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  • Meta-analysis of the Effectiveness of the Trier Social Stress Test in Eliciting Physiological Stress Responses in Children and Adolescents
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2020-01-16
    Jessica A. Seddon; Violeta J. Rodriguez; Yannick Provencher; Jacquelyn Raftery-Helmer; Jacqueline Hersh; Patrick R. Labelle; Kristel Thomassin

    The Trier Social Stress Test (TSST) is known to reliably induce physiological stress responses in adult samples. Less is known about its effectiveness to elicit these responses in youth samples. We performed a meta-analysis of stress responses to the TSST in youth participants. Fifty-seven studies were included representing 5,026 youth participants. Results indicated that the TSST was effective at eliciting stress responses for salivary cortisol (sCort; effect size [ES] = 0.47, p = .006), heart rate (HR; ES = 0.89, p < .001), pre-ejection period (PEP; ES = -0.37, p < .001), heart rate variability (HRV; ES = -0.33, p = .028), and systolic blood pressure (ES = 1.17, p < .001), as well as negative affect (ES = 0.57, p = .004) and subjective anxiety (ES = 0.80, p = .004) in youth samples. Cardiac output (ES = 0.15, p = .164), respiratory sinus arrhythmia (ES = -0.10, p = .064), and diastolic blood pressure (ES = 2.36, p = .072) did not reach statistical significance. Overall, effect sizes for the TSST varied based on the physiological marker used. In addition, several physiological markers demonstrated variance in reactivity by youth age (sCort, HR, HRV, and PEP), gender (sCort), type of sample (i.e., clinical versus community sample; sCort and HR), duration of TSST (sCort, HR, HRV, negative affect, and subjective anxiety), number of judges present in TSST (HR and subjective anxiety), gender of judges (sCort), and time of day the marker was assessed (morning versus afternoon/evening; sCort). Overall, the findings provide support for the validity of the TSST as a psychosocial stressor for inducing physiological and psychological stress responses in children and adolescents, but also highlight that some markers may capture the stress response more effectively than others.

    更新日期:2020-01-16
  • American Indian young adults display diminished cardiovascular and cortisol responses to acute psychological stress
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2020-01-11
    Neha A. John-Henderson; Hannah E. Gruman; Cory J. Counts; Annie T. Ginty

    American Indian adults are at an increased risk for cardiovascular disease compared with non-Hispanic white adults. Scant research exists examining the underlying physiological and psychological mechanisms associated with these risks. This study aimed to examine possible psychological and physiological stress-related mechanisms related to cardiovascular disease risk in healthy American Indian and non-Hispanic white adults. Forty American Indian (60% female, Mean age = 19.93, SD = 2.08 years) and 45 non-Hispanic white (70% female, Mean age = 20.18, SD = 2.22 years) participants attended an in-person laboratory session. Salivary cortisol and cardiovascular activity were measured before (baseline), during, and after exposure to a 10-minute mental arithmetic task. Compared to non-Hispanic white participants, American Indian had diminished salivary cortisol (p < .001), blood pressure (p’s < .001), and heart rate (p = .041) responses to acute psychological stress. These effects could not be accounted for by differences in task performance or self-reported engagement. Previous research has shown that exaggerated responses to stress are associated with increased risk of cardiovascular disease. However, diminished responses to stress are associated with early childhood stress and future adverse behaviors (e.g., addiction, obesity). Diminished reactivity may influence behaviors that can impact future development of cardiovascular disease in American Indian populations.

    更新日期:2020-01-13
  • Cumulative cortisol exposure increases during the academic term: Links to performance-related and social evaluative stressors
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2020-01-10
    Cinnamon A. Stetler; Victoria Guinn

    Objective To examine whether cumulative cortisol production changes during a period of increased demands when cortisol and stress are assessed concurrently. The study also compared stress perceptions vs. cumulative stressful events on their respective association with cortisol output. Finally, it explored whether certain types of stressful events, those involving school/job performance or social-evaluative threat, were linked to cortisol levels across multiple weeks. Method The current study assessed cumulative cortisol production via hair sample in 56 undergraduates (88% female) during both lower stress (summer break) and higher stress (academic term) periods. During the latter, both negative events (checklist) and stress perceptions were assessed weekly, and these reports were aggregated across the 10-weeks to minimize retrospective bias. Results Cortisol levels in hair samples were significantly higher (d = 0.84) during the academic term (M = 14.24 pg/mg, SD = 11.36) compared to summer break (M = 8.00 pg/mg, SD = 4.14), suggesting greater cumulative exposure to cortisol. Although perceived stress was not associated with cortisol levels (rpartial(53) = .10, p = .46), exposure to more stressful events (rpartial(53) = .27, p = .047), particularly events involving academic demands (rpartial(53) = .37, p = .006), or negative evaluation/social rejection (rpartial(53) = .27, p = .045), was positively associated with cumulative cortisol exposure. Conclusions This study demonstrates that cortisol levels in hair may be linked to cumulative exposure to stressors when measured concurrently (3 months), and that stressful events, rather than perceptions, are reflected in HPA axis activity. Real-world stressors involving performance demands and social-evaluative threat accumulate to enhance cortisol production, consistent with their acute HPA effects in the lab. Hair samples may provide a window into the past by allowing researchers to feasibly assess cortisol production before, during, and after the onset of a chronic stressor.

    更新日期:2020-01-11
  • Prenatal traumatic stress and offspring hair cortisol concentration: A nine year follow up to the Red River Flood Pregnancy Study
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2020-01-07
    Anna M. Strahm; Angela G. Bagne; Heidi A. Rued; Kate J. Larson; James N. Roemmich; Clayton J. Hilmert

    Introduction Findings concerning the relationship between maternal prenatal and child cortisol concentrations are inconsistent. This study examined whether the influence of an objective traumatic stressor during pregnancy, distance from a natural flood disaster, moderated the association between prenatal maternal diurnal cortisol and 9-year old offspring hair cortisol concentrations. Methods Data were collected from 56 of the mothers who took part in a study of flood-related pregnancy outcomes in 2009 and their children. Data included distance of the maternal home from evacuation areas, four maternal saliva cortisol assessments (waking, 30 minutes after waking, afternoon, and before bed) provided within 3-months of the flood crest and child hair samples to assess cortisol secretion over the past month. Results There was a significant interaction between proximity to flooding during pregnancy and maternal cortisol AUC predicting child hair cortisol, after controlling for maternal age, gestational age at cortisol sampling, sex of the child, current socioeconomic status and current maternal stress. At greater distance from flooding (lower stress conditions) there was a non-statistically significant positive association between maternal cortisol and child cortisol. In contrast, living closer to flooding (higher stress conditions) produced a significant negative association between maternal and child cortisol. Conclusion Experiencing a traumatic stressor during pregnancy may alter maternal-fetal programming of the hypothalamic-pituitary-adrenal axis. The direct threat of flooding led to offspring cortisol concentrations that resembled cortisol production seen in mothers with symptoms of PTSD and their offspring. This alteration is evident in nine-year-old offspring and may help explain inconsistencies in the previous literature.

    更新日期:2020-01-07
  • Oxytocin during breastfeeding and maternal mood symptoms
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-31
    Julia Whitley; Kathryn Wouk; Anna E Bauer; Karen Grewen; Nisha C Gottfredson; Samantha Meltzer-Brody; Cathi Propper; Roger Mills-Koonce; Brenda Pearson; Alison Stuebe

    This study aimed to quantify the relationship between postpartum depression and anxiety, oxytocin, and breastfeeding. We conducted a longitudinal prospective study of mother-infant dyads from the third trimester of pregnancy to 12 months postpartum. A sample of 222 women were recruited to complete the Beck Depression Inventory II and Spielberger State-Trait Anxiety Inventory-state subscale, participate in observed infant feeding sessions at 2 and 6 months postpartum, and provide venous blood samples during feeding. Maternal venous oxytocin levels in EDTA-treated plasma and saliva were determined by enzyme immunoassay with extraction and a composite measure of area under the curve (AUC) was used to define oxytocin across a breastfeeding session. Linear regression was used to estimate associations between postpartum depression and anxiety as predictors and oxytocin AUC during breastfeeding as the outcome at both 2 and 6 months postpartum. Mixed models accounting for correlations between repeated oxytocin measures were used to quantify the association between current depression and/or anxiety symptoms and oxytocin profiles during breastfeeding. We found no significant differences in oxytocin AUC across a feed between depressed or anxious women and asymptomatic women at either 2 or 6 months postpartum. Repeated measures analyses demonstrated no differences in oxytocin trajectories during breastfeeding by symptom group but possible differences by antidepressant use. Our study suggests that external factors may influence the relationship between oxytocin, maternal mood symptoms, and infant feeding.

    更新日期:2019-12-31
  • Inhibition of JNK ameliorates depressive-like behaviors and reduces the activation of pro-inflammatory cytokines and the phosphorylation of glucocorticoid receptors at serine 246 induced by neuroinflammation
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-27
    Juntao Zhang; Wenjuan Lin; Mingming Tang; Yawei Zhao; Ke Zhang; Xiaqing Wang; Yingcong Li

    Depression is associated with immune dysregulation and the aberrant activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, the neurobiological molecular mechanisms underlying these associations remain unclear. c-Jun amino-terminal kinase (JNK), an important modulator in inflammation and stress responses, is often critically implicated in the development of central nervous system diseases. However, whether and how JNK mediates neuroinflammation-induced depression remains largely unknown. In this study, we investigated the role of JNK in depressive-like behaviors induced by central lipopolysaccharide (LPS) infusion. The results showed that LPS infusion led to depressive-like behaviors, accompanied by increased proinflammatory cytokine expression, increased JNK activation, and upregulated glucocorticoid receptor (GR) phosphorylation at serine 246 (pGR-Ser246) in the habenula (Hb), amygdala (Amyg) and medial prefrontal cortex (mPFC). Treatment with SP600125, a known JNK inhibitor, prevented the LPS-induced hyper-activation of JNK and alleviated depressive-like behaviors. Moreover, LPS-induced increases in the expression levels of TNF-α, IL-1β and pGR-Ser246 in these brain regions were reduced when the rats were treated with SP600125. Our results show, for the first time, that JNK activities in the Hb, Amyg, and mPFC are involved in the modulation of neuroinflammation-induced depression and participate in the regulation of the expression of proinflammatory cytokines and GR phosphorylation, which are pathological factors associated with depression. Our findings provide new insights into the mechanism of neuroinflammation-associated depression and suggest that the JNK pathway may be a potential target for treating inflammation-related depression.

    更新日期:2019-12-27
  • The role of low-grade inflammation in ME/CFS (Chronic Fatigue Syndrome) - associations with symptoms
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-26
    Martin A Jonsjö; Gunnar L Olsson; Rikard K Wicksell; Kjell Alving; Linda Holmström; Anna Andreasson

    Background Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often present with a range of flu-like symptoms resembling sickness behavior as well as widespread pain and concentration deficits. The aim of this study was to explore the association between inflammatory markers previously shown to be related to fatigue severity in ME/CFS and common ME/CFS symptoms post-exertional fatigue, impaired cognitive processing, musculoskeletal pain and recurrent flu-like symptoms, and the moderating effect of sex on these associations. Methods 53 adult patients diagnosed with ME/CFS at a specialist clinic were included in the study. Fasting blood plasma was analyzed using the Olink Proseek Multiplex Inflammation panel (β-NGF, CCL11, CXCL1, CXCL10, IL-6, IL-7, IL-8, IL-10, IL-18, TGF-α, TGF-β-1 and SCF) and BioRad Human Cytokine Type 1 assay (TNF-α). Participants rated the average severity of symptoms (0-10) based on the 2011 International Consensus Criteria of ME/CFS during a structured clinical interview. Associations between inflammatory markers and symptom severity were analyzed using bivariate correlations and moderated regression analyses bootstrapped with 5000 repetitions. Results and conclusions Only β-NGF was associated with the fatigue severity measure. However, higher levels of CCL11, CXCL10, IL-7, TNF-α and TGF-β-1 were significantly associated with higher levels of impaired cognitive processing and musculoskeletal pain, and sex was a significant moderator for CXCL10, IL-7 and TGF-β-1. Future studies should investigate the relationship between inflammatory markers and key symptoms in ME/CFS in a longitudinal design in order to explore if and for whom low-grade inflammation may contribute to illness development.

