LAUSR

Complicated grief (CG) refers to the severe and prolonged (≥ 6 months) grief reaction following the loss of a beloved person that occurs in approximately 10 – 20% of bereaved individuals and is associated with an increased risk for the development of depression and anxiety disorders [1]. So far, the underlying processes contributing to the vulnerability to CG are not yet well understood but likely comprise the complex interplay of genetic, temperamental and psychological factors that interactively influence the severity and persistence of grief reactions. In light of its central role in social behavior, stress regulation and attachment, the oxytocin receptor (OXTR) gene may play a key role in the conferral of CG. Additionally, temperamental traits such as behavioral inhibition (BI) or psychological characteristics such as symptoms of separation anxiety (SA) may predispose to the development of CG. For instance, adult SA has been linked to higher symptom severity and impairment in individuals with CG [2]. Therefore, the present study for the first time aimed to address the involvement of OXTR gene variation in the emergence of CG and the potential moderating effects of BI and SA. To this end, 96 adult outpatients (70 female, 26 male; mean age ± SD = 39.96 ± 12.71 years) with DSM-IV mood and anxiety disorders were assessed for CG using the Inventory of Complicated Grief (ICG). All patients were genotyped for OXTR rs2254298 and characterized for BI using the Retrospective Self-Report of Inhibition (RSRI) and SA symptoms using the Adult Separation Anxiety Scale (ASA-27). Patients were grouped according to genotype (GG vs. AG/AA carriers). The influence of grouped OXTR genotype, RSRI and ASA-27 scores, respectively, on ICG score was investigated via hierarchical multiple regression analyses. No differences were observed with regard to age, sex, or questionnaire scores (all p ≥ 0.05). No main effects of OXTR genotype, RSRI or ASA-27 scores on CG were observed, however ICG scores differed as a function of OXTR genotype and RSRI score (OXTR x BI, p=0.031), and, on a trend-level, ASA-27 score (OXTR x ASA, p=0.064). Specifically, in patients homozygous for the OXTR G allele, increased levels of both BI and ASA were related to higher ICG scores. Of note, this pattern appears to be reversed under conditions of low BI or low ASA. In line with the ‘differential susceptibility hypothesis’ [3], the present findings suggest that while OXTR GG genotype carriers are more vulnerable to the development of CG in the presence of risk-increasing factors, they at the same time are the least likely to develop CG in the absence of these risk factors. Taken together, the present results for the first time provide evidence for an interaction of OXTR gene variation with BI and potentially also symptoms of adult SA in the moderation of clinically relevant grief reactions and may therefore inspire new insights into the development and improvement of therapeutic options in the prevention and treatment of CG.