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Biomedical subjects

C D Frith

Publications and source records attributed to C D Frith.

At least 217 records · Page 12Linked to original sources
PubMed1989

Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease.

Schizophrenia is associated with structural changes (eg, a mild degree of ventricular enlargement) in the brain, although whether these precede onset of illness or progress with episodes is not established. In a postmortem study, we find that ventricular enlargement affects the posterior and particularly the temporal horn of the lateral cerebral ventricle. By comparison with controls and with patients suffering from Alzheimer-type dementia (in which there is also temporal horn enlargement), the change is highly significantly selective to the left hemisphere. This deviation was not accompanied by an increase in glial cell number (examined chemically by assay of diazepam-binding inhibitor immunoreactivity and microscopically by density of staining with the Holzer technique). The findings are consistent with the view that schizophrenia is a disorder of the genetic mechanisms that control the development of cerebral asymmetry.

Alzheimer Disease↗
PubMed1989

The effects of scopolamine and clonidine upon the performance and learning of a motor skill.

Twenty-eight subjects practised a task involving procedural knowledge in which a moving target has to be followed for two 3-min sessions. They were then randomly allocated to receive an IV injection of 0.4 mg scopolamine, 0.15 mg clonidine or saline. General impairment due to both active treatments was seen 20 min later in significantly decreased tracking performance. Subjects then had to learn a mirror-reversed version of the tracking task. This involved acquiring novel procedural knowledge. Subjects who had either saline or clonidine treatment showed rapid temporary improvements and also considerable permanent learning. Subjects treated with scopolamine, however, showed only slow temporary improvement and little permanent improvement in their performance at this task. This result suggests that a normally functioning cholinergic system is necessary not only for an efficient working memory but also for the long term acquisition of some kinds of procedural knowledge.

Adolescent↗
PubMed1989

Automatic and strategic volitional saccadic eye movements in psychotic patients.

Drug-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.

Depressive Disorder↗
PubMed1989

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.

Bipolar Disorder↗
PubMed1989

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.

Affective Disorders, Psychotic↗
PubMed1989

Schizophrenic inability to judge facial emotion: a controlled study.

The ability of schizophrenics to judge facial emotion was examined using a new test derived to remedy methodological inadequacies in previous studies. The derivation procedure of the test is described. Five groups of 20 subjects each took part: acute schizophrenics, chronic schizophrenics, schizophrenics in remission, in-patients with depressive illness and normal subjects. They were asked to make a dichotomous emotion judgement ('happy' or 'sad') about a set of photographed faces: and then to make a dichotomous non-emotion judgement ('old' or 'young') on a set of photographs chosen from the same original pool to form a task of equal difficulty and discriminating ability. It was predicted, from previous studies, that acute schizophrenics would be specifically impaired on judging emotional expression in faces. Instead, they were found to be impaired on both an emotion and a non-emotion task on photographs of faces when these tasks were matched for difficulty and discriminating ability. They were significantly worse than remitted schizophrenics and normal subjects for both tasks, and for emotion, significantly worse then depressed subjects as well. The findings are considered in the light of current theories of visual processing in schizophrenia and of the neuropsychology of face processing.

Adult↗
PubMed1989

Temporal lobe structure as determined by nuclear magnetic resonance in schizophrenia and bipolar affective disorder.

Temporal lobe structure has been assessed by magnetic resonance imaging in groups of patients with schizophrenia (n = 21) bipolar affective disorder (n = 20) and normal controls (n = 21). In the temporal lobe area a significant (p less than 0.05) diagnosis by side interaction was present, the area being less on the left than on the right side in patients with schizophrenia in contrast to findings in the two other groups. Lateral ventricular and temporal horn area did not distinguish the groups as a whole. However, there was a significant (p less than 0.05) relationship between lateral ventricular area and poor outcome, and in an analysis confined to males, patients with schizophrenia (n = 15) were found to have significantly (p less than 0.05) enlarged temporal horns.

Adult↗
PubMed1988

The Northwick Park "functional" psychosis study: diagnosis and treatment response.

