Merazin hydrate produces rapid antidepressant effects by activating CaMKII to promote neuronal activities and proliferation in hippocampus.

In our previous studies, we demonstrated that merazin hydrate (MH) had rapid antidepressant effects, but the deep mechanism needed to be further investigated. In this study, we used depressive-like model, behavioral tests, molecular biology and pharmacological interventions to reveal the underlying mechanisms of MH's rapid antidepressants. We found that a single administration of MH was able to produce rapid antidepressant effects in chronic unpredictable mild stress (CUMS) exposed mice at 1 day later, similar to ketamine. Moreover, MH could not only significantly up-regulated the expressions of cFOS, but also obviously increased the number of Ki67 positive cells in hippocampal dentate gyrus (DG). Furthermore, we also found that the phosphorylated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) was significantly reduced by CUMS in hippocampus, which was also reversed by MH. In addition, pharmacological inhibition of CaMKII by using KN-93 (a CaMKII antagonist) blocked the MH's up-regulation of cFOS and Ki67 in hippocampal DG. To sum up, this study demonstrated that MH produced rapid antidepressant effects by activating CaMKII to promote neuronal activities and proliferation in hippocampus.

Longitudinal association of allostatic load with depressive symptoms among urban adults: Healthy Aging in Neighborhoods of Diversity across the Life Span study.

BACKGROUND: Evidence suggests that lifetime exposure to stressful life events and chronic stressors may be linked to geriatric depression. Allostatic load (AL) is considered a mediator of the stress-health relationship and has been linked to psychosocial factors reflecting health disparities. The purpose of this study was to examine the longitudinal associations of AL with depressive symptoms scores among urban adults, before and after stratifying by sex and race. METHODS: Secondary analyses were performed using Visit 1 (2004-2009), Visit 2 (2009-2013) and Visit 3 (2013-2017) data collected on 2298 Healthy Aging in Neighborhoods of Diversity across the Life Span study participants (baseline age: 30-64 y). AL at Visit 1 (ALv1) and z-transformed probability of higher AL trajectory (ALtraj) between Visits 1 and 3 were calculated using cardiovascular, metabolic and inflammatory risk indicators. The 20-item Center for Epidemiologic Studies Depression (CES-D) scale was used to calculate total and domain-specific depressive symptoms scores. Mixed-effects linear models controlled for socio-demographic, lifestyle and health characteristics. RESULTS: In fully adjusted models, a positive cross-sectional relationship was observed between ALv1 and "somatic complaints" depressive symptoms (ß = 0.21, P = 0.006) score at Visit 1, whereas ALtraj was associated with increasing depressive symptoms score (ß = 0.086, P = 0.003) between Visits 1 and 3. An inverse relationship was observed between ALtraj and "positive affect" depressive symptoms score at Visit 1 among women (ß = -0.31, P < 0.0001) and White adults (ß = -0.32, P = 0.004). Among women, ALtraj was also positively related to change in "somatic complaints" depressive symptoms score between Visits 1 and 3 (ß = 0.043, P = 0.020). CONCLUSIONS: Among urban adults, AL may be associated with "somatic complaints" depressive symptoms at baseline. Higher AL trajectories may predict increasing depressive symptoms (overall) and increasing "somatic complaints" depressive symptoms (among women). A higher AL trajectory may be associated with lower "positive affect" depressive symptoms at baseline among women and White adults only.

Psychobiological foundations of coping and emotion regulation: Links to maltreatment and depression in a racially diverse, economically disadvantaged sample of adolescent girls.

