Rohde, L. A. | bioRxiv Science

bioRxiv2019

Disentangling unity from diversity in developmental psychopathology

Developmental psychopathology has been a fruitful space for the investigation of the validity of multidimensionality. Nonetheless, previous studies in the field have not tested a model with a fine-grained division within the internalizing and externalizing spectra that also accounts for the contribution of a general psychopathology factor. The aim of this study is to test the validity and reliability of a theoretically-driven bifactor model with one general dimension and ten specific dimensions of psychopathology: fear, somatic complaints, distressful thoughts, low mood, low motivation/energy, inattention-hyperactivity, temper loss, aggression, noncompliance, and low concern for others. Our study evaluated 2,511 children aged 6-14 years-old from the Brazilian High-Risk Cohort for Psychiatric Disorders. There was support for the model in terms of its fit to the data, reliability, and external validity. Our findings highlight the potential of combined fine-grained approaches with models disentangling unity from diversity in developmental psychopathology.

animal behavior and cognition↗

bioRxiv2019

Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders.

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed a meta-analysis of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders identifying three groups of inter-related disorders. We detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

genomics↗