We investigated whether college students' resting Respiratory Sinus Arrhythmia (RSA) would moderate the association between parental negative dominant and submissive emotion expression and their negative emotions. Participants were 97 Chinese college students (28.87% male, Mage = 19.11, SD =.89). Participants reported their perceived maternal and paternal emotion expression, as well as their negative emotions. Resting RSA was assessed during a laboratory visit. Parental negative dominant emotion expression was positively related to students' negative emotions. Additionally, the association between paternal negative dominant emotion expression and negative emotions was stronger among students with low (versus high) levels of resting RSA. Nonetheless, no similar association was found in maternal negative emotion expression. Our findings contribute important information regarding the different roles of maternal and paternal negative emotion expression in college students' emotional outcomes, and signify the interaction between parental socialization and individual characteristics in human developmental process.

The neuroactive metabolite of progesterone, allopregnanolone (ALLO), has been implicated in premenstrual syndrome (PMS) physiopathology and preclinical studies suggested that low doses of fluoxetine increase the ALLO brain concentration. To assess which low dose of fluoxetine (2mg/d, 5mg/d or 10mg/d), administered exclusively during the luteal phase of menstrual cycle, has a potential effect for preventing or mitigating emotional PMS symptoms. In this randomized, double-blind, placebo-controlled pilot study, we followed 40 women (mean age = 29.7+/- 7.4 years) with emotional PMS, during two menstrual cycles: cycle 1, without pharmacological intervention; and cycle 2, with pharmacological intervention. Participants took capsules, on average, seven days preceding the likely date of menses. We assessed the severity of PMS symptoms in both cycles using the Daily Record of Severity of Problems scale (DRSP). There was an increase in the DRSP scores during the late luteal phase of cycle 1, confirming the diagnosis of emotional PMS. Low doses of fluoxetine (5mg/d: 33.5%; 10mg/d: 48.4%) reduced DRSP total score in the day before menses (day-1) at cycle 2 compared with day-1 at cycle 1. Fluoxetine 10mg/d had the most consistent decline in emotional PMS symptoms; 70% of the participants reported a reduction greater than 40% in the DRSP score. Low doses of fluoxetine, which may have no or few effect on the serotonergic system, but may interfere in the progesterone metabolization, seem to have some potential to mitigate emotional PMS symptoms. While the 10mg/d of fluoxetine had the best performance on reducing emotional PMS symptoms, the 5mg/d dose also seems to have some effect on emotional PMS symptoms. Further larger studies will help establish the lowest effective dose of flouxetine for PMS treatment.

Tobacco smoking is one of the critical public health threats all over the world. Since nicotine and its metabolite cotinine have been routinely used as the biomarkers to estimate the exposure to tobacco smoking, hair nicotine and cotinine analyses can provide of a retrospective index of nicotine and cotinine integrated over extended periods of several months prior to hair sampling to estimate the long-term exposure to tobacco smoking. Since the relationship between tobacco smoking and hypothalamic-pituitary-adrenal (HPA) axis is implicated in both stress response and nicotine addiction, better understanding of the association between hair nicotine, cotinine levels and hair cortisol, cortisone levels is an important prerequisite toward more adequate use of this method in future research. We here presented an online solid phase extraction (SPE) coupled with liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for quantification of long-term integrated nicotine and cotinine in human hair. This method was applied to the analysis of hair nicotine and cotinine in 40 participants of smokers and nonsmokers (mean ±SD age: 46.25±11.92 years; 40 % male) and the investigation of their association with hair cortisol and cortisone. Methanol together with glass tube was used for hair nicotine and cotinine extraction during the incubation time of 18-h. The limits of quantification were 1pg/mg for nicotine as well as 0.1pg/mg for cotinine. The inter- and intra-day coefficients of variation were below 15 %. The method recovery ranged between 90 % and 104 %. Group-level analyses revealed that smokers exhibited higher hair nicotine and cotinine levels compared to nonsmokers. Hair nicotine and cotinine levels showed significant positive associations with hair cortisol and cortisone levels in smokers (nicotine and cortisol: Spearman's ρ=0.619, p=0.005; cotinine and cortisol: Spearman's ρ=0.468, p=0.043; nicotine and cortisone: Spearman's ρ=0.773, p=0.000; cotinine and cortisone: Spearman's ρ=0.531, p=0.016), but not in nonsmokers. The presented online SPE LC-MS/MS method provides a simply and highly specific analytical strategy for the detection of nicotine and cotinine concentrations in human hair for the retrospective assessment of cumulative long-term nicotine and cotinine exposure. Furthermore, hair nicotine, cotinine levels correlate with hair cortisol, cortisone levels in smokers other than nonsmokers.

Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal (HPA) axis activity, which is related to emotion regulation. We compare hair cortisol concentrations (HCC), in clinically referred children with disruptive mood dysregulation disorder (DMDD) (n=19), children with other types of psychological disorders (n=48), and healthy subjects (n=36). We also investigate the association between HCC and irritability, age, and sex. Our results show that children with DMDD or other types of psychological disorders have higher HCC than healthy subjects, p<.001, ηp2 =.39. No difference between children with DMDD and those with other types of psychological disorders was found, p=.91, nor an association between HCC and irritability in the clinical sample, p=.32. We found a significant negative correlation between HCC and age in those with DMDD, r=-0.54, p<.05, but not in the normative sample, r=-0.20, p=.25. No differences in HCC between girls and boys were found in the normative sample, p=.49. Children in need of psychological treatment, including those with DMDD, seem to have dysregulated HPA-axis activity over time. Excessive accumulated cortisol concentrations in hair could be an indicator of a psychological disorder in children.

Identifying biological alterations in patients with depression, particularly those that differ between responders and non-responders, is of interest to clinical practice. Biomarker candidates involve neuroactive steroids, including pregnenolone (PREG) and allopregnanolone (ALLO). However, alterations in PREG and ALLO associated with treatment response are understudied. This study's main aim was to evaluate the effects of antidepressant treatment, clinical response, and treatment duration on PREG and ALLO in depression. In a 4-week, open-label trial, participants were allocated randomly to the venlafaxine (n=27) or mirtazapine (n=30) group. Urine concentrations of PREG and ALLO were assessed through gas chromatography-mass spectrometry. Participants collected night urine between 10:30p.m. and 8:00a.m. Two primary outcomes were analyzed. Firstly, the effect of treatment (mirtazapine or venlafaxine), clinical response (operationalized through the Hamilton Depression Rating Scale), and time (baseline compared to 28 days) on the urine concentrations of PREG or ALLO in depression. Finally, the effect of clinical response and time on the urine concentration of PREG or ALLO, independently of the antidepressant given (mirtazapine or venlafaxine). Linear mixed models were carried out. There was no significant difference in PREG and ALLO concentrations between baseline and 28 days in responders and non-responders when investigating the venlafaxine or the mirtazapine group. However, we found a significant reduction of urine PREG concentration after 28 days of treatment in responders who received either venlafaxine or mirtazapine (estimate = -0.56; p=0.016; 95CI [-1.003; -0.115]; Cohen's d = -0.61). Our main results indicate that responders in depression show reduced urinary PREG concentrations after 4-weeks of therapy, independently of the antidepressant used. More studies are needed to confirm these findings.

Oxytocin (OT) is known to play a major role in social cognition and behavior. In this study, we aimed to investigate whether OT also affects the motivational system, specifically, the regulatory focus. Because OT weakens the self- and promotes the other-bias, we hypothesized that OT would decrease promotion focus and increase prevention focus. To test this, we conducted two experiments. In each, male participants intranasally administered OT or a placebo and assessed their regulatory focus using validated paradigms. Results revealed that OT led to an increase of prevention focus (Studies 1 and 2) and a slight but non-significant decrease of promotion focus (Study 2). Thus, participants under OT (vs. placebo) saw potential losses as more important, while they tended to devaluate potential gains. This was unrelated to the perceived likelihood of success. These findings indicate that OT might provide adaption to the social environment by pursuing a vigilant motivational strategy.

Physical exercise can improve neurocognition in individuals with schizophrenia, presumably by facilitating neuroplasticity. There is, however, large inter-individual variation in response. The brain-derived neurotrophic factor (BDNF) has been proposed to mediate these effects. The current aim was to investigate the sparsely studied relationship between peripheral resting BDNF and neurocognitive response to physical exercise in individuals with schizophrenia. The current study reports secondary analyses of data from a randomized controlled trial (RCT), ClinicalTrials.gov number 02205684, recently reported according to the CONSORT guidelines. Eighty-two individuals with schizophrenia (mean age 37±14 years old, 61% men) were randomly allocated to high-intensity interval training (HIIT) or a comparison group performing low-intensity active video gaming (AVG). Both interventions consisted of 2 sessions/week for 12 weeks. In previously published primary RCT analyses, HIIT and AVG showed comparable small to moderate improvements in neurocognition. We now address the inter-individual variability in neurocognitive response. We apply mediation and moderation analyses for repeated measures designs (MEMORE) and mixed effects models. Baseline neurocognition was not significantly correlated with baseline levels of mature BDNF (baseline-mBDNF) or the precursor proBDNF. Nonetheless, baseline-mBDNF, but not baseline proBDNF, moderated the effect of exercise on neurocognition (p=0.025) and explained 7% of the variance. The neurocognitive improvement increased with increasing baseline-mBDNF values. The moderating effect of baseline-mBDNF remained significant in a more complex model adding the moderating effects of exercise mode, sex, age, duration of illness and baseline VO2max on the outcome (neurocognition). Mean baseline-mBDNF significantly decreased from baseline to post-intervention (p=0.036), regardless of exercise mode, differing by sex and associated with improved VO2max but not with change in neurocognition. A mediating role of mBDNF on the effect of physical exercise on neurocognition was not supported. Values of proBDNF mainly remained stable from baseline to post-intervention. We found that baseline-mBDNF moderated the effect of physical exercise on neurocognition in individuals with schizophrenia and explained a small part of the inter-individual variation in neurocognitive response. Mean mBDNF decreased from baseline to post-intervention, regardless of exercise mode. A mediating role of mBDNF on the effect of exercise on neurocognition was not supported. The inter-individual variation in neurocognitive response and the complex role of peripheral BDNF in physical exercise is still to be elucidated.

