Testosterone increases amygdala reactivity in middle-aged women to a young adulthood level

Contains fulltext : 77294.pdf (publisher's version ) (Closed access)Testosterone modulates mood and sexual function in women. However, androgen levels decline with age, which may relate to the age-associated change in sexual functioning and the prevalence of mood and anxiety disorders. These effects of testosterone are potentially mediated by the amygdala. In the present study, we investigated whether the age-related decline in androgen levels is associated with reduced amygdala activity, and whether exogenous testosterone can restore amygdala activity. Healthy young and middle-aged women participated during the early follicular phase of the menstrual cycle, and amygdala responses to biologically salient stimuli were measured with functional magnetic resonance imaging (fMRI). Androgen levels were lower in middle-aged than young women, which was associated with decreased amygdala reactivity. Endogenous testosterone levels correlated positively with amygdala reactivity across the young and middle-aged women. The middle-aged women received a single nasal dose of testosterone in a double-blind, placebo-controlled, crossover manner, which rapidly increased amygdala reactivity to a level comparable to the young women. The enhanced testosterone levels correlated positively with superior frontal cortex responses and negatively with orbitofrontal cortex responses across individuals, which may reflect testosterone-induced changes in amygdala regulation. These results show that testosterone modulates amygdala reactivity in women, and suggest that the age-related decline in androgen levels contribute to the decrease in amygdala reactivity

Testosterone is inversely related to brain activity during emotional inhibition in schizophrenia

Sex steroids affect cognitive function as well as emotion processing and regulation. They may also play a role in the pathophysiology of schizophrenia. However, the effects of sex steroids on cognition and emotion-related brain activation in schizophrenia are poorly understood. Our aim was to determine the extent to which circulating testosterone relates to brain activation in men with schizophrenia compared to healthy men during cognitive-emotional processing. We assessed brain activation in 18 men with schizophrenia and 22 age-matched healthy men during an emotional go/no-go task using fMRI and measured total serum testosterone levels on the same morning. We performed an ROI analysis to assess the relationship between serum testosterone and brain activation, focusing on cortical regions involved the emotional go/no-go task. Slower RT and reduced accuracy was observed when participants responded to neutral stimuli, while inhibiting responses to negative stimuli. Healthy men showed a robust increase in activation of the middle frontal gyrus when inhibiting responses to negative stimuli, but there was no significant association between activation and serum testosterone level in healthy men. Men with schizophrenia showed a less pronounced increase in activation when inhibiting responses to negative stimuli; however, they did show a strong inverse association between serum testosterone level and activation of the bilateral middle frontal gyrus and left insula. Additionally, increased accuracy during inhibition of response to negative words was associated with both higher serum testosterone levels and decreased activation of the middle frontal gyrus in men with schizophrenia only. We conclude that endogenous hormone levels, even within the normal range, may play an enhanced modulatory role in determining the neural and behavioural response during cognitive-emotional processing in schizophrenia