ABSTRACT
Neuroendocrine analyses of posttraumatic stress disorder (PTSD) have generally focused on hypothalamic-pituitary-adrenal (HPA) axis alterations. In the present analyses, we examine two additional neuroendocrine factors that have been previously implicated in biological stress responses: oxytocin (OT) and arginine vasopressin (AVP). Here we examined basal neuropeptide status in military veterans clinically diagnosed with PTSD (n = 29) and in two non-traumatized comparison groups with previous stress exposure (n = 11 SWAT trainees and n = 21 ultramarathon runners). PTSD patients showed low levels of plasma OT and high levels of AVP. The ratio of AVP/OT robustly related to PTSD status, and emerged as a statistically plausible mediator of relationships between the number of personal traumatic experiences and subsequent PTSD symptom burden. Over the course of behavioral therapy for PTSD, measures of OT showed a significant but modest normalization. Plasma cortisol levels were not statistically different among the three groups. This study suggests that AVP/OT ratios may represent a neuroendocrine predictor of severe PTSD, as well as a potential treatment response biomarker.
ABSTRACT
Despite evidence supporting a role for oxytocin (OT) in regulating social behavior, surprisingly little is known about how this neuropeptide is calibrated during development. We systematically reviewed empirical studies in humans (k = 86 publications reporting on 66 independent samples; N = 7319) that examined associations between early-life stress and three OT system components: endogenous OT, methylation of the OT receptor gene (OXTRm), and biological and behavioral responses to intranasally administered OT. In a series of meta-analyses, we found some evidence that people who grew up under more adverse conditions tend to have lower endogenous OT (children: r = .12; adults: r = .09), that early adversity is associated with higher levels of OXTRm (r = .02), and that adults who report lower levels of childhood adversity tend to show more positive responses to intranasally administered OT (r = .12). These results were found in typical populations, and were in most cases absent in clinical samples. We discuss these findings in terms of both the prevailing medical model (focusing on the harmful effects of early-life stress) and the adaptive calibration model (focusing on developmental adaptation of biobehavioral systems to early conditions) and suggest that an adaptation-based approach could meaningfully advance research and intervention on the sequelae of early adversity.
Subject(s)
Adverse Childhood Experiences , Oxytocin , Adult , Child , Humans , Receptors, Oxytocin/genetics , Social BehaviorABSTRACT
Mammals, including humans, are reliant for survival and reproduction on adaptations associated with sociality and physiological investment, which can be linked to interactions with their parents or other bonded adult conspecifics. A wide range of evidence in human and non-human mammal species links social behaviors and relationships - including those characterized by what humans call "love" - to positive health and longevity. In light of this evidence, we propose a Social Dependency Hypothesis of Longevity, suggesting that natural selection has favored longer and healthier adult lives in species or in individuals exhibiting enhanced caregiver responsibilities contributing to the success of the next generation. In highlighting cellular, physiological, and behavioral effects of mammalian reproductive hormones, we examine the specific hypothesis that the neuropeptide oxytocin links longevity to the benefits of parental investment and associated relationships. Oxytocin is a pleiotropic molecule with anti-oxidant and anti-inflammatory properties, capable of regulating the hypothalamic-pituitary-adrenal axis, the parasympathetic nervous system and other systems associated with the management of various challenges, including chronic diseases and therefore may be crucial to establishing the maximum longevity potential of a species or an individual.