    更新日期:2019-12-27
  • Prenatal Sex Hormones and Behavioral Outcomes in Children
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-24
    Drew B Day; Brent R Collett; Emily S Barrett; Nicole R Bush; Shanna H Swan; Christina Wang; Sheela Sathyanarayana

    Abnormal sex hormone levels in utero have been associated with child behavioral problems, but it is unclear if normal variation in prenatal sex hormones is associated with subsequent behavior in childhood. We assessed maternal sex hormones, including serum estrone (E1), estradiol (E2), estriol (E3), free testosterone (FT), and total testosterone (TT), during early pregnancy (gestational week 6-21 (mean = 11.1)) and evaluated child behavior at ages 4-5 using the Behavioral Assessment System for Children (BASC-2) and Social Responsiveness Scale (SRS-2) in 404 mother/child pairs (211 girls, 193 boys) within The Infant Development and Environment Study, a multi-site pregnancy cohort study. Associations between hormones and composite scores were evaluated using multiple linear regressions in both sexes combined, and separate models assessed effect modification by sex with the addition of interaction terms. A 10-fold increase in maternal FT or TT was associated in both sexes with a 4.3-point (95% CI: 0.5, 8.2) or 4.4-point (0.8, 8.0) higher BASC-2 internalizing composite T score, respectively. In addition, a 10-fold increase in FT or TT was associated with a 3.8-point (0.04, 7.5) or 4.0-point (0.5, 7.5) higher behavioral symptoms index composite score. In models evaluating effect modification by sex, a 10-fold increase in E1 was associated with a 4.3-point (1.2, 7.4) decrease in adaptive skills composite score in girls only (interaction p = 0.04). We observed associations between testosterone and internalizing behaviors and behavioral symptoms index in both sexes, as well as a female-specific association between E1 and adaptive skills. Sex hormones during pregnancy may play a key role in influencing later-life behavior, and additional studies should further examine different periods of susceptibility to hormonal signals.

    更新日期:2019-12-25
  • Differential regulation of Nrf2 is linked to elevated inflammation and nitrative stress in monocytes of children with autism
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-23
    Ahmed Nadeem; Sheikh F. Ahmad; Laila Y. AL-Ayadhi; Sabry M. Attia; Naif O. Al-Harbi; Khalid S. Alzahrani; Saleh A. Bakheet

    Autism spectrum disorder (ASD) is a very complex neurodevelopmental disorder characterized by deficits in social and communication skills. Innate immune cells like monocytes are believed to play a cardinal role in neuroimmune inflammation and nitrative stress. On the other hand, Nrf2, a basic leucine zipper transcription factor plays a significant role in protecting the immune cells against inflammation and oxidants. However, its role in monocytes of ASD children and typically developing control (TDC) children has not been elucidated in relation with inflammation and nitrative stress. Therefore, this study was undertaken to evaluate Nrf2 expression/activity along with parameters of inflammation (NFkB, IL-6, IL-1β) and nitrative stress (iNOS, nitrotyrosine) in monocytes of ASD/TDC children. Further, sulforaphane (SFN) was utilized as an Nrf2 activator to assess its effect on above said inflammatory and nitrative stress parameters. Our study shows that monocytes of ASD subjects have decreased Nrf2 expression/activity along with increased inflammation and nitrative stress. Further, monocytes from ASD have deficiency in induction of Nrf2 activity upon stimulation with LPS. However, activation of Nrf2 in vitro by SFN reverses LPS-induced effects on inflammation in monocytes by reduction in NFkB signaling. Further, treatment with SFN also reverses LPS-induced effects on nitrative stress (iNOS, nitrotyrosine) in monocytes of ASD subjects. This study propounds the idea that SFN protects against nitrative stress and inflammation by downregulating oxidative stress and inflammation through blockade of NFkB signaling in autistic children. This may be the reason behind reported ameliorative effects of SFN in ASD subjects.

    更新日期:2019-12-23
  • Changes in Appetite-Regulating Hormones Following Food Intake are Associated with Changes in Reported Appetite and a Measure of Hedonic Eating in Girls and Young Women with Anorexia Nervosa
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-23
    Christopher Mancuso; Alyssa Izquierdo; Meghan Slattery; Kendra R. Becker; Franziska Plessow; Jennifer J. Thomas; Kamryn T. Eddy; Elizabeth A. Lawson; Madhusmita Misra

    Background Females with anorexia nervosa (AN) have higher ghrelin and peptide YY (PYY) and lower brain-derived neurotropic factor (BDNF) levels than controls, and differ in their perception of hunger cues. Studies have not examined appetite-regulating hormones in the context of homeostatic and hedonic appetite in AN. Objective To examine whether alterations in appetite-regulating hormones following a standardized meal are associated with homeostatic and hedonic appetite in young females with AN vs. controls. Methods 68 females (36 AN, 32 controls) 10-22 years old were enrolled. Ghrelin, PYY and BDNF levels were assessed before, and 30, 60 and 120 minutes following a 400-kilocalorie standardized breakfast. Visual Analog Scales (VAS) assessing prospective food consumption, hunger, satiety, and hedonic appetite were administered before and 20 minutes after breakfast. A Cookie Taste Test (CTT) was conducted after a snack as a measure of hedonic eating behavior ∼3 hours after breakfast. Results AN had higher fasting ghrelin and PYY, and lower fasting BDNF (p = 0.001, 0.002 and 0.044 respectively) than controls. Following breakfast (over 120 minutes), ghrelin and PYY area under the curve (AUC) were higher, while BDNF AUC was lower in AN vs. controls (p = 0.007, 0.017 and 0.020 respectively). Among AN (but not controls), reductions in ghrelin and increases in PYY in the first 30-minutes following breakfast were associated with reductions in VAS scores for prospective food consumption. AN consumed fewer calories during the CTT vs. controls (p < 0.0001). In AN (particularly AN-restrictive subtype), BDNF AUC was positively associated with kilocalories consumed during the CTT Conclusions In young females with AN, changes in ghrelin and PYY following food intake are associated with reductions in a prospective measure of food consumption, while reductions in BDNF are associated with reduced hedonic food intake. Further studies are necessary to better understand the complex interplay between appetite signals and eating behaviors in AN.

    更新日期:2019-12-23
  • Dopamine D2 receptor signaling modulates pancreatic beta cell circadian rhythms
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-23
    Heather Wei; Rizaldy C. Zapata; Mariela Lopez-Valencia; Despoina Aslanoglou; Zachary J. Farino; Valerie Benner; Olivia Osborn; Zachary Freyberg; Michael J. McCarthy
    更新日期:2019-12-23
  • Psychosocial Well-Being and Quality of Life in Women with Turner Syndrome
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-23
    Ariane Liedmeier; David Jendryczko; Hedi Claahsen van der Grinten; Marion Rapp; Ute Thyen; Catherine Pienowski; Andreas Hinz; Nicole Reisch

    Background Turner syndrome (TS) affects approximately one out of 2,500 females. Previous research indicates that women with TS experience impairment in several psychosocial domains as well as in quality of life (QoL). Data, however, mainly focus on girls, whereas data on adult women is extremely scarce, inconsistent and mainly low in sample size. Separate analysis of adult women, however, is important since women face other challenges of TS than girls. Methods We compared 301 women with TS aged 16-73 years (from 14 centres in six European countries) to healthy controls with regard to depression, anxiety, self-esteem, attention deficit/hyperactivity disorder (ADHD), autism, romantic relationships, social participation, amount of working hours and satisfaction with income as well as with regard to psychological, physical, environmental, social and global QoL. The influence of psychosocial well-being on the different QoL-domains was examined via multiple regression models. Results Women with TS showed impairments in all psychosocial variables (anxiety, depression, ADHD, autism, self-esteem, social participation allp < 0.001) except for the amount of working hours (p = 0.062) and satisfaction with income (p = 0.369). They also showed lower social (p < 0.001), psychological (p < 0.001) and physical QoL (p < 0.001) compared to controls. Depression, satisfaction with income and self-esteem could be shown to be the best predictors for QoL. Conclusion In conclusion, quality of life in TS is impaired, in particular it seems to be negatively affected by depression and low self-esteem whereas satisfaction with income has a positive influence. These results implicate that medical staff needs to pay attention on possible psychosocial impairments when treating women with TS. Strengthening self-esteem and counteracting depression potentially raises their QoL.

    更新日期:2019-12-23
  • Prenatal stress and later metabolic consequences: systematic review and meta-analysis in rodents
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-20
    Adriana L. Burgueño; Yamila R. Juarez; Ana M. Genaro; Mariana L. Tellechea

    Background Numerous rodent studies have evaluated the effects of maternal stress (MS) on later in life susceptibility to Metabolic Syndrome (MetS) intermediate phenotypes with varying results. The aim of this study was to quantitatively synthesize the available data on the effects of MS on offspring obesity, estimated indirectly by body mass (BM), body fat (BF) and plasma leptin; systolic blood pressure (SBP); plasma glucose (and insulin) and blood lipid concentrations. Methods Literature was screened and summary estimates of the effect of MS outcomes were calculated by using random-effects models. Data on the effects of exogenous corticosteroid administration (or inhibition of 11β-HSD2) during pregnancy in rodents was analysed separately to characterize the direct phenotypic effects of prenatal corticosteroid excess (PCE). Results We conducted 14 separate meta-analyses and synthesized relevant data on outcomes scarcely reported in literature. Both MS and PCE were associated with low birth weight without rapid catch-up growth resulting in decreased body mass later in life. Our analysis also revealed significant and contradictory effects on offspring adiposity. Little evidence was found for effects on glucose metabolism and blood lipids. We identified increased SBP in offspring exposed to PCE; however, there is not enough data to draw any conclusion about effects of MS on SBP. Conclusions Neonatal weight proved to be decreased in offspring prenatally exposed to stress or corticosteroids, but laboratory rodents in the absence of a challenging environment did not show catch-up growth. The available evidence is inconclusive regarding the effect on adiposity revealing clear methodological and knowledge gaps. This meta-analysis also confirmed a significant positive association between PCE and SBP. Nevertheless, additional studies should address the association with MS.

    更新日期:2019-12-20
  • Does women’s anxious jealousy track changes in steroid hormone levels?
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-20
    Amanda C. Hahn; Lisa M. DeBruine; Lola A. Pesce; Andrew Diaz; Christopher L. Aberson; Benedict C. Jones

    Findings for progesterone and anxiety in non-human animals led to the hypothesis that women’s interpersonal anxiety will track changes in progesterone during the menstrual cycle. There have been few direct tests of this hypothesis, however. Consequently, we used a longitudinal design to investigate whether interpersonal anxiety (assessed using the anxious jealousy subscale of the relationship jealousy questionnaire) tracked changes in salivary steroid hormones during the menstrual cycle in a large sample of young adult women. We found no evidence for within-subject effects of progesterone, estradiol, their interaction or ratio, testosterone, or cortisol on anxious jealousy. There was some evidence that other components of jealousy (e.g., reactive jealousy) tracked changes in women’s cortisol, however. Collectively, these results provide no evidence for the hypothesis that interpersonal anxiety tracks changes in progesterone during the menstrual cycle.

