Murray B. Stein

Hippocampal volume in women victimized by childhood sexual abuse

BACKGROUNDnSeveral prior studies have found reduced hippocampal volume in victims of psychological trauma with post-traumatic stress disorder (PTSD). We were interested to determine if this finding was evident in women who were victimized by severe sexual abuse in childhood.nnnMETHODSnIn this study, hippocampal volume was measured using quantitative magnetic resonance imaging (MRI) in 21 women who reported being severely sexually abused in childhood and 21 socio-demographically similar women without abuse histories.nnnRESULTSnWomen who reported sexual victimization in childhood had significantly reduced (5% smaller) left-sided hippocampal volume compared to the non-victimized women. Hippocampal volume was also smaller on the right side, but this failed to reach statistical significance. Left-sided hippocampal volume correlated highly (rs = -0.73) with dissociative symptom severity, but not with indices of explicit memory functioning.nnnCONCLUSIONSnThese findings, which are generally consistent with prior reports of reduced hippocampal volume in combat veterans with PTSD, suggest that diminished hippocampal size may be either a consequence of trauma exposure or a risk factor for the development of psychiatric complications following trauma exposure. The observed relationship between symptom severity and hippocampal volume suggests that mesial temporal lobe dysfunction may directly mediate certain aspects of PTSD and dissociative disorder symptomatology.

Social phobia and potential childhood risk factors in a community sample

BACKGROUNDnThis study examined the relationship between potential childhood risk factors and social phobia in an epidemiological sample. Identifying risk factors such as childhood adversities can often uncover important clues as to the aetiology of a disorder. This information also enables health care providers to predict which individuals are most likely to develop the disorder.nnnMETHODSnData came from the Mental Health Supplement to the Ontario Health Survey of a survey of 8116 Canadian respondents, aged 15-64. Social phobia was diagnosed using the Composite International Diagnostic Interview (CIDI). Childhood risk factors were assessed by a series of standardized questions.nnnRESULTSnA positive relationship was observed between social phobia and lack of close relationship with an adult, not being first born (in males only), marital conflict in the family of origin, parental history of mental disorder, moving more than three times as a child, juvenile justice and child welfare involvement, running away from home, childhood physical and sexual abuse, failing a grade, requirement of special education before age 9 and dropping out of high school. Many of these variables remained significant after controlling for phobias, major depressive disorder and alcohol abuse. The data also suggest that some childhood risk factors may interact with gender to influence the development of social phobia.nnnCONCLUSIONSnAlthough an association was detected between social phobia and childhood risk factors, naturalistic prospective studies are needed to clarify the aetiological importance of these and other potential risk factors for the disorder.

Sleep in nondepressed patients with panic disorder: II. Polysomnographic assessment of sleep architecture and sleep continuity

This study assessed the EEG sleep of 16 patients with panic disorder who did not currently meet criteria for major depression in comparison to 16 age-comparable healthy controls. Patients with panic disorder had remarkably normal sleep, with only a modest reduction in total sleep time (374 +/- 46 min vs. 399 +/- 36 min) and delta sleep (11.4 +/- 6.2% vs. 16.4 +/- 6.6%) noted. Contrary to expectation, impairment in sleep maintenance and continuity was not found in the patients with panic disorder. We conclude (a) sleep in non-depressed patients with panic disorder is fairly unremarkable, and does not resemble that classically described for depressed patients, and (b) excessive arousability is not a characteristic feature of sleep in panic disorder.

Mixed anxiety-depression in a primary-care clinic

To determine the prevalence and clinical significance of a mixed anxiety-depressive (MAD) syndrome in primary care, a two-stage sampling design was applied to 796 consecutive clinic attendees without known psychiatric illness. Among 78 systematically interviewed subjects, 10.3% (n = 8) had a depressive disorder alone, 12.8% (n = 10) had an anxiety disorder alone, 19.2% (n = 15) had a comorbid anxiety and depressive disorder and 12.8% (n = 10) had a combination of subsyndromal anxiety and depressive features that fulfilled either ICD-10 or our own operational criteria for MAD. Patients with MAD rated their disability as being comparable to that of patients with anxiety or depressive disorders. These findings lend support to the notion that there is a sizeable subgroup of patients in primary care who appear to be suffering from a psychiatric syndrome with an admixture of subsyndromal depressive and anxiety features. Questions about the temporal stability of MAD and preferred approaches to treatment have yet to be answered.

Autonomic function in panic disorder: cardiorespiratory and plasma catecholamine responsivity to multiple challenges of the autonomic nervous system

Panic disorder has been widely hypothesized to be associated with dysfunction of the autonomic nervous system. In this study, 24 patients with panic disorder and 26 healthy control subjects took part in a broad battery of autonomic function tests, each designed to stress the autonomic nervous system in a particular fashion. Testing consisted of postural challenge, isometric exercise, cold pressor, and Valsalva maneuver. Dependent measures included heart rate, vagal tone, blood pressure, respiratory frequency, end-tidal CO2 levels, and plasma norepinephrine and epinephrine levels. The testing procedures reliably produced changes in autonomic output in the expected directions, but patients with panic disorder were not found to differ from healthy controls in their cardiorespiratory or plasma catecholaminergic responses. This pattern of normal autonomic responsivity in the patients with panic disorder was evident across multiple test conditions with varying autonomic demand characteristics, thereby supporting the integrity of autonomic regulatory systems in this illness. These data run counter to a simple notion of autonomic dysfunction in panic disorder.

