ReviewSex differences in salivary cortisol in response to acute stressors among healthy participants, in recreational or pathological gamblers, and in those with posttraumatic stress disorder
Introduction
Individuals respond to stressors in a variety of ways. Understanding how factors such as sex and/or hormone status mitigates stress response may shed light on how these factors can influence pathophysiological states. First, neuropsychiatric disorders, such as anxiety, depression, and posttraumatic stress disorder (PTSD), are stress-related and influenced by sex and gonadal hormones (Arborelius et al., 1999, Boyer, 2000, Cameron and Nesse, 1988, Esch et al., 2002, Gold and Chrousos, 2002, Kasckow et al., 2001, McEwen, 2002, Rasmusson et al., 2001, Steckler et al., 1999, Young, 1998). Second, stress also modulates engagement in, and effects of, rewarding and/or addictive behavior, and there are salient sex biases associated with these behaviors (Koob and Le Moal, 2008, Lynch, 2006, Lynch et al., 2002, Prendergast, 1994, Sinha, 2001, Sinha, 2008, Van Etten et al., 1999, Van Etten and Anthony, 2001). In particular, males tend to be more susceptible to engagement in drug abuse whereas females tend to be more labile with greater peaks in abuse behavior. Understanding these pathophysiological states is not only important for revealing the etiology of the disorders but is also crucial for elucidating possible mechanisms of the normative state, which may be influenced by interactions between adrenal and gonadal hormones. Research to identify the extent to which sex- and/or adrenal-hormones can influence response to acute, chronic, and/or pathophysiological stressors is a critical step in understanding treatment and prevention of health risks associated with various types of stress.
Although the extant literature examines how experiential factors, such as the history of stress-related disorder, may influence stress reactivity, here we consider how sex may contribute to stress responses across a variety of healthy and/or pathophysiological states. Our laboratory has investigated sex and/or hormonal differences in various behaviors using animal models, and has worked to elucidate the role that neurosteroids may play in mitigating these effects. We, and others, have found that one mechanism that precipitates neurosteroid biosynthesis to levels that exert effects on behavior is the activation of the hypothalamic–pituitary–adrenal (HPA) stress axis. We have been collaborating with clinical investigators to assess the role that HPA activation may play in healthy, subclinical, and clinical human samples and the following review summarizes a decade of this work.
Section snippets
Salivary cortisol as a research approach to investigate sex differences
Sex differences in vulnerability to stress are dependent on many factors including the type of stressor utilized as well as the endogenous hormonal status of the individuals examined. While some studies indicate that differences in neurobiological stress response favor men (Gallucci et al., 1993, Jezova et al., 1996), there have been many reports demonstrating the opposite effect (Kajantie and Phillips, 2006, Kudielka et al., 2009), and some reporting no differences between the sexes (Earle et
Acute vs. chronic activation of the hypothalamic–pituitary–adrenal axis
Acute stressors typically produce rapid enhancement in glucocorticoid levels and do not affect the basal (non-stress) activity of the HPA axis (Assenmacher et al., 1995). This glucocorticoid response to an acute stressor is typically considered “adaptive”. Acute increases in glucocorticoids enhance arousal and energy mobilization (the brain stimulates neurotransmitter release, the muscles increase protein metabolism, the adipose tissue mobilizes lipids, and the liver increases glycogen
Acute stress in men and women by induction of panic attack symptoms
Panic attacks, which occur in both nonclinical and clinically-anxious populations, are time-limited, highly aversive, abrupt neurobiological events. They are often accompanied by wide-ranging negative physiological, psychological, behavioral, and health-related consequences (Barlow, 2001, Gater et al., 1998, Kessler et al., 1994, Lewinsohn et al., 1998, Patel et al., 1999, Pearson, 1995). A model of acute stress/panic is exposure to carbon dioxide (CO2)-enriched air, which produces autonomic
Stress response among laboratory workers in the native environment
Our laboratory is situated in a new Life Sciences Research Building on The University at Albany-SUNY campus and infrequent construction is still necessary to conduct at times. Given the impact that auditory stimuli can have on behavioral outcomes of people and animals under laboratory conditions, routine construction is coordinated so as not to occur when experiments are being conducted. However, we have recently experienced an unanticipated situation wherein workers (6 male and 9 female
Salivary cortisol and restrained eating in the native environment
A common, sex-biased, stress-related disorder among college students is disordered eating, or aberrant eating/dieting behavior. With our collaborator, Dr. Drew Anderson, we have found that among non-obese, undergraduate college women, those identified by questionnaires (Herman and Polivy, 1980) as demonstrating restrained eating (n = 50; characterized by chronic, unsuccessful dieting and fluctuating weight; Anderson et al., 2002, Gorman and Allison, 1995, Heatherton et al., 1988) had
HPA activation in recreational and pathological gamblers in the laboratory setting
Neuroendocrine factors appear to play a role in impulsivity associated with motivated behavior. Pathological gamblers can exhibit levels of impulsivity that exceed those observed in non-gambling controls, recreational gamblers, and individuals with substance use addictions that include alcohol and cocaine (Blaszczynski et al., 1997, Castellani and Rugle, 1995, Steel and Blaszczynski, 1998). Moreover, impulsivity has been related to severity of gambling as measured by the South Oaks Gambling
Stress response and engagement in gambling behavior in the native environment
We have observed that HPA arousal is attenuated among pathological gamblers in a laboratory setting when exposed to gambling cues, but whether engaging in gambling in the native environment would differentially influence HPA function was of interest. Engagement in motivated behaviors in the native situation presents a unique circumstance under which HPA-related effects on behavior can be observed. A reciprocal relationship between pharmacological addiction and HPA activation may exist, such
Chronic stress in posttraumatic stress disorder
We have found that, among healthy individuals in the described studies, HPA activity is greater among women than men in response to acute stressors. When considering a pathological state, such as gambling addiction, this sex difference may be reversed and this reflects the behavioral phenotype wherein men may be more vulnerable to pathology. It is also important to understand the influence that sex may have in cases of extreme pathology caused by stress.
Stress is a cause of PTSD, which results
Role of hypothalamic–pituitary–gonadal axis
An important question is what processes may underlie these sex differences in cortisol response. Sexual differentiation is initiated by early organizational effects of androgens and estrogens in humans and animals. Throughout life, production of steroids (primarily androgens from the testes of males and estrogens/progestogens from the ovaries of females) will have activational effects to alter physiological and psychological processes. Secretion of gonadotropin releasing hormone from
Conclusion
Together our data and the findings of others reveal that HPA function can influence, and be influenced by, pathophysiological state and this may have implications for neuropsychiatric disorders (such as panic attack, disordered eating, and PTSD) as well as development of pathological engagement in reward behavior such as drug use and gambling. Further, these data elucidate the nature of sex differences when observing situations wherein sex biases are minimized or are atypical. The sex-specific
Acknowledgments
We would like to thank Jennifer Courtney for providing information on the history and background of posttraumatic stress disorder. These investigations were supported by funding from The University at Albany-SUNY Faculty Research Award Program, the National Institute of Mental Health (MH06769801), and the National Institute of Child Health and Human Development (K23HD041428, R01HD039129).
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