The influence of schizotypy traits on prepulse inhibition in young healthy controls.

Deficits in sensorimotor gating or prepulse inhibition (PPI) have been demonstrated repeatedly in patients with schizophrenia or with schizotypal personality disorder, but not consistently in schizotypal non-psychiatric controls. The appearance of normal PPI in this group has been interpreted as reflecting a discontinuous underlying vulnerability to psychosis in high-risk groups. An alternative interpretation is that underlying vulnerability to psychosis is continuously distributed in the normal population (Claridge, 1972, 1987), and therefore that performance on information processing tasks should vary continuously with increasing levels of schizotypy in non-clinical populations. We attempted to examine further the notion of a continuous relationship between PPI and schizotypy in 44 (17 female, 27 male) healthy, non-smoking subjects controlling for menstrual phase. In this selected sample, the findings do not support a continuum model, and suggest that PPI deficits may indeed be the result of a discontinuous neurophysiological change in those with psychotic illness, rather than one continuously distributed in the normal population.

Distractor cueing effects on choice reaction time and their relationship with schizotypal personality.

BACKGROUND AND OBJECTIVES: Although usually displaying increased distractibility, schizophrenic patients sometimes show a reduced influence of distractors during selective attention tasks. This study explored whether reduced distractor processing effects can also occur in healthy individuals with high levels of schizotypal personality traits. DESIGN AND METHOD: In all, 36 healthy volunteers completed schizotypal personality scales and a choice reaction time (RT) task in which they responded to the central letter of triads (XMX, YCY), ignoring the flanking distractors. RT increases on low-probability probe trials (YMY, XCX) measured distractor processing ('the distractor cueing effect'). Correlations between schizotypy scores and distractor cueing were evaluated. RESULTS: Healthy participants with high positive schizotypy scores (i.e. those reporting more hallucination-like experiences and delusion-like beliefs) showed smaller distractor cueing effects than those with lower scores. This association was independent of the influence of other schizotypal personality traits (disorganized, negative or asocial schizotypy) and was significant only for right-hand responses. These findings closely parallel the previously reported reduced distractor cueing effect, for right-hand responses, among acute-phase schizophrenic patients. CONCLUSION: Finding reduced distractor cueing effects in healthy participants with high levels of positive schizotypy increases confidence that reduced distractor cueing is a specific feature, rather than a non-specific consequence, of acute-phase schizophrenia.

Neuroimaging correlates of negative priming.

Many theoretical accounts of selective attention and memory retrieval include reference to active inhibitory processes, such as those argued to underlie the negative priming effect. fMRI was used in order to investigate the areas of cortical activation associated with Stroop interference, Stroop facilitation and Stroop negative priming tasks. The most significant activation within the negative priming task was within the inferior parietal lobule, left temporal lobe and frontal lobes. Areas of cortical activation are discussed with reference to theoretical accounts of the negative priming effect.

The National Adult Reading Test as a measure of premorbid IQ in schizophrenia.

OBJECTIVES: To investigate the validity of the NART as an estimate of premorbid IQ in schizophrenia. DESIGN: A within-in participants, follow-back design was adopted. METHODS: A sample of adults with schizophrenia who had presented to psychiatric services and had a measure of IQ routinely taken during childhood were traced and subject to follow-up WAIS-R and NART IQ assessment (N = 24). Measures of current IQ and NART estimated premorbid IQ were compared with the measure of IQ taken 'premorbidly', i.e. in childhood. RESULTS: There were no significant differences between childhood and adult measures of IQ. However there were significant differences between these two indices and NART estimated IQ, particularly where IQ deviated from general population means. The Vocabulary subtest of the WAIS-R performed better as an estimate of both premorbid and current IQ in the sample. CONCLUSION: Use of a word-reading test such as the NART to predict past levels of intellectual function should proceed with caution, particularly where IQ does not fall in the 'average' category. Use of more than one index of prior level of function is recommended.

