D. G. C. Owens

Schizophrenia and the brain: a prospective clinico-neuropathological study

The neuropathological results from a prospective, systematically assessed, series of 56 schizophrenic patients and 56 age- and sex-matched normal controls have been presented. When compared with the normal controls, the brains of the schizophrenic subjects showed a significant reduction in brain weight and brain length with a concomitant increase in ventricular size. (All findings relate to measurements made after formalin fixation). In addition, the brains of the schizophrenic patients contained significantly more non-specific focal pathology and fibrillary gliosis than the controls. After exclusion of cases with moderate and severe Alzheimer-type change, cerebro-vascular disease and all forms of focal pathology, the structural brain changes (i.e. decrease in brain weight and brain length) continued to distinguish the schizophrenia group from the controls. Furthermore, an analysis of the clinical data showed that the structural brain changes were correlated in the schizophrenic patients with a measurement of pre-morbid function. The findings and their possible aetiological implications have been discussed.

Theory of mind and psychoses

BACKGROUND A cardinal feature of schizophrenia is the sufferers difficulty in interacting appropriately within the social milieu. This deficit has recently been associated with the concept of theory of mind, more commonly constructed as a working model to understand behavioural patterns in autistic children. In this paper the complex relationships between theory of mind, IQ and psychoses are addressed. METHODS Five experimental groups were used; non-psychiatric controls, affective disorder, schizophrenia with normal pre-morbid IQ, schizophrenia with pre-morbid IQ in the mildly learning disabled range, and mild learning disability with no history of psychiatric illness. All subjects were given a first order Theory of Mind Task and if successful, a second order Theory of Mind Task was then administered. All subjects were rated using the Positive and Negative Symptom Scale (PANSS). RESULTS Subjects with schizophrenia and subjects with mild learning disability show impaired ability on a second order theory of mind task. However, when patients who are unable to answer reality questions are removed from the analysis specific impairment of theory of mind is only seen in subjects with schizophrenia. Furthermore, this impairment is relatively specific to particular psychopathological clusters in subjects with schizophrenia. Even though the same clusters of psychopathology are also seen in patients with affective disorder, their presence is not associated with poor second order theory of mind performance. CONCLUSIONS Impaired theory of mind on second order tests is specific to schizophrenia when compared to mild learning disability and affective disorder control groups. Subjects with schizophrenia and pre-morbid mild learning disability show greater impairment than subjects with schizophrenia and a pre-morbid IQ within the normal range.

The spectrum of structural brain changes in schizophrenia: age of onset as a predictor of cognitive and clinical impairments and their cerebral correlates

A range of cerebral structures was assessed in a series of 172 CT scans of groups of psychiatric patients (including 101 in-patients with chronic schizophrenia) and related to assessments of clinical state and psychological function. Ventricular indices were increased in patients with schizophrenia by comparison with patients with other psychiatric disorders: brain area, which is modestly positively correlated with ventricular indices, was significantly (P less than 0.01) reduced in patients with schizophrenia. Among in-patients with chronic schizophrenia, measures of increased ventricular size were significantly associated with impaired social behaviour and with movement disorder. Memory for famous names in the distant past (a test of remote memory) was the only psychological test which showed significant associations with indices of ventricular size; this suggests that ventricular enlargement and its psychological sequelae occur relatively early in the disease process. Dichotomization of the sample of schizophrenic patients around the mean age of onset revealed that a range of clinical and psychological functions are significantly more abnormal in those with an early age of onset than in those in whom the onset was later. Early onset cases also perform less well academically and occupationally before illness onset. Within the early onset group some significant correlations between cognitive function and brain area were seen. The findings suggest that: (i) some at least of the structural changes in schizophrenia arise at a time when the brain is still developing; and (ii) age of onset is an important determinant of social and intellectual impairment and is relevant to the relationship between brain structure and cognitive deficits.

Integration of schematic faces and other complex objects in schizophrenia.

Twenty-one acute schizophrenic patients and 26 neurotic patients sorted each of six sets of 15 objects into three groups. A set consisted either of schematic faces, nonsense objects, or histoforms, each composed of five independently varying features. For the faces and nonsense objects these features could be integrated into a whole, whereas for the histoforms they could not. The distribution of four of the features was such that a set could be divided into three groups. The fifth feature either remained constant and had no, effect on sorting performance or it varied randomly and acted as a distractor. Performance was assessed from the variance in common between the grouping actually present in a set and the grouping produced by the subject. For the control patients faces were sorted much better than histoforms if no distractor was present. However, performance with faces was massively impaired by a distractor while performance with histoforms was not. For the schizophrenic patients faces were not sorted better than histoforms and the effect of distraction was similar for every type of material. The performance of the controls suggests that the gestalt quality of the faces dominated over their constituent details. This enabled more features to be handled at once, thus achieving better sorting with faces than histoforms. However, it also made it more difficult for subjects to ignore a distracting component in the faces. The performance of the schizophrenics suggests that for them the integrated gestalt of the face was not dominant over its components.

