Dataset Information

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

ABSTRACT: Lower testosterone levels are associated with greater negative symptoms in men with schizophrenia. Testosterone signals via androgen receptor (AR). A functional variant in the AR gene (CAG trinucleotide repeat polymorphism) is associated with circulating testosterone and mood-related symptoms in healthy people. Raloxifene increases testosterone in healthy males and reduces symptom severity and improves cognition in schizophrenia; however, whether raloxifene increases testosterone in men with schizophrenia is unknown. We assessed the interaction of a functional AR gene variant and adjunctive raloxifene on peripheral testosterone and symptom severity in schizophrenia. Patients with schizophrenia (59 males and 38 females) participated in a randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene (120 mg/day). Healthy adults (46 males and 41 females) were used for baseline comparison. Baseline circulating testosterone was decreased in male patients compared to male controls and positively correlated with CAG repeat length in male controls and female patients. Male patients with short, compared to long, CAG repeat length had higher stress scores. Raloxifene treatment increased testosterone in male patients, but was unrelated to AR CAG repeat length, suggesting that raloxifene's effects may not depend on AR activity. Sex-specific alterations of the relationship between AR CAG repeat length and testosterone suggest that altered AR activity may impact perceived stress in men with schizophrenia.

SUBMITTER: Owens SJ

PROVIDER: S-EPMC6465742 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Owens Samantha J SJ Weickert Thomas W TW Purves-Tyson Tertia D TD Ji Ellen E White Christopher C Galletly Cherrie C Liu Dennis D O'Donnell Maryanne M Shannon Weickert Cynthia C

Molecular neuropsychiatry 20181120 1

Lower testosterone levels are associated with greater negative symptoms in men with schizophrenia. Testosterone signals via androgen receptor (AR). A functional variant in the AR gene (CAG trinucleotide repeat polymorphism) is associated with circulating testosterone and mood-related symptoms in healthy people. Raloxifene increases testosterone in healthy males and reduces symptom severity and improves cognition in schizophrenia; however, whether raloxifene increases testosterone in men with sch ...[more]

PMID: 31019916

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Project description:There is a distinct increase in the prevalence of depression with the onset of puberty. The role of peripubertal testosterone levels in boys in this context is insufficiently understood and may be modulated by a functional polymorphism of the androgen receptor gene (AR), a variable number of CAG repeats. Moreover, there is preliminary evidence that the relationship between testosterone, CAG repeat length, and the severity of depressive symptoms may differ between subclinical and overt depression, but this has neither been studied in a clinical sample of adolescents with depression nor compared between subclinical and overt depression in an adequately powered study. To investigate the relationship between free testosterone, CAG repeat length of the AR, depression status (subclinical vs. overt), and the severity of depressive symptoms, 118 boys treated as in- or daycare patients at a single psychiatric hospital were studied. Of these, 73 boys had at least mild depressive symptoms according to the Beck Depression Inventory-II (BDI-II > 13). Higher-order moderation analysis in the multiple regression framework revealed a constant relationship between free testosterone and depression severity irrespective of the number of CAG repeats in adolescents with a BDI-II score ≤ 13. In adolescents with a BDI-II score > 13, however, there was a significant negative relationship between free testosterone and BDI-II score in patients with <19 CAG repeats and a significant positive relationship regarding free testosterone and BDI-II score in those with more than 28 CAG repeats, even when considering important covariates. These results suggest that the effects of testosterone on mood in male adolescents with depression depend on the genetic make-up of the AR as well as on depression status. This complex relationship should be considered by future studies addressing mental health issues against an endocrine background and may, moreover, contribute to tailored treatment concepts in psychiatric medicine, especially in adults.

Dataset Information

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

Publications

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

Similar Datasets

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