Neuroendocrinology of a Male-Specific Pattern for Depression Linked to Alcohol Use Disorder and Suicidal Behavior

Abstract

Epidemiological studies show low rates of diagnosed depression in men compared to women. At the same time, high rates of alcohol use disorders (AUDs) and completed suicide are found among men. These data suggest that a male-specific pattern for depression may exist that is linked to AUDs and suicidal behavior. To date, no underlying neuroendocrine model for this specific pattern of male depression has been suggested. In this paper, we integrate findings related to this specific pattern of depression with underlying steroid secretion patterns, polymorphisms, and methylation profiles of key genes in order to detail an original neuroendocrine model of male-specific depression. Low circulating levels of sex steroids seem to increase the vulnerability for male depression, while concomitant high levels of glucocorticoids further intensify this vulnerability. Interactions of hypothalamus–pituitary–gonadal (HPG) and hypothalamus–pituitary–adrenocortical (HPA) axis-related hormones seem to be highly relevant for a male-specific pattern of depression linked to AUDs and suicidal behavior. Moreover, genetic variants and the epigenetic profiles of the androgen receptor gene, well-known depression related genes, and HPA axis-related genes were shown to further interact with men’s steroid secretion and thus may further contribute to the proposed male-specific pattern for depression. This mini-review points out the multilevel interactions between the HPG and HPA axis for a male-specific pattern of depression linked to AUDs and suicidal behavior. An integration of multilevel interactions within the three-hit concept of vulnerability and resilience concludes the review.

Everybody was Kung-Fu fighting—The beneficial effects of Tai Chi Qigong and self-defense Kung-Fu training on psychological and endocrine health in middle aged and older men

“…12 In contrast, higher levels of C, and especially an elevated cortisol/testosterone (CTr) ratio reflecting the general (im)balance between the mutually inhibiting HPG and HPA axes, were shown to be associated with depression and overall worse health. [13][14][15] Tai Chi is considered health protective and was originally used as combatting style but slowly transformed to an exercise form aiming to perform soft, flowing, and mindful movements, which require balance, strength, agility, coordination, concentration, and flexibility. Beneficial effects of Tai chi with regard to sleep disturbances or frailty have been shown for older adults.…”

Associations between digit ratio (2D4D), mood, and autonomic stress response in healthy men

“…In utero T exposure in men might therefore be further investigated with regard to its effect on stress-related disorders such as depressive disorders. Attempts to formulate a male-specific pathophysiology for affective disorders are emerging, which integrate in utero and postnatal testosterone's organizational effects (Walther, Penz, Ijacic, & Rice, 2017;Walther, Rice, Kufert, & Ehlert, 2017) as well as the effect of testosterone in adulthood (Fiacco, Walther, & Ehlert, 2018;Walther, Breidenstein, & Miller, 2018).…”

Bipolar Spectrum Disorders in Male Youth: The Interplay between Symptom Severity, Inflammation, Steroid Secretion, and Body Composition

“…The aforementioned differences in BSD with regard to sex might originate from influences of sex steroids on BSD development and progression. Changes in sex steroids have also been linked to depression ( 32 – 34 , 44 , 45 ). Different studies show altered androgen levels (e.g., testosterone or dehydroepiandrosterone) in BSD.…”