Testosterone in Newly Diagnosed, Antipsychotic-Naive Men With Nonaffective Psychosis: A Test of the Accelerated Aging Hypothesis

Objective: Schizophrenia has been associated with age-related abnormalities, including abnormal glucose tolerance, increased pulse pressure, increased inflammation, abnormal stem cell signaling, and shorter telomere length. These metabolic abnormalities and other findings suggest that schizophrenia and related disorders might be associated with accelerated aging. Testosterone activity has a progressive decline with increasing age. Methods: We tested the hypothesis that circulating biologically active testosterone is lower in newly diagnosed, antipsychotic-naive male patients with nonaffective psychosis than in matched control subjects. Results: Patients (n = 33) were matched to control subjects (n = 33) for age, sex, body mass index, socioeconomic status of the family of origin, and smoking. The free androgen index, a measure of biologically active testosterone, was significantly lower in the psychosis group (mean [standard deviation] = 57.7% [26.1]) than in control subjects (71.6% [27.0], p = .04), with an effect size of 0.53. Multivariate analysis also supported the findings. In the psychosis group, free androgen index had a significant negative correlation with the conceptual disorganization item (r = -0.35, p = .049) but not with reality distortion (r = -0.21, p = .24), negative symptoms (r = 0.004, p = .98), or depression (r = -0.014, p = .94). Conclusions: Lower testosterone level is consistent with accelerated aging in nonaffective psychosis, but further testing of this hypothesis is needed.