    更新日期:2019-12-20
  • Mindfulness-based focused attention training versus progressive muscle relaxation in remitted depressed patients: effects on salivary cortisol and associations with subjective improvements in daily life
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-20
    Theresa Beddig; Christina Timm; Bettina Ubl-Rachota; Vera Zamoscik; Ulrich Ebner-Priemer; Iris Reinhard; Peter Kirsch; Christine Kuehner

    Major Depression is a stress-related disorder characterized by altered hypothalamic-pituitary-adrenal axis function. Mindfulness-based interventions have shown to improve subjective parameters of stress and to reduce relapse rates in depressed patients. However, research on their effects on diurnal patterns of cortisol and associations with subjective outcomes is lacking. The present Ambulatory Assessment study investigated possible changes in daily rhythm cortisol parameters (cortisol awakening response (CAR), daily slope, total cortisol) in currently remitted individuals with recurrent depression who were randomized to a four-week mindfulness-based focused attention training (MBAT, n = 39) or a progressive muscle relaxation training (PMR, n = 39). A second aim was to investigate whether changes in cortisol were linked to improvements in affective and cognitive daily life states. On three weekdays before and after the intervention, seven saliva cortisol samples per day were collected. For analysis, multilevel models were applied. Results revealed no group-specific or general change in CAR and daily slopes from pre- to postintervention. In contrast, total cortisol increased across groups, which was however moderated by group and subjective improvement status. While cortisol increased irrespective of subjective improvement in PMR participants, MBAT participants with larger reductions in negative affect and rumination maintained their initial cortisol levels, whereas those with lower improvement paralleled the PMR group. Thereby, MBAT appeared to buffer an increase in overall cortisol secretion over time, but only in patients showing marked improvements in those affective and cognitive states that constitute core elements for depressive relapses in the vulnerability model of mindfulness-based cognitive therapy.

    更新日期:2019-12-20
  • Opioid Receptor Blockade Inhibits Self-Disclosure During a Closeness-Building Social Interaction
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-20
    Kristina Tchalova; Geoff MacDonald

    Social ties are critical to human health and well-being; thus, it is important to gain a better understanding of the neurobiological mechanisms involved in the development of interpersonal closeness. Prior research indicates that endogenous opioids may play a role in social affiliation by elaborating feelings of social connection and warmth; however, it is not currently known whether opioids mediate affiliative behavior and emerging feelings of closeness in humans at the relationship initiation stage. This randomized, double-blind study examined opioidergic processes in the context of a naturalistic, face-to-face social interaction. Eighty pairs of unacquainted participants (final N = 159 due to removal of one dyad member from analysis) received either 50 mg of the opioid receptor antagonist naltrexone or placebo prior to completing a closeness-building exercise centered on escalating self-disclosure (sharing of personal information about the self). Compared to the placebo group, naltrexone participants held lower social reward expectations prior to the interaction, engaged in less intimacy-fostering behavior (self-disclosure) during the interaction, and reported wanting less closeness with their partner. Feelings of social connection were not significantly lower in the naltrexone group. However, placebo participants experienced improvements in mood after the closeness-building task whereas naltrexone participants did not. These findings suggest that endogenous opioids may contribute to behavioral, affective, and motivational processes related to the development of initial closeness.

    更新日期:2019-12-20
  • Testosterone replacement causes dose-dependent improvements in spatial memory among aged male rats
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-19
    Eliza C.B. Jaeger; L. Erin Miller; Emily C. Goins; Chloe E. Super; Christina U. Chyr; John W. Lower; Lauren S. Honican; Daryl E. Morrison; Rajan A. Ramdev; Mark D. Spritzer

    Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the mechanism by which testosterone regulates memory is unknown, but may involve changes in brain-derived neurotrophic factor (BDNF) within specific brain regions. We tested the effects of age and testosterone on spatial memory among male rats using two spatial memory tasks: an object-location memory task (OLMT) and the radial-arm maze (RAM). Castration had minimal effect on performance on the RAM, but young rats (2 months) performed significantly fewer working memory errors than aged rats (20 months), and aged rats performed significantly fewer reference memory errors. Both age and castration impaired performance on the OLMT, with only the young rats with intact gonads successfully performing the task. Subsequent experiments involved daily injections of either drug vehicle or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) given to castrated aged males. On the RAM, a low physiological dose (0.125 mg) and high doses (0.500-1.000 mg) of testosterone improved working memory, while an intermediate dose (0.250 mg) did not. On the OLMT, only the 0.250 mg T group showed a significant increase in exploration ratios from the exposure trials to the testing trials, indicating that this group remembered the position of the objects. Brain tissue (prefrontal cortex, hippocampus, and striatum) was collected from all subjects to assay BDNF. We found no evidence that testosterone influenced BDNF, indicating that it is unlikely that testosterone regulates spatial memory through changes in BDNF levels.

    更新日期:2019-12-19
  • Remote CB1 receptor antagonist administration reveals multiple sites of tonic and phasic endocannabinoid neuroendocrine regulation
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-19
    R.J. Newsom; R.J. Garcia; J. Stafford; C. Osterlund; C.E. O’Neill; H.E.W. Day; S. Campeau

    Endogenous cannabinoids (endocannabinoids, eCB) are expressed throughout the body and contribute to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and general stress reactivity. This study assessed the contributions of CB1 receptors (CB1R) in the modulation of basal and stress-induced neural and HPA axis activities. Catheterized adult male rats were placed in chambers to acclimate overnight, with their catheters connected and exteriorized from the chambers for relatively stress-free remote injections. The next morning, the CB1R antagonist AM251 (1 or 2 mg/kg) or vehicle was administered, and 30 minutes later, rats were exposed to loud noise stress (30 minutes) or no noise (basal condition). Blood, brains, pituitary and adrenal glands were collected immediately after the procedures for analysis of c-fos and CB1R mRNAs, corticosterone (CORT) and adrenocorticotropin hormone (ACTH) plasma levels. Basally, CB1R antagonism induced c-fos mRNA in the basolateral amygdala (BLA) and auditory cortex (AUD) and elevated plasma CORT, indicating disruption of eCB-mediated constitutive inhibition of activity. CB1R blockade also potentiated stress-induced hormone levels and c-fos mRNA in several regions such as the bed nucleus of the stria terminalis (BST), lateral septum (LS), and basolateral amygdala (BLA) and the paraventricular nucleus of the hypothalamus (PVN). CB1R mRNA was detected in all central tissues investigated, and the adrenal cortex, but at very low levels in the anterior pituitary gland. Interestingly, CB1R mRNA was rapidly and bidirectionally regulated in response to stress and/or antagonist treatment in some regions. eCBs therefore modulate the HPA axis by regulating both constitutive and activity-dependent inhibition at multiple levels.

    更新日期:2019-12-19
  • Biological stress response in women at risk of postpartum psychosis: the role of life events and inflammation
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-19
    Monica Aas; Costanza Vecchio; Astrid Pauls; Mitul Mehta; Steve Williams; Katie Hazelgrove; Alessandra Biaggi; Susan Pawlby; Susan Conroy; Gertrude Seneviratne; Valeria Mondelli; Carmine M. Pariante; Paola Dazzan

    Background Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth, and the risk is particularly high in women with a history of bipolar disorder, schizoaffective disorder or in those who have suffered previous episodes of PP. While studies in patients with psychosis not related to the puerperium have demonstrated that abnormalities in stress response are important risk factors for psychosis, it remains unknown whether this is also the case for PP. Methods This study includes 30 postpartum women, assessed, on average, at postpartum week 14.8 ± 10.1 either with a current episode of PP (n = 14), or at-risk of PP because of a history of bipolar/schizoaffective disorder but who were well (n = 16), and a group of healthy women (n = 26). Details about recent stressful life events were obtained using the List of Threatening Experiences questionnaire, while perceived stress was evaluated using the Perceived Stress Scale. We estimated hypothalamic-pituitary adrenal (HPA) activity by measuring salivary cortisol at awakening; at 15, 30, and 60 minutes after awakening; at noon; and at 8 pm. An Area Under the Curve analysis was performed to assess the awakening response (AUCi) and cortisol levels during the day (AUCg). Immune markers, including high sensitivity C-Reactive Protein (hs-CRP) and Interleukin (IL)-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, Tumor Necrosis Factor (TNFa), Vascular Endothelial Growth Factor (VEGF), Interferon gamma (INFγ), Monocyte Chemoattractant Protein 1 (MCP-1), and Epidermal Growth Factor (EGF) were evaluated from peripheral blood samples. Results Women with current PP reported more frequent recent stressful life events, and higher perceived stress than healthy women. They also showed an activation of the stress and immune response, with higher levels of cortisol AUCg and hs-CRP (but not of other inflammatory markers) than healthy controls. Women at-risk of PP who remained well had values on these measures that were intermediate between those of women with a current episode of PP and those of healthy women. Stress measures and markers of stress and immune response explained 78% of the variance of in group status between PP and healthy women, and 46% of variance of in group status between women at-risk and healthy women. Conclusion These findings suggest that an immune-HPA axis dysregulation, together with current stress may represent an important underlying pathophysiological mechanism in the onset of psychosis after childbirth in vulnerable women.

    更新日期:2019-12-19
  • Exogenous testosterone increases status-seeking motivation in men with unstable low social status
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-19
    A.B. Losecaat Vermeer; I. Krol; C. Gausterer; B. Wagner; C. Eisenegger; C. Lamm

    Testosterone is associated with status-seeking behaviors such as competition, which may depend on whether one wins or loses status, but also on the stability of one’s status. We examined (1) to what extent testosterone administration affects competition behavior in repeated social contests in men with high or low rank, and (2), whether this relationship is moderated by hierarchy stability, as predicted by the status instability hypothesis. Using a real effort-based design in healthy male participants (N = 173 males), we first found that testosterone (vs. placebo) increased motivation to compete for status, but only in individuals with an unstable low status. A second part of the experiment, tailored to directly compare stable with unstable hierarchies, indicated that exogenous testosterone again increased competitive motivation in individuals with a low unstable status, but decreased competition behavior in men with low stable status. Additionally, exogenous testosterone increased motivation in those with a stable high status. Further analysis suggested that these effects were moderated by individuals’ trait dominance, and genetic differences assessed by the androgen receptor (CAG-repeat) and dopamine transporter (DAT1) polymorphisms. Our study provides evidence that testosterone specifically boosts status-related motivation when there is an opportunity to improve one’s social status. The findings contribute to our understanding of testosterone’s causal role in status-seeking motivation in competition behavior, and indicate that testosterone adaptively increases our drive for high status in a context-dependent manner. We discuss potential neurobiological pathways through which testosterone may attain these effects on behavior.