Cerebral lateralization of global-local processing in people with schizotypy.

Patients with schizophrenia have been described as being poor at processing Gestalt aspects of stimuli, but efficient in processing their local aspects. The present study examined Gestalt processing in normal subjects classified according to the positive dimensions of schizotypy. It further explored whether the Gestalt deficit is due to a more fundamental deficit in rapid global processing which occurs at an early stage and precedes local processing. In addition, it was postulated that the right hemisphere should be more involved in dysfunctional global processing. Thirty-three normal individuals assessed as having high or low scores on schizotypy scales were asked to recall the name of a set of hierarchically formed letters in a divided visual field paradigm. The results support a deficit in involuntary rapid global processing and an underlying right-hemisphere dysfunction in high scorers on the unusual experiences' (UnEx) and STA scales of schizotypy. This indicates that in such subjects local stimuli excessively intrude into the processing of global information in the right hemisphere.

Effects of d-amphetamine and haloperidol on latent inhibition in healthy male volunteers.

Latent inhibition (LI) refers to a retardation of learning about the consequences of a stimulus when that stimulus has been passively presented a number of times without reinforcement. Acute positive-symptom schizophrenics, normal volunteers who score high on questionnaire measures of schizotypy and non-patients or animals treated with dopamine agonists show reduced LI. Neuroleptic drugs, such as haloperidol, administered at low doses, potentiate LI and effectively reverse disruption of LI induced by dopamine agonists in animals. However, a high dose of haloperidol, administered on its own, has been found to reduce LI. We examined the effects on LI of acute oral administration of an indirect dopamine-agonist, d-amphetamine (5 mg), and a nonselective dopamine receptor antagonist, haloperidol (5 mg), in normal male volunteers, using an associative learning task. Replicating previous reports, we found that d-amphetamine reduced LI; haloperidol also reduced LI, but only in subjects who scored low on the Psychoticism scale of the Eysenck Personality Questionnaire. In a subsequent study, no effect was found of 2 mg oral haloperidol administration on LI. The effect of 5 mg haloperidol on LI is interpreted as similar to that observed with a high dose of haloperidol in rats.

The disruption of the 'sense of self' in schizophrenia: potential links with disturbances of information processing.

It is argued in this paper that the disruption of one aspect of the 'sense of self' in schizophrenia, that relating to the continuity of conscious experience and the organization of action, may be linked to current models of the information-processing disturbance prominent in the disorder. The 'sense of self' in normal persons in part results from the consistent manner in which contextually appropriate stored material operates of sensory input. If, as has been proposed, there is in schizophrenia a disruption in the moment-by-moment integration of these sources of information, then a disturbance in the 'sense of self' is implicit in the cognitive model. A consideration of action identification theory (Vallacher & Wegner, 1987) permits further links to be made, since higher-level action identities are viewed as being practically synonymous with self-defining significance. It is suggested that the information-processing disturbance results in a tendency to low-level action identification and a gradually developing instability in the sense of personal identity.

Oxford-Liverpool Inventory of Feelings and Experiences: reliability in an experimental population.

Further to the recent development of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), a short multidimensional schizotypy questionnaire, the present study set out to identify the reliability of all scales of this questionnaire within the same population. Participants were required to complete the O-LIFE on two separate occasions, whilst taking part in latent inhibition and negative priming experiments. All scales correlated highly, thus lending further support to the reliability of this time efficient questionnaire.

Cognitive functioning and GABAA/benzodiazepine receptor binding in schizophrenia: a 123I-iomazenil SPET study.

BACKGROUND: The role of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in schizophrenia has previously been investigated using postmortem material. Recently, using single photon emission tomography (SPET) with the selective benzodiazepine antagonist 123I-Iomazenil as the radioligand, we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia. The present study aimed to build on this using the same in vivo scanning techniques, and relating findings to cognitive functioning. METHODS: Ten nonpsychiatric control subjects and 15 schizophrenic patients, matched for age and handedness, were scanned. A battery of neuropsychologic tests was also administered. RESULTS: Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance, in the schizophrenic group compared to the control group. CONCLUSIONS: Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning, involving memory and visual attention processes, in the schizophrenic group but not in the control group. A role for GABA in the pathophysiology of schizophrenia is suggested. Limitations of the present study and suggestions for future research are discussed.

