fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia.

Schizophrenia is a highly heritable disorder that typically develops in early adult life. Structural imaging studies have indicated that patients with the illness, and to some extent their unaffected relatives, have subtle deficits in several brain regions, including prefrontal and temporal lobes. It is, however, not known how this inherited vulnerability leads to psychosis. This study used a covert verbal initiation fMRI task previously shown to elicit frontal and temporal activity (the Hayling sentence completion task) to examine this issue. A large (n = 69) number of young participants at high risk of developing schizophrenia for genetic reasons took part, together with a matched group of healthy controls (n = 21). At the time of investigation, none had any psychotic disorder, but on detailed interview some of the high-risk participants (n = 27) reported isolated psychotic symptoms. The study aimed to determine: (i) whether there were activation differences that occurred in all subjects with a genetic risk of schizophrenia (i.e. 'trait' effects); and (ii) whether there were activation differences that only occurred in those at high risk who had isolated psychotic symptoms ('state' effects). No activation differences were found in regions commonly reported to be abnormal in the established illness, namely the dorsolateral prefrontal cortex or in the temporal lobes, but group differences of apparent genetic cause were evident in medial prefrontal, thalamic and cerebellar regions. In addition, differences in activation in those with symptoms were found in the intraparietal sulcus. No significant differences in performance were found between the groups, and all subjects were antipsychotic naïve. These findings therefore suggest that vulnerability to schizophrenia may be inherited as a disruption in a fronto-thalamic-cerebellar network, and the earliest changes specific to the psychotic state may be related to hyperactivation in the parietal lobe.

Left ventricular function in scleroderma.

Scleroderma affects the left heart directly and indirectly via the effects of systemic hypertension. Using transthoracic echocardiography, we evaluated 35 patients with scleroderma and compared them with matched control subjects. Compared with controls, there were no differences between left ventricular dimensions, wall thickness, calculated mass or fractional shortening. However, the left atrium was enlarged (P = 0.006) and the mitral deceleration time was prolonged (P = 0.0005) in patients with scleroderma; suggesting abnormal diastolic function. After adjusting for potential confounders, duration of Raynaud's was found to be an independent predictor of deceleration time (P = 0.04), E/A peak velocity ratio (P = 0.04), A peak velocity (P = 0.004) and A velocity time integral (P = 0.0001), all measures of diastolic function. This group of individuals with scleroderma have evidence of abnormal diastolic function of the left ventricle despite normal left ventricular size and systolic function, and in the absence of hypertrophy. This finding is independent of the use of vasoactive medications and history of systemic hypertension, and thus may be due to primary myocardial involvement by scleroderma. The tendency to abnormal diastolic function of the left ventricle correlated with the duration of Raynaud's phenomenon.

Comparison of a self-rating questionnaire with a diagnostic checklist for the assessment of DSM-III-R personality disorders.

Two instruments for the assessment of the DSM-III-R personality disorders were compared: The Personality Disorders Questionnaire--Revised (PDQ-R) and the Munich Diagnostic Checklist for the assessment of DSM-III-R Personality Disorders (MDCL-P). Using kappa value as a measure of agreement, the diagnostic agreement was less than 0.40 for personality disorder vs. no personality disorder as well as for the specific personality disorders. The PDQ-R diagnosed more frequently personality disorders (58%) than did the MDCL-P (43%).

The Munich Diagnostic Checklist for the assessment of DSM-III-R Personality Disorders for use in routine clinical care and research.

Diagnostic checklists for the assessment of DSM-III-R Axis I diagnoses have proven to be a reliable and feasible instrument in research and routine clinical care. Therefore, a checklist for the assessment of the DSM-III-R Personality Disorders (MDCL-P) has been developed. An English version of the MDCL-P is available. The MDCL-P has been tested for reliability in a test-retest design. The average duration of the interview was 36 min. Of the patients, 48% received a diagnosis of at least one personality disorder. The Kappa value concerning the distinction personality disorder as opposed to no personality disorder was 0.62. The range of Kappa values of specific personality disorders, which were diagnosed at least five times, was from 0.35 to 0.79.

A comparison of the effects of fluvoxamine and amitriptyline on autonomic functions in healthy volunteers.

We have compared the effects of single oral doses of fluvoxamine (50 mg and 100 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced, double-blind, crossover design. Amitriptyline significantly reduced salivation, the miosis evoked by locally applied pilocarpine, and the sweat secretion evoked by locally applied carbachol. Fluvoxamine also significantly attenuated carbachol-evoked sweat gland activity, although to a smaller degree than amitriptyline; fluvoxamine did not significantly alter salivation or pilocarpine-evoked miosis. Neither treatment significantly altered the miotic responses evoked by brief light stimuli. Heart rate and blood pressure were not greatly affected by either treatment, although the fall in heart rate (erect posture) with placebo was significantly reduced by amitriptyline (100 mg). The results suggest that fluvoxamine has some anti-muscarinic activity in man, but is considerably less potent in this respect than amitriptyline.