    更新日期:2019-12-19
  • Hair cortisol as a biomarker of stress and resilience in South African mixed ancestry females
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-17
    Leigh Luella van den Heuvel; Debbie Acker; Stéfan du Plessis; Tobias Stalder; Sharain Suliman; Marguerite Yvonne Thorne; Clemens Kirschbaum; Soraya Seedat

    Background Hair cortisol concentrations (HCC) are increasingly used as a biomarker of stress, however limited research exists regarding the relationship between HCC and protective factors, such as resilience. Additionally, studies measuring HCC need to account for possible confounders, and these factors have not been examined in sufficiently diverse settings. Objectives Our objectives were to identify determinants of HCC in a sample of mixed ancestry adults and investigate the association of HCC with measures of self-perceived stress and resilience. Methods Our sample comprised 164 females (mean age 46.5 years, SD = 15.0), self-identifying as mixed ancestry, who were control participants in a cross sectional case-control study (SHARED ROOTS), conducted in Cape Town, South Africa from May 2014 until June 2017. We examined which socio-demographic, hair related, clinical and behavioural factors were associated with HCC in both unadjusted and adjusted linear regression models. Furthermore, the relationship of HCC with self-perceived stress and resilience scores were also examined. Results HCC (Mdn 4.4 pg/ml; IQR 2.8; 11.4) were significantly positively associated with hair product use and breastfeeding, and significantly negatively associated with age, level of education, duration of sun exposure, duration of storage, and demonstrated a trend towards significance with frequency of hair washing, in adjusted models. HCC were inversely associated with CD-RISC scores (adj β = -0.179, p = 0.012) scores but were not significantly associated with PSS scores (adj β = -0.001, p = 0.989). Conclusions We identified specific determinants of HCC in our sample, including the first indication that sun exposure has an effect on HCC under naturalistic conditions. These potential confounders need to be controlled for in the design and analysis of future studies. HCC may be a biomarker of resilience to stress, rather than perceived stress. Further research measuring HCC in more diverse settings and populations and including constructs related to resilience are needed.

    更新日期:2019-12-18
  • Use of an estradiol-based combined oral contraceptives has no influence on attentional bias or depressive symptoms in healthy women
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-16
    Andrea Scheuringer; Cecilia Lundin; Birgit Derntl; Belinda Pletzer; Inger Sundström Poromaa

    Combined oral contraceptive (COC) use is associated with small, albeit significant, increases in mental symptom scores, predominantly irritability, depressed mood, and anxiety. Yet, randomized prospective trials are needed to better characterize the women at risk for COC-induced negative mood change. Thus, the primary aim of this sub-study to a placebo-controlled randomized trial was to determine whether COC use influences emotional interference by negative and positive stimuli. Secondly, we wanted to evaluate what factors would predict depressive symptoms at the end of the trial, taking personality factors, history of mental disorders and other demographic factors into account. Sixty-nine women were included, randomized to three cycles of treatment with a COC (1.5 mg estradiol and 2.5 mg nomegestrolacetate) or placebo. An emotional verbal Stroop task was used to measure interference of emotional stimuli, in which participants were asked to only name the color of a presented word, while ignoring the meaning of the word. Four different word categories were used; neutral, positive, depression, and anxiety. For the second aim of the study, rating on the Montgomery-Åsberg Depression Rating Scale during the final days of the trial was used as outcome. We found no interaction between emotional verbal Stroop word category and treatment, indicating that COC treatment did not evoke any differences in emotional interference to the three word categories. Significant predictors for depressive symptoms at the end of the trial were trait anxiety at baseline and prior adverse mood effects by hormonal contraceptive use. Treatment (i.e. whether women had been treated with the COC or placebo) did not play a role in predicting depression scores at the end of the trial. In conclusion, we found no evidence that combined oral contraceptive use is associated with impaired cognitive-emotional processing. Instead, the main predictors of self-rated depression at the end of the trial were baseline trait anxiety and previous mental symptoms during hormonal contraceptive use.

    更新日期:2019-12-17
  • Regulation of defeat-induced social avoidance by medial amygdala DRD1 in male and female prairie voles
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-16
    Maria C. Tickerhoof; Luanne H. Hale; Michael J. Butler; Adam S. Smith

    Social interaction with unfamiliar individuals is necessary for species-preserving behaviors such as finding mates and establishing social groups. However, social conflict is a potential negative outcome to interaction with a stranger that can be distressing enough to cause an individual to later avoid interactions with other unfamiliar conspecifics. Unfortunately, stress research using a prominent model of social conflict, social defeat stress, has largely omitted female subjects. This has left a void in the literature regarding social strain on female stress biology and adequate comparison of the effect of sex in stress pathways. The prairie vole (Microtus ochrogaster) exhibits aggressive behavior in both sexes, making voles an attractive candidate to model social defeat in both sexes. This study sought to establish a model of social defeat stress in both male and female prairie voles, characterize behavioral changes in response to this stressor, and investigate the role of dopamine signaling in the response to social defeat stress. Defeated male and female prairie voles displayed social avoidance as well as an increase in expression of dopamine receptor D1 (DRD1) in the medial amygdala (MeA). Pharmacological manipulation of DRD1 signaling in the MeA revealed that increased DRD1 signaling is sufficient to induce a social avoidant state, and could be a necessary component in the defeat-induced social avoidance response. These findings provide the prairie vole as a model of social defeat in both sexes, and implicate the MeA in avoidance of unfamiliar conspecifics after a distressing social encounter.

    更新日期:2019-12-17
  • ALLOSTATIC OVERLOAD IN PATIENTS WITH ESSENTIAL HYPERTENSION
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-16
    Jenny Guidi; Marcella Lucente; Antonio Piolanti; Renzo Roncuzzi; Chiara Rafanelli; Nicoletta Sonino

    The role of psychosocial stress in the development of essential hypertension has attracted increasing attention in the last decades, even though research findings have been often inconclusive. We specifically investigated allostatic overload (AO) in hypertensive patients using a clinimetric approach. Allostatic overload was assessed by a semi-structured research interview based on clinimetric criteria in 80 consecutive outpatients with essential hypertension (46.3% females; mean age 62.18 ± 8.59 years; age range 47-74 years) and 80 normotensive matched controls. Three clinical interviews and two self-rating questionnaires for assessing psychological distress and well-being were also administered. Cardiac variables were collected.AO was present in 26 (32.5%) of the hypertensive patients based on clinical interviewing, and in only 6 normotensive controls (p < .001). Hypertensive patients with AO had significantly higher levels of psychological distress than those without. Further, patients with AO displayed significantly lower levels of well-being and quality of life (p < .001). A significantly greater prevalence of psychosomatic syndromes was found to be associated with the presence of AO (p < .05), whereas no significant association was detected as to psychiatric diagnoses. Significantly greater cardiovascular risk was found among hypertensive patients reporting AO compared to those without (p < .05). The results of this study support the clinical relevance of a psychological assessment of hypertensive patients, with important implications for the non-pharmacological management of hypertension.

    更新日期:2019-12-17
  • LC-MS/MS-based Reference Intervals for Hair Cortisol in Healthy Children
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-06
    Ineke de Kruijff, Gerard Noppe, Noera Kieviet, Vandhana Choenni, Mijke P Lambregtse-van den Berg, Dominique G.A. Begijn, Ellen Tromp, Kristien Dorst, Elisabeth F.C. van Rossum, Yolanda. B. de Rijke, Erica L.T. van den Akker

    Background Human scalp hair is a valuable matrix for determining long-term cortisol concentrations, with wide-spread applicability in clinical care as well as research. However, pediatric reference intervals are lacking. The aim of this cross-sectional study is to establish age-adjusted reference intervals for hair cortisol in children and to gain insight into hair growth velocity in children up to 2 years old. Methods A total of 625 healthy children were enrolled through recruitment in pregnancy, infant-welfare clinics, and school visits. Scalp hair cortisol levels were measured using liquid chromatography-tandem mass spectrometry. Age-adjusted reference intervals were established in children from birth to 18 years old. Hair growth velocity was determined in children 0-2 years of age by measuring hair length at 4- to 10-week intervals. Results Hair cortisol levels were high (162.4 pg/mg, 2.5th-97.5th percentile: 28.8-961) after birth with a sharp fall in the first 3 months of life. This is followed by lower values until age 6 and then by graduated and subtle higher values to adult concentrations are reached at the age of 18 years (3.0 pg/mg, 2.5th-97.5th percentile: 0.53-17.8). Average hair growth velocity measured in mm/month was significantly lower in infants 0–6 months of age compared to children 12–24 months (3.5 versus 9.4, P < 0.001). Conclusions This is the first study to provide age-adjusted reference intervals for hair cortisol in children from 0-18 years. Higher hair cortisol concentrations in infants might be explained by the significantly lower hair growth rate in the first year of life. The establishment of pediatric hair cortisol reference ranges broadens the potential applications of this biomarker in pediatric clinical care.

    更新日期:2019-12-07
  • Pituitary dysmaturation affects psychopathology and neurodevelopment in 22q11.2 Deletion Syndrome
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-06
    Corrado Sandini, Maëlle Chambaz, Maude Schneider, Marco Armando, Daniela Zöller, Marie Schaer, Carmen Sandi, Dimitri Van De Ville, Stephan Eliez

    Background 22q11.2 Deletion Syndrome (22q11DS) confers strongly increased genetic risk for multiple psychiatric disorders. Similarly to the general population, rates of psychiatric comorbidity suggest that common disease mechanisms are shared across dimensions of psychopathology. Such pleiotropic disease mechanisms remain however currently unknown. We hypothesized that pituitary dysmaturation, indicative of HPA-axis dysregulation, could correlate to reduced tolerance to daily life stressors and reflect pleiotropic risk factor for psychopathology. Moreover HPA-axis dysregulation could affect atypical cortical and hippocampal development previously described in 22q11DS. Methods Pituitary volume, hippocampal volume and cortical thickness measures were obtained from T1-weighted MRI images in a large longitudinal cohort of youth with 22q11DS (115 subjects, 260 scans, age-range = 5.4-31.6 ) and healthy controls (151 subjects, 280 scans, age-range = 5.1-32.3). We explored effects of pituitary dysmaturation on tolerance to stress, psychopathology and neurodevelopment employing mixed-models linear regression. Associations of pituitary and cortical development were correlated with the expression pattern of glucocorticoid receptor gene NR3C1 obtained from the Allen-Human-Brain-Atlas. Results We observed aberrant pituitary developmental trajectories in 22q11DS, with volumetric reductions emerging by young-adulthood (P = 0.0006). Longitudinal pituitary decline was associated with to reduced tolerance to stress (P = 0.04), higher overall psychopathology (P = 0.0003) and increased risk of psychiatric comorbidity (P = 0.02). Moreover, pituitary decline correlated with blunted growth of the right hippocampus (P = 0.03) and to increased cortical thinning of mostly temporal and orbitofrontal regions mediated by NR3C1 gene expression. Conclusion Atypical pituitary development could reflect progressive extinction of HPAA due to chronic hyper-activation, in agreement with existing biochemical evidence in 22q11DS. HPAA dysregulation could represent and endophenotype that confers pleiotropic vulnerability to psychopathology and atypical neurodevelopment in 22q11DS.

    更新日期:2019-12-07
  • Serum Oxytocin Levels Are Elevated in Body Dysmorphic Disorder and Related to Severity of Psychopathology
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-06
    Angela Fang, Ryan J. Jacoby, Clare Beatty, Laura Germine, Franziska Plessow, Sabine Wilhelm, Elizabeth A. Lawson

    The neurobiological mechanisms underlying the pathophysiology of body dysmorphic disorder (BDD) are not well-understood. Oxytocin is a central nervous system peptide which regulates socioemotional functioning and may mediate physiologic processes in a range of psychiatric disorders, particularly those characterized by interpersonal dysfunction. Examining the role of oxytocin in the development and maintenance of BDD may elucidate new targets for intervention. The present study examined endogenous serum oxytocin levels in BDD. Given the prominent deficits in social functioning in BDD, we expected that BDD would be characterized by low basal serum oxytocin concentrations, relative to healthy controls, and that low oxytocin levels would be associated with BDD symptom severity as well as poor performance on measures of social cognition. Twenty individuals with BDD and 28 healthy controls completed a fasting blood draw consisting of frequent sampling every five minutes for one hour to measure pooled levels of oxytocin. Contrary to our hypotheses, people with BDD displayed higher concentrations of oxytocin, compared to their healthy control counterparts, and their oxytocin levels were positively correlated with BDD symptom severity. There were no associations between oxytocin levels and measures of social cognition. These findings suggest increased production of endogenous oxytocin in BDD. Prospective research is needed to determine whether this contributes to or is a consequence of BDD symptomatology.

