AIM OF THE STUDY: To investigate the association of personality traits with the severity of vasomotor symptoms (VMS) in a predominantly Greek population. MATERIAL AND METHODS: A questionnaire-based study of women from the Menopause Clinic of a University Hospital in Athens, Greece. Sociodemographic parameters were documented through a structured interview. All women completed the Menopause Rating Scale (MRS) for the assessment of severity of menopausal symptoms, the Hot Flush Beliefs Scale (HFBS) for the assessment of how women were coping with their symptoms and the Big Five Inventory questionnaires for the assessment of personality traits. Associations between baseline parameters and menopausal symptoms were assessed with univariate and multivariate regression analyses. RESULTS: One hundred women were included. Employed women had lower MRS sub-scores (psychological p< 0.001, somatic p< 0.047, urogenital p< 0.008). Married women scored higher in the psychological and somatic domains. Women of university educational level coped significantly better with hot flushes (β coefficient [SE]: 0.72 [0.25], p< 0.01) and night sweats (0.57 [0.19], p< 0.01) than women of primary education, although the significance of these findings was not replicated when taking into account confounders. Regarding personality traits, women with low openness (-0.33 [0.11], p< 0.01) and empathy (-0.83 [0.37], p = 0.03) and high agreeableness (1.13 [0.21], p< 0.001) had more severe menopausal symptoms. In contrast, women with high agreeableness could better cope with their menopausal symptoms (-0.75 [0.36], p = 0.04). These associations were independent of sociodemographic factors. CONCLUSIONS: Personality traits, especially agreeableness, openness and empathy are associated with menopausal symptoms and functionality in postmenopausal women. These associations might serve as indicators of women at risk of experiencing more severe VMS.

Brain disorders and mental diseases, in particular, are common and considered as a top global health challenge for the twenty-first century. Interestingly, women suffer more frequently from mental disorders than men. Moreover, women may respond to psychotropic drugs differently than men, and, through their lifespan, they endure sex-orientated social stressors. In this chapter, we present how women may differ in the development and manifestation of mental health issues and how they differ from men in pharmacokinetics and pharmacodynamics. We discuss issues in clinical trials regarding women participation, issues in the use of psychotropic medications in pregnancy, and challenges that psychiatry faces as a result of the wider use of contraceptives, of childbearing at older age, and of menopause. Such issues, among others, demand further women-oriented psychiatric research that can improve the care for women during the course of their lives. Indeed, despite all these known sex differences, psychiatry for both men and women patients uses the same approach. Thereby, a modified paradigm for women's psychiatry, which takes into account all these differences, emerges as a necessity, and psychiatric research should take more vigorously into account sex differences.

Chronic stress, a suggested precipitant of brain pathologies, such as depression and Alzheimer's disease, is known to impact on brain plasticity by causing neuronal remodeling as well as neurogenesis suppression in the adult hippocampus. Although many studies show that stressful conditions reduce the number of newborn neurons in the adult dentate gyrus (DG), little is known about whether and how stress impacts on dendritic development and structural maturation of these newborn neurons. We, herein, demonstrate that chronic stress impacts differentially on doublecortin (DCX)-positive immature neurons in distinct phases of maturation. Specifically, the density of the DCX-positive immature neurons whose dendritic tree reaches the inner molecular layer (IML) of DG is reduced in stressed animals, whereas their dendritic complexity is increased. On the contrary, no change on the density of DCX-positive neurons whose dendritic tree extends to the medial/outer molecular layer (M/OML) of the DG is found under stress conditions, whereas the dendritic complexity of these cells is diminished. In addition, DCX+ cells displayed a more complex and longer arbor in the dendritic compartments located in the granular cell layer of the DG under stress conditions; on the contrary, their dendritic segments localized into the M/OML were shorter and less complex. These findings suggest that the neuroplastic effects of chronic stress on dendritic maturation and complexity of DCX+ immature neurons vary based on the different maturation stage of DCX-positive cells and the different DG sublayer, highlighting the complex and dynamic stress-driven neuroplasticity of immature neurons in the adult hippocampus.

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has long been implicated in the pathophysiology of depression, and HPA axis-based compounds have served as potential new therapeutic targets, but with no success. This review details sex differences from animal and human studies in the function of HPA axis elements (glucocorticoids, corticotropin releasing factor, and vasopressin) and related compounds tested as candidate antidepressants. We propose that sex differences contribute to the failure of novel HPA axis-based drugs in clinical trials. Compounds studied preclinically in males were tested in clinical trials that recruited more, if not exclusively, women, and did not control, but rather adjusted, for potential sex differences. Indeed, clinical trials of antidepressants are usually not stratified by sex or other important factors, although preclinical and epidemiological data support such stratification. In conclusion, we suggest that clinical testing of HPA axis-related compounds creates an opportunity for targeted, personalized antidepressant treatments based on sex. LINKED ARTICLES: This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc.

BACKGROUND: Major depression is associated with endothelial dysfunction and arterial stiffening, which may mediate development of hypertension and increased cardiovascular risk. The effect of response to antidepressant treatment on these vascular parameters has not been elucidated. AIMS: We aimed to assess the net effect of antidepressant therapy on endothelial function and arterial stiffness in patients with psychotic depression. METHOD: Thirty-seven patients with major psychotic depression, according to DSM-IV-TR, were treated with titrated citalopram 20-60 mg and risperidone 0.5-1 mg and were followed for 6 months. Twelve additional patients who denied treatment, or were non-compliant, were also followed for the same time period. Vascular function was assessed by flow-mediated dilatation (FMD), carotid-femoral pulse wave velocity (PWV) and augmentation index (AI), at baseline and at the end of follow-up. RESULTS: Aortic and peripheral blood pressure (BP), PWV, FMD and AI (p < 0.05 for all) were significantly improved in the group that received treatment. Overall, only responders to treatment (n = 24) presented significant improvements in all hemodynamic and vascular parameters (p < 0.05 for all), irrespectively of traditional cardiovascular risk factors (TRFs), vasoactive medication and BP lowering. In a secondary analysis, patients with psychotic depression presented worse endothelial function as compared to controls matched for TRFs. LIMITATIONS: Non-randomized study. CONCLUSIONS: Patients who respond to therapy for major psychotic depression present sustained improvement in vascular function. Given that depressed patients are considered to be at high cardiovascular risk and are often non-compliant with treatment, further research to assess cardiovascular benefits of vigilant monitoring of antidepressant therapy is warranted.

Environmental enrichment (EE), comprising positive physical (exercise) and cognitive stimuli, influences neuronal structure and usually improves brain function. The promise of EE as a preventative strategy against neuropsychiatric disease is especially high during early postnatal development when the brain is still amenable to reorganization. Despite the fact that male and female brains differ in terms of connectivity and function that may reflect early life experiences, knowledge of the neural substrates and mechanisms by which such changes arise remains limited. This study compared the impact of EE combined with physical activity on neuroplasticity and its functional consequences in adult male and female rats; EE was provided during the first 3 months of life and our analysis focused on the hippocampus, an area implicated in cognitive behavior as well as the neuroendocrine response to stress. Both male and female rats reared in EE displayed better object recognition memory than their control counterparts. Interestingly, sex differences were revealed in the effects of EE on time spent exploring the objects during this test. Independently of sex, EE increased hippocampal turnover rates of dopamine and serotonin and reduced expression of 5-HT(1A) receptors; in addition, EE upregulated expression of synaptophysin, a presynaptic protein, in the hippocampus. As compared to their respective controls, EE-exposed males exhibited parallel increases in phosphorylated Tau and the GluN2B receptor, whereas females responded to EE with reduced hippocampal levels of glutamate and GluN2B. Together, these observations provide further evidence on the differential effects of EE on markers of hippocampal neuroplasticity in males and females.