Brain-imaging studies of posttraumatic stress disorder (PTSD) have rapidly increased in recent years. Structural studies have identified potential smaller volumes of the hippocampus of traumatized and/or PTSD subjects. Functional activation studies have implicated hyperactive or altered functioning of brain regions, such as the amygdala and the insula, and a failure to engage emotional regulatory structures, such as the medial prefrontal and anterior cingulate cortex. Recent neurochemical investigations have suggested that neuromodulatory systems (eg, γ-aminobutyric acid, μ-opioid) may underlie these aberrant brain activation patterns. This article reviews the literature on structural, functional, and neurochemical brain-imaging studies of PTSD.

Studies of the hypothalamic-pituitary-adrenal (HPA ) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at γ-arninobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.

What biological responses characterize those acute trauma reactions that develop into chronic psychiatric disorder? The need to understand the genesis of posttraumatic psychological disorders has resulted in much attention on biological reactions in the initial aftermath of trauma exposure. This review outlines the prevailing biological models of acute stress reaction and critiques the available evidence concerning biological responses to trauma that are associated with subsequent psychological disorder. The roles of peritraumatic dissociation and vulnerability factors for acute stress reaction are also reviewed. The major challenges for research on psychobiological responses to trauma are highlighted.

Traditional methods for analyzing trends in longitudinal data have typically emphasized average group change over time. In this article, we propose multilevel, regression-based methods for examining inter-individual differences in intra-individual change and apply these methods to research in trauma and posttraumatic stress disorder (PTSD). The outcome or dependent variable of interest is reconceptualized as an index of dynamic change reflecting the trend or trajectory of an individual's PTSD symptom severity scores across time. A basic statistical model is presented, and analyses and findings are demonstrated with an existing database used in previously published studies. The methods offer promise for future study of the natural course of PTSD chronicity or recovery, risk and resilience factors that influence individual growth or decline, and critical timepoints for intervention.

Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder marked by behavioral, physiologic, and hormonal alterations. PTSD is disabling and commonly follows a chronic course. The etiology of PTSD is unknown, although exposure to a traumatic event constitutes a necessary, but not sufficient, factor. A twin study of Vietnam veterans has shown significant genetic contribution to PTSD. The fact that PTSD's underlying genotypic vulnerability is only expressed following trauma exposure limits the usefulness of family-based linkage approaches. In contrast to the other major psychiatric disorders, large studies for the search of underlying genes have not been described in PTSD to date. Complementary approaches for locating involved genes include association-based studies employing case-control or parental genotypes for transmission dysequilibrium analysis and quantitative trait loci studies in animal models. Identification of susceptibility genes will increase our understanding of traumatic stress disorders and help to elucidate their molecular basis. The current review provides an up-to-date outline of progress in the field of PTSD.