    更新日期:2019-12-07
  • The glucocorticoid receptor in the nucleus accumbens plays a crucial role in social rank attainment in rodents
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-03
    Aurélie Papilloud, Meltem Weger, Alexandre Bacq, Ioannis Zalachoras, Fiona Hollis, Thomas Larrieu, Dorian Battivelli, Jocelyn Grosse, Olivia Zanoletti, Sébastien Parnaudeau, François Tronche, Carmen Sandi

    Social hierarchy in social species is usually established through competitive encounters with conspecifics. It determines the access to limited resources and, thus, leads to reduced fights among individuals within a group. Despite the known importance of social rank for health and well-being, the knowledge about the processes underlying rank attainment remains limited. Previous studies have highlighted the nucleus accumbens (NAc) as a key brain region in the attainment of social hierarchies in rodents. In addition, glucocorticoids and the glucocorticoid receptor (GR) have been implicated in the establishment of social hierarchies and social aversion. However, whether GR in the NAc is involved in social dominance is not yet known. To address this question, we first established that expression levels of GR in the NAc of high anxious, submissive-prone rats are lower than that of their low anxious, dominant-prone counterparts. Furthermore, virally-induced downregulation of GR expression in the NAc in rats led to an improvement of social dominance rank. We found a similar result in a cell-specific mouse model lacking GR in dopaminoceptive neurons (i.e., neurons containing dopamine receptors). Indeed, when cohabitating in dyads of mixed genotypes, mice deficient for GR in dopaminoceptive neurons had a higher probability to become dominant than wild-type mice. Overall, our results highlight GR in the NAc and in dopaminoceptive neurons as an important regulator of social rank attainment.

    更新日期:2019-12-03
  • Childhood trauma and glucose metabolism in patients with First-Episode Psychosis
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-12-03
    Sarah Tosato, Chiara Bonetto, Simona Tomassi, Roberta Zanardini, Carlo Faravelli, Caterina Bruschi, Armando D’Agostino, Alessandra Minelli, Paolo Scocco, Antonio Lasalvia, Karin Furlato, Massimiliano Imbesi, Antonio Preti, Mirella Ruggeri, Massimo Gennarelli, Luisella Bocchio Chiavetto

    Although the associations between first-episode psychosis (FEP) and metabolic abnormalities on one side, and childhood trauma (CT) and risk of developing psychosis on the other are both well established, evidence on the relationship between CT and metabolic dysregulation in terms of abnormal glucose metabolism is very limited. We tested whether, already at illness onset, FEP patients with a history of CT show dysregulation of a broad range of glucose metabolism markers. In particular, in 148 FEP patients we evaluated serum concentrations of c-peptide, insulin, plasminogen-activator-inhibitor–1 (PAI-1), resistin, visfatin, glucagon, glucagon-like peptide-1 (GLP-1), gastric-inhibitor-peptide (GIP), leptin, and ghrelin. We also assessed CT with the Childhood Experience of Care and Abuse Questionnaire, and stressful life events (SLEs) with a semi-structured interview. Psychopathology, cannabis and tobacco habits, Body Mass Index (BMI) were recorded. Serum concentrations of markers were analyzed from peripheral blood. Ninety-five patients (56% males, mean age 29.5) reported CT. Multivariate models showed that CT is associated only with the concentrations of c-peptide and insulin after adjusting for age, sex, BMI and SLEs. FEP patients who had experienced CT showed higher c-peptide and insulin serum concentrations. Our study reports that CT might be associated with the metabolic abnormalities in the first stage of psychosis, suggesting that a thorough anamnestic evaluation at psychosis onset that would include the history of CT could be helpful for clinicians in order to implement early programmes of healthy lifestyle education and to guide choice of therapeutic interventions for trauma.

    更新日期:2019-12-03
  • Plasma luteinizing hormone level affects the brain activity of patients with polycystic ovary syndrome
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-28
    Wanlin Lai, Xuan Li, Huili Zhu, Xi Zhu, Huiwen Tan, Peimin Feng, Lei Chen, Cheng Luo

    Objective Cognitive function has been reported to be impaired in women with polycystic ovary syndrome (PCOS). This study aimed to investigate the effect of PCOS on brain activity and explore the relationship between brain activity and sex hormone levels in women with PCOS (WPCOS). Methods Twenty-one women aged 18 to 45 years old with new-diagnosed PCOS were enrolled. Plasma levels of six sex hormones including luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were tested during the 2-5 days of their menstrual periods. Twenty-seven healthy controls (HC) were recruited. Every subject underwent a resting-state functional magnetic resonance imaging (fMRI). The amplitude of low-frequency fluctuation (ALFF) of the whole brain was evaluated followed by the functional connectivity (FC) analysis. Finally, the correlation between the ALFF, FC of the significant areas and the plasma hormone levels were analyzed. Results The patients showed increased ALFF value in the left inferior temporal gyrus (ITG.L) and decreased ALFF value in the left inferior occipital gyrus (IOG.L) as well as the superior frontal gyrus (SFG.R, P < 0.005). For the FC analysis, patients showed decreased FC in SFG.R with the right middle frontal gyrus (MFG.R, P < 0.05). The FC between SFG.R and MFG.R was negatively correlated with LH level (R=-0.594, P = 0.005) and with the LH/FSH ratio (R=-0.521, P = 0.015). Conclusion PCOS can induce changes in activities of brain regions responsible for visuospatial working memory, face processing and episodic memory. The reduced functional connectivity within the right frontal lobe is related with the high LH level in WPCOS.

    更新日期:2019-11-29
  • Morning and evening type: The cortisol awakening response in a sleep laboratory
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-20
    Katja Petrowski, Bjarne Schmalbach, Tobias Stalder

    Background Earlier evidence indicated an association between chronotype and the cortisol awakening response (CAR). However, these earlier data were collected without objective control for participant compliance being available, which, following recent guidelines, is considered critical for ensuring data validity. Here, we are seeking to replicate these earlier findings within a well-controlled sleep laboratory set up. Methods The sample consisted of 103 young males, including 12 participants defined as ‘evening’ (MEQ < 41) and 20 participants defined as ‘morning type’ (MEQ > 59) types. All participants slept for one night in a sleep laboratory and were wakened at 6:30 AM the next morning. Saliva samples for the assessment of the CAR were collected under strict supervision at 0, 15, and 30 min post-awakening. Results Significant effects of chronotype emerged consistently from both dimensional analyses across the entire sample and from comparisons between morning vs. evening type. Overall, greater morningness was associated with an increased cortisol level upon awakening (S1) as well as with a greater overall cortisol output (AUCG), however, it was not associated with the CAR (AUCI). Discussion Our data corroborate earlier evidence by showing that, under well-controlled sleep-laboratory conditions, chronotype is related to an altered cortisol secretion over the post-awakening period with no association with the CAR. However, the results have to be replicated since it is only a single day study design.

    更新日期:2019-11-21
  • Reward-related brain activity and behavior are associated with peripheral ghrelin levels in obesity
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-20
    Volodymyr B. Bogdanov, Olena V. Bogdanova, Sandra Dexpert, Ines Delgado, Helen Beyer, Agnès Aubert, Bixente Dilharreguy, Cédric Beau, Damien Forestier, Patrick Ledaguenel, Eric Magne, Bruno Aouizerate, Sophie Layé, Guillaume Ferreira, Jennifer Felger, Giuseppe Pagnoni, Lucile Capuron

    Background/Objectives While excessive food consumption represents a key factor in the development of obesity, the underlying mechanisms are still unclear. Ghrelin, a gut-brain hormone involved in the regulation of appetite, is impaired in obesity. In addition to its role in eating behavior, this hormone was shown to affect brain regions controlling reward, including the striatum and prefrontal cortex, and there is strong evidence of impaired reward processing in obesity. The present study investigated the possibility that disrupted reward-related brain activity in obesity relates to ghrelin deficiency. Subjects/Methods Fifteen severely obese subjects (BMI > 35 kg/m2) and fifteen healthy non-obese control subjects (BMI < 30 kg/m2) were recruited. A guessing-task paradigm, previously shown to activate the ventral striatum, was used to assess reward-related brain neural activity by functional magnetic resonance imaging (fMRI). Fasting blood samples were collected for the measurement of circulating ghrelin. Results Significant activations in the ventral striatum, ventromedial prefrontal cortex and extrastriate visual cortex were elicited by the fMRI task in both obese and control subjects. In addition, greater reward-related activations were present in the dorsolateral prefrontal cortex, and precuneus/posterior cingulate of obese subjects compared to controls. Obese subjects exhibited longer choice times after repeated reward and lower circulating ghrelin levels than lean controls. Reduced ghrelin levels significantly predicted slower post-reward choices and reward-related hyperactivity in dorsolateral prefrontal cortices in obese subjects. Conclusion This study provides evidence of association between circulating ghrelin and reward-related brain activity in obesity and encourages further exploration of the role of ghrelin system in altered eating behavior in obesity.

    更新日期:2019-11-20
  • No association between anti-thyroidperoxidase antibodies and bipolar disorder A study in the Dutch Bipolar Cohort and a meta-analysis
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-16
    G.J.L.J. Snijders, L.D. de Witte, D. van den Berk, C. van der Laan, E. Regeer, M. Begemann, A. Berdenis van Berlekom, M. Litjens, M.P. Boks, R.A. Ophoff, R.S. Kahn, M.H.J. Hillegers

    Background Thyroid autoimmunity has been associated with bipolar disorder (BD). However, results from previous studies on the seroprevalence of anti-thyroid peroxidase antibodies (TPO-abs) in BD are inconsistent. Objectives The aim of the present study is to investigate whether the seroprevalence and titer levels of TPO-abs are related to BD. Method TPO-abs were measured in plasma samples of 760 patients with bipolar disorder, 261 first-degree relatives and 363 controls by enzyme-linked immunosorbent assay (ELISA). To address methodological limitations of previous studies, we assessed clinical characteristics with several (self-reported) questionnaires to investigate whether TPO-abs positivity is related to particular clinical subgroups of BD patients. We performed an additional meta-analysis of seroprevalences of TPO-abs in BD patients including data from present and previous studies. Results Seroprevalence or titer levels of TPO-abs did not significantly differ between patients with BD, their first-degree relatives, and controls. In BD patients, the prevalence of TPO-abs was unrelated to specific clinical factors, including lithium use. Our meta-analysis of twelve studies showed an overall odds ratio of 1.3 (CI 95%: 0.7–2.3; p = 0.30), reaffirming the absence of an association of BD with TPO-abs. Conclusions In the largest study of TPO-abs in BD to date, our findings indicate that TPO-abs are not associated with (the risk for) bipolar disorder.

