I. Harvey

Reduction of cortical volume in schizophrenia on magnetic resonance imaging

The MRI scans of 48 schizophrenic patients, fulfilling RDC criteria, were compared to those of 34 healthy controls matched for age, ethnicity and parental social class. The volume of the frontal and anterior parietal lobes was significantly reduced in the schizophrenic group as a result of a selective decrease in cortical volume, with a corresponding increase in the volume of sulcal fluid. Reduction in the volume of the temporal grey matter was more marked on the right, but was not in excess of the loss of volume observed in other areas of the cortex. MRI abnormalities correlated poorly with clinical parameters, although both unemployment and poor pre-morbid adjustment predicted reduced cerebral volume and increased sulcal volume. These results question whether the medial temporal lobes are the only site of structural pathology in schizophrenia.

Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls

Twenty-six patients with RDC bipolar disorder were compared with a previously reported group of 48 RDC schizophrenics and 34 healthy controls, using volumetric MRI measurements of cerebral, cortical and sulcal volumes. The bipolar group appeared no different from the controls, and both of these groups had significantly larger cerebral and cortical volumes than the schizophrenics. Our previous report of a significantly reduced cortical volume in the schizophrenic group, with a corresponding increase in the volume of sulcal fluid is, therefore, not a generalized feature of psychotic illness but may be more specific to schizophrenia.

Psychopathological syndromes in the functional psychoses : associations with course and outcome

The aim of this study was to identify underlying dimensions of psychopathology in a cohort of patients with functional psychosis of recent onset, and to examine their prognostic value. Factor analysis of the psychopathological features of 166 consecutively admitted patients with functional psychosis of recent onset revealed seven psychopathological dimensions, which explained 63% of the variance. Five of these seven syndromes bore differential associations with subsequent treatment and illness course, independent of: (i) associations with DSM-III-R diagnosis; (ii) associations with other prognostic factors; and (iii) associations with the baseline values of outcome variables. The most striking associations were shown for an early and insidious onset syndrome with affective flattening, which predicted a more disabled course of illness on three of four outcome dimensions, and which was more common in males and unmarried individuals. A second syndrome, characterized by bizarre behaviour, inappropriate affect, catatonia, and poor rapport showed similar, slightly less striking, associations with illness course, as well as with poor pre-morbid social functioning. A third syndrome, characterized by positive psychotic symptoms was to a lesser degree associated with poorer outcome, whereas a fourth syndrome distinguished by manic symptomatology predicted a more benign illness course. A fifth syndrome identified by lack of insight predicted more time in hospital and admission under a section of the Mental Health Act during the follow-up period. A further finding was that dimensional representations of psychopathological features were considerably more useful than categorical representations (DSM-III-R and ICD-10) as predictors of illness course and treatment decisions.

Morbid risk of schizophrenia for relatives of patients with cannabis-associated psychosis

Twenty-three patients admitted with acute psychosis who were cannabis positive on urinary screening were each matched, with respect to sex, with two psychotic controls who screened negatively for all substances. The lifetime morbid risk of psychiatric disorder was estimated among the first degree relatives of cases and controls, using RDC-FH criteria to define diagnoses, and Weinbergs shorter method of age correction. The cases had a significantly greater familial morbid risk of schizophrenia (7.1%) than the controls (0.7%), while the risks of other psychoses, and of non-psychotic conditions were similar. The same pattern of familial risk was evident when the analysis was restricted to patients with DSM-III schizophrenia. The data suggest that the development or recurrence of acute psychosis in the context of cannabis use may be associated with a genetic predisposition to schizophrenia.

Minor physical anomalies in psychoses : associations with clinical and putative aetiological variables

This study of patients with functional psychoses set out to examine associations between minor physical anomalies (MPAs) and demographic, clinical, CT scan measures, and putative aetiological variables. 157 psychotic patients had minor physical anomalies assessed using a modified Waldrop scale. RDC diagnoses for these patients were: schizophrenia (n = 79), schizoaffective disorder (n = 31), mania (n = 24), major depression (n = 13), unspecified functional psychosis (n = 8), other organic psychosis (n = 2). 63 healthy white controls were also assessed with the modified Waldrop scale. Minor physical anomalies were not associated with any particular diagnosis. For white subjects, patients had significantly more MPAs than well controls. Anomalies of the palate were the most frequent item reported in patients and controls. For males, there was a weak association between the presence of MPAs and positive family history of a major psychiatric disorder. Those with MPAs required more frequent and longer psychiatric admissions, and showed impaired ability on a test sensitive to left parietal system function. Within the patient group, there were no associations between MPAs and gender, age at onset, negative symptoms, premorbid level of functioning, estimated premorbid intelligence, pregnancy and birth complications, and selected CT variables. Minor physical anomalies are found in a range of functional psychoses. There may be overlap between the various genes that predispose to psychiatric illness (especially in males) and those genes that predispose to developmental instability.

