Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT1A expression

Abstract

The long-term behavioral, psychological, and neurobiological effects of exposure to potentially traumatic events vary within the human population. Studies conducted on trauma-exposed human subjects suggest that differences in trauma type and extent of exposure combine to affect development, maintenance, and treatment of a variety of psychiatric syndromes. The serotonin 1-A receptor (5-HT1A) is an inhibitory G protein-coupled serotonin receptor encoded by the HTR1A gene that plays a role in regulating serotonin release, physiological stress responding, and emotional behavior. Studies from the preclinical and human literature suggest that dysfunctional expression of 5-HT1A is associated with a multitude of psychiatric symptoms commonly seen in trauma-exposed individuals. Here, we synthesize the literature, including numerous preclinical studies, examining differences in alterations in 5-HT1A expression following trauma exposure. Collectively, these findings suggest that the impact of trauma exposure on 5-HT1A expression is dependent, in part, on trauma type and extent of exposure. Furthermore, preclinical and human studies suggest that this observation likely applies to additional molecular targets and may help explain variation in trauma-induced changes in behavior and treatment responsivity. In order to understand the neurobiological impact of trauma, including the impact on 5-HT1A expression, it is crucial to consider both trauma type and extent of exposure.

Peritraumatic tonic immobility and posttraumatic symptoms among LGBTQ+ versus straight cisgender female sexual assault survivors.

“…These findings were partially accounted for by differences in negative life experiences, with more life stressors reported in the Black American group compared to the White American group. This is consistent with the broader literature on threat responding, which suggests that chronic exposure to stressors, particularly interpersonal stressors, throughout the lifetime influences subsequent physiological threat responding and emotional behavior (Lewis et al, 2020). Furthermore, results from one study among LGBTQ+ students examining risk factors for sexual violence suggested that minority stress may influence peritraumatic reactions in the context of SA, specifically decreasing the likelihood that an individual will respond assertively (i.e., fight or flee) when confronted with sexual threat (Murchison et al, 2017).…”

Multiverse analyses of fear acquisition and extinction retention in posttraumatic stress disorder

“…Thus, future studies using neuroimaging measures may also benefit from application of multiverse analysis to investigate the impact of methodological heterogeneity on clinical fear learning findings. Finally, although our study focuses on the conventional DSM‐based diagnosis of PTSD, PTSD is clinically and biologically heterogeneous (Galatzer‐Levy et al, 2017; Lewis et al, 2020; Liberzon, 2018). Thus, fear extinction retention deficits may exist in only a yet to be confirmed subset of PTSD patients (Liberzon, 2018; Lonsdorf & Merz, 2017), and we recommend that future studies apply multiverse analysis to the exploration of fear extinction retention in theory‐based (e.g., hypo versus hyper reactive (Lang et al, 2016)) or statistically‐derived (Galatzer‐Levy et al, 2017; Lewis et al, 2021) PTSD subgroups.…”

Impact of Trauma Type on Startle Reactivity to Predictable and Unpredictable Threats

“…There is growing recognition that traumas can be classified into different categories including interpersonal trauma (e.g., sexual assault and harassment, physical assault, threatened assault with a weapon), accidental traumas (e.g., life-threatening car accident), natural disasters, and other stressful incidents (Wamser-Nanney et al, 2018). Preclinical studies have demonstrated trauma type can impact gene expression related to physiological stress responding and emotional behavior (Lewis et al, 2020). Trauma type is also associated with differential risk for psychopathology and other posttrauma outcomes (Shakespeare-Finch and Armstrong, 2010).…”

“…, life-threatening car accident), natural disasters, and other stressful incidents (Wamser-Nanney et al, 2018). Preclinical studies have demonstrated trauma type can impact gene expression related to physiological stress responding and emotional behavior (Lewis et al, 2020). Trauma type is also associated with differential risk for psychopathology and other posttrauma outcomes (Shakespeare-Finch and Armstrong, 2010).…”