Schizophrenia and the myth of intellectual decline.

OBJECTIVE: The authors' goal was to investigate the issue of intellectual deterioration in schizophrenia. METHOD: They examined the childhood IQs of adult patients with schizophrenia who had attended a child psychiatry service where measurement of intelligence was routine. Follow-up IQs of 34 of these patients were obtained an average of 19.4 years later. RESULTS: The mean child and adult IQs were greater than one standard deviation lower than those of the general population. There were no significant differences between the child and adult IQs, however, suggesting that the impairment in intelligence during childhood was stable over the follow-up period. CONCLUSIONS: The deficit in intellectual function observed in these patients, and reported in the literature, is lifelong and predates the onset of schizophrenia.

Kamin blocking is not disrupted by amphetamine in human subjects.

The effect of oral amphetamine administration on the Kamin-blocking effect in healthy volunteer subjects was investigated. Against predictions, Kamin blocking was not disrupted by either a high or low oral dose of D-amphetamine under conditions which have, in previous studies, led to disruption of a related learning phenomenon (latent inhibition). This lack of effect of amphetamine administration upon Kamin blocking weakens hypotheses that this cognitive process is mediated by the same changes in dopaminergic activity which affect latent inhibition. Currently, the only data which show strong comparative associations between Kamin blocking and latent inhibition are when they are applied to schizophrenic populations. These results may suggest that Kamin blocking and latent inhibition may be measuring different aspects of schizophrenic cognitive dysfunction.

Schizophrenia. A cognitive model and its implications for psychological intervention.

It is argued in this article that information-processing models enable us to link psychotic phenomena to their neural bases. The core abnormality is viewed as a disturbance in the integration of sensory input with stored material. The performance of schizophrenic subjects on tasks derived from both animal learning theory and human experimental psychology is consistent with the model. The way in which such a disturbance relates to schizophrenic symptoms is outlined. It may result from an abnormality at one or more points in the neural circuit responsible for generating predictions of subsequent sensory input; in particular the hippocampus and related brain structures are implicated. The potential relevance of the model for psychological intervention is discussed.

The role of mesolimbic dopaminergic and retrohippocampal afferents to the nucleus accumbens in latent inhibition: implications for schizophrenia.

Latent inhibition (LI) consists in a retardation of conditioning seen when the to-be-conditioned stimulus is first presented a number of times without other consequence. Disruption of LI has been proposed as a possible model of the cognitive abnormality that underlies the positive psychotic symptoms of acute schizophrenia. We review here evidence in support of the model, including experiments tending to show that: (1) disruption of LI is characteristic of acute, positively-symptomatic schizophrenia; (2) LI depends upon dopaminergic activity; (3) LI depends specifically upon dopamine release in n. accumbens; (4) LI depends upon the integrity of the hippocampal formation and the retrohippocampal region reciprocally connected to the hippocampal formation; (5) the roles of n. accumbens and the hippocampal system in LI are interconnected.

Stereotypy, schizophrenia and dopamine D2 receptor binding in the basal ganglia.

Animal models suggest a relationship between disturbed striatal dopaminergic function and stereotyped behaviour. Several studies show increased stereotypy in schizophrenic patients compared to normal controls. We investigated the performance of 12 antipsychotic-drug-free schizophrenic patients, and 15 healthy control subjects on a neuropsychological measure of stereotypy--the two-choice guessing task--and correlated this with in vivo striatal dopamine D2 receptor binding, as measured by 123I-iodobenzamide single photon emission tomography. Patients and controls did not differ with respect to the measures of stereotypy derived from the task. However, there was a significant correlation between one of these measures (RR Information) and the degree of striatal D2 receptor binding asymmetry in the patient group only. In view of research connecting striatal and frontal lesions with stereotypy in animals and cognitive inflexibility in humans, these data could suggest a similar disturbance underlying the phenomenon in schizophrenia.

