Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors.

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation.

Joint Effect of Childhood Abuse and Family History of Major Depressive Disorder on Rates of PTSD in People with Personality Disorders.

Objective. Childhood maltreatment and familial psychopathology both lead to an increased risk of the development of posttraumatic stress disorder (PTSD) in adulthood. While family history of psychopathology has traditionally been viewed as a proxy for genetic predisposition, such pathology can also contribute to a stress-laden environment for the child. Method. Analyses were conducted to evaluate the joint effect of childhood abuse and a family history of major depressive disorder (MDD) on diagnoses of PTSD and MDD in a sample of 225 adults with DSM-IV Axis II disorders. Results. Results showed that the rate of PTSD in the presence of both childhood abuse and MDD family history was almost six-fold (OR = 5.89, P = .001) higher relative to the absence of both factors. In contrast, the rate of MDD in the presence of both factors was associated with a nearly three-fold risk relative to the reference group (OR = 2.75, P = .01). Conclusions. The results from this observational study contribute to a growing understanding of predisposing factors for the development of PTSD and suggest that joint effects of family history of MDD and childhood abuse on PTSD are greater than either factor alone.

Deficient visual sensitivity in schizotypal personality disorder.

Schizotypal personality disorder is a personality disorder in the schizophrenia spectrum, sharing genetic and neurobiologic characteristics with schizophrenia. Visual contrast detection, found to be abnormal in chronic schizophrenia, was investigated in schizotypal personality disorder (SPD). Since dopamine in the retina enhances visual contrast detection and SPD patients have relatively reduced dopaminergic activity in the brain compared to schizophrenia patients, it was hypothesized that SPD patients would have decreased to normal contrast sensitivity. Twenty-one subjects with DSM-IV diagnosed SPD, 18 healthy controls, and 12 subjects with a personality disorder unrelated to schizophrenia (OPD) were evaluated for contrast detection using a sinusoidal grating presented at varying temporal frequencies. Subjects also were evaluated neuropsychologically using several standardized neurocognitive tests. A significant effect of subject group was found on the contrast detection threshold (p<0.01) with a significant difference between the SPD group and the healthy control group but not between the OPD group and the healthy control group. The SPD group had higher contrast detection thresholds at all temporal frequencies tested. Correlations were found between contrast detection and performance on the Trail-Making, N-Back, and CPT tasks in SPD patients. These results, based upon a paradigm reflecting dopamine activity in the early visual system, highlight the differences as well as similarities between SPD and schizophrenia with regard to the dopamine system in schizophrenia spectrum (Siever and Davis, 2004).

Smaller superior temporal gyrus volume specificity in schizotypal personality disorder.

BACKGROUND: Superior temporal gyrus (STG/BA22) volume is reduced in schizophrenia and to a milder degree in schizotypal personality disorder (SPD), representing a less severe disorder in the schizophrenia spectrum. SPD and Borderline personality disorder (BPD) are severe personality disorders characterized by social and cognitive dysfunction. However, while SPD is characterized by social withdrawal/anhedonia, BPD is marked by hyper-reactivity to interpersonal stimuli and hyper-emotionality. This is the first morphometric study to directly compare SPD and BPD patients in temporal lobe volume. METHODS: We compared three age-, sex-, and education-matched groups: 27 unmedicated SPD individuals with no BPD traits, 52 unmedicated BPD individuals with no SPD traits, and 45 healthy controls. We examined gray matter volume of frontal and temporal lobe Brodmann areas (BAs), and dorsal/ventral amygdala from 3-T magnetic resonance imaging. RESULTS: In the STG, an auditory association area reported to be dysfunctional in SPD and BPD, the SPD patients had significantly smaller volume than healthy controls and BPD patients. No group differences were found between BPD patients and controls. Smaller BA22 volume was associated with greater symptom severity in SPD patients. Reduced STG volume may be an important endophenotype for schizophrenia-spectrum disorders. SPD is distinct from BPD in terms of STG volume abnormalities which may reflect different underlying pathophysiological mechanisms and could help discriminate between them.

Independent evaluator knowledge of treatment in a multicenter comparative treatment study of panic disorder.

The purpose of this study was to examine independent evaluators' (IEs) blindness to treatment condition during a Multicenter Comparative Treatment Study of Panic Disorder. IEs were 15 doctoral- and masters-level clinicians in psychology, social work, and medicine. They conducted three post-treatment assessments with each patient. Immediately after each assessment interview, IEs completed a form indicating which of the five possible treatments they believed the patient had received and any specific information that provided IEs with information about a patient's treatment condition. These forms were completed for 170 patients. Analyses were conducted to determine the accuracy of guesses about treatment condition by IEs during post-treatment assessments, the relationship between accuracy of IE guessing and actual treatment assignment, the relationship between accurate guessing and outcome ratings, and contributors to the breaking of the blind. A significant relationship was found between IE guesses and actual treatment at all three assessment points, across individual IEs, treatment sites, and IE professional affiliations. IEs were no more accurate in their guessing about patients taking medication than those receiving behavior therapy. Patients and project staff inadvertently provided information to IEs that enhanced the rates of accurate guessing. Implications of these findings on interpretation of the treatment study are discussed, and recommendations are made for improving blindness procedures.