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Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men

  • Stuart N Seidman
    Correspondence
    Address reprint requests to Stuart N. Seidman, MD, College of Physicians & Surgeons of Columbia University, Department of Psychiatry, 1051 Riverside Drive, Unit 98, New York, NY 10032
    Affiliations
    Department of Clinical Psychopharmacology at the New York State Psychiatric Institute, College of Physicians & Surgeons of Columbia University, New York, New York, USA (SNS, SPR)
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  • Andre B Araujo
    Affiliations
    New England Research Institutes (ABA, JBM), Watertown, MA, USA
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  • Steven P Roose
    Affiliations
    Department of Clinical Psychopharmacology at the New York State Psychiatric Institute, College of Physicians & Surgeons of Columbia University, New York, New York, USA (SNS, SPR)
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  • John B McKinlay
    Affiliations
    New England Research Institutes (ABA, JBM), Watertown, MA, USA
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      Abstract

      Background: Testosterone (T) level declines progressively with age. Psychiatric symptoms of T deficiency (e.g., dysphoria, fatigue, irritability, low libido) are also symptoms of depression, and appear to be variably expressed.
      Methods: We assessed independent measures of hypothalamic-pituitary-gonadal axis functioning, i.e., total T level and androgen receptor (AR) CAG repeat length (CAG RL), a genetic trait marker associated with AR function; and depression (diagnosed by above-threshold score on the Center for Epidemiologic Studies-Depression Scale [CES-D]) in 1000 men (mean age = 62.6 years; SD = 8.3) who participated in the Massachusetts Male Aging Study.
      Results: There were 110 (11%) men with “depression” (CES-D score ≥ 16) in the analysis sample. Neither total T level nor CAG RL was associated with depression in bivariate analyses. Among men with shorter CAG RLs, the percentage of men with depression was 21.6% in the lowest subgroup of total T (defined by quintiles) and 4.2% in the highest subgroup of total T. This was confirmed in simple logistic regression models with depression as the dependent variable and continuous total T as the predictor, run separately within the three CAG RL subgroups: depression was significantly and inversely associated with total T in men with shorter CAG RLs but not in men with moderate and longer CAG RLs.
      Conclusions: CAG isotype, a genetic trait marker of androgen receptor function, may mediate the expression of the central nervous system effects of T deficiency in men.

      Keywords

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