Adolescent risk for depression and passive or active suicidal ideation (PASI) involves disturbance across multiple systems (e.g., arousal regulatory, affective valence, neurocognitive). Exposure to maltreatment while growing up as a child or teenager may potentiate this risk by noxiously impacting these systems. However, research exploring how coordinated disturbance across these systems (i.e., profiles) might be uniquely linked to depressogenic function, and how past maltreatment contributes to such disturbance, is lacking. Utilizing a racially diverse, economically disadvantaged sample of adolescent girls, this person-centered study identified psychobiological profiles and linked them to maltreatment histories, as well as current depressive symptoms and PASI. Girls (N = 237, Mage=13.98, SD=0.85) who were non-depressed/non-maltreated (15.1%), depressed/non-maltreated (40.5%), or depressed/maltreated (44.4%) provided morning saliva samples, completed questionnaires, a clinical interview, and a neurocognitive battery. Latent profile analysis of girls' morning cortisol:C-reactive protein ratio, positive and negative affect levels, and attentional set-shifting ability revealed four profiles. Relative to Normative (66.6%), girls exhibiting a Pro-inflammatory Affective Disturbance (13.1%), Severe Affective Disturbance (10.1%), or Hypercortisol Affective Neurocognitive Disturbance (n = 24, 10.1%) profile reported exposure to a greater number of maltreatment subtypes while growing up. Girls exhibiting these dysregulated profiles were also more likely (relative to Normative) to report current depressive symptoms (all three profiles) and PASI (only Pro-inflammatory Affective Disturbance and Hypercortisol Affective Neurocognitive Disturbance). Of note, girls' cognitive reappraisal utilization moderated profile membership-depression linkages (depressive symptoms, but not PASI). A synthesis of the findings is presented alongside implications for person-centered tailoring of intervention efforts.

Brain-derived neurotrophic factor, depressive symptoms and somatic comorbidity in patients with coronary heart disease.

OBJECTIVE: Depression and coronary heart disease (CHD) are highly comorbid conditions. Brain-derived neurotrophic factor (BDNF) plays an important role in cardiovascular processes. Depressed patients typically show decreased BDNF concentrations. We analysed the relationship between BDNF and depression in a sample of patients with CHD and additionally distinguished between cognitive-affective and somatic depression symptoms. We also investigated whether BDNF was associated with somatic comorbidity burden, acute coronary syndrome (ACS) or congestive heart failure (CHF). METHODS: The following variables were assessed for 225 hospitalised patients with CHD: BDNF concentrations, depression [Patient Health Questionnaire-9 (PHQ-9)], somatic comorbidity (Charlson Comorbidity Index), CHF, ACS, platelet count, smoking status and antidepressant treatment. RESULTS: Regression models revealed that BDNF was not associated with severity of depression. Although depressed patients (PHQ-9 score >7) had significantly lower BDNF concentrations compared to non-depressed patients (p = 0.04), this was not statistically significant after controlling for confounders (p = 0.15). Cognitive-affective symptoms and somatic comorbidity burden each closely missed a statistically significant association with BDNF concentrations (p = 0.08, p = 0.06, respectively). BDNF was reduced in patients with CHF (p = 0.02). There was no covariate-adjusted, significant association between BDNF and ACS. CONCLUSION: Serum BDNF concentrations are associated with cardiovascular dysfunction. Somatic comorbidities should be considered when investigating the relationship between depression and BDNF.

Mental Effects of Excess Parathyroid Hormone in Hemodialysis Patients: A Possible Role for Parathyroid 2 Hormone Receptor?

Depression as measured by the kidney disease quality of life (KDQOL) form is known to be an independent risk factor for mortality dialysis patients. Excess parathyroid hormone (PTH) has long been associated with neuropsychiatric disturbances. Those psychiatric complications are currently attributed to hypercalcemia with very little evidence; however, with the discovery of the parathyroid hormone 2 receptor (PTH2R) in the brain which can be activated by PTH, PTH2R might indicate a direct effect of PTH. As secondary and tertiary hyperparathyroidism is common in dialysis patients where the serum calcium is low or normal, we chose to investigate a possible relationship between PTH levels and depression in dialysis patients. This was a matched pair observational study with 10 patients with intact PTH values above 1000 pg/mL who were matched with 10 patients who had PTH values less than 400 pg/mL for the presence of diabetes, years on dialysis, duration of dialysis time, Kt/V, hemoglobin, and 25 OH vitamin D levels, as well as intravenous iron and erythropoietin administration. The Kidney Disease Quality of Life questionnaire (KDQOL-36) scores and patient Health Questionnaire scores were analyzed during that time. All variables underwent tests for normality and matched pair t-test. All subscales of the KDQOL-36 were worse in the high PTH group with the effect on daily life reaching P = 0.01 and the burden of disease and symptoms both reaching P = 0.02. PTH and PTH2R may be appropriate targets for investigations to improve the quality of life in hemodialysis patients.