Functional psychosis is conventionally subdivided into schizophrenia and manic depressive psychosis. Response to treatment is assumed to be a validating criterion for these diagnoses. The efficacy of pimozide (a dopamine antagonist neuroleptic), lithium, and a combination of the two was compared with that of placebo in a 4 week trial in 120 functionally psychotic patients each of whom was assessed for psychotic symptoms, manic symptoms, and depressive symptoms. The sample was subdivided into patients with predominantly elevated mood, predominantly depressed mood, and no consistent mood change. Pimozide reduced psychotic symptoms in all groups of patients. The only significant effect of lithium was to reduce elevated mood. Thus dopamine blockade seems relevant to the resolution of psychotic symptoms in all types of "functional" psychosis but the mode of action of lithium in psychotic patients concerns only mood. Application of standardised classifications of functional psychosis to these data did not change this conclusion.

Adolescent↗
PubMed1988

Stereotyped responding on a two-choice guessing task by marmosets and humans treated with amphetamine.

The performance of normal human volunteers and marmosets on a 2-choice guessing task was assessed after saline (control) or amphetamine administration. In human subjects the drug increased the number of alternation responses, which can be interpreted as an increase in stereotyped switching and which is similar to the response pattern produced by some groups of psychotic patients on the same task (Frith and Done 1983; Lyon et al. 1986). Marmosets treated with amphetamine showed an increase in perseverative responding compatible with that seen on other types of task. Our conclusion is that dopaminergic systems are involved in behavioural choice mechanisms and that a dysfunction of these systems may contribute to the symptomatology of psychosis.

Animals↗
PubMed1988

Anticipation in Huntington's disease is inherited through the male line but may originate in the female.

Data from the US National Huntington's Disease Roster have been analysed in terms of the difference in age of onset (AO) between affected parents and affected offspring, that is, in terms of 'anticipation'. While mean AO in offspring of affected mothers did not differ greatly from AO in their mothers, the distribution of AO in the offspring of affected fathers falls into two groups, the larger group showing an AO only slightly younger than their affected fathers and a small group whose AO was, on average, 24 years younger than their affected fathers. Analysis of the grandparental origin of the Huntington allele suggests that while propensity to anticipation is heritable for a number of generations through the male line, it originates at the time of differentiation of the germ line of a male who acquires the Huntington allele from his mother. It is suggested that major anticipation indicates an epigenetic change in methylation of the nucleic acid of the genome, which is imposed in the course of the 'genomic imprinting', that is, in the mechanism by which the parental origin of alleles is indicated.

Adolescent↗
PubMed1988

Towards a neuropsychology of schizophrenia.

A viable neuropsychology of schizophrenia requires, first, that signs and symptoms be understood in terms of underlying psychological processes and, second, that these underlying processes be related to brain systems. We propose that the negative signs of schizophrenia reflect a defect in the initiation of spontaneous action, while the positive symptoms reflect a defect in the internal monitoring of action. The spontaneous initiation of action depends upon brain systems linking the prefrontal cortex and the basal ganglia. Internal monitoring, carried out in the hippocampus, of spontaneous action, depends upon links between the prefrontal cortex and the hippocampus via the parahippocampal cortex and the cingulate cortex.

Brain↗
PubMed1988

Phenomenology of organic and functional psychoses and the overlap between them.

The Present State Examination was conducted upon 328 recently admitted psychotic patients, of whom 23 were later found to have underlying organic illness. The phenomenology in these 23 was compared with that of 92 matching controls drawn from the parent sample who conformed to DSM-III criteria for schizophrenia, mania and depression. Few significant differences were present and there was considerable overlap between the diagnostic groups.

Adolescent↗
PubMed1987

The positive and negative symptoms of schizophrenia reflect impairments in the perception and initiation of action.

