Neurobiological candidate endophenotypes of social anxiety disorder.
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 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.
Institute of Psychology, Leiden University, Wassenaarseweg 52, 2333 AK Leiden, The Netherlands; Department of Psychiatry, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands. Electronic address: j.m.hoogendam@fsw.leidenuniv.nl.
Janna Marie
JM
Bas-Hoogendam
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Psychology, Vanderbilt University, Nashville, TN, USA. Electronic address: jenni.blackford@Vanderbilt.Edu.
Jennifer U
JU
Blackford
Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Department of Psychiatry, Psychotherapy, and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland. Electronic address: abb41@medschl.cam.ac.uk.
Annette B
AB
Brühl
National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, USA. Electronic address: blair.karina@gmail.com.
Karina S
KS
Blair
Department of Psychiatry, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands. Electronic address: N.J.A.van_der_Wee@lumc.nl.
Nic J A
NJA
van der Wee
Institute of Psychology, Leiden University, Wassenaarseweg 52, 2333 AK Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands. Electronic address: westenberg@fsw.leidenuniv.nl.
P Michiel
PM
Westenberg
D001921:Brain; D058068:Endophenotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D000072861:Phobia, Social
Amygdala; Connectivity; Endophenotypes; Genetic vulnerability; Medial prefrontal cortex; Neuroimaging; Social anxiety disorder; Uncinate fasciculus