Neurobiological candidate endophenotypes of social anxiety disorder

Janna Marie Bas-Hoogendam; Jennifer U Blackford; Annette B Brühl; Karina S Blair; Nic J A van der Wee; P Michiel Westenberg

doi:10.1016/j.neubiorev.2016.08.040

Neurobiological candidate endophenotypes of social anxiety disorder

Neurosci Biobehav Rev. 2016 Dec:71:362-378. doi: 10.1016/j.neubiorev.2016.08.040. Epub 2016 Sep 1.

Authors

Janna Marie Bas-Hoogendam¹, Jennifer U Blackford², Annette B Brühl³, Karina S Blair⁴, Nic J A van der Wee⁵, P Michiel Westenberg⁶

Affiliations

¹ 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: [email protected].
² Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Psychology, Vanderbilt University, Nashville, TN, USA. Electronic address: [email protected].
³ 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: [email protected].
⁴ National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, USA. Electronic address: [email protected].
⁵ 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: [email protected].
⁶ Institute of Psychology, Leiden University, Wassenaarseweg 52, 2333 AK Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands. Electronic address: [email protected].

PMID: 27593443
DOI: 10.1016/j.neubiorev.2016.08.040

Abstract

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.

Keywords: Amygdala; Connectivity; Endophenotypes; Genetic vulnerability; Medial prefrontal cortex; Neuroimaging; Social anxiety disorder; Uncinate fasciculus.

Publication types

Review

MeSH terms

Brain
Endophenotypes*
Humans
Magnetic Resonance Imaging
Phobia, Social*