Depressive Symptoms in Men Aged 50 Years and Older and Their Relationship to Genetic Androgen Receptor Polymorphism and Sex Hormone Levels in Three Different Samples

Salivary testosterone: Associations with depression, anxiety disorders, and antidepressant use in a large cohort study

“…The androgen receptor gene (located on the X chromosome) contains a polymorphic CAG repeat sequence affecting androgen sensitivity. Previous studies yielded inconsistent results; CAG repeat length and depressive symptoms were positively associated [35], unrelated [36], or associated only in subgroups of black men [37] or patient groups [38]. In another study, low testosterone levels were associated with depressive symptoms in men with short CAG repeat lengths only [34].…”

“…We also analyzed current psychiatric disorders within the preceding month for depressive disorder and anxiety disorders (i.e., social phobia, panic disorder and/or agoraphobia, and generalized anxiety disorder). The total score of the Inventory of Depressive Symptomatology Self Report (IDS-SR) was used to assess overall depression severity, [60] and subdivided into five severity groups, i.e., low (total score 0-13), mild (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), moderate (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), severe (39)(40)(41)(42)(43)(44)(45)(46)(47)(48), and very severe . Item 22 (i.e., interest in sex) from the IDS-SR was analyzed separately as an internal validation of the salivary testosterone assessment, that was rated on a four-point scale: 0 (i.e., usual interest), 1 (i.e., somewhat less interest or pleasure), 2 (i.e., little interest or pleasure), and 3 (i.e., no interest or pleasure).…”

“…Inconsistencies may partly be due to the link or interaction with the genetic cytosine-adenosine-guanine (CAG) repeat length polymorphism. Longer CAG repeats may diminish the androgen receptor transactivation capacity and has been linked to the vulnerability to depression and anxiety [34,35], though not consistently [36][37][38]. Evidence on the role of testosterone in women is scarce, but there is some evidence that low DHEA(S) is involved in depression in women [39,40].…”

Hypogonadism: Biochemical Diagnosis, Treatment, and the Myth of Uniform Thresholds

“…This is especially essential in older men in regard to psychological problems related to testosterone levels and general androgen action facilitated/ modulated by the androgen receptor polymorphism. [16][17][18] In addition, effects of externally applied testosterone can be markedly influenced by the (CAG)n polymorphism and become clinically overt in a differential manner according to the regarded symptom; thus, pharmacogenetic implications and tissue-specificity are likely to influence indications as well as modalities of testosterone treatment of hypogonadal men. 4,6,19 …”

Sex-Specific Associations of Androgen Receptor CAG Trinucleotide Repeat Length and of Raloxifene Treatment with Testosterone Levels and Perceived Stress in Schizophrenia

“…Genetic variation in the AR gene is also shown to be associated with affective symptoms. A series of studies in older males (≥50 years of age) with psychosomatic conditions (exclusive of psychosis) [68-71] showed that longer AR CAG repeat length was associated with greater depressive symptoms [68, 69] and more anxiety [70]. Conversely, shorter AR CAG repeat length was found in adolescents with major depressive disorder [72, 73] and was associated with depression and anxiety symptoms in male patients [72].…”