM AUTHOR]

Difficulties imitating gestures have been found in several studies in children and adolescents with Autism Spectrum Disorders (ASD). It has been hypothesized that imitation abilities might be precursors of language abilities in young children with autism. No study on imitation and language abilities in adolescents with ASD has been performed to date. Fifteen male adolescents with ASD, 16 male and 13 female controls were compared regarding imitation abilities of upper and lower facial movements, and language skills as assessed by the pragmatic rating scale and the Aachen Aphasia test (AAT). Autism Spectrum Disorder subjects showed reduced imitation abilities of facial movements and non-meaningful combined hand-and-finger gestures. Regarding language, ASD subjects showed difficulties in AAT spontaneous speech measures and reduced pragmatic language abilities. Correlations of imitation and language measures differed between ASD, male and female controls. The weak and differential correlations of imitation and language measures in the three comparison groups might imply a differential organization of language and imitation networks in the three comparison groups. Pragmatic abilities, which are a central feature in ASD, were not related to imitation abilities. Therefore, imitation and language abilities in ASD might not be as closely correlated as previously expected. [ABSTRACT FROM AUTHOR]

Theory of mind (ToM), or the ability to infer and predict the intentions, thoughts and beliefs of others, involves cognitive perspective taking (cognitive ToM/cToM) and understanding emotions (affective ToM/aToM). While behavioral evidence indicates that ToM is influenced by sex and age, no study has examined the influence of these variables on the neural correlates of cToM and aToM in late childhood/adolescence. Using fMRI with 35 typically-developing youths (aged 9–18 years, 12 males), we investigated the influence of sex and age on the neural correlates of cToM and aToM. We also examined how callous-unemotional traits, indexing a lack of empathy, were related to brain responses during aToM. Across both conditions, we found convergent activity in ToM network regions, such as superior temporal sulcus/temporoparietal junction (TPJ) and precuneus across males and females, but males recruited the left TPJ significantly more than females during cToM. During aToM, age was negatively correlated with brain responses in frontal, temporal and posterior midline regions, while callous-unemotional traits were positively correlated with right anterior insula responses. These results provide the first evidence in youth that sex influences the neural correlates of cToM, while age and callous-unemotional traits are specifically related to brain responses during aToM. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the observation that genetic variants influence pain sensitivity in humans.

A correction to the article "DIRAS2 is Associated with Adult ADHD, Related Traits, and Co-Morbid Disorders," published online in the July 13, 2011 issue of the journal.