    更新日期:2019-11-18
  • The association between abuse history in childhood and salivary rhythms of cortisol and DHEA in postmenopausal women
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-14
    Olivia R. Orta, Tianyi Huang, Laura D. Kubzansky, Kathryn L. Terry, Brent A. Coull, Michelle A. Williams, Shelley S. Tworoger

    A history of child abuse (CA) is associated with morbidity and mortality in adulthood, and one proposed mechanism is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we evaluated whether a history of physical and sexual CA was associated with daily rhythms of HPA hormones (cortisol and dehydroepiandrosterone (DHEA)) among postmenopausal women (mean age: 60.6 years). In 2013, 233 participants from the Nurses’ Health Study II provided up to 5-timed saliva samples over the course of a day: immediately upon awakening, 45 minutes, 4 hours, and 10 hours after waking, and prior to going to sleep. Among these 233 participants, 217 provided ≥4 timed saliva samples. Assessment of physical and sexual CA history occurred in 2001 using the Revised Conflict Tactics Scale. Cumulative CA history was derived by combining reports of physical and sexual abuse prior to age 18. Piecewise linear mixed models compared diurnal rhythms of cortisol and DHEA between participants with none-to-moderate CA (n = 104, reference group) versus high-to-severe CA (n = 113). Models adjusted for characteristics at each saliva collection, health status, sleep quality, medications, and hormone use. Compared to those with none-to-moderate CA, women with high-to-severe CA had different diurnal rhythms in the early and evening hours, including blunted (less steep) early declines in DHEA (% difference (%D) = 10.7, 95% CI 4.3, 17.5), and steeper evening declines in both cortisol and DHEA (cortisol %D = -2.5, 95% CI -4.8, -0.1, and DHEA %D= -3.9, 95% CI -6.0, -1.8). In conclusion, high-to-severe abuse history prior to age 18 was more strongly associated with differences in DHEA rather than cortisol, suggesting that early life abuse may be related to dysregulation of stress-response mechanisms later in life.

    更新日期:2019-11-14
  • Increased interleukin 18 activity in adolescents with early-onset psychosis is associated with cortisol and depressive symptoms
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-14
    Kirsten Wedervang-Resell, Svein Friis, Vera Lonning, Runar E. Smelror, Cecilie Johannessen, Elina J. Reponen, Siv H. Lyngstad, Tove Lekva, Pål Aukrust, Thor Ueland, Ole A. Andreassen, Ingrid Agartz, Anne M. Myhre

    Objective Evidence indicates that the pathophysiology of adult psychosis involves immune dysregulation, but its associations with stress are often not considered. The inflammatory cytokine interleukin (IL)-18, which is elevated in adult schizophrenia, is suggested to be sensitive to stress. We compared the associations of IL-18 with cortisol and clinical variables in adolescents with early-onset psychosis (EOP) aged 12–18 years and age-matched healthy controls (HC). Method We measured serum IL-18, IL-18 binding protein (IL-18BP), IL-18 receptor accessory protein (IL-18RAP), IL-18 receptor 1 (IL-18R1) and cortisol, and calculated the IL-18/IL-18BP ratio in patients (n = 31) and HC (n = 60). Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale and depressive symptoms by the Mood and Feelings Questionnaire-Child version (MFQ-C). Bivariate correlation analysis was used to explore relationships between IL-18/IL-18BP ratio and cortisol, depression and other clinical characteristics. Hierarchical multiple linear regression analysis was used to assess their individual contributions to the variance of the IL-18/IL-18BP ratio. Results Patients had significantly higher IL-18 levels and IL-18/IL-18BP ratios than HC, but similar IL-18BP, IL-18RAP and IL-18R1. Both cortisol (R2 change = 0.05) and the MFQ-C score (R2 change = 0.09) contributed significantly to the variance in IL-18/IL-18BP ratios after controlling for confounders. Conclusion We found increased IL-18 system activity in adolescents with EOP. Cortisol and depressive symptoms each contributed to the variance in the IL-18/IL-18BP ratio. Our findings support activation of inflammatory pathways in adolescent psychosis and suggest interactions between stress, inflammation and depressive symptoms in EOP.

    更新日期:2019-11-14
  • Daytime Melatonin Levels in Saliva are Associated with Inflammatory Markers and Anxiety Disorders
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-14
    Isak Sundberg, Annica J. Rasmusson, Mia Ramklint, David Just, Lisa Ekselius, Janet L. Cunningham

    Background The bidirectional interaction between melatonin and the immune system has largely gone unexplored in a clinical context and especially in a psychiatric population. This study explored the association between melatonin during the day and inflammatory cytokines in young adult patients seeking psychiatric care. Methods Samples and data were collected from 108 young adults (mean age 21, SD = 2) at an outpatient clinic for affective disorders. Daytime saliva melatonin levels were analyzed with enzyme-linked immunosorbent assay (ELISA) in relation to normalized serum expression levels of 72 inflammatory markers in a proximity extension assay (PEA). In a post hoc analysis the markers associated with melatonin were tested in a generalized linear model to see whether there is a relationship to anxiety disorder or depression. Results After Bonferroni correction for multiple testing, melatonin levels at 11:00 were positively correlated with CD5 (p = 4.2e-4). Melatonin levels after lunch were correlated with CCL2/MCP-1 (p = 4.2e-4), CCL3/MPI-1α (p = 6.5e-4) and VEGF-A (p = 5.3e-6). In the generalized linear model, positive associations were found for the presence of any anxiety disorder with melatonin after lunch (p = 0.046), VEGF-A (p = 0.001) and CCL3/MPI-1α (p = 0.001). Conclusion Daytime saliva levels of melatonin were related to several inflammatory markers in young adults with psychiatric disorders. This observation likely reflects the bidirectional relationship between melatonin production and the immune system. These findings may have relevance for the understanding of psychiatric disorders and other conditions associated with low-grade inflammation.

    更新日期:2019-11-14
  • The Allopregnanolone to Progesterone Ratio Across the Menstrual Cycle and in Menopause
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-14
    Allison Kimball, Laura E. Dichtel, Maren B. Nyer, David Mischoulon, Lauren B. Fisher, Cristina Cusin, Christina M. Dording, Nhi-Ha Trinh, Albert Yeung, Melanie S. Haines, Joshua C. Sung, Graziano Pinna, Ann M. Rasmusson, Linda L. Carpenter, Maurizio Fava, Anne Klibanski, Karen Klahr Miller

    The neuroactive steroid 3α-5α-tetrahydroprogesterone (allopregnanolone), a metabolite of progesterone, is a positive allosteric modulator of GABAA receptors, and low levels have been implicated in the etiology of mood disorders. However, it is not known whether metabolism of progesterone to allopregnanolone varies across the menstrual cycle or is low after menopause. We hypothesized that the allopregnanolone/progesterone ratio would decrease from the follicular to luteal phase. We also hypothesized that postmenopausal women would have lower levels of progesterone and allopregnanolone but similar allopregnanolone/progesterone ratios as premenopausal women in the follicular phase. Serum fasting allopregnanolone and progesterone levels were measured by gas chromatography-mass spectrometry in ten premenopausal women at the follicular, mid-cycle, and luteal phases of the menstrual cycle and in twenty-four postmenopausal women. Although allopregnanolone and progesterone levels increased from the follicular to luteal phase, the allopregnanolone/progesterone ratio decreased 8-fold [0.33 ± 0.08 (follicular) vs 0.16 ± 0.09 (mid-cycle) vs 0.04 ± 0.007 (luteal), p = 0.0003]. Mean allopregnanolone and progesterone levels were lower in postmenopausal than premenopausal women at all menstrual cycle phases (p < 0.01). The mean allopregnanolone/progesterone ratio was similar in postmenopausal and premenopausal women in the follicular phase (0.39 ± 0.08 vs 0.33 ± 0.08, p = 0.94) but was significantly lower at mid-cycle and in the luteal phase than in postmenopausal women (p < 0.01). In conclusion, the serum allopregnanolone/progesterone ratio decreases 8-fold from the follicular to luteal phase and is lower at mid-cycle and the luteal phase than in postmenopausal women. Whether these data have implications for luteal phase and other mood disorders merits further study.

    更新日期:2019-11-14
  • Going the Distance: The Diurnal Range of Cortisol and its Association with Cognitive and Physiological Functioning
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-14
    Susan T. Charles, Jacqueline Mogle, Jennifer Piazza, Arun Karlamangla, David M. Almeida

    Cortisol features prominently in theories describing how chronic stress wears away at physical and cognitive health. The current study examines composite measures of physiological and cognitive functioning in relation to two aspects of daily cortisol: total daily output and change in levels throughout the day. Participants (N = 1001; aged 28–84 years-old) from the Midlife Development in the United States (MIDUS) study provided 4 daily saliva samples across four consecutive days and underwent a physical exam that provided information about six inter-related physiological systems that were combined into a measure of allostatic load. They also completed a phone-based battery of cognitive tasks, which provided a composite score combining memory, reasoning, and speed of processing performance. Total daily cortisol output was captured using area under the curve, with respect to ground (AUCg). Change in cortisol levels was assessed using two methods: slope, calculated through piecewise spline models, and dynamic range, calculated by the difference between the day’s highest and lowest log-cortisol levels. Findings indicate that, when examined together, overall cortisol output was not associated with either outcome, but a greater range in cortisol throughout the day was associated with both lower allostatic load and higher cognitive functioning. Results emphasize the importance of dynamic daily processes, assessed either using slopes or dynamic range, to both physiological and cognitive functioning.

    更新日期:2019-11-14
  • Connecting cognition, cardiology, and chromosomes: Cognitive reappraisal impacts the relationship between heart rate variability and telomere length in CD8+CD28– cells
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-14
    Anoushka D. Shahane, Angie S. LeRoy, Bryan T. Denny, Christopher P. Fagundes

    Individuals who poorly regulate emotion exhibit premature aging and worse general health. Telomere shortening, a prognostic biomarker of physical health, is related to aging, poor immunocompetence and autonomic nervous system functioning. Cognitive reappraisal is one type of emotion regulation strategy, which involves changing one’s appraisal of an aversive situation to modify its emotional impact. Heart rate variability (HRV; i.e., oscillations in heart rate) relates to emotion regulatory processes, such that higher HRV typically reflects greater regulatory capacity. Previous research has identified a positive association between HRV and telomere length. Importantly, the association between HRV and telomere length may change depending on how often an individual uses cognitive reappraisal. One hundred and thirty-seven healthy participants completed measures of cognitive reappraisal frequency, HRV, and underwent blood draws to measure telomere length (computed with the relative ratio of telomere repeat copy number to single copy gene number) in the T cell effector population, CD8+CD28–.Cognitive reappraisal moderated the relationship between telomere length and HRV such that individuals with high cognitive reappraisal frequency had a significant positive association between HRV and telomere length, while individuals with average and less than average frequency did not exhibit this relationship. The results suggest that frequent usage of cognitive reappraisal enhances the already positive influence of HRV on chromosomal integrity in CD8+CD28– T lymphocytes. Although future research is needed to test these effects causally, these findings suggest that regularly using emotion regulation techniques may buffer the relationship between autonomic nervous system functioning and chromosomal integrity in immune cells.

    更新日期:2019-11-14
  • Perceived Stress, Psychological Resilience, Hair Cortisol Concentration, and Metabolic Syndrome Severity: A Moderated Mediation Model
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-10
    H. Matthew Lehrer, Mary A. Steinhardt, Susan K. Dubois, Mark L. Laudenslager

    Background Psychological resilience is considered to protect against detrimental effects of perceived stress on cardiovascular and metabolic health, but few studies have tested biological mechanisms underlying these relationships. Purpose This study examined whether psychological resilience moderated the indirect association of perceived stress with Metabolic Syndrome (MetS) severity via hair cortisol concentration (HCC), a retrospective index of hypothalamic pituitary adrenal (HPA) axis activity. Method Participants included 228 adults (73 White, 86 Hispanic, 69 African American; mean age 45.29 years; 68% females). Participants completed questionnaires assessing perceived stress (Perceived Stress Scale) and resilience (Brief Resilience Scale). The first 3 cm of scalp-near hair were analyzed for cortisol concentration using enzyme-linked immunoassay analysis. Cardiometabolic risk factors including blood glucose, lipids, blood pressure, and waist circumference were assessed, from which a sex- and race/ethnicity-specific continuous MetS severity score was calculated. A moderated mediation model was tested using path analysis. Results Psychological resilience moderated the association of perceived stress with HCC (R2 change for interaction = 0.014, p = 0.043), such that the association of perceived stress and HCC decreased as resilience scores increased. Resilience also moderated the indirect association of perceived stress with MetS severity via HCC (b = -0.039, 95% CI [-0.001; -0.100]), such that HCC mediated the association of greater perceived stress with greater MetS severity only for individuals reporting Brief Resilience Scale scores 3 or below (range: 1.17-5.00). Psychological resilience was also associated with lower MetS severity (β = -0.227, p = 0.014) independent of perceived stress and HCC. Conclusion Findings suggest that psychological resilience may serve as both a stress buffer and as a direct determinant of cardiometabolic health. These results extend literature on psychological resilience to measures of retrospective HPA axis function and MetS severity in a diverse sample.

