Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men.
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 > or = 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.
Seidman
S N
SN
Department of Clinical Psychopharmacology, New York State Psychiatric Institute, College of Physicians & Surgeons of Columbia University, New York, NY 10032, USA.
Araujo
A B
AB
Roose
S P
SP
McKinlay
J B
JB
D000368:Aged; D003863:Depression / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D013739:Testosterone / Q000097:blood*; D018911:Trinucleotide Repeats
D011944:Receptors, Androgen; D013739:Testosterone