OXTR moderates adverse childhood experiences on depressive symptoms among incarcerated males

Abstract

Objectives

This study examined the moderation of an oxytocin receptor (OXTR) gene in the link between childhood adversity and depressive symptoms among incarcerated males.

Methods

Questionnaires about adverse childhood experiences and depressive symptoms, as well as genomic DNA from blood were collected among 608 incarcerated males (M_age = 32.4 years, SD = 9.41, 18–74 years). Moderation analysis was applied to examine the interaction between adverse childhood experiences (including abuse, neglect, and household dysfunction) and the OXTR polymorphisms (rs2254298, rs53576) in predicting depressive symptoms.

Results

Incarcerated males had relatively higher prevalence of childhood adversity (70.2%) and depressive symptoms (49.8%). Higher childhood adversity was associated with increased depressive symptoms, and the effect was more pronounced in the GG homozygotes of OXTR rs2254298 (b = 0.406, p < .001), as compared with the AA/AG carriers (b = 0.236, p < .001). By contrast, the OXTR rs53576 did not interact with childhood adversity in predicting depressive symptoms.

Conclusions

Chinese incarcerated males with the GG genotype of OXTR rs2254298 have higher vulnerability in the effect of childhood adversity on depressive symptoms.

Introduction

High prevalence and severity of depression have been reported among prisoners (Forry et al., 2019; Murdoch et al., 2008), which are important factors for high rates of suicide attempts among inmates (47.1%, Wittouck et al., 2016) and leads to a great challenge to prison mental health care. Extensive literature has documented that depression in adulthood or later life stages is partially attributed to adverse childhood experiences (ACEs, Cheong et al., 2017; Stern and Thayer, 2019; Tracy et al., 2019), including abuse, neglect, and household dysfunction. Especially, the accumulation of these adverse experiences would increase the depressive risk later in life (Bielas et al., 2016; Chapman et al., 2004). Besides, the prevalence of ACEs is especially high among incarcerated individuals (Baglivio and Epps, 2016); the association of ACEs with depression has also been found among the incarcerated populations (Sánchez et al., 2018), particularly stronger in incarcerated males (Goddard and Pooley, 2019).

Accumulating literature has indicated the interactions of genetic variants with environmental factors on depression (Gottfredson et al., 2015; Ksinan and Vazsonyi, 2019). Based on the diathesis-stress model (Bleuler, 1963; Rosenthal, 1963), individuals with different genotypes have differential susceptibility to the adverse environment, and thus have different risk of developing depression (e.g., Colodro-Conde et al., 2018; van Ijzendoorn et al., 2020). Furthermore, emerging literature has revealed the moderation of OXTR single nucleotide polymorphisms (SNPs) in the effects of ACEs on depression (Cataldo et al., 2018; Myers et al., 2014; Smearman et al., 2016; Thompson et al., 2011). The OXTR gene, located at 3p25.3, encodes the oxytocin receptor for exerting plasma oxytocin biological functions (Yamasue, 2013) and reduction of plasma oxytocin, which would probably lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system in major depression (Scantamburlo et al., 2007).

Two of the most studied OXTR polymorphisms (i.e., rs2254298 and rs53576, located in intron 3) have been found to moderate the link between early life environment and depression (Cataldo et al., 2018; Toepfer et al., 2017), although the directions of moderation were mixed (Bradley et al., 2011; McInnis et al., 2015; McQuaid et al., 2013; Smearman et al., 2016; Thompson et al., 2011; Tollenaar et al., 2017). For instances, some studies indicated that the A allele carriers of rs2254298 were more vulnerable to unfavorable early environments, leading to severer symptoms of depression as compared with individuals with the GG genotype (e.g., Thompson et al., 2011). Contradictorily, the GG homozygotes of rs2254298 were also found to be associated with increased vulnerability to the experience of childhood abuse (Smearman et al., 2016) and higher risk of unipolar depression (Costa et al., 2009). As for the rs53576, some studies suggested that the G allele of rs53576 was linked to severer depressive symptoms among the individuals who experienced child adversity (Bradley et al., 2011; McQuaid et al., 2013). On the contrary, other studies found that rs53576 A-carriers were more vulnerable to the negative childhood experiences (McInnis et al., 2015; Thompson et al., 2014). Therefore, more literature should be accumulated for further understanding the moderation of the OXTR SNPs (rs2254298 and rs53576) in the link between childhood adversity and depressive symptoms.

Incarcerated life is full of challenges and stress for inmates, due to restrictions in daily living such as limited freedom and social connection. More attention should be paid to depression of the prisoners, with restricted living situation, and relatively higher prevalence of depression as well as ACEs (Baglivio and Epps, 2016; Fazel et al., 2016). Considering a relatively stronger association between depression and ACEs in incarcerated males (Goddard and Pooley, 2019), it is necessary to know more about the genetic effects in the ACEs-depression link, so as to screen or further prevent psychological or behavioral risk (e.g., suicide attempts, Wittouck et al., 2016). So far, less has been explored about the moderation of the OXTR polymorphisms in the ACEs-depression link among the incarcerated males (Cataldo et al., 2018; Li et al., 2020). Thus, this study aimed to examine the moderations of rs2254298 and rs53576 in the ACEs-depression link among the incarcerated males. Based on prior studies, we hypothesized that different genotypes of either rs2254298 (GG vs. AA/AG) or rs53576 (GG/AG vs. AA) would have different associations between ACEs and depressive symptoms. Due to limited studies and inconsistent findings, no specific direction regarding the moderations were hypothesized.