Latino adolescents' cultural values associated with diurnal cortisol activity.

Hypothalamic-pituitary-adrenal (HPA) axis activity has been identified as a mechanism through which daily life stress contributes to health problems and racial/ethnic health disparities. Stress-related changes in neuroendocrine function are evident as early as adolescence, but the ways in which promotive cultural factors may also contribute to variation in diurnal HPA activity have received little empirical attention. Grounded in cultural models of resilience, dual dimensions of Latino adolescents' cultural values (ethnic heritage and U.S. mainstream) were examined as promotive and protective factors in relation to their diurnal salivary cortisol patterns using ecological momentary assessment (N = 209; Mage = 18.10; 64.4% female). Participants provided 5 daily saliva samples for 3 days while completing corresponding electronic diary reports and using time-sensitive compliance devices (track caps, actigraphs). Results from 3-level growth curve models indicated that higher U.S. mainstream cultural values (e.g., self-reliance, competition, material success) were associated with higher average waking cortisol levels and a more rapid rate of diurnal cortisol decline (i.e., "steeper" slope). Regarding situational deviations from the diurnal rhythm (within-person differences), cortisol levels were higher in relation to diary-reported ongoing stress (vs. completed). Accounting for these situational differences in stress timing, a cross-level interaction (i.e., between-person difference in within-person process) indicated that higher perceived stress than usual was associated with lower cortisol levels for adolescents with stronger alignment to Latino ethnic heritage values (e.g., familism, respect, religiosity), compared to relatively higher cortisol levels for those with less alignment to these values. Results were consistent adjusting for participants' sex, immigrant generation, parents' education level, depressive symptoms, medication use, sleep duration, and other self-reported health behaviors. These findings join the growing science of cultural neurobiology by demonstrating the promotive and potentially regulating influence of cultural values in the daily HPA functioning of Latino adolescents.

Anhedonia following mild traumatic brain injury in rats: A behavioral economic analysis of positive and negative reinforcement.

Psychiatric disorders affect nearly 50% of individuals who have experienced a traumatic brain injury (TBI). Anhedonia is a major symptom of numerous psychiatric disorders and is a diagnostic criterion for depression. It has recently been appreciated that reinforcement may be separated into consummatory (hedonic), motivational and decisional components, all of which may be affected differently in disease. Although anhedonia is typically assessed using positive reinforcement, the importance of stress in psychopathology suggests the study of negative reinforcement (removal or avoidance of aversive events) may be equally important. The present study investigated positive and negative reinforcement following a rat model of mild TBI (mTBI) using lateral fluid percussion. Hedonic value and motivation for reinforcement was determined by behavioral economic analyses. Following mTBI, the hedonic value of avoiding foot shock was reduced. In contrast, the hedonic value of escaping foot shock or obtaining a sucrose pellet was not altered by mTBI. Moreover, motivation to avoid or escape foot shock or to acquire sucrose was not altered by mTBI. Our results suggest that individuals experiencing mTBI find avoidance of aversive events less reinforcing, and therefore are less apt to utilize proactive control of stress.

The costs of high self-control in Black and Latino youth with asthma: Divergence of mental health and inflammatory profiles.

Emerging evidence in psychology suggests a paradox whereby high levels of self-control when striving for academic success among minority youth can have physical health costs. This study tested the skin-deep resilience hypothesis in asthma- whether minority youth who are striving hard to succeed academically experience good psychological outcomes but poor asthma outcomes. Youth physician-diagnosed with asthma (N = 276, M age = 12.99; 155 = White, 121 = Black/Latino) completed interviews about school stress and a self-control questionnaire. Outcomes included mental health (anxiety/depression) and ex-vivo immunologic processes relevant to asthma (lymphocyte Th-1 and Th-2 cytokine production, and sensitivity to glucocorticoid inhibition). Physician contacts were tracked over a one-year follow-up. For minority youth experiencing high levels of school stress, greater self-control was associated with fewer mental health symptoms (beta = -0.20, p < .05), but worse asthma inflammatory profiles (larger Th-1 and Th-2 cytokine responses, lower sensitivity to glucocorticoid inhibition), and more frequent physician contacts during the one-year follow-up (beta's ranging from 0.22 to 0.43, p's < .05). These patterns were not evident in White youth. In minority youth struggling with school, high levels of self-control are detrimental to asthma inflammatory profiles and clinical outcomes. This suggests the need for health monitoring to be incorporated into academic programs to ensure that 'overcoming the odds' does not lead to heightened health risks in minority youth.

