Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress
Section snippets
Background
Oxytocin (OXT) is a mammalian hormone that is best known for its role in lactation, parturition and maternal behavior. It is synthesized in the hypothalamic paraventricular and supraoptic nuclei, transported to the posterior pituitary and released into the general circulation. It is also found in extra-hypothalamic brain areas. OXT has been shown to exert effects on memory (de Wied et al., 1993, Lerer et al., 2008), anxiety (Heinrichs et al., 2003) and social interaction (Kosfeld et al., 2005,
Sample
A total of 1226 participants in the BRAINnet Foundation Database www.brainnet.net, (Koslow et al., 2013) which includes the Brain Resource International Database administered for scientific purposes (Gordon, 2003, Gordon et al., 2005)) have been assessed using the DASS measure (Kemp et al., 2005, Lovibond, 1995), a 42-item self report designed to measure the negative emotional states of depression, anxiety and stress. The Depression scale assesses dysphoria, hopelessness, devaluation of life,
Symptoms and early life stress
For TEST 1, we found a greater number of traumatic events was associated with greater severity of symptoms for stress (p-value = 7.604E-09), anxiety (p-value = 3.604E-06) and depression symptom scores (p-value = 2.245E-11). These results are shown in Fig. 2.
Symptoms-ELS relationship and covariates
For TEST 2, we found that none of our demographic variables (gender, age or years of education) were significant covariates (Table 1) when corrected for multiple testing. Additionally, none of these variables significantly interacted with
Discussion
The physiological role of oxytocin has been intensively investigated. Initial work demonstrated its role in labor and lactation (Thorburn and Challis, 1979). More recent work has focused on oxytocin's effects on human social behavior (Ebstein et al., 2010) including work demonstrating that intranasal administration of oxytocin increases trust in humans (Kosfeld et al., 2005) and is a potent antagonist of amygdala activation and brainstem activation in autonomic and behavioral manifestations of
Role of funding source
Genotyping was sponsored by an Australian Research Council Linkage Project grant (LP0455104) with Brain Resource Ltd as the industry partner. Data analysis was supported by NIA AG041232 and NIMH MH094759.
Disclosures
Drs. Myers, McAuley-Clark & Dobson-Stone report no competing interests. Dr. Williams has previously consulted with and held stock in Brain Resource Ltd. Dr. Gatt has previously received consultancy fees with Brain Resource Ltd for unrelated projects, and is a stock holder in Freedomsway Corp. Pte. Ltd. Dr. Schofield reports receiving speaking fees from Janssen-Cilag. This activity does not present a conflict with the current data. Dr Nemeroff consults for Xhale, Takeda, SK Pharma, Shire, Roche,
Contributors
AJM was responsible for the design, analysis and write-up of all experiments, LW manages the cohort and was involved in data collection and edited the manuscript, JMG helped with data collection and edited the manuscript, EZMC helped with data collection and edited the manuscript, CDS helped with data collection and edited the manuscript, PRS coordinated the genetic data collection and edited the manuscript, CBN edited the manuscript.
Acknowledgments
AJM is supported by NIA AG041232 and NIMH MH094759. This project was supported by an Australian Research Council Linkage Project grant (LP0455104) held by LMW and with Brain Resource Ltd as the industry partner. JMG is supported by the National Health & Medical Research Council of Australia (NHMRC) Career Development Fellowship APP1062495. CDS is supported by the National Health & Medical Research Council of Australia (NHMRC) Project Grant 630428. PRS is supported by NHMRC Program Grant 1037196
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