    更新日期:2019-11-11
  • Maternal distress, HPA activity, and antenatal interventions: A systematic review
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-09
    Soha Fassaie, John McAloon

    Background Elevated antenatal distress has been associated with negative outcomes for both mothers and, as a result, their infants. One mechanism hypothesised to underlie these associations is the maternal hypothalamic pituitary adrenal (HPA) axis. Though research has examined whether biopsychosocial antenatal interventions can reduce maternal HPA activity, only one review has summarized the nature of findings to date. The present study examined randomised control trials (RCTs) specifically; our primary aim was to assess the effectiveness of antenatal interventions in reducing HPA activity in pregnant women, our secondary aim was to examine whether antenatal interventions reduced maternal self-report of depression and/or anxiety. Methods This study systematically reviewed RCTs that evaluated biopsychosocial interventions that reported subjective and objective markers of maternal distress in pregnant women within the clinical population. Results Eight studies met inclusion criteria and women were in their second or third trimester. HPA-activity was primarily assessed through salivary cortisol (n = 7) and self-reported maternal distress was assessed using a variety of validated screening measures. Included trials demonstrated significant methodological heterogeneity and small sample sizes, poor treatment adherence, and poor reliability in cortisol measurement indicated low methodological quality. Conclusions Due to the high heterogeneity across studies, small sample sizes, and unreliable sampling methods, firm conclusions about the efficacy and effectiveness of antenatal interventions cannot be drawn. Despite this, interventions which targeted pregnancy-specific influencers of maternal mood were more likely to result in reduced depression and anxiety symptomatology as reported by mothers.

    更新日期:2019-11-11
  • Interpersonal capitalization moderates the associations of chronic caregiving stress and depression with inflammation
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-09
    J.P. Gouin, C. Wrosch, J. McGrath, L. Booij

    Chronic stress and depression can enhance chronic low-grade inflammation. Interpersonal factors may buffer the impact of stress and depression on inflammation. Interpersonal capitalization is a social support process in which one discloses positive personal events and experiences to close others. Greater capitalization may attenuate the deleterious impact of chronic stress and depression. The goal of the current study was to assess whether interpersonal capitalization is associated with inflammation and whether it moderates the association of chronic stress and depression with inflammation. In this cross-sectional study of chronic caregiving stress, 222 caregiving mothers of adolescents with developmental disabilities or comparison mothers of typically developing adolescents completed a self-reported daily diary assessment of capitalization, the Center for Epidemiological Study-Depression scale, and provided blood samples to assess interleukin-6, tumor necrosis factor-α, and C-reactive protein, three circulating inflammatory markers. Regression analysis indicated that there was no main effect of capitalization on inflammation, p = .24, R2 = .006. However, there was a significant three-way interaction among capitalization, chronic caregiving stress, and depressive symptoms, p = .01, R2 = .02. Among participants with lower capitalization, greater depressive symptoms were associated with higher inflammation in the caregiving group, but not in the comparison group. Among participants with higher capitalization, greater depressive symptoms were no longer significantly associated with higher inflammation among caregivers, but were marginally related to inflammation in the comparison group. Capitalization may thus be an interpersonal process mitigating the effects of chronic stress and depression on inflammation.

    更新日期:2019-11-11
  • Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-09
    Anastasiya Nestsiarovich, Berit Kerner, Aurélien J. Mazurie, Daniel C. Cannon, Nathaniel G. Hurwitz, Yiliang Zhu, Stuart J. Nelson, Tudor I. Oprea, Annette S. Crisanti, Mauricio Tohen, Douglas J. Perkins, Christophe G. Lambert

    Objective To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM). Methods The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus “No drug”. Results The annual incidence of new-onset diabetes during the exposure period was 3.09% (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to “No drug”. A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed. Conclusions There is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.

    更新日期:2019-11-11
  • Sex difference or hormonal difference in mental rotation? The influence of ovarian milieu
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-09
    Diana Peragine

    Sex differences in visuospatial cognition have long been reported, with men being advantaged on the Mental Rotations Test (MRT). The data, however, are variable, and sensitive to design parameters. When men and women are compared directly, with women in different hormonal milieus combined, there seem to be sex differences. When women alone are studied, taking into account different ovarian steroid concentrations and treatments, MRT performance varies with these changes. Indeed, several reports describe better performance among women with reduced estrogens. To better understand whether the sex difference in MRT persists once hormonal status is considered, we recruited reproductive age adults designated male and female at birth (MAB, FAB), and administered the Vandenberg-Kuse (V/K) MRT—comparing performance among MAB (n = 169) and FAB (n = 219). For FAB combined, we found a sex difference with MAB performing better than FAB. However, when FAB were analyzed by current menstrual cycle phase (Early Follicular (EF), Periovulatory (PO), Midluteal (ML)) or by hormone therapy (transmasculine testosterone administration (TM+), oral contraceptive (OC) ingestion prior to (OC+) or after cognitive testing (OC-)), low-estradiol groups (EF, OC-, TM+) performed as strongly as MAB, and had better MRT than cycling FAB in high-estradiol menstrual cycle phases (PO, ML). On a verbal memory control task, neither a sex difference nor a low estrogen advantage was detected, although performance varied with hormonal milieu. Our findings support a dynamic model of spatial performance and suggest that both MAB and FAB perform strongly on MRT, contingent on hormonal status.

    更新日期:2019-11-11
  • Attachment Orientations and Loss Adjustment Among Bereaved Spouses
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-07
    A. S LeRoy, T. Gabert, L. Garcini, K. W Murdock, C. Heijnen, C.P Fagundes

    Stressful life events such as losing a spouse can enhance inflammation. Responses to loss may depend, in part, on individual differences in attachment anxiety and avoidance. An individual’s attachment orientation (i.e., an individual’s levels of attachment anxiety and avoidance) reflects how an individual relates to others-- specifically, whether they feel their trusted others will reliably be there for them, and whether they feel comfortable opening up to and depending on their relationship partners. This study investigated the association between attachment orientations and poor loss adjustment in recently bereaved individuals (N = 100). Poor loss adjustment was operationalized as greater levels of inflammation and grief symptoms, as well as poorer self-reported mental and physical health. Attachment anxiety was associated with increased stimulated monocyte IL-6 and CCL4 production, but not TNFα. Likewise, attachment anxiety was associated with greater grief symptoms as well as poorer mental and physical health. In contrast, attachment avoidance was not associated with inflammation; it was, however, associated with less grief symptoms as well as better self-reported mental and physical health. Our findings provide evidence that attachment orientations may be associated with loss adjustment and adverse health outcomes following the recent loss of a spouse.

    更新日期:2019-11-08
  • Adversity exposure during sensitive periods predicts accelerated epigenetic aging in children
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-06
    Sandro Marini, Kathryn A. Davis, Thomas W. Soare, Yiwen Zhu, Matthew J. Suderman, Andrew J. Simpkin, Andrew D.A.C. Smith, Erika J. Wolf, Caroline L. Relton, Erin C. Dunn

    Objectives Exposure to adversity has been linked to accelerated biological aging, which in turn has been shown to predict numerous physical and mental health problems. In recent years, measures of DNA methylation-based epigenetic age––known as “epigenetic clocks”––have been used to estimate accelerated epigenetic aging. Although a small number of studies have found an effect of adversity exposure on epigenetic age in children, none have investigated if there are “sensitive periods” when adversity is most impactful. Methods Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 973), we tested the prospective association between repeated measures of childhood exposure to seven types of adversity on epigenetic age assessed at age 7.5 using the Horvath and Hannum epigenetic clocks. With a Least Angle Regression variable selection procedure, we evaluated potential sensitive period effects. Results We found that exposure to abuse, financial hardship, or neighborhood disadvantage during sensitive periods in early and middle childhood best explained variability in the deviation of Hannum-based epigenetic age from chronological age, even after considering the role of adversity accumulation and recency. Secondary sex-stratified analyses identified particularly strong sensitive period effects. These effects were undetected in analyses comparing children “exposed” versus “unexposed” to adversity. We did not identify any associations between adversity and epigenetic age using the Horvath epigenetic clock. Conclusions Our results suggest that adversity may alter methylation processes in ways that either directly or indirectly perturb normal cellular aging and that these effects may be heightened during specific life stages.

    更新日期:2019-11-06
  • Becoming a mother entails anatomical changes in the ventral striatum of the human brain that facilitate its responsiveness to offspring cues
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-05
    Elseline Hoekzema, Christian K. Tamnes, Puck Berns, Erika Barba-Müller, Cristina Pozzobon, Marisol Picado, Florencio Lucco, Magdalena Martínez-García, Manuel Desco, Agustín Ballesteros, Eveline A. Crone, Oscar Vilarroya, Susanna Carmona

    In mothers, offspring cues are associated with a powerful reinforcing value that motivates maternal care. Animal studies show that this is mediated by dopamine release into the nucleus accumbens, a core component of the brain’s reward system located in the ventral striatum (VStr). The VStr is also known to respond to infant signals in human mothers. However, it is unknown whether pregnancy modifies the anatomy or functionality of this structure, and whether such modifications underlie its strong reactivity to offspring cues. Therefore, we analyzed structural and functional neuroimaging data from a unique pre-conception prospective cohort study involving first-time mothers investigated before and after their pregnancy as well as nulliparous control women scanned at similar time intervals. First, we delineated the anatomy of the VStr in each subject’s neuroanatomical space and examined whether there are volumetric changes in this structure across sessions. Then, we tested if these changes could predict the mothers’ brain responses to visual stimuli of their infants. We found decreases in the right VStr and a trend for left VStr reductions in the women who were pregnant between sessions compared to the women who were not. Furthermore, VStr volume reductions across pregnancy were associated with infant-related VStr responses in the postpartum period, with stronger volume decreases predicting stronger functional activation to offspring cues. These findings provide the first indications that the transition to motherhood renders anatomical adaptations in the VStr that promote the strong responsiveness of a mother’s reward circuit to cues of her infant.

    更新日期:2019-11-06
  • Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-11-02
    Alexandra Labanski, Jost Langhorst, Harald Engler, Sigrid Elsenbruch

    The broad role of stress in the brain-gut axis is widely acknowledged, with implications for multiple prevalent health conditions that are characterized by chronic gastrointestinal symptoms. These include the functional gastrointestinal disorders (FGID), such as irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel diseases (IBD) like ulcerative colitis and Crohn’s disease. Although the afferent and efferent pathways linking the gut and the brain are modulated by stress, the fields of neurogastroenterology and psychoneuroendocrinology (PNE)/ psychoneuroimmunology (PNI) remain only loosely connected. We aim to contribute to bringing these fields closer together by drawing attention to a fascinating, evolving research area, targeting an audience with a strong interest in the role of stress in health and disease. To this end, this review introduces the concept of the brain-gut axis and its major pathways, and provides a brief introduction to epidemiological and clinical aspects of FGIDs and IBD. From an interdisciplinary PNE/PNI perspective, we then detail current knowledge regarding the role of chronic and acute stress in the pathophysiology of FGID and IBD. We provide an overview of evidence regarding non-pharmacological treatment approaches that target the central or peripheral stress mechanisms, and conclude with future directions, particularly those arising from recent advances in the neurosciences and discoveries surrounding the gut microbiota.