Autonomic responsivity in generalized social phobia.

To determine whether patients with generalized social phobia exhibit evidence of abnormal autonomic nervous system (ANS) functioning, 15 non-depressed, medication-free subjects with DSM-IV social phobia (generalized type) and 15 healthy control subjects participated in a series of autonomic function tests. Generalized social phobics exhibited increased blood pressure responsivity to Valsalva and exaggerated vagal withdrawal in response to isometric exercise, but normal cardiovascular responsivity to all other tasks. Plasma norepinephrine and epinephrine levels were also normal. Studies with larger sample sizes and the use of specific neuropharmacologic probes seem warranted to further delineate a role for autonomic dysfunction in the pathophysiology of this disorder.

A brain single photon-emission computed tomography (SPECT) study of generalized social phobia

Social phobia is an anxiety disorder whose neurobiology has been little studied (Tancer et al 1995). In contrast to the rich literature on regional cerebral blood flow and/or glucose metabolism in other anxiety disorders such as panic (Reiman et al 1989; Nordahl et al 1990) and obsessive-compulsive disorder (OCD) (Baxter et al 1988; Nordahl et al 1989; Machlin et al 1991; Rubin et al 1992; Adams et al 1993; McGuire et al 1994; Rauch et al 1994), to the best of our knowledge, there have been no such studies to date in social phobia. To investigate brain regions that might be involved in the pathophysiology of social phobia, we examined brain perfusion patterns in a group of these patients and psychiatrically healthy controls using technetium-99m-hexamethyl-proplyenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT). We included only patients who met diagnostic criteria for the generalized subtype of social phobia (Mannuzza et al 1995), to limit syndromal heterogeneity. Studies in OCD using HMPAO-SPECT have found increased regional cerebral blood flow in medial-frontal cortex (Machlin et al 1991), reduced neostriatal blood flow (Rubin et ai 1992), and/or assymetric basal ganglia perfusion (Adams et al 1993). Given the high comorbidity between social phobia and other anxiety disorders such as OCD, we elected to a priori focus our analyses

A preliminary analysis of pulmonary function in panic disorder: Implications for the dyspnea-fear theory☆

Abstract The present study investigated the relationship between pulmonary function and panic symptomatology in 15 panic disordered (PD) patients. Patients were divided into two groups based on high and low FEF 50% scores, a relatively effort-independent measure of pulmonary function that has been used as an early indicator of obstructive lung disease, using a median-split procedure. Overall, the PD patients did not exhibit any significant impairements in pulmonary function. However, low FEF 50% patients had significantly lower FEV1/FVC ratios compared to the high FEF 50% patients. Low FEF 50% PD patients also reported experiencing a greater severity of panic-related respiratory symptoms and cognitive/fear symptoms during episodes of panic. They did not, however, differ from high FEF 50% patients in termsof fear of general anxiety symptoms, state anxiety, past-week respiratory difficulty, or past-week panic episodes. These results suggest that the subgroup of PD patients with lower FEF 50% scores are the subgroup most likely to experience respiratory and cognitive/fear symptoms during panic attacks. Further, it seems plausible that the low FEF 50% scores, low FEV1/FVC ratio, and associated respiratory symptoms may be representative of the early signs of chronic pulmonary obstruction in these patients. Implications to the dyspnea-fear theory and treatment issues are discussed.

[3H Paroxetine binding to platelets of patients with social phobia: Comparison to patients with panic disorder and healthy volunteers

Recent studies suggest that serotonergic functioning may be aberrant in patients with social phobia. Capacity of the serotonin (5-HT) transporter, as determined by 3H-paroxetine binding, was measured in 18 drug-free patients with generalized social phobia and compared to 15 drug-free patients with panic disorder and 23 healthy control subjects. The density (Bmax) and affinity (1/Kd) of 3H-paroxetine binding sites was similar in all three groups. To the extent that the serotonin transporter in platelets and neurons is comparable, these findings suggest that this aspect of serotonergic function is normal in patients with social phobia.

Epithelia as bubble rafts: A new method for analysis of cell shape and intercellular adhesion in embryonic and other epithelia☆

Abstract Cell-cell interactions may often be characterized by a work of adhesion or equivalent surface tension between cells. This intercellular surface tension may vary from one part of an epithelium to another. Such gradients in surface tension may be important driving factors in morphogenesis. A computational method for the measurement of parameters of cell shape involved in surface tension has been developed. It permits detailed observational analysis of cell-cell interface curvature. The information thus obtained is utilized in an algorithm for estimating gradients of surface tension in epithelia. The use of these methods should permit cell biologists and embryologists to decide whether or not developing cells behave like bubbles, and if so, to what extent their adhesive forces contribute to various aspects of embryogenesis.