interacts with CU traits to impact socioaffective brain systems in youngsters with CD.\n × CU trait interactions on corticolimbic activity and amygdala subregional connections during recognition... Show moreinteracts with CU traits to impact socioaffective brain systems in youngsters with CD.\n × CU trait interactions on corticolimbic activity and amygdala subregional connections during recognition and resonance of distressing socioaffective stimuli (angry and fearful faces), in juvenile offenders with CD (n = 39) versus matched healthy control youths (n = 27).\n and CU levels in youths with CD additionally predicted centromedial amygdala decoupling from ventromedial/orbitofrontal regions during emotion recognition, along with basolateral amygdala decoupling from precuneal and temporoparietal cortices during emotion resonance.\n and CU traits in youths with CD may affect brain systems critical to decoding and integrating socioaffective information. Developmental models of CU traits and psychopathy could thus possibly advance by further examining OXTR epigenetic effects, which may hold promise for indicated prevention and personalized treatment by targeting oxytocinergic function.\nBACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONS Show less
Bas, J.M.; Steenbergen, H. van; Tissier, R.L.M.; Houwing-Duistermaat, J.J.; Westenberg, P.M.; Van der Wee, N.J.A. 2018
Background:Social anxiety disorder (SAD) is a disabling psychiatric condition with a genetic background. Brainalterations in gray matter (GM) related to SAD have been previously reported, but it... Show moreBackground:Social anxiety disorder (SAD) is a disabling psychiatric condition with a genetic background. Brainalterations in gray matter (GM) related to SAD have been previously reported, but it remains to be elucidatedwhether GM measures are candidate endophenotypes of SAD. Endophenotypes are measurable characteristicson the causal pathway from genotype to phenotype, providing insight in genetically-based disease mechanisms.Based on a review of existing evidence, we examined whether GM characteristics meet two endophenotypecriteria, using data from a unique sample of SAD-patients and their family-members of two generations. First,we investigatedwhether GMcharacteristics co-segregate with socialanxiety within families genetically enrichedfor SAD. Secondly, heritability of the GM characteristics was estimated.Methods:Families with a genetic predisposition for SAD participated in the Leiden Family Lab study on SAD;T1-weighted MRI brain scans were acquired (n= 110, 8 families). Subcortical volumes, cortical thickness andcortical surface area were determined for a-priori determined regions of interest (ROIs). Next, associationswith social anxiety and heritabilities were estimated.Findings:Several subcortical and cortical GM characteristics, derived from frontal, parietal and temporal ROIs, co-segregated with social anxiety within families (uncorrected p-level) and showed moderate to high heritability.Interpretation:Thesefindings provide preliminary evidence that GM characteristics of multiple ROIs, which aredistributed over the brain, are candidate endophenotypes of SAD. Thereby, they shed light on the genetic vulner-ability for SAD. Future research is needed to confirm these results and to link them to functional brain alterationsand to genetic variations underlying these GM changes.Fund:Leiden University Research Profile‘Health, Prevention and the Human Life Cycle’. Show less
Van Hoof, M.J.; Van den Bulk, B.; Rombouts, S.A.R.B.; Rinne-Albers, M.A.W.; Van der Wee, N.J.A.; IJzendoorn, M.H. van; Vermeiren, R.R.J.M. 2017
Social anxiety disorder (SAD) is a disabling psychiatric disorder with a complex pathogenesis. Studies indicate a genetic component in the development of SAD, but the search for genetic mechanisms... Show moreSocial anxiety disorder (SAD) is a disabling psychiatric disorder with a complex pathogenesis. Studies indicate a genetic component in the development of SAD, but the search for genetic mechanisms underlying this vulnerability is complicated. A focus on endophenotypes instead of the disorder itself may provide a fruitful path forward. Endophenotypes are measurable characteristics related to complex psychiatric disorders and reflective of genetically-based disease mechanisms, and could shed light on the ways by which genes contribute to the development of SAD. We review evidence for candidate MRI endophenotypes of SAD and discuss the extent to which they meet the criteria for an endophenotype, focussing on the amygdala, the medial prefrontal cortex, whole-brain functional connectivity and structural-anatomical changes. Strongest evidence is present for the primary endophenotype criterion of association between the candidate endophenotypes and SAD, while the other criteria, involving trait-stability, heritability and co-segregation of the endophenotype with the disorder within families, warrant further investigation. We highlight the potential of neuroimaging endophenotypes and stress the need for family studies into SAD endophenotypes. Show less
Bulk, B.G. van den; Somerville, L.H.; Van Hoof, M.J.; Van Lang, N.D.J.; Van der Wee, N.J.A.; Crone, E.A.M.; Vermeiren, R.R.J.M. 2016