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BackgroundAlterations in the brain’s oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse.MethodsWe examined salivary oxytocin in school-aged children with (n=80) and without (n=40) ASD (boys/girls 4/1), as well as characterizations of DNA methylation (DNAm) of the oxytocin receptor gene (OXTR). Cortisol levels were also assessed to examine links between the oxytocinergic system and hypothalamic-pituitary-adrenal (HPA) axis signaling.ResultsChildren with ASD displayed altered (diminished) oxytocin levels in the morning, but not in the afternoon, after a mildly stress-inducing social interaction session. Notably, in the control group, higher oxytocin levels were predictive of lower stress-induced cortisol, likely reflective of aprotectivestress-regulatory mechanism for buffering HPA stress activity. In children with ASD, on the other hand, a morereactivestress regulatory mechanism was evident, involving a significant rise in oxytocin levels from the morning to the afternoon upon stress-induced cortisol release, i.e., to reactively cope with heightened HPA activity.Regarding epigenetic modifications, no overall pattern ofOXTRhypo- or hypermethylation was evident in ASD. In control children, a notable association betweenOXTRmethylation and levels of cortisol was evident, likely indicative of a compensatory downregulation ofOXTRmethylation (higher oxytocin receptor expression) in children with heightened HPA axis activity.ConclusionTogether, these observations bear important insights into altered oxytocinergic signaling in ASD, which may aid in establishing relevant biomarkers for diagnostic and/or treatment evaluation purposes targeting the oxytocinergic system in ASD.

This is an exploratory study, its aims are twofold. First, to test whether the rMIST poses any aversive effect on participants by assessing whether there are any significant changes in overall affect and physiology pre- versus post- task. That is an increase in average levels of NA, HR, and SLC, and a decrease in RMSSD. Likewise, whether there is a significant increase in reactivity in the days post- task compared to the days pre- task. Secondly, whether these changes are different between individuals low versus high in psychopathology.

Background : Work-related stress and burnout have become major occupational health concerns. Dysregulation of HPA axis is considered one of the central mechanisms and is potentially moderated through epigenetics. In the present study, we aim to investigate epigenetic regulation of the HPA axis in burnout, by focusing on salivary cortisol and cortisone and DNA methylation of the glucocorticoid receptor gene (NR3C1) and the serotonin transporter gene (SLC6A4). Methods : We conducted a cross-sectional study with 59 subjects with burnout and 70 healthy controls recruited from the general population. All participants underwent a clinical interview and psychological assessment. Saliva samples were collected at 0, 30 and 60 min after awakening and were used to quantify cortisol and cortisone. Pyrosequencing was performed on whole blood-derived DNA to assess DNA methylation. Results : There were no between-group differences in cortisol levels, whereas burnout participants had higher levels of cortisone. Job stress was associated with increased cortisol and cortisone. We observed both increased and decreased NR3C1 and SLC6A4 methylation in the burnout group compared to the control group. Some of these methylation changes correlated with burnout symptoms dimensionally. Increased methylation in a specific CpG in the SLC6A4 promoter region moderated the association between job stress and burnout. DNA methylation in this CpG was also associated with increased cortisol. In addition, average methylation of NR3C1 was negatively associated with cortisone levels. Limitations : This is a cross-sectional study and therefore no conclusions on causality could be made. Conclusions : We provide first evidence of changes in DNA methylation of NR3C1 and SLC6A4 in burnout, which were further associated with cortisol and cortisone. Further, increased cortisol and cortisone seemed to reflect job stress rather than burnout itself. keywords: burnout, methylation, glucocorticoid receptor, serotonin transporter, HPA axis, cortisol ispartof: Journal of Affective Disorders vol:295 pages:505-512 ispartof: location:Netherlands status: published

Psychosocial stress tasks, such as the Trier social stress test (TSST) and the Montreal imaging stress test (MIST) induce mild stress in a controlled environment ideally suited to study the stress response (Mortensen & Cialdini, 2010). These tasks typically result in a physiological stress response, characterized by changes in the autonomous nervous system (ANS) such as increased heart rate (HR) and skin conductance level (SCL), and decreased heart rate variability (HRV), but also changes in affect such as an increase in negative affect (NA). Findings from studies on stress tasks are used to make inferences on how individuals respond to stress in their natural environment. However, given the “artificial” nature of such tasks (Klein et al., 2012; Mortensen & Cialdini, 2010), the extent of their ecological validity remains unclear. In other words, it is not known if these findings are in fact related to reactivity to daily-life stressors. To date, ecological validity has mostly focused on comparing the ANS response to a stress task with either a measure of variability (e.g. standard deviation, minimum, maximum values) in a 24h recording (Gerin et al., 1998; Kamarck et al., 2003; Pollak, 1991; Turner et al., 1994), or alternatively the response to a similar pre-specified stressor in daily-life such as giving a presentation, or engaging in marital conflict (Baucom et al., 2018; Gerin et al., 1998; Johnston, Tuomisto, & Patching, 2008). Arguably, these methods are either too broad to capture stress, or on the contrary too restrictive to represent the general stress response, which may in turn limit their validity. Ideally, stress tasks should reflect reactivity to daily-life stressors in general rather than to a single specific stressor. Likewise, validity should extend from the ANS response (i.e. heart rate, blood pressure) to also cover affective reactivity, which has largely been neglected. Experience sampling methodology (ESM) may be the solution to both of these limitations. ESM is a diary method where participants receive a set number of assessments at random times during the day, for multiple days. Assessments consist of various self-report items on affect, behavior, context, and appraisals (Myin-Germeys et al., 2018; Vaessen et al., 2017). ESM captures affective changes in daily-life with minimal intervention, and as such may be ideally suited to measure the response to daily-life stressors in general. To our knowledge, ESM has yet to be used to assess the ecological validity of a stress task. In time-contingent sampling with ESM, assessment occurs independent of stress onset, meaning that stress occurs sometime between the current and the previous assessment. This in turn suggests that rather than capturing peak-stress, it likely captures the response already in the recovery phase, when measures are returning to baseline. For this reason, it is possible that we are actually capturing recovery in daily-life rather than reactivity. Consequently, laboratory recovery may be a better predictor of daily-life “reactivity” than laboratory reactivity. The current study aims to test the ecological validity of the repeated Montreal Imaging Stress Task (rMIST), a psychosocial stress task where participants are under the illusion to be competing against another participant on an arithmetic task (Dedovic et al., 2005). More specifically, we assess whether reactivity and recovery to the rMIST are associated with general daily-life stress reactivity for all measures of affect (i.e. NA), and ANS reactivity (i.e. HR, RMSSD, and SCL).