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The current status of child and adolescent psychiatric genetics appears promising in light of the initiation of genome-wide association studies (GWAS) for diverse polygenic disorders and the molecular elucidation of monogenic Rett syndrome, for which recent functional studies provide hope for pharmacological treatment strategies. Within the last 50 years, tremendous progress has been made in linking genetic variation to behavioral phenotypes and psychiatric disorders. We summarize the major findings of the Human Genome Project and dwell on largely unsuccessful candidate gene and linkage studies. GWAS for the first time offer the possibility to detect single nucleotide polymorphisms and copy number variants without a priori hypotheses as to their molecular etiology. At the same time it is becoming increasingly clear that very large sample sizes are required in order to enable genome wide significant findings, thus necessitating further large-scaled ascertainment schemes for the successful elucidation of the molecular genetics of childhood and adolescent psychiatric disorders. We conclude by reflecting on different scenarios for future research into the molecular basis of early onset psychiatric disorders. This review represents the introductory article of this special issue of the European Child and Adolescent Psychiatry.

Summary: There is good evidence from recent studies that depression is familial, and that a substantial proportion of the variation in liability is explained by genes. Suicidal behavior, including completed suicide, also seems to cluster in families. First-degree relatives of individuals who have committed suicide (included dizygotic twins) have more than twice the risk of the general population. For identical co-twins of suicides, the relative risk increases to about 11. Applying a simple structural equation model to the published data suggests a heritability for completed suicide of about 43% (95% confidence intervals 25-60). It is not known at present whether the genes predisposing to suicide are identical with those predisposing to affective disorder, but since only about half of those committing suicide have a diagnosis of depression, it seems probable that the overlap is incomplete. The mode of inheritance of suicidal behavior is almost certain to be complex, involving many genes. There have already been some initial studies of allelic association with polymorphisms in candidate genes such as those involved in serotonergic transmission. Further progress is likely to come from candidate gene and linkage disequilibrium studies that are capable of detecting multiple genes of small effect.

Irving I. Gottesman played an important role for psychiatric genetic research in Denmark through more than 40 years of collaboration with Danish scientists, resulting in important twin and family studies based upon the unique national registers available in Denmark.

Background:There continues to be significant investment in the detection of genotype × environment interaction (G × E) in psychiatric genetics. The implications of the method of assessment for the genetic analysis of psychiatric disorders are examined for simulated twin data on symptom scores and environmental covariates.Methods: Additive and independent genetic and environmental risks were simulated for 10,000 monozygotic (MZ) and 10,000 dizygotic (DZ) twin pairs and the 'subjects' administered typical simulated checklists of clinical symptoms and environmental factors. A variety of standard tests for G × E were applied to the simulated additive risk scores, sum scores derived from the checklists and transformed sum scores.Results:All analyses revealed no evidence for G × E for latent risk but marked evidence for G × E and other effects of modulation in the sum scores. These effects were all removed by transformation. An integrated genetic and psychometric model, accounting for both the causes of latent liability and a theory of measurement, was fitted to a sample of the simulated sum-score data and showed that there was no significant modulation of the parameters of the genetic model by environmental covariates (i.e., no G × E).Conclusions:Claims to detect G × E based on analytical methods that ignore the theory of measurement must be subjected to greater scrutiny prior to publication.

<b><i>Background:</i></b> Psychiatric genetics has had limited success in translational efforts. A thorough understanding of the present state of translation in this field will be useful in the facilitation and assessment of future translational progress. <b><i>Purpose:</i></b> A narrative literature review was conducted. Combinations of 3 groups of terms were searched in EBSCOhost, Google Scholar, and PubMed. The review occurred in multiple steps, including abstract collection, inclusion/exclusion criteria review, coding, and analysis of included papers. <b><i>Results:</i></b> One hundred and fourteen articles were analyzed for the narrative review. Across those, 4 bottlenecks were noted that, if addressed, may provide insights and help improve and increase translation in the field of psychiatric genetics. These 4 bottlenecks are emphasizing linear translational frameworks, relying on molecular genomic findings, prioritizing certain psychiatric disorders, and publishing more reviews than experiments. <b><i>Conclusions:</i></b> These entwined bottlenecks are examined with one another. Awareness of these bottlenecks can inform stakeholders who work to translate and/or utilize psychiatric genetic information. Potential solutions include utilizing nonlinear translational frameworks as well as a wider array of psychiatric genetic information (e.g., family history and gene-environment interplay) in this area of research, expanding which psychiatric disorders are considered for translation, and when possible, conducting original research. Researchers are urged to consider how their research is translational in the context of the frameworks, genetic information, and psychiatric disorders discussed in this review. At a broader level, these efforts should be supported with translational efforts in funding and policy shifts.

AbstractDisordered gambling (DG) is a rare but serious condition that results in considerable financial and interpersonal harms. Twin studies indicate that DG is heritable but are silent with respect to specific genes or pathways involved. Existing genomewide association studies (GWAS) of DG have been substantially underpowered. Larger GWAS of other psychiatric disorders now permit calculation of polygenic risk scores (PRSs) that reflect the aggregated effects of common genetic variants contributing risk for the target condition. The current study investigated whether gambling and DG are associated with PRSs for four psychiatric conditions found to be comorbid with DG in epidemiologic surveys: major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). Genotype data and survey responses were analyzed from the Wave IV assessment (conducted in 2008) of the National Longitudinal Study of Adolescent to Adult Health, a representative sample of adolescents recruited in 1994–1995 and followed into adulthood. Among participants classified as having European ancestry based on genetic analysis (N= 5215), 78.4% reported ever having gambled, and 1.3% reported lifetime DG. Polygenic risk for BD was associated with decreased odds of lifetime gambling,OR= 0.93 [0.87, 0.99],p= .045, pseudo-R2(%) = .12. The SCZ PRS was associated with increased odds of DG,OR= 1.54 [1.07, 2.21],p= .02, pseudo-R2(%) = .85. Polygenic risk scores for MDD and ADHD were not related to either gambling outcome. Investigating features common to both SCZ and DG might generate valuable clues about the genetically influenced liabilities to DG.

As a dynamic, interdisciplinary field, behavior genetics and its evolution are being followed closely by scientists across the psychological and medical domains. The discoveries surrounding the human genome and the advancement in molecular genetic technologies have ?led to studies becoming increasingly sophisticated and yielding ?yet more conclusive and useful results. This is certainly the case in the area of child and adult psychopathology.?Behavior Genetics of Psychopathology summarizes the state of the field, examiningthe role of genes and environment as they affect common neurodevelopmental and psychiatric conditions. Emphasizing key research areas (comorbidities, twin studies, the integration of methods), the book assesses the current literature, offers up-to-date findings, sorts through lingering controversies, and identifies a clear future agenda for the field. Expertly-written chapters focus on issues of both general salience that shape behavior genetics of psychopathology, to specific disorders of major clinical importance, among them:?ADHD: the view from quantitative genetic research.Autism spectrum disorders and their complex heterogeneityGenetic influences on anxiety and depression in childhood and adolescence.Evidence for etiologically-defined subgroups within the construct of antisocial behavior.Sleep and psychopathology: the reasons for their co-occurrence. Behavioral genetic approaches to the etiology of comorbidity.Epigenetics of psychopathology.?This combination of timeliness and depth of coverage make Behavior Genetics of Psychopathology a frontline resource for behavior geneticists, psychologists, psychiatrists, and neuroscientists, and is perfectly suited to graduate students looking to join these fields.