In this article, the authors present evidence regarding a dissociative subtype of PTSD, with clinical and neurobiological features that can be distinguished from nondissociative PTSD. The dissociative subtype is characterized by overmodulation of affect, while the more common undermodulated type involves the predominance of reexperiencing and hyperarousal symptoms. This article focuses on the neural manifestations of the dissociative subtype in PTSD and compares it to those underlying the reexperiencing/hyperaroused subtype. A model that includes these two types of emotion dysregulation in PTSD is described. In this model, reexperiencing/hyperarousal reactivity is viewed as a form of emotion dysregulation that involves emotional undermodulation, mediated by failure of prefrontal inhibition of limbic regions. In contrast, the dissociative subtype of PTSD is described as a form of emotion dysregulation that involves emotional overmodulation mediated by midline prefrontal inhibition of the same limbic regions. Both types of modulation are involved in a dynamic interplay and lead to alternating symptom profiles in PTSD. These findings have important implications for treatment of PTSD, including the need to assess patients with PTSD for dissociative symptoms and to incorporate the treatment of dissociative symptoms into stage-oriented trauma treatment.

We have previously reported smaller hippocampal volume and deficits in short-term memory in patients with combat-related posttraumatic stress disorder (PTSD) relative to comparison subjects. The purpose of this study was to compare hippocampal volume in adult survivors of childhood abuse to matched controls. Magnetic resonance imaging was used to measure volume of the hippocampus in adult survivors of childhood abuse (n = 17) and healthy subjects (n = 17) matched on a case-by-case basis for age, sex, race, handedness, years of education, body size, and years of alcohol abuse. All patients met criteria for PTSD secondary to childhood abuse. PTSD patients had a 12% smaller left hippocampal volume relative to the matched controls (p < .05), without smaller volumes of comparison regions (amygdala, caudate, and temporal lobe). The findings were significant after controlling for alcohol, age, and education, with multiple linear regression. These findings suggest that a decrease in left hippocampal volume is associated with abuse-related PTSD.

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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.

Objective-Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects.Method-Study participants were 32 women with current unipolar major depressive disorder-21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse-and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects' diagnoses.Results-The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects.Conclusions-A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder.Stressful life events are frequently associated with the onset of episodes of major depression (1, 2). Elevated levels of plasma cortisol (3, 4) and deficits in declarative memory mediated by the hippocampus (5-7) have also been reported in subgroups of patients with unipolar major depressive disorder. Preclinical studies have confirmed that chronic psychosocial stress and cortisol administration inhibit neurogenesis in the dentate gyrus (8-10) and cause atrophy or remodeling of the apical dendrites of the pyramidal neurons in the CA3 region of the hippocampus (reviewed in references 11-13). Morphometric techniques based on magnetic resonance imaging have been used to determine whether these preclinical findings of hippocampal damage can be extended to patients with major depression and other stress-related disorders. Over the last 5 years, several groups have confirmed smaller than normal volumes of the left hippocampus (14, 15) and of the left and right hippocampus (5, 16, 17) in unipolar major depressive disorder. A smaller hippocampal volume was correlated with the total duration of depression (5, 16). Other groups, however, have not found significant differences in hippocampal volume between patients with unipolar major depressiv...

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

These results are consistent with deficits in hippocampal function and structure in abuse-related PTSD.

We recommend that consideration be given to adding a dissociative subtype of PTSD in the revision of the DSM. This facilitates more accurate analysis of different phenotypes of PTSD, assist in treatment planning that is informed by considering the degree of patients' dissociativity, will improve treatment outcome, and will lead to much-needed research about the prevalence, symptomatology, neurobiology, and treatment of individuals with the dissociative subtype of PTSD.