Psychoneuroendocrinology
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Psychoneuroendocrinology · Aug 2019
Serotonin transporter gene methylation predicts long-term cortisol concentrations in hair.
Epigenetic signatures, such as DNA methylation (DNAM), have been implicated in long-term dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis and related health risks. Based on a wealth of neuroendocrine studies on genetic polymorphisms in the serotonin transporter gene (SLC6A4), this locus constitutes a key candidate to explore associations of DNAM patterns and HPA-axis functioning. The few studies addressing this link so far exclusively relied on spot measurements of HPA-axis activity, which may not adequately reflect cortisol output over prolonged periods of time. ⋯ Comparable to the pattern we had previously observed concerning cortisol stress reactivity, the S allele relates to increased HCC in individuals displaying low levels of SLC6A4 DNAM. By contrast, no such effect occurred under conditions of high SLC6A4 DNAM, indicating that epigenetic changes may compensate for genotype-dependent differences in long-term cortisol output. Together, respective findings support the idea of an epigenetic contribution to long-term HPA-axis activity and further highlight the usefulness of combining genetic and epigenetic information in future neuroendocrine studies.
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Psychoneuroendocrinology · Jun 2019
Does sex hormone treatment reverse the sex-dependent stress regulation? A longitudinal study on hypothalamus-pituitary-adrenal (HPA) axis activity in transgender individuals.
Studies in mammals indicate a role for sex hormones in the regulation of hypothalamic-pituitary-adrenal (HPA)-axis reactivity. However, in humans, experimental paradigms investigating long-term exposure to sex hormones are sparse, limiting the understanding of the influence of sex hormones on HPA-axis activity. Gender-affirming hormone therapy (GAHT) in transgender persons enables to study the physiological role of sex steroids partially uncoupled from the distinct genetic background of men and women. ⋯ This is the first study demonstrating long-term effects of a complete reversal of the sex-hormonal milieu on HPA-axis activity in humans. Our findings hereby expand the current knowledge of the physiology of HPA-axis regulation. and may be particularly relevant for transgender and cisgender people undergoing hormonal suppression or substitution therapies.
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Psychoneuroendocrinology · Apr 2019
Relationships between cerebrospinal fluid GABAergic neurosteroid levels and symptom severity in men with PTSD.
Allopregnanolone and pregnanolone (together termed allo + pregnan) are neurosteroid metabolites of progesterone that equipotently facilitate the action of gamma-amino-butyric acid (GABA) at GABAA receptors. The adrenal steroid dehydroepiandrosterone (DHEA) allosterically antagonizes GABAA receptors and facilitates N-methyl-D-aspartate (NMDA) receptor function. In prior research, premenopausal women with posttraumatic stress disorder (PTSD) displayed low cerebrospinal fluid (CSF) levels of allo + pregnan [undifferentiated by the gas chromatography-mass spectrometry (GC-MS) method used] that correlated strongly and negatively with PTSD reexperiencing and negative mood symptoms. ⋯ A PTSD-related decrease in the 5α-DHP to progesterone ratio indicated a block in allopregnanolone synthesis at 5α-reductase. This study suggests that CSF allo + pregnan levels correlate negatively with PTSD and negative mood symptoms in both men and women, but that the enzyme blocks in synthesis of these neurosteroids may be sex-specific. Consideration of sex, PTSD severity, and function of 5α-reductase and 3α-HSD thus may enable better targeting of neurosteroid-based PTSD treatments.
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Psychoneuroendocrinology · Mar 2019
Short- and long-term alterations of FKBP5-GR and specific microRNAs in the prefrontal cortex and hippocampus of male rats induced by adolescent stress contribute to depression susceptibility.
Maladaptation of the hypothalamic-pituitary-adrenal (HPA) axis is involved in susceptibility to depression. Glucocorticoid receptors (GRs) and the co-chaperone protein, FK506 binding protein 51 (FKBP5), play crucial roles in dysfunction of the HPA axis. Further, certain microRNAs (miRNAs), such as miR-124a and miR-18a, which could reduce GR protein expression, contribute to affective disorders, while miR-511 as a regulator of FKBP5 is involved in an increased risk of depression. ⋯ Furthermore, the similar long-term changes on behaviors and expressions of GR, FKBP5 and GR-related microRNAs were found in the adult rats following CUMS and dexamethasone treatment in adolescence. However, reduced miR-511 expression was observed only in the prefrontal cortex of adult rats exposed to adolescent CUMS or dexamethasone administration. These data suggested that the downregulation of GR, upregulation of FKBP5, miR-124a, and miR-18a in the prefrontal cortex and hippocampus, and downregulation of miR-511 in the prefrontal cortex were relevant to depressive-like behaviors.
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Despite the high prevalence of neural and immune disorders, their etiology and molecular mechanisms remain poorly understood. As the zebrafish (Danio rerio) is increasingly utilized as a powerful model organism in biomedical research, mounting evidence suggests these fish as a useful tool to study neural and immune mechanisms and their interplay. ⋯ As many human brain diseases are based on complex interplay between the neural and the immune system, here we discuss zebrafish models, as well as recent successes and challenges, in this rapidly expanding field. We particularly emphasize the growing utility of zebrafish models in translational immunopsychiatry research, as they improve our understanding of pathogenetic neuro-immune interactions, thereby fostering future discovery of potential therapeutic agents.