The CNS maintains a fundamental distinction between actions elicited by external stimuli and actions elicited by internal goals (acts of will). As a result the intact organism can monitor centrally three aspects of its own actions: (1) the action appropriate to current external stimulation (stimulus intention or meaning); (2) the action appropriate to current goals (willed intention); and (3) the action which was actually selected (corollary discharge). In Type I (acute) schizophrenic patients, intentions of will lead to actions, but these willed intentions are not monitored correctly. This apparent discrepancy between will and action gives rise to experiential (1st rank) positive symptoms (e.g. delusions of control and passivity). In Type II (chronic) patients, intentions of will are no longer properly formed and so actions are rarely elicited via this route. This gives rise to behavioural negative signs (e.g. poverty of speech). The behaviour of Type II schizophrenics has surface similarities to that shown by patients with Parkinson's disease and patients with frontal lobe lesions in that all three types of patient show a relative deficit of actions elicited by willed intentions. Dopamine blocking drugs reduce positive symptoms in Type I patients precisely because they induce Parkinsonism, i.e. reduce the likelihood of actions being initiated by willed intentions. This in turn reduces the likelihood that actions will occur for which the patient had no awareness of his intention to act.

Animals↗
PubMed1987

A comparison of some retrograde and anterograde effects of electroconvulsive shock in patients with severe depression.

Seventy severely depressed patients were randomly assigned to receive either a standard course of bilateral electroconvulsive therapy (ECT) or a course of simulated ECT (muscle relaxant and anaesthesia) identical to the real course except that the shock was omitted. Anterograde amnesia due to the shock was demonstrated in recognition memory for word lists and in recall of labels for faces, but this was eliminated by priming. Retrograde amnesia was also present for labels for faces learned the day before a treatment, but this was not eliminated by priming. Recognition memory for material learned in the remote past was better in the patients who had received shock than in those who had received only anaesthetic.

Adult↗
PubMed1987

The relative stability of positive and negative features in chronic schizophrenia.

The mental states of 92 inpatients with chronic schizophrenia were assessed on two occasions 4 years apart. The relationship between the two ratings was examined in the 84 patients who were either consistently on or consistently off neuroleptics. Negative features were more stable than positive, but were not irreversible. Every feature examined was shown to resolve in some cases.

Antipsychotic Agents↗
PubMed1987

Selective decreases in MAO-B activity in post-mortem brains from schizophrenic patients with type II syndrome.

The activities of the A and B forms of the enzyme monoamine oxidase (MAO, E.C. 1.4.3.4) have been assessed with the substrates 5-hydroxytryptamine and benzylamine respectively in seven areas of the brains of 39 patients with schizophrenia and 44 control subjects. Whereas previous studies have found the enzyme unchanged in brain in schizophrenia, in this study there was a modest but significant decrease in the activity of MAO-B in frontal and temporal cortices and in amygdala. This decrease could not be accounted for by neuroleptic medication, age, sex or post-mortem variables. In a series of 22 patients who had been assessed in life, the reduction in MAO-B activity was found to be associated specifically with the presence of negative symptoms (flattening of affect and paucity of speech). The findings are therefore consistent with other evidence for structural and neurochemical change in the temporal lobe that have been associated with the type II (defect state) syndrome of schizophrenia. The change in enzyme activity is unlikely to be related to a change in monoamine metabolism but may reflect a disturbance in glial function. The change in MAO-B activity in brain in this study is confined to particular areas of brain and a subgroup of patients; it is thought to be entirely unrelated to earlier reports of reductions of enzyme activity in platelets, which are probably attributable to prolonged neuroleptic medication.

Aged↗
PubMed1986

Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder.

The brains of 232 patients with a case-note diagnosis of schizophrenia or affective disorder who died in one mental hospital over a period of 22 years were weighed, and were assessed in a coronal section at the level of the interventricular foramina. From this sample were eliminated the brains of patients whose illnesses did not meet the Washington University criteria for a diagnosis of definite schizophrenia or primary affective disorder and those brains that showed significant histopathologic evidence of Alzheimer's-type change or cerebrovascular disease. This left a sample of 41 patients with schizophrenia and 29 patients with affective disorder. With age, sex, and year of birth controlled for, the brains of the patients with schizophrenia were 6% lighter, had lateral ventricles that were larger in the anterior (by 19%), and particularly in the temporal, (by 97%) horn cross section, and had significantly thinner parahippocampal cortices (by 11%). The findings provide postmortem confirmation of reports of ventricular enlargement in radiological studies and suggest that such enlargement is associated with tissue loss in the temporal lobe. The changes in schizophrenia were of a lesser degree than those seen in a sample of brains of patients with Alzheimer's-type dementia and Huntington's chorea.

Aged↗