Tuesday, May 6, 2014

(en)Gendering psychiatric disease: what does sex/gender have to do with posttraumatic stress disorder (PTSD)?

Mallory Bowers is a 5th year Neuroscience doctoral candidate working with Dr. Kerry Ressler at Emory University. Prior to graduate school, Mallory received her Bachelor of Arts from the University of Pennsylvania. Mallory is interested in behavioral neuroscience, with a particular focus on how neural plasticity contributes to learning. With Dr. Ressler, Mallory is using a mouse model of exposure-based psychotherapy to better understand the neurobiology of learned fear. Specifically, her research focuses on a potential interaction between the cholecystokinin and endogenous cannabinoid systems that may underlie extinction of cued fear. Mallory was on the organizing committee for the 2013 “Bias in the Academy” Conference and is President of Emory Women in Neuroscience (E-WIN).

As I’ve become more entrenched in the PTSD field, I’ve been struck by the prominent sex/gender difference in the prevalence of PTSD (among many other psychiatric disorders) and the categorical use of male animal models. As researchers begin to explore sex differences in animal models of stress, anxiety, and fear, evidence suggests that male animals are more vulnerable to acute and chronic stress, while females appear to be more resilient (Cohen and Yehuda 2011). The results of these animal studies contradict the human epidemiological data, with lifetime prevalence of PTSD at 10-14% in women and 5-6% in men in the United States (Breslau, Davis, et al. 1991, Breslau, Davis, et al. 1997, Kessler, Sonnega, et al. 1995, Resnick, Kilpatrick, et al. 1993). In this post, I’d like to explore the ways in which socio-cultural conditioning genders an individual’s sense of self, influences definitions and language surrounding mental health, and supports frameworks of gender bias (a putative low-grade, chronic stressor) - potentially contributing to sex/gender differences observed in the prevalence of certain psychiatric disorders, specifically PTSD.

Sex and Gender Primer

Sex refers to the biological and physiological characteristics that define men and women, including sex chromosomes, gonads, and hormones. The definition of gender is more complicated, but generally refers to socially and culturally endorsed roles, behaviors, and activities for men and women. Gender can describe the relationship between one’s traits and one’s sense of self as male, female, or somewhere in between. Social and cultural influences promote gender scripts from infancy throughout adulthood. For the purposes of this post, I use the term sex/gender to acknowledge the importance of both physical and cultural features, particularly in describing the interpretations of data from human research.
Via BigStockPhoto.com

Importance of self-definition

Consistently, evidence from psychology research suggests that sense of self and self-definition (also referred to as self-construal) can function as a lens through which individuals can interpret information (Wyer and Srull 1984). Rigid gender roles in Western cultures, some have suggested, could differentially impact the development of self-construal (Cross and Madson 1997, Cross, Bacon, et al. 2000). In considering sex/gender differences in prevalence of PTSD, could a gendered self-construal precipitate risk for PTSD by influencing interpretation of trauma? In fact, trauma severity is thought to contribute to prevalence of PTSD, where trauma severity is defined by subjective emotional response that varies based on individual perception (Foa, Zinbarg, et al. 1992, Kessler, Sonnega, et al. 1995, Yehuda 2002, Yehuda 2004).

Interestingly, analysis of US epidemiological data reveals sex/gender differences in PTSD for certain types of trauma – specifically, trauma that involves interpersonal conflict. Kessler et al. find significant sex/gender differences in rates of PTSD when trauma involves molestation, physical attack, combat, shock, threat with a weapon, physical abuse, or witnessing injury or death (Breslau, Davis, et al. 1991, Kessler, Sonnega, et al. 1995). Men and women develop PTSD at comparable rates when trauma involves sudden injury, accident, natural disaster with fire, or witnessing injury or death (Breslau, Davis, et al. 1991, Kessler, Sonnega, et al. 1995). This suggests that it is not merely the presence of trauma, but the interpretation of a specific trauma that results in sex/gender differences in the prevalence of PTSD. If trauma severity - shaped by an individual’s subjective perception - influences risk for PTSD and perception (or self-construal) is gendered according to socio-cultural conditioning, then researchers need to address whether strict gender binaries influence self-construal and/or traits that differentially precipitate risk for PTSD.

Gendered representations of PTSD

Although I propose that gendered self-construals could interact with particular types of trauma, manifesting in differential rates of PTSD among men and women, this is likely not the sole mechanism contributing to sex/gender differences in rates of PTSD. One possibility is that sex/gender specific presentations of PTSD in men leads to “misdiagnosis”. Young girls who are exposed to trauma are more likely to report “internalizing” symptoms - depression, anxiety, and hyperarousal, whereas boys more often report “externalizing” symptoms, such as aggression and conduct problems (Buckner, Beardslee, et al. 2004, Gustafsson, Larsson, et al. 2009). Men present with more denial, emotion control, behavioral problems, suicidality, violence, and substance abuse following sexual trauma (Darves-Bornoz, Choquet, et al. 1998, Kaufman, Divasto, et al. 1980). These externalizing versus internalizing symptoms, some have posited, contribute to sex/gender differences in the diagnosis of antisocial personality disorder (ASPD) and borderline personality disorder (BPD) – which some have suggested are the same disorder with gender specific presentations (Hudziak, Boffeli, et al. 1996, Lobbestael, Arntz, et al. 2005). With differential rates of PTSD among men and women, potentially derived from differences in symptomatology, one reasonable question to ask is - are there gender essential psychiatric disorders? This is particularly interesting, as most psychiatric disorders are not diagnosed by “objective” measures, such as biomarkers, but by suites of symptoms characterized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). This question might be clarified by comparing the symptomatology of psychiatric disorders that present with sex/gender differences.

The stress of gender bias

Moreover, is gender inequality generally stressful – possibly contributing to higher rates of PTSD and other psychiatric disorders in women? Notably, several international studies (conducted in Canada, Australia, Germany, and Switzerland) have not found significant sex/gender differences in the prevalence of PTSD (Creamer, Burgess, et al. 2001, Lukaschek, Kruse, et al. 2013, Maercker, Forstmeier, et al. 2008, Stein, Walker, et al. 1997). According to the 2013 Global Gender Gap report, these countries rank equal to or higher than the United States on an index measuring the percentage of inequality between men and women that has been closed (meaning, these countries have lower rates of sex/gender inequality than the United States). The stress of microaggressions (Sue 2010) related to gender bias and discrimination is likely to exert long-term ramifications, potentially contributing to rates of psychiatric disease like PTSD, as research demonstrates that pre-trauma risk factors like life stress predict PTSD (Brewin, Andrews, et al. 2000).

Interestingly, researchers have begun to uncover links between chronic stress - which often precipitates psychiatric disease - and rates of cellular aging. Cellular environment, which can be regulated by perceived stress via oxidative stress, plays an important role in controlling telomere length (Epel, Blackburn, et al. 2004). Telomeres are regions of repetitive nucleotide sequences that protect the end of chromosomes. Telomeres protect gene truncation during DNA replication, as DNA polymerases are unable to continue DNA duplication through the end of chromosomes (Blackburn and Gall 1978). Studies suggest that oxidative stress shortens telomeres, and that antioxidants can decrease the rate of shortening (von Zglinicki 2002). African-Americans who are subject to significant racial discrimination, due to “weathering” or higher psychosocial stress, exhibit greater rates of telomere shortening compared to Caucasians (Rewak, Buka, et al. 2014). Further, African-Americans who report more interpersonal experiences of racial discrimination and have greater internalized negative racial bias have shorter telomere lengths compared to other African-Americans (Chae, Nuru-Jeter, et al. 2014). Some researchers report higher rates of PTSD among African-Americans compared to other races, although the literature is mixed, potentially due to problems of underreporting of psychiatric disease in African-Americans (Breslau and Anthony 2007, Kessler, Sonnega, et al. 1995). As in African-Americans, telomere length could provide a biological correlate of psychosocial stress due to gender bias, which could, in part, offer an explanation as to why women are more likely to develop PTSD. Addressing the question of whether the stress of gender inequality contributes to higher rates of PTSD and other psychiatric disorders is likely to be extremely complicated. However, the results of these studies could be transformative in how we think about psychiatric disease and how we might design and conduct future research to identify novel targets for treating and preventing PTSD.

Telomere Shortening (via nia.nih.gov)

Future directions and recommendations

By exclusively focusing on animal studies, or worse – conflating sex and gender in human research, researchers may accidentally disregard an important source of influence on neurobiology – society and culture. To avoid this ambiguity, scientists are advised to be discerning when referring to “sex” and “gender” in the interpretation of data (e.g. gender may not be appropriate when discussing a mouse model). As most human research is correlative, researchers will be unable to tease apart whether differences are attributed to sex or gender (to state otherwise would be un-scientific). Additionally, sex and gender influences are not necessarily mutually exclusive. Therefore, data interpretations should acknowledge as much.

Future scientific endeavors, particularly in the investigation of sex/gender differences in the prevalence of PTSD, will benefit from an alliance with the humanities who can provide a rich knowledge on how sociocultural factors shape conceptions of not only gender, but also illness. In this way, researchers can more thoroughly parse through risk factors for PTSD, such as differences in self-construal and gender bias. Furthermore, cross disciplinary, collaborative dialogue between the sciences would create more inclusive definitions of mental illness, as outlined by the DSM-V.

In highlighting the ways that society and culture influence the etiology and definition of PTSD, I hope I’ve underlined the work that needs to be done in order to bridge the gap in our understanding of psychiatric disease.


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Want to cite this post?

Bowers, M. (2014). (en)Gendering psychiatric disease: what does sex/gender have to do with posttraumatic stress disorder (PTSD)? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/05/engendering-psychiatric-disease-what.html

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