Curcumin restores rotenone induced depressive-like symptoms in animal model of neurotoxicity: assessment by social interaction test and sucrose preference test.

Environmental toxin rotenone has been associated to with increased Parkinson's disease (PD) prevalence in population. Depression is one of the main non-motor symptoms of PD. Curcumin exhibits neuroprotective action in neurodegenerative diseases. In the study we investigated the effect of pre- and post-treatment of curcumin on rotenone-induced depressive-like behaviors and neurotransmitter alterations in rat model of PD. In pre-treatment phase rats were administered with curcumin (100 mg/kg/day, p.o.) for 2 weeks. After curcumin treatment rotenone (1.5 mg/kg/day, s.c.) was administered in Pre-Cur + Rot group and rotenone alone group for 8 days. Meanwhile, in Post-Cur + Rot group rotenone was injected for 8 days in order to develop PD-like symptoms. After rotenone administration curcumin (100 mg/kg/day, p.o.) was administered in Post-Cur + Rot group for 2 weeks. Depressive-like behaviors were monitored by the forced swim test (FST), open field test (OFT), sucrose preference test (SPT) and social interaction test (SIT). Animals were decapitated after behavioral analysis, striatum and hippocampus were dissected out for neurochemical estimations. Results showed that the rotenone administration significantly (p < 0.01) produced depressive-like symptoms in all depression-related behavioral test. All these behavioral deficits were accompanied by the reduction of striatal and hippocampal neurotransmitter levels following rotenone administration. Pre- and post-treatment with curcumin significantly (p < 0.01) reversed the depressive-like behavior induced by rotenone and significantly (p < 0.01) improved neurotransmitter levels as compared to rotenone injected rats. Our results strongly suggest that normalization of neurotransmitter levels particularly highlights the antidepressant effect of curcumin against rotenone-induced depressive behavior.

Assessment of Placental Cortisol Pathway Gene Expression in Term Pregnant Women with Anxiety.

INTRODUCTION: The aim of this study was to expand on this field of work by examining, within a cohort of pregnant women with diagnosed clinical anxiety, the mRNA expression of a panel of genes associated with the cortisol pathway and comparing them to controls. METHODS: Placental samples were obtained from 24 pregnant women, 12 with a diagnosed anxiety disorder and 12 with no psychiatric history, within 30 min of delivery. Differential expression analysis of 85 genes known to be involved in glucocorticoid synthesis, metabolism or signalling was conducted for the: (1) full sample, (2) those at term without labour (5 cases, 7 controls) and (3) those at term with labour (7 cases, 5 controls). Correlation analyses between gene expression and measures of anxiety and depressive symptom severity were also conducted. RESULTS: No robust difference in placental gene expression between pregnant women with and without anxiety disorder was found nor did we detect robust differences by labour status. However, correlational analyses putatively showed a decrease in PER1 expression was associated with an increase in anxiety symptom severity, explaining up to 32% of the variance in anxiety symptom severity. DISCUSSION: Overall, the strongest correlation was found between a decrease in placental PER1 expression and increased anxiety scores. Labour status was found to have a profound effect on mRNA expression. The placental samples obtained from women following labour produced greater numbers of significant differences in mRNA species expression suggesting that in long-standing anxiety the placenta may respond differently under conditions of chronic stress.

Perimenstrual exacerbation of symptoms in borderline personality disorder: evidence from multilevel models and the Carolina Premenstrual Assessment Scoring System.

