Testosterone levels in suicide attempters with bipolar disorder

Abstract

Objective

The best known neurobehavioral effects of testosterone are on sexual function and aggression. However, testosterone and other androgens may be involved in the pathophysiology of mood disorders and suicidal behavior. This is the first study to examine whether there is a relation between testosterone levels and clinical parameters in bipolar suicide attempters.

Methods

Patients with a DSM-IV diagnosis of a bipolar disorder (16 males and 51 females), in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters, including lifetime suicidal behavior, were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure.

Results

The number of major depressive episodes, the maximum lethality of suicide attempts, and the testosterone levels were higher in men compared to women. Current suicidal ideation scores were higher in women compared to men. Controlling for sex, we found that testosterone levels positively correlated with the number of manic episodes and the number of suicide attempts.

Conclusion

Our findings are consistent with previous observations of the association between testosterone levels and parameters of mood and behavior. This study suggests that testosterone levels may be related to the course of bipolar disorder and suicidal behavior. Further studies of the role of testosterone in the neurobiology of mood disorders and suicidal behavior are merited.

Introduction

In addition to its gonadal functions, testosterone has many central nervous system effects (Rubinow and Schmidt, 1996; Schmidt and Rubinow, 1997; Zarrouf et al., 2009; Ebinger et al., 2009). Testosterone can influence neuronal function through binding to intracellular receptors, through modulation of ligand-gated ion channels, and through binding to neurotransmitter receptors. It is also involved in modeling the developing brain and influences the continuous process of neuronal adaptation to new environmental demands.

The best known neurobehavioural effects of testosterone are on sexual function and aggression (Rubinow and Schmidt, 1996; Ebinger et al., 2009). However, testosterone and other androgens might be involved in the pathophysiology of mood disorders and suicidal behavior.

Depressed men have lower plasma or serum testosterone levels (Barrett-Connor et al., 1999; Schweiger et al., 1999; Almeida et al., 2004; Ebinger et al., 2009) although this association is not observed consistently (Levitt and Joffe, 1988; O'Connor et al., 2004; Ebinger et al., 2009). Hypogonadal men frequently show depressive symptoms, and testosterone replacement may improve these symptoms (Wang et al., 1996; Pope et al., 2003). Testosterone and other androgens might have antidepressant properties (Altschule and Tillotson, 1948; Itil et al., 1984; Pope et al., 2003; Amiaz and Seidman, 2008; Zarrouf et al., 2009). For example, it has been shown that testosterone gel may produce antidepressant effects in depressed men with low testosterone levels (Pope et al., 2003).

The data on the relationship of testosterone to suicidal behavior have been less consistent. Some studies reported low plasma testosterone levels after suicide attempts (Tripodianakis et al., 2007; Markianos et al., 2009). However, a study of male veterans with posttraumatic stress disorder showed that in this patient population, serum levels of testosterone were not associated with a history of suicide attempt (Butterfield et al., 2005). A recent study reported that there was no difference in testosterone levels between male suicide attempters and healthy controls (Perez-Rodriguez et al., 2011).

We have performed an exploratory study to examine whether there is a relationship between testosterone levels and suicidal behavior and related clinical parameters in bipolar disorder.