'Cognitive inhibition' and positive symptomatology in schizotypy.

The negative priming paradigm (Tipper, 1985) was used to investigate the relationship between 'cognitive inhibition' and symptoms of reality distortion in schizotypy, after previous findings that the negative priming effect is reduced in both acute schizophrenics and high schizotypes (Beech, Powell, McWilliam & Claridge, 1989; Beech, Baylis, Smithson & Claridge, 1989). Following Frith's (1979) model, which suggests that the positive symptoms of schizophrenia are due to a failure of the inhibitory processes which normally limit the contents of consciousness, it was predicted that negative priming would be inversely correlated with levels of positive symptomatology, as measured by the CSTQ (Bentall, Claridge & Slade, 1989). The results supported the hypothesis, which confirms the usefulness of a symptom-oriented approach as well as providing some validation for the concept of schizotypy. It was concluded that high schizotypes, similarly to acute schizophrenics, show a reduction in 'cognitive inhibition', as was predicted by Frith's (1979) model.

A cognitive model for schizophrenia and its possible neural basis.

It is proposed that the basic disturbance in schizophrenia corresponds to a disruption of the normal relationship between stored material and current sensory input. The link between information processing disturbances and their biological bases may be facilitated by the use of paradigms derived from animal learning theory. A model for the emergence of schizophrenic symptoms is presented. The core cognitive abnormality may result from a disturbance at any point in the neural circuit involved in the prediction of subsequent sensory input.

A simple (or simplistic?) cognitive model for schizophrenia.

An approach which views schizophrenia as a disturbance of information processing appears promising as a way of linking biological and clinical aspects of the disorder. A review of research in this area led to the suggestion that the basic disturbance in schizophrenia is "a weakening of the influences of stored memories of regularities of previous input on current perception". This formulation leads to the prediction that in certain circumstances, schizophrenics may perform better than normal subjects. Recent studies employing tasks derived from human experimental psychology provide evidence in support of the model. It is argued that the link between information processing disturbances and biological abnormalities may be facilitated by the use of paradigms derived from animal learning theory (latent inhibition and Kamin's blocking effect). On both tasks the pattern of performance of acute schizophrenics is consistent with the cognitive model. The ways in which such an information processing disturbance may lead to schizophrenic symptomatology are outlined, with particular reference to the formation and maintenance of delusional beliefs. The core cognitive abnormality may result from a disturbance in any of the brain structures involved in the prediction of subsequent sensory input. The proposed circuit, which draws heavily on Gray's model, implicates in particular the hippocampus and related areas and is consistent with studies of brain pathology in schizophrenia.

Loss of the Kamin blocking effect in acute but not chronic schizophrenics.

Differences between research diagnostic criteria (RDC)-diagnosed acute and chronic schizophrenics and normal controls were studied using a Kamin blocking procedure. Blocking is an established animal learning procedure, thought by some researchers to reflect selective attention; decreased blocking indicates increased processing of irrelevant stimuli. It was predicted that this pattern would be obtained in acute schizophrenics, tested soon after admission, for two reasons: (1) evidence from previous clinical studies indicates that acute schizophrenics are more aware of nonsalient aspects of their environment than controls; and (2) blocking is disrupted in animals in a hyperdopaminergic state and restored by neuroleptic medication. This was the case: acute, but not chronic, schizophrenics showed disrupted blocking. This disruption was especially clear in those acute schizophrenics tested within 2 weeks of hospital admission. By the second test session (in a cross-over design), there was some evidence of normalization in performance in the acute schizophrenics. These findings are considered with regard to the dopamine hypothesis of schizophrenia.