Cerebral ventricle dimensions as risk factors for schizophrenia and affective psychosis: an epidemiological approach to analysis

A case-control study was undertaken of volumetric computerized tomographic scan measures in 216 consecutive admissions for functional psychosis and 67 healthy community controls. Odds ratio analysis demonstrated significant linear trends in the association between increasing lateral and third ventricle volumes, and both RDC schizophrenia (N = 121) and schizo-affective disorder (N = 41); cases were consistently associated with larger volumes than controls. There was an association between larger third, but not lateral, ventricle size in affective psychoses (N = 54). These associations were statistically independent of intracranial volume, sex, social class and ethnicity, factors which were significantly associated with ventricular measures in the controls. There was no evidence of a threshold corresponding to the notion of normal versus enlarged ventricles. Within the schizophrenia group, there were no large or significant associations between ventricle dimensions and age at onset, duration of illness or pre-morbid social functioning. Neither obstetric complications nor a family history of schizophrenia or other psychiatric illness was associated with large ventricles in these cases.

Tardive dyskinesia: Who is at risk?

Tardive dyskinesia (TD) has been associated with female gender, affective symptoms and good outcome, but also with negative symptoms, cognitive deterioration and deteriorating illness course. Furthermore, antipsychotic medication is thought to be an important risk factor, yet abnormal movements also occur in patients who have never received such medication. We followed 166 subjects with recent onset of psychotic illness and brief previous exposure to antipsychotic medication. Information on 17 previously reported risk factors was available for 125 patients at baseline and, for factors that vary over time, again at follow‐up 4 years later (median, 50 months; interquartile range, 29‐70). Movement disorder was assessed at follow‐up using the Abnormal Involuntary Movement Scale (AIMS). Six non‐interacting variables were independently associated with the 4‐year risk of TD: male sex (OR, 2.5; 95% CI, 1.1‐5.0), age (OR over quartiles at baseline, 1.6; 95% CI, 1.1‐2.2), lack of insight at baseline (OR over four categories, 2.0; 95% CI, 1.2‐3.2), time on antipsychotics during the follow‐up period (OR over quartiles, 2.3; 95% CI, 1.5‐3.4), an increase in negative symptoms during the follow‐up period (OR over quartiles, 1.7; 95% CI, 1.2‐2.5), and alcohol/drug misuse at follow‐up (OR, 3.0; 95% CI, 1.3‐7.4). The presence of individual risk factors was found to be of little use as a screening test for subsequent clinically relevant TD. Given the absence of a risk factor, however, the probability that an individual would not develop TD was high. These results suggest that two discrete effects may operate to increase the risk of TD, namely an exogenous factor (medication, drugs), and an illness‐related factor, the highest risk being conferred by deteriorating illness course in male patients.

Cerebral hemispheric asymmetry revisited : effects of handedness, gender and schizophrenia measured by radius of gyration in magnetic resonance images

Abnormal patterns of cerebral hemispheric asymmetry have been inconsistently reported in association with schizophrenia. Radius of gyration (Rg) is a measure of the mean dispersion of points in a radially organized structure about that structures centre of gravity. We developed computerized methods for estimating Rg of the magnetic resonance image (MRI) boundary between cortex and subcortex, and applied these methods to measurement of cerebral hemispheric asymmetry in 37 schizophrenics (SZs) and 30 controls (CONs). In right-handed CONs, Rg of right brain boundaries was significantly greater than Rg of left brain boundaries; in left-handed CONs, Rg of left brain boundaries was significantly greater than Rg of right brain boundaries. In right-handed males (both SZ and CON) there were significant differences in Rg between hemispheres; whereas in females (both SZ and CON), there were no such differences. Right-handed male SZs (N = 26) were distinguished by reversal of the right-handed male CON pattern of interhemispheric difference in Rg, and by global reduction in Rg of right brain boundaries. These was no evidence for significant abnormality of Rg in right-handed female SZs (N = 7). There findings suggest an important interactive effect of gender and schizophrenia on lateralized cerebral structure.

Factor analysis of symptoms in schizophrenia: differences between White and Caribbean patients in Camberwell

BACKGROUND The incidence of schizophrenia among African-Caribbeans living in Britain has been frequently reported to be increased. We sought to determine whether the symptom profile in schizophrenic patients from this group differed from that of their White counterparts. METHODS Factor analysis was applied to symptom data obtained by the Present State Examination (PSE) from a group of White (N = 96) and Afro-Caribbean (N = 64) patients who satisfied Research Diagnostic Criteria criteria for broad schizophrenia. We identified six symptom dimensions: mania, depression, first-rank delusions, other delusions, hallucinations and one which comprised both manic and catatonic symptoms. RESULTS The only difference between the two ethnic groups was seen on the mixed mania-catatonia dimension with the Afro-Caribbean group being over-represented. There were no other significant differences between the groups. Discriminant analysis, however, revealed no significant differences between the groups in any dimension. CONCLUSIONS These results indicate that there are no differences between White and African-Caribbean patients with schizophrenia in terms of the core symptoms of the disorder, however, the African-Caribbean patients may present with more symptoms of a mixed affective nature.

Focal signal hyperintensities in schizophrenia.

The presence of focal signal hyperintensities on MRI images of the brain was compared in 48 schizophrenic patients, 26 patients with bipolar disorder and 34 healthy controls. Significantly larger areas of brain were affected by focal signal hyperintensities, particularly in the frontal lobes, in the schizophrenic group compared to the bipolar group and the controls. Although the bipolar group had more such foci than controls, this difference did not reach statistical significance.