The impact of gender on behavioral and neural correlates of stress reactions

To be female or male is one of the most important biological determinants of life with critical consequences on many aspects ranging from cognitive and emotional behavior as far as human health. Physiological and psychological responses to stress have a severe impact on human health and previous studies indicate gender differences in the subjective, physiological, and neural correlates of these stress responses. During social stress, females show increases in subjective distress ratings, a decreased cortisol response, and increased neural activation in limbic regions. Interestingly, males show decreased subjective stress ratings and stronger physiological responses when experiencing achievement stress. Additionally, the neural activation in prefrontal regions suggests a more regulatory reaction in males than in females. Despite the behavioral evidence of the impact of stressor-type on gender-specific stress responses there is no neuroimaging study which directly compared achievement vs. social stress and their neural underpinnings in both, females and males. Using high field functional magnetic resonance imaging (fMRI) we aim at investigating gender differences in subjective, physiological and neural reactions to stress and the modulation of these stress responses by stressor type (achievement versus social stress). Applying a three level approach (subjective, physiological, and neural level) provides the opportunity to elucidate complex effects and interactions regarding a comprehensive model of stress responsiveness. Especially, the examination of neural network models can provide further insights on regulatory mechanisms by exploring complex interactions of several brain regions in addition to a mere localization-based analysis of fMRI data. The neural regions of interest based on previous studies are both cortical (e.g., prefrontal cortex) and subcortical brain regions (e.g., hippocampus and amygdala). On the physiological level we are particularly interested in analyzing the impact of cortisol and sex hormones on the subjective and neural stress responses. Investigating the mechanisms underlying gender-specific stress responses can essentially contribute to our knowledge of gender-associated prevalence differences in stress-related diseases, e.g. depression in females and cardiovascular diseases in males. In addition, the project proposed has a high societal relevance regarding the immense financial burden to be carried by the health care system to either prevent disease onset or treat these patients, respectively.

To be female or male is one of the most important biological determinants of life with critical consequences on many aspects including human health. To investigate whether our stress response is also affected by gender was the main aim of the current project. Although we did not observe a significant gender difference in stress experience, gender affected the stress response in the brain: Men showed stronger activation of brain regions associated with stress processing and emotions. Moreover, we found a significant, gender-specific impact of self-esteem on stress reactivity: Women with low self-esteem showed stronger activation of brain areas involved in cognitive control, while men with low self-esteem revealed stronger activation of self-referential brain regions during stress. Thus, our data indicate a significant, gender-specific correlation between (neural) stress response and self-esteem for the first time. In a follow-up study we investigated the impact of reappraisal as stress regulation method on stress reactivity. Again, we observed significant gender differences: the additional instruction to regulate and reappraise the negative emotions that might arise during the stress task led to a significant increase in subjective stress experience only in women. Moreover, neural activation differences emerged in regions associated with attention, emotion and reward processing. The functional connectivity of these regions even in the so-called resting-state is further affected by cortisol concentration, again in a gender-specific fashion: Our results indicate that the regulatory mechanism of cortisol on neural networks to adapt behavior in arousing situations differs between women and men. Hence, the gender-specific association between endocrine parameters and brain activation as well as connectivity support gender differences in stress reactivity and indicate potential gender effects regarding stress coping. To explain and model individual differences in stress vulnerability is one major challenge for contemporary stress research. Based upon our data, gender is such an essential contributing factor with an impact on different levels of stress reactivity. The presented results should also encourage the development of gender-sensitive and gender-specific stress-management concepts that have far reaching relevance to prevent and treat stress-associated disorders. Within the funded period we also addressed essential aspects regarding the functional neuroimaging method: in particular the disturbing influence of extra cerebral pulsation and venous blood flow on subcortical brain activation during tasks as well as during resting-state has been investigated. The reported findings/methods lead to an improvement in data acquisition as well as data analyses and increase sensitivity but more essentially, specificity and reliability of the measured MR signal.