C-reactive protein (CRP) tends to be elevated in individuals with psychiatric disorders. Recent findings have suggested a protective effect of the genetic liability to elevated CRP on schizophrenia risk and a causative effect on depression despite weak genetic correlations, while causal relationships with bipolar disorder were inconclusive. We investigated the shared genetic underpinnings of psychiatric disorders and variation in CRP levels. Genome-wide association studies for CRP (n=575,531), bipolar disorder (n=413,466), depression (n=480,359), and schizophrenia (n=130,644) were used in causal mixture models to compare CRP with psychiatric disorders based on polygenicity, discoverability, and genome-wide genetic overlap. The conjunctional false discovery rate method was used to identify specific shared genetic loci. Shared variants were mapped to putative causal genes, which were tested for overrepresentation among gene ontology gene-sets. CRP was six to ten times less polygenic (n=1400 vs 8600-14,500 variants) and had a discoverability one to two orders of magnitude higher than psychiatric disorders. Most CRP-associated variants were overlapping with psychiatric disorders. We identified 401 genetic loci jointly associated with CRP and psychiatric disorders with mixed effect directions. Gene-set enrichment analyses identified predominantly CNS-related gene sets for CRP and each of depression and schizophrenia, and basic cellular processes for CRP and bipolar disorder. In conclusion, CRP has a markedly different genetic architecture to psychiatric disorders, but the majority of CRP associated variants are also implicated in psychiatric disorders. Shared genetic loci implicated CNS-related processes to a greater extent than immune processes, which may have implications for how we conceptualise causal relationships between CRP and psychiatric disorders.

Social interactions regulate our behavior and physiology, and strong social bonds can buffer us from stress. Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that display strong social bonds. Infants form selective bonds with their fathers, making them ideal for studying father-daughter bonds. We established a method for quantifying variability in expression of bond-related behaviors in females (n=12), and the present study is the second to use this method for explaining titi monkey responses to behavioral tests. We also investigated how manipulations of oxytocin (OT) and vasopressin (AVP) influenced juvenile behavior and physiology. Subjects received acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or OT receptor antagonist (OTA) prior to an acute social separation. General linear mixed-effects model results revealed fathers were significant behavioral and physiological stress buffers for their daughters, as evidenced by fewer distress vocalizations (p<0.001), less locomotion (p<0.001), and lower plasma cortisol (p<0.001) in a social separation paradigm. Females vocalized less if they exhibited greater expression of bond-related behaviors with their fathers as infants (p=0.01), and this stress-buffering effect remained even when the daughter was separated from the father (p=0.001). While treatments did not alter behaviors, OTA treatment caused the largest rise in plasma cortisol (p<0.001), suggesting blockade of OT receptors can inhibit fathers' stress-buffering effects. Remarkably, females with greater expression of father-daughter bond-related behaviors exhibited an overall reduced physiological separation distress response (p=0.04). Findings from the present study advance current knowledge of the neurobiological mechanisms foundational to female bonds and help inform how social disruptions may differently impact individuals based on expression of bond-related behaviors.

Epidemiological studies increasingly use hair samples to assess people's cumulative exposure to steroid hormones, but how the use of different psychoactive substances may affect steroid hormone levels in hair is, so far, largely unknown. The current study addresses this gap by establishing the substance exposure correlates of cortisol, cortisone, and testosterone in hair, while also accounting for a number of relevant covariates. Data came from a large urban community-sample of young adults with a high prevalence of substance use (N=1002, mean age=20.6 years, 50.2% female), who provided 3cm of hair samples. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantified cortisol, cortisone, and testosterone, as well as delta-9-tetrahydrocannabinol (THC), 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), cocaine, several opioids, and their respective metabolites. Multiple linear regression models with covariates were used to predict steroid hormone levels from substance exposure in a four-step approach: In the full sample, low and high substance hair concentrations (median split) were first tested against no use for each substance individually (step 1) and for all substances together (step 2). Then, within the participants with any substance in hair only, the continuous hair concentration of each substance in pg/mg (step 3) and finally of all substances together, were regressed (step 4). Low, high, and continuous levels of THC in hair were robustly associated with higher levels of cortisol (sig. in step 1 low THC: β=0.29, p=.021; high THC: β=0.42, p=.001; step 2: low THC: β=0.27, p=0.036, and high THC: β=0.40, p=.004, and step 4: β=0.12, p=.041). Participants with high MDMA levels had higher levels of cortisone without adjusting for other substances (step 1: β=0.34, p=.026), but this effect was not significant in the other models. While high THC levels were associated with lower levels of testosterone in step 2 (β=-0.35, p=.018), MDMA concentration was positively related to testosterone concentration with and without adjusting for other substances (step 3: β=0.24, p=.041; step 4: β=0.17, 95%, p=.015) in male participants. The use of psychoactive substances, especially of cannabis and ecstasy, should be considered in studies investigating steroid hormones in hair.