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Sex Differences in Depression Caused by Early Life Stress and Related Mechanisms.

ABSTRACT: Depression is a common psychiatric disease caused by various factors, manifesting with continuous low spirits, with its precise mechanism being unclear. Early life stress (ELS) is receiving more attention as a possible cause of depression. Many studies focused on the mechanisms underlying how ELS leads to changes in sex hormones, neurotransmitters, hypothalamic pituitary adrenocortical (HPA) axis function, and epigenetics. The adverse effects of ELS on adulthood are mainly dependent on the time window when stress occurs, sex and the developmental stage when evaluating the impacts. Therefore, with regard to the exact sex differences of adult depression, we found that ELS could lead to sex-differentiated depression through multiple mechanisms, including 5-HT, sex hormone, HPA axis, and epigenetics.

SUBMITTER: An X

PROVIDER: S-EPMC9157793 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Sex Differences in Depression Caused by Early Life Stress and Related Mechanisms.

An Xianquan X Guo Wanxu W Wu Huiying H Fu Xiying X Li Ming M Zhang Yizhi Y Li Yanlin Y Cui Ranji R Yang Wei W Zhang Zhuo Z Zhao Guoqing G

Frontiers in neuroscience 20220518

Depression is a common psychiatric disease caused by various factors, manifesting with continuous low spirits, with its precise mechanism being unclear. Early life stress (ELS) is receiving more attention as a possible cause of depression. Many studies focused on the mechanisms underlying how ELS leads to changes in sex hormones, neurotransmitters, hypothalamic pituitary adrenocortical (HPA) axis function, and epigenetics. The adverse effects of ELS on adulthood are mainly dependent on the time ...[more]

PMID: 35663561

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Project description:Rates of alcohol use disorder (AUD) have increased in women by 84% over the past ten years relative to a 35% increase in men. This substantive increase in female drinking is alarming given that women experience greater alcohol-related health consequences compared to men. Stress is strongly associated with all phases of alcohol addiction, including drinking initiation, maintenance, and relapse for both women and men, but plays an especially critical role for women. The purpose of the present narrative review is to highlight what is known about sex differences in the relationship between stress and drinking. The critical role stress reactivity and negative affect play in initiating and maintaining alcohol use in women is addressed, and the available evidence for sex differences in drinking for negative reinforcement as it relates to brain stress systems is presented. This review discusses the critical structures and neurotransmitters that may underlie sex differences in stress-related alcohol use (e.g., prefrontal cortex, amygdala, norepinephrine, corticotropin releasing factor, and dynorphin), the involvement of sex and stress in alcohol-induced neurodegeneration, and the role of ovarian hormones in stress-related drinking. Finally, the potential avenues for the development of sex-appropriate pharmacological and behavioral treatments for AUD are identified. Overall, women are generally more likely to drink to regulate negative affect and stress reactivity. Sex differences in the onset and maintenance of alcohol use begin to develop during adolescence, coinciding with exposure to early life stress. These factors continue to affect alcohol use into adulthood, when reduced responsivity to stress, increased affect-related psychiatric comorbidities and alcohol-induced neurodegeneration contribute to chronic and problematic alcohol use, particularly for women. However, current research is limited regarding the examination of sex in the initiation and maintenance of alcohol use. Probing brain stress systems and associated brain regions is an important future direction for developing sex-appropriate treatments to address the role of stress in AUD.

Project description:BackgroundsChronic stress could induce depression-like phenotype in animal models. Previous data showed that sex differences exist after chronic stress model establishment, however, the detailed information about the difference of blood biochemical indexes is not clear. In this study, we aim to supply comparison of monoamine transmitters and related hormone markers in serum between male and female depressed mice, and in order to better understand the sex difference in transmitters and hormone levels in depression occurrence and development.MethodsSixty C57BL/6 mice (both male and female) were divided into two groups by gender. Same gender mice were then divided randomly into the non-treated control group and chronic stress group which was exposed to 8 weeks of chronic unpredictable mild stress (CUMS). Depression-like behavior was assessed with open-field test and sucrose preference test. Blood sample was collected and monoamine transmitter and related hormone in serum were measured by ELISA.ResultsThe depression-like phenotype mice model was established successfully after 8 weeks of chronic stress. The locomotion activity scores in male stressed mice declined more than that in female stressed mice, while the exploratory behavior scores in female stressed mice declined more than that in male stressed mice. Compared to non-treated control group mice, mice in the chronic stress group in response to stress showed greater declines in monoamine transmitters (5-HT, dopamine, norepinephrine) and sex hormones (androgen, estrogen, oxytocin and prolactin), while stress hormones (adrenaline, corticosterone and ACTH) were significantly increased. The decrease of norepinephrine, androgen and estrogen in female stressed mice was greater than in male stressed mice, whereas the 5-HT and oxytocin in male stressed mice decreased more than in female stressed mice, and the corticosterone in male stressed mice increased more than in female stressed mice.ConclusionSex differences of monoamine transmitter and related hormone levels in serum occurred in chronic stress induced depression-like phenotype mice model. It may provide a useful reference to guide precise antidepressant treatment in different gender population in clinical care.

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Sex Differences in Depression Caused by Early Life Stress and Related Mechanisms.

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Sex Differences in Depression Caused by Early Life Stress and Related Mechanisms.

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