Depression during pregnancy and postpartum: Contribution of stress and ovarian hormones

Depression is the most common psychiatric disease among women, exhibiting a prevalence which is 2–3× higher than in men. The postpartum period is considered the time of greatest risk for women to develop major depression and postpartum depression affects approximately 15% of women. A dysregulation of the hypothalamus–pituitary–adrenal (HPA) axis is the most prominent endocrine change seen in depression and normalization of the HPA axis is a major target of recent therapies. Females exhibit different stress sensitivities than males which might contribute to their increased vulnerability for depression. Maternal stress or depression during pregnancy and/or postpartum is particularly concerning as early developmental influences can affect the maturation of the offspring as well as the mental health of the mother. Despite the urgent need for more information on depression in females, especially during pregnancy and postpartum, most animal models of depression have utilized only males. Given the sex differences in incidence of depression and treatment, it is vitally important to create or validate animal models of depression in females. This review will focus on the association between stress, glucocorticoids and depression in humans, with a special focus on depression in women during pregnancy and postpartum and on animal models of postpartum depression and the consequences for the offspring.     

ACTH expression in synovium of patients with rheumatoid arthritis and Lewis rats with adjuvant arthritis

 Adrenocorticotropic hormone (ACTH) and another pro-opiomelanocortin-derived neuropeptide, β-endorphin (β-End), are stimulated by corticotropin-releasing hormone (CRH) at the anterior pituitary. CRH and β-End have predominantly proinflammatory effects in peripheral inflammatory sites. We have supposed that inflammatory stimuli develop ACTH as well as β-End. In this study, we investigated the expression of ACTH in inflamed synovial tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and at inflammatory joints with adjuvant-induced arthritis (AA) in female Lewis (LEW/N) rats. The expression of ACTH immunostaining was significantly greater in synovium of RA patients than in that of OA patients (P < 0.0001), and correlated with the extent of inflammatory mononuclear cell infiltration. Extensive and intense intracellular ACTH immunostaining, which correlated with the advance in arthritis score, was observed in the synovial lining layer, inflammatory mononuclear cells, and fibroblast-like cells of synovium and chondrocytes in LEW/N rats with AA. In addition, we performed double immunostaining of the same sections from arthritic joints in rats with anti-ACTH and anti-CRH antibodies. ACTH and CRH colocalized in inflammatory mononuclear cells and fibroblast-like cells. ACTH may play a role in the pathogenesis of RA as well as CRH. Received: July 4, 2001 / Accepted: January 23, 2002 Correspondence to: H. Sano     

从血浆促肾上腺皮质素释放素样生物活性和神经递质类药物的作用探讨Cushing病病因

用大鼠垂体细胞灌流技术和ACTH直接法放射免疫测定研究了正常人、Cushing病患者和其他下丘脑-垂体-肾上腺轴疾病患者血浆中的促肾上腺皮质素释放素样生物活性,结合Cushing病患者对神经递质类药物的反应所作观察提出如下假设:绝大多数Cushing病原发于垂体,在发病过程中,高皮质醇血症损害海马,削弱其对下丘脑-垂体-肾上腺轴的抑制作用是一个重要环节。     

Diet,behavior and immunity across the lifespan

It is increasingly appreciated that perinatal events can set an organism on a life-long trajectory for either health or disease, resilience or risk. One early life variable that has proven critical for optimal development is the nutritional environment in which the organism develops. Extensive research has documented the effects of both undernutrition and overnutrition, with strong links evident for an increased risk for obesity and metabolic disorders, as well as adverse mental health outcomes. Recent work has highlighted a critical role of the immune system, in linking diet with long term health and behavioral outcomes. The present review will summarize the recent literature regarding the interactions of diet, immunity, and behavior.     

Does the CRH binding protein shield the anterior pituitary from placental CRH?

Corticotropin releasing factor (CRH) is released from the hypothalamus and travels to the anterior pituitary where it stimulates the release of adrenocorticotropin (ACTH). In turn, ACTH travels through the blood and stimulates the release of cortisol from the adrenal. The placenta is also a source of CRH and is responsible for the dramatic rises in CRH plasma levels in the third trimester of pregnancy. A CRH binding protein may stop placental CRH from overstimulating the pituitary and may contribute to the reason that pregnant women show only mildly elevated levels of ACTH in the blood. There is evidence to suggest, however, that the CRH binding protein does not completely shield the corticotrope from placental CRH.     

Regulation of forebrain GABAergic stress circuits following lesion of the ventral subiculum

Ventral subiculum (vSUB) lesions enhance corticosterone responses to psychogenic stressors via trans-synaptic influences on paraventricular nucleus (PVN) neurons. Synaptic relays likely occur in GABA-rich regions interconnecting the vSUB and PVN. The current study examines whether vSUB lesions compromise stress-induced c-fos induction and GABA biosynthetic capacity in putative limbic-hypothalamic stress relays. Male Sprague-Dawley rats received bilateral ibotenate or sham lesions of the vSUB. Animals were divided into two groups, with one group receiving exposure to novelty stress and the other left unstressed. Exposure to novelty stress increased c-fos mRNA expression in the PVN to a greater degree in vSUB lesion relative to shams, consistent with an inhibitory role for the vSUB in the HPA stress response. However, c-fos induction was not affected in other forebrain GABAergic stress pathways, such as the lateral septum, medial preoptic area or dorsomedial hypothalamus. vSUB lesions increased GAD65 or GAD67 mRNA levels in several efferent targets, including anterior and posterior subnuclei of the bed nucleus of the stria terminalis and lateral septum. Lesions did not effect stress-induced increases in GAD65 expression in principal output nuclei of the amygdala. The current data suggest that loss of vSUB innervations produces a compensatory increase in GAD expression in subcortical targets; however, this up-regulation is insufficient to block lesion-induced stress hyperresponsiveness, perhaps driven by amygdalar disinhibition of the PVN.     

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation

Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropin-releasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer.