C. D. Frith

CEREBRAL VENTRICULAR SIZE AND COGNITIVE IMPAIRMENT IN CHRONIC SCHIZOPHRENIA

By comparison with age-matched controls in employment, 17 institutionalised schizophrenic patients were shown by computerised axial tomography of the brain to have increased cerebral ventricular size. Within the group of schizophrenic patients increased ventricular size was highly significantly related to indices of cognitive impairment.

Experiences of alien control in schizophrenia reflect a disorder in the central monitoring of action

Twenty-three acute psychotic patients who were drug free at the time of testing performed a motor task designed to elicit many errors. Normal subjects and many of the psychotic patients were able to correct these errors in the absence of visual feedback. The ability to make such corrections depends on the subject knowing what response he has just made. Patients with experiences of alien control of their thoughts and actions who formed a subgroup of those classified as schizophrenic, were significantly less likely to make error corrections in the absence of visual feedback. This result is consistent with our previous suggestion (Frith, 1987) that these symptoms are a consequence of problems with the central monitoring of responses.

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.

Lateral ventricular size in schizophrenia: relationship to the disease process and its clinical manifestations.

Using computed tomography, lateral ventricular size was studied in a sample of 112 institutionalized chronic schizophrenic patients (selected from 510 cases to investigate the correlates of the defect state and intellectual decline and the effects of insulin, electroconvulsive and neuroleptic treatment), and compared with matched groups of non-institutionalized schizophrenics, patients with first schizophrenic episodes, institutionalized and non-institutionalized patients with primary affective disorder, and neurotic out-patients. Age was significantly correlated (P less than 0.0002) with lateral ventricular size, but the institutionalized schizophrenic patients had significantly larger (P less than 0.025) lateral ventricles than the neurotics when age was taken into account. Ventricular enlargement was unrelated to past physical treatment (neuroleptics, insulin coma and electroconvulsive therapy). Within the group of institutionalized schizophrenic patients few correlates of ventricular enlargement were identified; thus in this population increased ventricular size was not clearly associated with the features of the defect state (negative symptoms and intellectual impairment). However, there was a curvilinear (inverted-U) relationship between intellectual function and ventricular size. Increased ventricular size was significantly related to absence of hallucinations, impairment of social behaviour, inactivity and the presence of abnormal involuntary movements. The findings confirm that structural brain changes do occur in chronic schizophrenia, but illustrate some of the difficulties in elucidating the clinical significance of ventricular enlargement. Lateral ventricular size is strongly age-related and the distribution in chronic schizophrenia is skewed and not bimodal; the relationship to particular features of the disease is complex and likely to emerge only in studies with a large sample size.

Routes to action in reaction time tasks

SummaryTwo-choice tactile RTs are no faster than 8-choice tasks, implying the existence of a ‘direct’ route. However, simple tactile RTs are much faster than choice tactile RTs (Leonard, 1959). In Experiment I we show that this is not due to subjects anticipating the stimulus in simple tactile RT tasks. Increasing probability of stimulus occurrence at a particular time led to equally decreased tactile RTs for simple and choice tasks.We suggest that an alternative route is available for simple RTs which is faster than the ‘direct’ route available for choice tactile RTs. This route is faster because (a) the response can be specified in advance, and (b) the stimulus does not need to be identified. The subject needs merely to register that it has occurred. In Experiment II we show that simple RTs to a visual stimulus are decreased by a simultaneous uninformative tactile stimulus even when this is to the wrong finger. This confirms that exact stimulus identification is not necessary in the ‘fast’ route. In Experiment III we show that a secondary task slows down simple tactile RTs to the same level as choice tactile RTs while the latter are hardly affected. This suggests that focussed attention is not needed for the ‘direct’ route, but it is needed for the ‘fast’ route. We propose that a useful distinction can be made between action largely controlled by external stimuli (the ‘direct’ route) and action largely controlled by internal intentions of will (the fast route).

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.

Automatic and strategic volitional saccadic eye movements in psychotic patients

SummaryDrug-free schizophrenics were compared with depressive psychotics and normal controls on two saccade initiation tasks which differed with respect to the type of stimulus that initiated a saccadic response. Strategic initiation (SIS) appears to use a route different from that in automatic initiation (AIS). The SIS task revealed slowed responding in psychiatrically ill patients if their cognition was impaired, but all groups responded similarly on the AIS task. Schizophrenics could be separated from depressed psychotics by their inability to utilize temporal redundancy to speed up saccade initiation on the SIS task. Neurophysiological evidence implicates specific impairments in the frontal eye field (FEF) and/or basal ganglia.

Arousal related to excretion of noradrenaline metabolites and clinical aspects of unmedicated chronic schizophrenic patients

Abstract 1. 1. The interrelationship between the following psychophysiological, biochemical and clinical measures have been investigated in a group of unmedicated chronic schizophrenics; skin conductance level and orienting responses to tones; heart rate; excretion of vanillylmandelic acid (VMA), sulphate and total methoxyhydroxyphenylglycol (MHPG); clinical ratings of symptom severity. 2. 2. More severely ill subjects showed evidence of overarousal and had higher skin conductance levels and heart rates, and less habituation of skin conductance orienting responses to tones than the less severely ill. These measures were not related to ratings of anxiety. 3. 3. Physiological measures of peripheral autonomic function (skin conductance level and heart rate) were unexpectedly inversely related to VMA excretion, a noradrenaline metabolite putatively of peripheral origin, and to MHPG excretion. 4. 4. The central processes of habituation and symptom severity were more closely related to excretion of MHPG than VMA. This offers support for the suggestion that this noradrenaline metabolite more closely reflects brain noradrenaline turnover than VMA. The inverse relationship between MHPG excretion and measures of arousal suggests that brain noradrenergic transmission is not directly related to arousal levels in schizophrenia. 5. 5. Studies of these variables in control subjects will determine whether these findings are specific to schizophrenia.