A Multi-Modal Investigation of Neurophysiological Deficits in PTSD

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Project Summary Women are twice as likely as men to be diagnosed with posttraumatic stress disorder (PTSD), and sex hormones have been implicated in this difference. While research has begun to elucidate neurophysiological contributions to PTSD, there is a dearth of knowledge regarding how sex hormones influence these dynamics to confer greater risk among women. For example, while PTSD is generally associated with increased resting state activity of the dorsal anterior cingulate cortex (dACC) and decreased activity of the ventromedial prefrontal cortex (vmPFC), women may exhibit lower activity in these regions compared to men. Other research has shown that PTSD is associated with decreased functional connectivity of frontal brain regions. However, no prior research has tested dACC-vmPFC functional connectivity in men versus women, which could provide insight into mechanisms underlying PTSD sex differences. Further, low estradiol and high progesterone have been associated with worse fear inhibition in women with PTSD, and testosterone levels have been implicated in PTSD among men, though findings are mixed. No prior studies have examined how sex hormone levels modulate dACC-vmPFC activity or functional connectivity in PTSD, and no studies have compared these effects in men versus women. This proposed supplement will directly address these gaps by adding a new sample of men to the ongoing Parent K23 study, as well as by adding testosterone assays to existing assays of estradiol and progesterone. By examining the effects of sex hormones (estradiol, progesterone, testosterone) in both men and women, this proposal will characterize the role of sex in the neurophysiological deficits seen in PTSD. The proposed supplement will be embedded within the existing Parent K23 study, which has recruited 60 women thus far. The supplement will include a new sample of 30 men with PTSD. The goals of the Parent K23 and this proposed supplement are directly in line with Strategic Goal 1 of the 2019-2023 Trans- NIH Strategic Plan for Women's Health Research: “Advance rigorous research that is relevant to the health of women.” In particular, Objective 1.2 is to “Investigate the influence of sex and gender on disease presentation,” and the proposed supplement will probe the role of three different sex hormones (sex) on neurophysiological deficits in both men and women with PTSD.