Post-traumatic stress disorder

Abstract

Post-traumatic stress disorder (PTSD) occurs in 5-10% of the population and is twice as common in women as in men. Although trauma exposure is the precipitating event for PTSD to develop, biological and psychosocial risk factors are increasingly viewed as predictors of symptom onset, severity and chronicity. PTSD affects multiple biological systems, such as brain circuitry and neurochemistry, and cellular, immune, endocrine and metabolic function. Treatment approaches involve a combination of medications and psychotherapy, with psychotherapy overall showing greatest efficacy. Studies of PTSD pathophysiology initially focused on the psychophysiology and neurobiology of stress responses, and the acquisition and the extinction of fear memories. However, increasing emphasis is being placed on identifying factors that explain individual differences in responses to trauma and promotion of resilience, such as genetic and social factors, brain developmental processes, cumulative biological and psychological effects of early childhood and other stressful lifetime events. The field of PTSD is currently challenged by fluctuations in diagnostic criteria, which have implications for epidemiological, biological, genetic and treatment studies. However, the advent of new biological methodologies offers the possibility of large-scale approaches to heterogeneous and genetically complex brain disorders, and provides optimism that individualized approaches to diagnosis and treatment will be discovered.

Altered stress system reactivity after pediatric injury: Relation with post-traumatic stress symptoms

“…In relation to avoidance and numbing PTSS clusters in adults, functional imaging studies reported negative correlation with activation in dorsomedial prefrontal cortex (Frewen et al, 2012) and rostral anterior and subcallosal cingulate regions, in conjunction with positive correlation with superior temporal cortex activation (Hopper et al, 2007). These findings are consistent with an emotion dysregulation model positing post-traumatic alteration in pathway integrity and network connectivity of structures involved in top-down inhibition of limbic structures that regulate emotional reactivity (Yehuda et al, 2015). High levels of noradrenergic signaling may contribute to emotion dysregulation through inhibition of prefrontal regulatory systems, resulting in increased activity and reactivity in the amygdala (Hendrickson and Raskind, 2016).…”

New translational perspectives for blood-based biomarkers of PTSD: From glucocorticoid to immune mediators of stress susceptibility

“…Although numerous changes in HPA-axis (re)activity have been observed in PTSD, some of the findings have not followed those described as part of classic acute or chronic responses to challenge. GC alterations in PTSD [recently reviewed in: (Yehuda et al, 2015d)] involve: Altered adrenal production of GCs. PTSD has been mostly associated with lower levels of the stress hormone cortisol (Yehuda et al, 2015d).…”

“…GC alterations in PTSD [recently reviewed in: (Yehuda et al, 2015d)] involve:

Altered adrenal production of GCs. PTSD has been mostly associated with lower levels of the stress hormone cortisol (Yehuda et al, 2015d). However, some studies failed to observe differences in the basal GC tone and others reported increased basal cortisol levels (Klaassens et al, 2012; Meewisse et al, 2007; Morris et al, 2012).

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“…While there has been progress in identifying blood-based biological perturbations, such as dysregulation of the HPA-axis and the immune system that are associated with vulnerability to stress-related mental disorders (Michopoulos et al, 2015; Pitman et al, 2012; Yehuda et al, 2015d; Zoladz and Diamond, 2013), it has been difficult to identify reliable blood biomarkers for use as diagnostic tools. The development of new system-wide techniques (i.e., genomic, epigenomic, transcriptomic, proteomic and metabolomic profiling) has permitted a greater examination of potential drivers or functional outcomes of stress-related dysregulation, advancing unbiased discovery of novel biomarkers implicated in PTSD susceptibility.…”

Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

“…Although there have been recent reviews of PTSD that have included a discussion of the functional neuroimaging literature 12 and several recent reviews of the microcircuitry involved in brain regions implicated in PTSD-related circuits 7,8,10 , there has not yet been an attempt to bridge human and animal literatures in the discussion of PTSD pathophysiology. Because the DSM-5 remains dominant in clinical academic medicine, we have chosen to structure this Review according to its criteria rather than the categories outlined in the RDoC; however, we provide an attempt to align the DSM-5 criteria with the current RDoC matrix (TABLE 1).…”