BACKGROUND: Individuals with a borderline personality disorder (BPD) suffer from a constellation of rapidly shifting emotional, interpersonal, and behavioral symptoms. The menstrual cycle may contribute to symptom instability among females with this disorder. METHODS: Fifteen healthy, unmedicated females with BPD and without dysmenorrhea reported daily symptoms across 35 days. Urine luteinizing hormone and salivary progesterone (P4) were used to confirm ovulation and cycle phase. Cyclical worsening of symptoms was evaluated using (1) phase contrasts in multilevel models and (2) the Carolina Premenstrual Assessment Scoring System (C-PASS), a protocol for evaluating clinically significant cycle effects on symptoms. RESULTS: Most symptoms demonstrated midluteal worsening, a perimenstrual peak, and resolution of symptoms in the follicular or ovulatory phase. Post-hoc correlations with person-centered progesterone revealed negative correlations with most symptoms. Depressive symptoms showed an unexpected delayed pattern in which baseline levels of symptoms were observed in the ovulatory and midluteal phases, and exacerbations were observed during both the perimenstrual and follicular phases. The majority of participants met C-PASS criteria for clinically significant (⩾30%) symptom exacerbation. All participants met the emotional instability criterion of BPD, and no participant met DSM-5 criteria for premenstrual dysphoric disorder (PMDD). CONCLUSIONS: Females with BPD may be at elevated risk for perimenstrual worsening of emotional symptoms. Longitudinal studies with fine-grained hormonal measurement as well as hormonal experiments are needed to determine the pathophysiology of perimenstrual exacerbation in BPD.

Psychological pathways from racial discrimination to cortisol in African American males and females.

The association between racial discrimination (discrimination) and stress-related alterations in the neuroendocrine response-namely, cortisol secretion-is well documented in African Americans (AAs). Dysregulation in production of cortisol has been implicated as a contributor to racial health disparities. Guided by Clark et al. (Am Psychol 54(10):805-816, 1999. doi: 10.1037/0003-066X.54.10.805 ) biopsychosocial model of racism and health, the present study examined the psychological pathways that link discrimination to total cortisol concentrations in AA males and females. In a sample of 312 AA emerging adults (45.5% males; ages 21-23), symptoms of anxiety, but not depression, mediated the relation between discrimination and total concentrations of cortisol. In addition, the results did not reveal sex differences in the direct and indirect pathways. These findings advance our understanding of racial health disparities by suggesting that the psychological consequences of discrimination can uniquely promote physiologic dysregulation in AAs.

Low subjective social status in the police is linked to health-relevant changes in diurnal salivary alpha-amylase activity in Swiss police officers.

The objective of this study was to assess basal autonomic nervous system (ANS) activity as a pathway linking subjective social status to health in a high-demand work environment. It was hypothesized that officers with a lower status experienced more chronic stress (higher basal ANS activity) and that chronic stress was related to more health problems. Fifty-six male and female Swiss police officers self-reported on subjective social status (country, community, friends, police) and their health (depression, post-traumatic stress, physical symptoms) and collected 12 saliva samples over two days for basal α-amylase activation (sAA) assessment. Multilevel regression analyses revealed that subjective social status in the police and physical symptoms explained a significant part of the variance in diurnal sAA activity patterns. The current findings support the idea that more narrowly defined subjective social status may be more closely linked to biological stress mechanisms. Additionally, sAA activity was specifically related to physical, but not mental health problems. These results suggest that subjective social status referencing one's work environment may be a promising early indicator of health-relevant changes in stress-related physiological systems.

Quantitative assessment of the bidirectional relationships between diabetes and depression.

Diabetes and depression impose an enormous public health burden and the present study aimed to assess quantitatively the bidirectional relationships between the two disorders. We searched databases for eligible articles published until October 2016. A total of 51 studies were finally included in the present bidirectional meta-analysis, among which, 32 studies were about the direction of depression leading to diabetes, and 24 studies about the direction of diabetes leading to depression. Pooled results of the 32 eligible studies covering 1274337 subjects showed that depression patients were at higher risk for diabetes (odds ratio (OR) = 1.34, 95% confidence intervals (CI) = [1.23, 1.46]) than non-depressive subjects. Further gender-subgroup analysis found that the strength of this relationship was stronger in men (OR = 1.63, 95%CI = [1.48, 1.78]) than in women (OR = 1.29, 95%CI = [1.07, 1.51]). For the direction of diabetes leading to depression, pooled data of 24 articles containing 329658 subjects showed that patients with diabetes were at higher risk for diabetes (OR = 1.28, 95%CI = [1.15, 1.42]) than non-diabetic subjects. The available data supports that the relationships between diabetes and depression are bidirectional and the overall strengths are similar in both directions. More mechanistic studies are encouraged to explore the molecular mechanisms underlying the relationships between the two diseases.

MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition in premenopausal women. The syndrome is characterized by hyperandrogenism, irregular menses and polycystic ovaries when other etiologies are excluded. Obesity, insulin resistance and low vitamin D levels are present in more than 50% patients with PCOS, these factors along with hyperandrogenism could have adverse effects on long-term health. Hyperinflammation and impaired epithelial function were reported to a larger extent in women with PCOS and could particularly be associated with hyperandrogenism, obesity and insulin resistance. Available data from register-based and data linkage studies support that metabolic-vascular and thyroid diseases, asthma, migraine, depression and cancer are diagnosed more frequently in PCOS, whereas fracture risk is decreased. Drug prescriptions are significantly more common in PCOS than controls within all diagnose categories including antibiotics. The causal relationship between PCOS and autoimmune disease represents an interesting new area of research. PCOS is a lifelong condition and long-term morbidity could be worsened by obesity, sedentary way of life, Western-style diet and smoking, whereas lifestyle intervention including weight loss may partly or fully resolve the symptoms of PCOS and could improve the long-term prognosis. In this review, the possible implications of increased morbidity for the clinical and biochemical evaluation of patients with PCOS at diagnosis and follow-up is further discussed along with possible modifying effects of medical treatment.

Depressive symptomatology and cortisol concentrations in elderly community residents: a cross-sectional study.

BACKGROUND: Researches seek to understand the links between adverse health outcomes and cortisol concentrations. However, the relationship between depressive symptomatology and cortisol concentrations is controversial in the literature. AIM: To analyze the relationship between the depressive symptomatology and the cortisol concentrations in elderly community residents in the Brazilian Northeast. METHODS: Cross-sectional study is composed of 256 elderly (≥65 years). Depressive symptomatology was evaluated by the Center for Epidemiologic Studies-Depression Scale and cortisol concentrations by salivary collection (upon waking, 30 and 60 min after waking, at 3 pm and before bed), in addition to composite measurements. Sociodemographic and health conditions were evaluated. For analysis of the cortisol measurements in relation to depressive symptomatology, and between genders, the Student's t test was used. For cortisol measurements in every curve, analysis of variance for repeated measurements with Bonferroni post hoc test was used. RESULTS: There were significant salivary cortisol differences upon awakening, among elderly with and without depressive symptomatology (p = 0.04). There was no significance in relation to gender. Between measurements of each curve, elderly with depressive symptomatology showed no significant difference between the 1st measure in relation to the 2nd and 3rd, and also between the 4th and 5th, demonstrating higher cortisol night levels in elderly with depressive symptomatology, without decline, with curve plane aspect. CONCLUSION: The relationship between depressive symptomatology and hypocortisolism throughout the day seems to exist. However, in Brazil, adverse life conditions can lead to chronic stress and be sufficient factors to superpose biggest differences that could exist in relation to the presence of depressive symptomatology.

Hormonal and psychosocial correlates of psychological well-being and negative affectivity in young gynecological-endocrinological patients.

To study the relationship between hormones, psychosocial factors and psychological well-being or negative affectivity (NA), 102 women (aged 15-31) responded to the 12-item well-being questionnaire (W-BQ12), with subscales for positive well-being (PWB), negative well-being (NWB) and energy (ENE); the Hospital Anxiety and Depression Scale (HADS), consisting of depression (HADS-D) and anxiety (HADS-A) subscales; the Beck Depression Inventory (BDI), and the Hamilton Depression Scale (HAMD). The univariate analysis revealed significant negative correlations between luteinizing hormone (LH) and HADS-T, HADS-D and HADS-A, and between follicle stimulating hormone (FSH) and HADS-A. Positive correlations were shown for thyroid stimulating hormone (TSH), HADS-T, and HADS-A. Cortisol and prolactin levels strongly correlated with BDI and HAMD scores, respectively. In a multivariate analysis, TSH significantly predicted the mood impairment in HADS-T (ß = 0.68) and HADS-A (ß = 0.68), while economic status predicted the general well-being (ß = 0.75), NWB (ß = -0.83), ENE (ß = 0.89), and HADS-A (ß = -0.63). We could not detect any significant differences in NA or well-being in patients with versus without PCOS or with versus without hirsutism, but almost all psychometric parameters differed significantly according to the economic status. In conclusion, TSH was the only hormonal predictor of overall NA and anxiety, and low-economic status overtrumped the impact of hormones on the psychological well-being.

