In this review we summarize the results and conclusions of five studies as presented in a symposium at the 42nd annual meeting of the International Society for Psychoneuroendocrinology, in New York in September 2012. Oxytocin administration has received increasing attention for its role in promoting positive social behavior and stress regulation, and its potential as a therapeutic intervention for addressing various aspects of psychiatric disorders. However, it has been noted that the observed effects are not uniformly beneficial. In this paper we present five new studies each concluding that contextual and interindividual factors moderate the effects of oxytocin, as well as peripheral oxytocin levels. These findings are in accordance with the recent idea that oxytocin administration may increase sensitivity to social salience cues and that the interpretation of these cues may be influenced by contextual (i.e. presence of a stranger versus friend) or interindividual factors (i.e. sex, attachment style, or the presence of psychiatric symptoms). When social cues in the environment are interpreted as "safe" oxytocin may promote prosociality but when the social cues are interpreted as "unsafe" oxytocin may promote more defensive and, in effect, "anti-social" emotions and behaviors. Likewise, oxytocin appears to promote such agonistic tendencies in individuals who are chronically pre-disposed to view the social milieu in uncertain and/or in negative terms (e.g., those with borderline personality disorder, severe attachment anxiety and/or childhood maltreatment). In all, these studies in pre-clinical animal, healthy humans and patients samples further reinforce the importance of considering both contextual and interindividual factors when trying to understand the role of oxytocin as a biological substrate underlying social bonding and stress regulatory processes and when studying the effects of oxytocin administration in particular in patients with (increased risk for) psychiatric disorders.

Combined, these altered resting-state connectivity and activity patterns could represent neurobiological correlates of increased salience processing and hypervigilance (SN), at the cost of awareness of internal thoughts and autobiographical memory (DMN) in PTSD. However, several discrepancies between findings of the meta-analysis and systematic review were observed, stressing the need for future studies on resting-state abnormalities in PTSD patients.

BACKGROUND Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma.