Larry A. Tupler

Assessment of a new self-rating scale for post-traumatic stress disorder

BACKGROUND In post-traumatic stress disorder (PTSD) there is a need for self-rating scales that are sensitive to treatment effects and have been tested in a broad range of trauma survivors. Separate measures of frequency and severity may also provide an advantage. METHODS Three hundred and fifty-three men and women completed the Davidson Trauma Scale (DTS), a 17-item scale measuring each DSM-IV symptom of PTSD on 5-point frequency and severity scales. These subjects comprised war veterans, survivors of rape or hurricane and a mixed trauma group participating in a clinical trial. Other scales were included as validity checks as follows: Global ratings, SCL-90-R, Eysenck Scale, Impact of Event Scale and Structured Clinical Interview for DSM-III-R. RESULTS The scale demonstrated good test-retest reliability (r = 0.86), internal consistency (r = 0.99). One main factor emerged for severity and a smaller one for intrusion. In PTSD diagnosed subjects, and the factor structure more closely resembled the traditional grouping of symptoms. Concurrent validity was obtained against the SCID, with a diagnostic accuracy of 83% at a DTS score of 40. Good convergent and divergent validity was obtained. The DTS showed predictive validity against response to treatment, as well as being sensitive to treatment effects. CONCLUSIONS The DTS showed good reliability and validity, and offers promised as a scale which is particularly suited to assessing symptom severity, treatment outcome and in screening for the likely diagnosis of PTSD.

Hypercortisolemia and hippocampal changes in depression

Hypercortisolemia is a frequently observed abnormality in patients with major depression. It has been hypothesized that the hippocampus, as a major feedback site for glucocorticoids, is involved in the pathophysiology of hypercortisolemia. Some have in fact posited that the hippocampus is marked by diminished size in depressed patients with hypercortisolemia. We tested this hypothesis by examining the relationship between hippocampal volume, assessed with magnetic resonance imaging, and hypercortisolemia using the dexamethasone suppression test (DST) in a group of 19 depressed patients. No differences in hippocampal volume were observed between patients and control subjects (n = 30). Within the patient group, DST suppressors did not differ from DST nonsuppressors in hippocampal volume. However, a relationship between hippocampal volume and 11 p.m. cortisol concentration was observed after covariance adjustment for age and sex. Furthermore, significant negative correlations were observed between hippocampal volume and both age of depressive onset and number of hospitalizations. The results of this study therefore provide limited support for the hypothesis regarding an essential role of the hippocampus in the neuroendocrine elevation of glucocorticoids in depression.

Cognitive sequelae of blast-related versus other mechanisms of brain trauma.

The use of improvised explosive devices has become the hallmark of modern warfare and has resulted in an ever-increasing number of blast-related traumatic brain injuries (TBIs). Despite this fact, very little is actually known about the cognitive sequelae of blast-related TBIs. The purpose of the current study was to compare patterns of performance on neuropsychological measures in subjects who have sustained TBIs as a result of blast (or explosion) with those who have sustained TBIs from non-blast or blunt force trauma (motor vehicle accident, fall, assault, etc.). Participants were categorized as blast-related TBI or non-blast-related TBI and according to severity of injury (mild or moderate-to-severe). No main effects were observed in analysis of covariance between blast-related TBI participants and non-blast-related TBI participants across any of the neuropsychological variables, although an interaction was observed on a visual memory test showing stronger performance for mild blast-related and poorer performance for moderate-to-severe blast-related participants compared with both non-blast groups. Overall, the results do not provide any strong evidence that blast is categorically different from other TBI mechanisms, at least with regard to cognitive sequelae on select measures. Additional findings included a marginally increased incidence of reported posttraumatic stress disorder symptoms among blast-injured participants. (JINS, 2009, 15, 1-8.).

Neuroanatomical substrates of depression in the elderly

SummaryThe etiology of depression in the elderly is poorly understood. In this study, magnetic resonance imaging was used to evaluate the role of subcortical structures in the pathophysiology of depression in the elderly. Elderly depressed patients were found to have smaller caudate nuclei, smaller putaminal complexes and in increased frequency of subcortical hyperintensities compared with normal, healthy controls. These findings were more pronounced in patients with lateonset depression. Based on these findings, the authors discuss the role of the basal ganglia in the pathophysiology of depression in the elderly.

The Brief Social Phobia Scale: a psychometric evaluation.

The Brief Social Phobia Scale (BSPS) is an observer-rated scale designed to assess the characteristic symptoms of social phobia, using three subscales-fear, avoidance, and physiological arousal-which may be combined into a total score. Each of 18 BSPS items is anchored to a 5-point rating scale. Psychometric evaluation of the BSPS in a sample of 275 social-phobia patients yielded a high level of reliability and validity. Test-retest reliability was excellent, as was internal consistency. The fear and avoidance subscales demonstrated highly significant correlations with remaining item totals; however, the physiological subscale did not. The BSPS also demonstrated significant relationships with other established scales that assess anxiety and disability, and it proved sensitive to treatment effects in a trial of a 5-HT3 antagonist and placebo. Factor analysis yielded six meaningful factors. We conclude that the BSPS provides a reliable, valid, and sensitive measure for the evaluation of social phobia.