Determinants of hair cortisol and hair cortisone concentrations in adults.

BACKGROUND: The analysis of hair cortisol concentrations (HairF) is a promising new tool for the assessment of long-term cortisol. With the development of multiple steroid analyses by means of liquid chromatography tandem-mass spectrometry (LC-MS/MS), the analysis of cortisone in hair (HairE) has also been facilitated. However, the influence of various types of determinants on HairF and HairE is still largely unknown. This study systematically assesses the influence of sociodemographic, health, lifestyle, and hair (treatment) characteristics on HairF and HairE. METHOD: Data of 760 psychiatrically healthy participants (71.8% female, mean age 45.89 years) of the Netherlands Study of Depression and Anxiety (NESDA) were used. HairF and HairE were measured in the proximal 3 cm of scalp hair, using LC-MS/MS. FINDINGS: HairF and HairE strongly correlated. In simple linear regressions, HairF and HairE were higher in older age, in presence of diabetes mellitus, and in men compared to women. More frequent washing of the hair was associated with lower HairF and HairE. Darker hair colours were associated with higher HairF and HairE. An effect of season and of use of oral contraceptives was found for HairF. After full mutual adjustment, only age, presence of diabetes mellitus, hair washing frequency, and season remained significant determinants of HairF. INTERPRETATION: This large-scale study shows that HairF and HairE are upregulated in older age and in the presence of diabetes mellitus. This suggests that these levels are important for somatic health and should be taken into account when using hair corticosteroid analysis in future studies.

Cross-cultural gene- environment interactions in depression, post-traumatic stress disorder, and the cortisol awakening response: FKBP5 polymorphisms and childhood trauma in South Asia.

Despite increased attention to global mental health, psychiatric genetic research has been dominated by studies in high-income countries, especially with populations of European descent. The objective of this study was to assess single nucleotide polymorphisms (SNPs) in the FKBP5 gene in a population living in South Asia. Among adults in Nepal, depression was assessed with the Beck Depression Inventory (BDI), post-traumatic stress disorder (PTSD) with the PTSD Checklist-Civilian Version (PCL-C), and childhood maltreatment with the Childhood Trauma Questionnaire (CTQ). FKBP5 SNPs were genotyped for 682 participants. Cortisol awakening response (CAR) was assessed in a subsample of 118 participants over 3 days. The FKBP5 tag-SNP rs9296158 showed a main effect on depressive symptoms (p = 0.03). Interaction of rs9296158 and childhood maltreatment predicted adult depressive symptoms (p = 0.02) but not PTSD. Childhood maltreatment associated with endocrine response in individuals homozygous for the A allele, demonstrated by a negative CAR and overall hypocortisolaemia in the rs9296158 AA genotype and childhood maltreatment group (p < 0.001). This study replicated findings related to FKBP5 and depression but not PTSD. Gene-environment studies should take differences in prevalence and cultural significance of phenotypes and exposures into account when interpreting cross-cultural findings.

[Animal Models of Depression: Behavior as the Basis for Methodology, Assessment Criteria and Classifications].

Analysis of the current state modeling of depression in animals is presented. Criteria and classification systems of the existing models are considered as well as approaches to the assessment of model validity. Though numerous approaches to modeling of depressive states based on disturbances of both motivational and emotional brain mechanisms have been elaborated, no satisfactory model of stable depression state has been developed yet. However, the diversity of existing models is quite positive since it allows performing targeted studies of selected neurobiological mechanisms and laws of depressive state development, as well as to investigate mechanisms of action and predict pharmacological profiles of potential antidepressants.