Contents lists available at ScienceDirect Psychoneuroendocrinology journal homepage: www.elsevier.com/locate/psyneuen Interactions of OXTR rs53576 and emotional trauma on hippocampal volumes and perceived social support in adolescent girls Gin S Malhi a,b,c,d, *, Pritha Das a,b,c,d , Tim Outhred a,b,c,d , Carol Dobson-Stone e,f , Erica Bell a,b,c , Danielle Gessler a,b,c,d,e,g , Richard Bryant h , Zola Mannie a,b,c,d,i a The University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Department of Psychiatry, Sydney, NSW, Australia b Academic Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia c CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia d ARCHI, Sydney Medical School Northern, The University of Sydney, NSW, 2006, Australia e The University of Sydney, Brain and Mind Centre, Faculty of Medicine and Health, NSW, Australia f School of Medical Sciences, University of New South Wales, NSW, Australia g School of Psychology, University of Sydney, NSW, Australia h School of Psychology, University of New South Wales, NSW, Australia i NSW Health, Northern Sydney Local Health District, Royal North Shore Hospital, St Leonards, NSW, Australia ARTICLE INFO Keywords: Emotional trauma Oxytocin receptors Adolescence Hippocampus Mood disorders Vulnerability/Resilience ABSTRACT Oxytocin (OXT) is a neuropeptide involved in social behaviour and is sensitive to environmental influences to alter individual vulnerability or resilience to stress resulting in both negative and positive outcomes. The effects of the OXT receptor (OXTR) single nucleotide polymorphism (SNP) rs53576 on hippocampal and amygdala structure and functions in adults are differentially associated with susceptibility to adversity and social beha- viours, but this evidence is lacking in healthy adolescents. Adolescence is a developmental period characterised by neurobiological and psychosocial changes resulting in higher susceptibility to mood disorders, particularly among girls. As the brain is highly plastic at this stage, to understand psychosocial and emotional development, clarity of the interactions between rs53576 and adversity on hippocampal and amygdala volumes and social behaviours is needed. In this study, we investigated the interactions between rs53576 and emotional trauma (ET) exposure on hippocampal and amygdala volumes of adolescent girls, and associations with parenting style, perceived social support and bullying behaviour. Based on an unbiased and corrected analytical approach, we found smaller left hippocampal volumes in higher (hET) compared to minimally (mET) exposed AA homo- zygotes, but no differences in G allele carriers nor in the amygdala. Within the mET AA group, larger volumes were associated with peer perceived social support, but in their hET counterparts, smaller volumes were asso- ciated with familial perceived social support. This evidence supports an important role for the hippocampus in social behaviours but extends current knowledge to suggest that hippocampal social behavioural features are contextually dependent on rs53576. 1. Introduction Oxytocin (OXT) is a neuropeptide involved in social behaviour and individual perception of the social world via its sensitivity to contextual social and environmental information, resulting in both positive and negative outcomes (Norman et al., 2012). The biological actions of oxytocin are exerted via single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR), which is widely expressed throughout the brain, including regions involved in social cognition (Lamblin et al., 2017) e.g. the hippocampus and amygdala (Lin and Hsu, 2018; Quintana et al., 2019), . The sensitivity of OXTR is modulated by en- vironmental influences (Kumsta and Heinrichs, 2013) to alter in- dividual vulnerability or resilience to stress (Donadon et al., 2018). Indeed, OXTR polymorphisms have been shown to mediate the re- lationship between childhood attachment security and amygdala vo- lumes (Schneider-Hassloff et al., 2016), to be associated with positive parenting as well as haemodynamic responses in the hippocampus (Michalska et al., 2014), to interact with emotional neglect in asso- ciation with left hippocampal volume reductions in adults (Womersley et al., 2019). In youth, from childhood to mid-adolescence, an OXTR https://doi.org/10.1016/j.psyneuen.2020.104635 Received 20 December 2019; Accepted 19 February 2020 ⁎ Corresponding author at: Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, NSW, 2065, Australia. E-mail address: gin.malhi@sydney.edu.au (G.S. Malhi). Psychoneuroendocrinology 115 (2020) 104635 0306-4530/ © 2020 Published by Elsevier Ltd. T