    更新日期:2019-11-04
  • EFFECTS OF CHRONIC INTRANASAL OXYTOCIN ON BEHAVIOR AND CEREBRAL GLUCOSE UPTAKE IN JUVENILE TITI MONKEYS
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-10-31
    Rocío Arias del Razo, Trish Berger, Alan J. Conley, Sara M. Freeman, Leana R. Goetze, Suma Jacob, Rebecca H. Lawrence, Sally P. Mendoza, Emily S. Rothwell, Logan E. Savidge, Marjorie Solomon, Tamara A.R. Weinstein, Lynea R. Witczak, Karen L. Bales

    Intranasal oxytocin (IN OXT) has been proposed as a treatment for autism spectrum disorder (ASD); however, little is known about the effects of long-term exposure. This is the first study in a non-human primate species to examine how developmental exposure to chronic IN OXT affects juvenile’s interactions with family members, social preference for parents versus strangers, anxiety-like behavior, and cerebral glucose metabolism. Titi monkeys are socially monogamous and biparental; their family bonds share important characteristics with human family bonds. Fourteen males and 15 females were treated intranasally with saline (n = 14) or 0.8 IU/kg OXT (n = 15), daily from 12 to 18 months of age. Compared to SAL-treated animals, OXT-treated animals of both sexes spent significantly more time grooming other family members (F1 = 8.97, p = 0.006). Overall, OXT-treated subjects were more social (F1 = 8.35, p = 0.005) during preference tests. OXT-treated females displayed an enhanced preference for their parents (t = 2.265, p = 0.026). OXT-treated males had a blunted preference for their parents and an increase in the time spent near unfamiliar pairs (F1 = 10.89, p = 0.001). During anxiety tests, OXT-treated males refused to complete the task more often than SAL-treated males and had longer latencies (p < 0.0001). Neuroimaging studies revealed that OXT-treated animals had higher glucose uptake across the social salience network as a whole after one month of treatment (F1,9 = 1.07, p = 0.042). Our results suggest moderate prosocial effects of chronic IN OXT, that did not depend on anxiolytic properties. We also found important sex differences that should be considered in a translational context.

    更新日期:2019-11-01
  • Activation of the G protein-coupled estrogen receptor, but not estrogen receptor α or β, rapidly enhances social learning.
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2015-05-10
    Kelsy Sharice Jean Ervin,Erin Mulvale,Nicola Gallagher,Véronique Roussel,Elena Choleris

    Social learning is a highly adaptive process by which an animal acquires information from a conspecific. While estrogens are known to modulate learning and memory, much of this research focuses on individual learning. Estrogens have been shown to enhance social learning on a long-term time scale, likely via genomic mechanisms. Estrogens have also been shown to affect individual learning on a rapid time scale through cell-signaling cascades, rather than via genomic effects, suggesting they may also rapidly influence social learning. We therefore investigated the effects of 17β-estradiol and involvement of the estrogen receptors (ERs) using the ERα agonist propyl pyrazole triol, the ERβ agonist diarylpropionitrile, and the G protein-coupled ER 1 (GPER1) agonist G1 on the social transmission of food preferences (STFP) task, within a time scale that focused on the rapid effects of estrogens. General ER activation with 17β-estradiol resulted in a modest facilitation of social learning, with mice showing a preference up to 30min of testing. Specific activation of the GPER1 also rapidly enhanced social learning, with mice showing a socially learned preference up to 2h of testing. ERα activation instead shortened the expression of a socially learned food preference, while ERβ activation had little to no effects. Thus, rapid estrogenic modulation of social learning in the STFP may be the outcome of competing action at the three main receptors. Hence, estrogens' rapid effects on social learning likely depend on the specific ERs present in brain regions recruited during social learning.

    更新日期:2019-11-01
  • Activation of GPR30 attenuates chronic pain-related anxiety in ovariectomized mice.
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2015-01-24
    Shui-bing Liu,Zhen Tian,Yan-yan Guo,Nan Zhang,Bin Feng,Ming-gao Zhao

    Estrogen regulates neuroendocrine and inflammatory processes that play critical roles in neuroinflammation, anxiety, and chronic pain. Patients suffering from chronic pain often complain of anxiety. However, limited information is available regarding the neural circuitry of chronic pain-related anxiety and the related function of estrogen. Hindpaw injection of complete Freund's adjuvant (CFA) and chronic constriction injury (CCI) of the sciatic nerve induced notable pain sensitization and anxiety-like behavior in ovariectomized (OVX) mice. We found that the level of G-protein-coupled receptor 30 (GPR30), a membrane estrogen receptor, was significantly increased in the basolateral amygdala (BLA) of ovariectomized (OVX) mice suffering from chronic inflammatory and neuropathic pain. Subcutaneous injection or BLA local infusion of the GPR30 agonist G1 significantly reduced anxiety-like behavior in CFA-injected and CCI-OVX mice; however, this treatment did not alter the nociceptive threshold. GPR30 knock down by shRNA in the BLA of OVX mice inhibited the anxiolytic effects of GPR30 activation. G1 administration reversed the upregulation of GluR1 subunit in AMPA and NR2A-containing NMDA receptors and the downregulation of GABAA receptors in the BLA of CFA-injected and CCI-OVX mice. Electrophysiological recording revealed that GPR30 activation could prevent imbalance between excitatory and inhibitory transmissions in the BLA synapses of CFA-injected OVX mice. In conclusion, GPR30 activation induced anxiolytic effects but did not affect the nociceptive threshold of mice under chronic pain. The anxiolytic effects of GPR30 were partially due to maintaining the balance between excitatory and inhibitory transmissions in the BLA.

    更新日期:2019-11-01
  • Estrogen receptor GPR30 exerts anxiolytic effects by maintaining the balance between GABAergic and glutamatergic transmission in the basolateral amygdala of ovariectomized mice after stress.
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2013-05-15
    Zhen Tian,Yu Wang,Nan Zhang,Yan-Yan Guo,Bin Feng,Shui-Bing Liu,Ming-Gao Zhao

    G-protein-coupled receptor 30 (GPR30)/G-protein-coupled estrogen receptor is a novel estrogen membrane receptor that localizes to the cell membrane and endoplasmic reticulum. GPR30 is widely distributed and has numerous physiological functions in the central nervous system. We found that GPR30 is highly expressed in the basolateral amygdala (BLA). Additionally, GPR30 expression in the amygdala of ovariectomized (OVX) mice significantly increased after acute stress and was accompanied by anxiety-like behaviors. These effects, however, were reversed by local infusion of the GPR30 agonist (G1) in the BLA. Protein assessments revealed that G1 attenuated the up-regulation of the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and NR2A-containing N-methyl-d-aspartate receptors (NMDARs) in the BLA of OVX mice using an acute stress paradigm. In the same model, we found that the agonist also blocked the down-regulation of γ-aminobutyric acid A (GABAA) receptors and NR2B-containing NMDARs. Electrophysiological recording showed that the activation of GPR30 increased the inhibitory synaptic transmission in the BLA. Overall, our results indicate that estradiol reduces anxiety-like behaviors induced by acute stress at least partially through GPR30 signaling, maintaining the balance between GABAergic and glutamatergic transmission in the BLA of OVX-stressed mice.

    更新日期:2019-11-01
  • Corrigendum to "Childhood maltreatment, behavioral adjustment, and molecular markers of cellular aging in preschool-aged children: A cohort study" [Psychoneuroendocrinology 107 (2019) 261-269].
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-10-13
    Kathryn K Ridout,Stephanie H Parade,Hung-Teh Kao,Stevie Magnan,Ronald Seifer,Barbara Porton,Lawrence H Price,Audrey R Tyrka

    更新日期:2019-11-01
  • Corrigendum to "Changes in cytokines during treatment of elderly, hospitalized psychiatric patients-A naturalistic study" [Psychoneuroendocrinology, 108C (2019), 135-139].
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-09-21
    Erlend Bugge,Rolf Wynn,Tom Eirik Mollnes,Solveig Klabo Reitan,Maria I Lapid,Ole Kristian Gronli

    更新日期:2019-11-01
  • Corrigendum to "Loving-kindness meditation slows biological aging in novices: Evidence from a 12-week randomized controlled trial" [Psychoneuroendocrinology 108 (2019) (October) 20-27].
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-09-19
    Khoa D Le Nguyen,Jue Lin,Sara B Algoe,Mary M Brantley,Sumi L Kim,Jeffrey Brantley,Sharon Salzberg,Barbara L Fredrickson

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Examining reactivity patterns in burnout and other indicators of chronic stress.
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2019-04-20
    Magdalena K Wekenborg,Bernadette von Dawans,LaBarron K Hill,Julian F Thayer,Marlene Penz,Clemens Kirschbaum

    INTRODUCTION Burnout symptomatology is associated with various negative health consequences; however, the mechanisms underlying these associations remain unclear. One potential pathway involves alterations in the acute stress response. The aims of the present study were to examine burnout-associated alterations in stress-reactivity patterns, during a standardized social stressor compared to a control condition, as well as to examine whether effects associated with greater burnout symptomatology were distinct from other, conceptually overlapping indicators of chronic stress (i.e. depressive symptomatology and elevated hair cortisol concentration [HCC]). MATERIALS AND METHODS In a randomized two-factor design a total of 70 employed males with varying burnout symptoms but without evidence of physical or psychiatric disease were exposed to the Trier Social Stress Test for Groups (TSST-G) or a non-stressful control condition. Acute stress reactivity was assessed using self-report stress measures and non-invasive biomarkers. Associations among acute stress reactivity, burnout and depressive symptoms (assessed with self-report measures), as well as HCC were analysed using repeated measure ANCOVAs and moderation analysis. RESULTS Burnout symptomatology was associated with elevated stress perception independent of the experimental condition. In addition, depressive symptomatology was associated with enhanced anticipatory appraisal, whereas HCC was not related to any subjective stress measure. On a physiological level, burnout and depressive symptomatology, as well as HCC were associated with a pattern of blunted cardiovascular reactivity, however the timing of this effect varied. CONCLUSION Our results indicate burnout-associated modulations in stress reactivity, which diverge, at least partly, from other indicators of chronic stress.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Brief report: Neighborhood disadvantage and hair cortisol among older urban African Americans.
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2017-03-21
    Samuele Zilioli,Richard B Slatcher,Heather Fritz,Jason C Booza,Malcolm P Cutchin

    Previous studies have shown that living in poor neighborhoods is associated with increased morbidity and mortality. However, researchers are now investigating the biological pathways responsible for the deleterious effects of neighborhood disadvantage on health. This study investigated whether neighborhood disadvantage (i.e., a measure of relative neighborhood quality derived by combining social and built environmental conditions) was associated with hair cortisol-a retrospective indicator of long-term hypothalamic pituitary adrenal (HPA) axis activation-and whether this link would be mediated by self-reported neighborhood satisfaction. Forty-nine older African Americans were recruited from thirty-nine Detroit census tracts across five strata of census tract adversity. Participants were interviewed face-to-face to collect psychosocial measures. Each provided a hair sample for analysis of cortisol. Multiple regression analyses revealed that higher neighborhood disadvantage was associated with higher levels of hair cortisol levels and that neighborhood satisfaction partially explained this association. These results are the first to our knowledge to demonstrate a direct link between neighborhood disadvantage and hair cortisol in a sample of older adults and to show that self-reported neighborhood satisfaction may be a psychological intermediary of this association.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
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