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Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher order psychopathology (e.g., the general factor), whereas other genes conferring more specific risk for individual spectra (e.g., internalizing), subfactors (e.g., fear disorders), or narrow symptoms (e.g., mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Background Maladaptive cognitive biases such as negative attributional style and hopelessness have been implicated in the development and maintenance of depression. According to the hopelessness theory of depression, hopelessness mediates the association between attributional style and depression. The aetiological processes underpinning this influential theory remain unknown. The current study investigated genetic and environmental influences on hopelessness and its concurrent and longitudinal associations with attributional style and depression across adolescence and emerging adulthood. Furthermore, given high co-morbidity between depression and anxiety, the study investigated whether these maladaptive cognitions constitute transdiagnostic cognitive content common to both internalizing symptoms.\ud \ud Method A total of 2619 twins/siblings reported attributional style (mean age 15 and 17 years), hopelessness (mean age 17 years), and depression and anxiety symptoms (mean age 17 and 20 years).\ud \ud Results Partial correlations revealed that attributional style and hopelessness were uniquely associated with depression but not anxiety symptoms. Hopelessness partially mediated the relationship between attributional style and depression. Hopelessness was moderately heritable (A = 0.37, 95% confidence interval 0.28–0.47), with remaining variance accounted for by non-shared environmental influences. Independent pathway models indicated that a set of common genetic influences largely accounted for the association between attributional style, hopelessness and depression symptoms, both concurrently and across development.\ud \ud Conclusions The results provide novel evidence that associations between attributional style, hopelessness and depression symptoms are largely due to shared genetic liability, suggesting developmentally stable biological pathways underpinning the hopelessness theory of depression. Both attributional style and hopelessness constituted unique cognitive content in depression. The results inform molecular genetics research and cognitive treatment approaches.

Increased anxiety and depression symptoms have been reported in individuals with neurodevelopmental disorders, and have been found to be associated with motor coordination difficulties, but little is known about the aetiology of these associations. This study aimed to assess genetic, shared (making twins/siblings alike) and non-shared (individual-specific) environmental influences on the association between poor coordination and symptoms of anxiety and depressed mood using a sample of adult twin and sibling pairs. Participants were asked about their coordination skill and anxiety and depression symptoms. About half of the variance in coordination difficulty was explained by familial (combined genetic and shared environmental) influences, with the remaining variance explained by non-shared environmental influences. Phenotypic associations between coordination and anxiety (r = .46) and depression symptoms (r = .44) were largely underpinned by shared familial liability for the three traits. Non-shared environment accounted for about a third of the phenotypic association. Results suggest that both familial and non-shared environmental influences play a role in the aetiology of coordination difficulty and its association with internalizing symptoms. The current study highlights that both biological and environmental pathways shared between these symptoms should be examined in future research to inform prevention and treatment approaches in clinical settings.

Background. Depression and anxiety persist within and across diagnostic boundaries. The manner in which common v. disorder-specific genetic and environmental influences operate across development to maintain internalizing disorders and their co-morbidity is unclear. This paper investigates the stability and change of etiological influences on depression, panic, generalized, separation and social anxiety symptoms, and their co-occurrence, across adolescence and young adulthood.\ud \ud Method. A total of 2619 twins/siblings prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and 20 years.\ud \ud Results. Each symptom scale showed a similar pattern of moderate continuity across development, largely underpinned by genetic stability. New genetic influences contributing to change in the developmental course of the symptoms emerged at each time point. All symptom scales correlated moderately with one another over time. Genetic influences, both stable and time-specific, overlapped considerably between the scales. Non-shared environmental influences were largely time- and symptom-specific, but some contributed moderately to the stability of depression and anxiety symptom scales. These stable, longitudinal environmental influences were highly correlated between the symptoms.\ud \ud Conclusions. The results highlight both stable and dynamic etiology of depression and anxiety symptom scales. They provide preliminary evidence that stable as well as newly emerging genes contribute to the co-morbidity between depression and anxiety across adolescence and young adulthood. Conversely, environmental influences are largely time-specific and contribute to change in symptoms over time. The results inform molecular genetics research and transdiagnostic treatment and prevention approaches.

Background The classification of anxiety and depressive disorders has long been debated and has important clinical implications. The present study combined a genetically sensitive design and multiple time points to investigate cognitive content specificity in anxiety and depressive disorder symptoms across anxiety sensitivity dimensions, a cognitive distortion implicated in both disorders.\ud \ud Method Phenotypic and genetic correlations between anxiety sensitivity dimensions, anxiety and depressive disorder symptoms were examined at five waves of data collection within childhood, adolescence and early adulthood in two representative twin studies (n pairs = 300 and 1372).\ud \ud Results The physical concerns dimension of anxiety sensitivity (fear of bodily symptoms) was significantly associated with anxiety but not depression at all waves. Genetic influences on physical concerns overlapped substantially more with anxiety than depression. Conversely, mental concerns (worry regarding cognitive control) were phenotypically more strongly associated with depression than anxiety. Social concerns (fear of publicly observable symptoms of anxiety) were associated with both anxiety and depression in adolescence. Genetic influences on mental and social concerns were shared to a similar extent with both anxiety and depression.\ud \ud Conclusions Phenotypic patterns of cognitive specificity and broader genetic associations between anxiety sensitivity dimensions, anxiety and depressive disorder symptoms were similar at all waves. Both disorder-specific and shared cognitive concerns were identified, suggesting it is appropriate to classify anxiety and depression as distinct but related disorders and confirming the clinical perspective that cognitive therapy is most likely to benefit by targeting cognitive concerns relating specifically to the individual's presenting symptoms across development.