Segmented Hippocampal Volume in Children and Adolescents with Posttraumatic Stress Disorder

BACKGROUND Although many studies of adults with posttraumatic stress disorder (PTSD) have reported smaller hippocampal volume compared with control subjects, comparable studies of children and adolescents have failed to replicate these findings or have noted opposite trends suggesting a larger hippocampus. We therefore performed a secondary analysis combining data from prior studies to examine the hypothesis that hippocampus would be larger in pediatric subjects with PTSD compared with non-maltreated control subjects. We also hypothesized that differences in PTSD subjects would be observed between boys and girls. METHODS Sixty-one subjects (31 boys, 30 girls) with maltreatment-related PTSD and 122 control subjects matched on age and gender underwent magnetic resonance imaging. RESULTS As hypothesized, we observed a significantly larger hippocampus controlling for cerebral volume in PTSD subjects compared with control subjects. Segmented hippocampal white-matter volume was greater in PTSD subjects but not gray-matter volume. Hippocampal volume was positively related to age of trauma onset and level of psychopathology, particularly externalizing behavior. No interactions with group were observed for age or gender. CONCLUSIONS Future longitudinal studies with trauma control subjects and neuropsychological measures are indicated to further elucidate the relationship between hippocampus and behavioral abnormalities in young PTSD subjects.

An effect-size analysis of pharmacologic treatments for generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a prevalent and impairing disorder, associated with extensive psychiatric and medical comorbidity and usually characterized by a chronic course. Different drugs have been investigated in GAD; among them are the following: 1) SSRIS: paroxetine, sertraline, fluvoxamine and escitalopram; 2) SNRI1S: venlafaxine; 3) benzodiazepines (BZS): alprazolam, diazepam and lorazepam; 4) azapirones (AZAS): buspirone; 5) antihistamines (AHS): hydroxyzine; 6) pregabalin (PGB); and 7) complementary/alternative medicine (CAM): kava-kava and homeopathic preparation. We conducted an effect size (ES) analysis of 21 double-blind placebo-controlled trials of medications treating DSM-III-R, DSM-IV or ICD-10 GAD using HAM-A change in score from baseline or endpoint score as the main efficacy measure. Literature search was performed using MEDLINE and PsycINFO databases including articles published between 1987 and 2003 and personal communications with investigators and sponsors. comparing all drugs versus placebo, the Es was 0.39. Mean Ess, excluding children, were PGB: 0.50, AH: 0.45, SNRI: 0.42, BZ: 0.38, SSRI: 0.36, AZA: 0.17 and CAM: -0.31. comparing ES for adults versus children/adolescents (excluding CAM) and conventional drugs versus CAM (excluding children/adolescents) we found significantly higher ES for children/adolescents and for conventional drugs (p < 0.001 and p < 0.01, respectively). No significant differences were found when comparing date of publication, location of site (i.e. US versus other), fixed versus flexible dosing, number of study arms, or number of outcome measures used. Medications varied in the magnitude of their Es, ranging from moderate to poor. AdolesCents and Children showed a muCh greater ES Compared with adultS. SubjeCts taking CAM had worse outComes than plaCebo.

Magnetic-resonance morphometry in patients with major depression

Magnetic-resonance morphometry performed on 72 patients with major depression compared with 38 control subjects replicated previously reported, statistically significant reductions in the volumes of the caudate (P < 0.03) and putamen (P < 0.05) in depressed patients. Borderline statistical significance was observed for whole-brain (P < 0.07) and frontal volume (P < 0.10) in a subsample of 32 patients matched on age and sex with 32 control subjects, whereas statistical significance was observed for the full sample (P < 0.007 and P < 0.03, respectively). Chronological age was related to volume of the frontal lobes (P < 0.0002), caudate (P < 0.0001), putamen (P < 0.008), thalamus (P < 0.002), cerebellum (P < 0.007), lateral ventricles (P < 0.0001), and ratios of [whole brain]/[whole brain + cerebrospinal fluid (CSF)] (P < 0.0001) and [frontal]/[frontal + CSF] (P < 0.0001). Age of first depressive episode was related to putamen volume after accounting for chronological age (R2= 0.16, P < 0.005), and a correlation of 0.26 (P < 0.04) was observed between caudate volume and global mental status. Results are in accord with previous reports of basal-ganglia abnormalities in depressed patients and support the role of subcortical structures in mediating affective disorder.

Anatomic location and laterality of MRI signal hyperintensities in late-life depression

OBJECTIVES Evidence is mounting linking cerebrovascular disease with the development of major depression in the elderly. Lesions in both white and gray matter have been associated with geriatric depression. In addition, the literature on poststroke depression suggests that left-sided lesions are associated with depression. We sought to examine the severity and location of white- and gray-matter lesions in a group of elderly depressives and nondepressed control subjects. METHOD 115 depressed patients (69 with late onset, 46 with early onset) and 37 controls, all over age 45, received magnetic resonance imaging (MRI). Semiquantitative severity ratings and quantitative measurements of number and size of MRI hyperintensities were obtained, and groups were compared using Cochran-Mantel-Haenszel (CMH) analyses and repeated-measures analyses of covariance adjusting for age. RESULTS Late-onset depressed patients had more severe hyperintensity ratings in deep white matter than early-onset patients and controls. Late- and early-onset patients had more severe subcortical gray-matter hyperintensities (particularly in the putamen) compared with controls. Left-sided white-matter lesions were significantly associated with older age of depression onset, whereas right-anterior white matter and left-subcortical lesions (particularly in the putamen) were associated with melancholia in the depressed group. CONCLUSION These findings extend previous reports of an association between cerebrovascular disease and depression, as well as recent studies showing lateralized lesion involvement in geriatric depression. Such vascular pathology may disrupt neural pathways involved in affective processing and the maintenance of a normal mood and psychomotor state.

Age and sex effects on brain morphology

1. Brain morphology can be assessed readily in vivo using magnetic resonance imaging (MRI). 2. In this study, the effects of age and sex on whole-brain morphology were examined using an operator-controlled computer-segmentation protocol. 3. Results indicated that age was associated with gray-matter volume reduction. 4. Brain-size differences between males and females were primarily attributable to white-matter volume. 5. This study confirms the importance of controlling for age and sex in brain-morphology studies.