The Northwick Park ‘Functional’ Psychosis Study: diagnosis and outcome

Three hundred and twenty-six consecutively admitted patients with functional psychotic illnesses to which no diagnostic classification had been applied were followed up after 2.5 years. They were examined in social, clinical and psychological terms and the CATEGO programme and DSM-III criteria were applied to data concerning the index episode to derive diagnostic classifications. The deterioration in occupational functioning and the hospital careers of patients with diagnostic classifications of schizophrenia were worse than those in the other groups and positive and negative features were also more severe in patients with a classification of schizophrenia. By contrast, no differences in psychological test performance were found between the groups based upon diagnostic classification. Impaired psychological test performance was found and it was strongly related to concurrent mental state abnormalities, particularly negative symptoms. It is concluded that the diagnostic classifications used were of limited value in predicting outcome in functional psychosis.

CHARACTERISTICS OF PATIENTS WITH SCHIZOPHRENIA OR NEUROLOGICAL DISORDER AND VIRUS-LIKE AGENT IN CEREBROSPINAL FLUID

A virus-like agent (V.L.A.) with a cytopathic effect on cultured cells was found in the cerebrospinal fluid of 18 of 47 patients with schizophrenia, of whom 10 had nuclear schizophrenic symptoms. In most patients with V.L.A., blood and C.S.F. protein concentrations were normal. Patients with and without V.L.A. had similar clinical characteristics but serum IgA levels were higher in those with V.L.A. V.L.A. was also detected in the C.S.F. of 8 of 11 patients with serious or chronic neurological disease (Huntingtons chorea, multiple sclerosis, and unexplained alterations of consciousness).

The relationships between clinical response, psychophysiological variables and plasma levels of amitriptyline and diazepam in neurotic outpatients

In a 4 week study of the response of neurotic outpatients to treatment with amitriptyline, diazepam, amitriptyline and diazepam, or placebo, clinical and psychophysiological variables and plasma levels of the drug were assessed. Clinical improvements were substantial in all treatment groups but clear relationships between clinical change, psychophysiological change and plasma levels of the drugs were not established. There was no relationship between plasma levels of the drugs and cigarette smoking. It is concluded that neither plasma levels of amitriptyline and diazepam nor change in skin conductance responsivity offer a useful guide to clinical response to drug treatment.

The northwick park «functional» psychosis study. Phase 2 : maintenance treatment

This study blindly compared the value as a prophylaxis against relapse over a period of up to 6 years, of pimozide, lithium, pimozide+lithium and placebo of 30 patients with functional psychotic illness who had achieved satisfactory recovery on the same medications during an acute episode of illness. Pimozide was significantly more effective than placebo pimozide in preventing relapse (p=0.01). No significant effect for lithium was found. There was a significant deterioration in positive symptoms (p < 0.05) as relapse approached, but otherwise features of impending relapse were not detected. It is concluded that prophylactic neuroleptic medication is of value even in patients who have recovered from an acute episode of psychosis without active neuroleptics. Such an acute response does not identify a group of patients who can be predicted to do well without continued medication.

Depression in Functional Psychosis

Despite a recent reappraisal of the concept of Unitary Psychosis (1), the Kraepelinian dichotomy of functional psychotic illnesses remains the theoretical and clinical orientation of most psychiatrists. The validity of this in defining separate disease entities is, of course, crucially based on outcome. Thus in establishing a diagnosis, Kraepelin urged consideration of... “the entire picture... especially... the changes which it undergoes in the course of the disease” (2). Such longitudinal methodology has, however, largely been abandoned in favour of the cross-sectional evaluation of symptomatology. Schneider, for example, stated that: “Psychiatric diagnosis must be based on the presenting situation, not on the course taken by the illness” (3).

The Phenomenological, Pharmacological and Psychophysiological Characteristics of Neurotic Outpatients to whom no Diagnosis has been Applied

ABSTRACT 240 neurotic outpatients with moderate to severe symptoms of anxiety and/or depression were randomly and blindly assigned to four treatment regimes: Amitriptyline, Diazepam, Amitriptyline and Diazepam, Placebo. The patients were rated on a number of scales of anxiety and depression at the beginning and the end of the four week treatment period. In addition psychophysiological measures were taken. In terms of initial symptoms there was no evidence for the separate existence of anxiety states and neurotic depressions. However predominantly depressed patients showed more rapid skin conductance habituation than predominantly anxious patients. There were no differential effects of the different treatment regimes on the different symptoms. Amitripytyline was marginally better than the other treatments for both symptoms of anxiety and depression. The group receiving Diazepam showed no more improvement in symptoms than the group receiving placebo.