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.

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.

Abolition of latent inhibition by a single 5 mg dose of d-amphetamine in man.

The performance of healthy volunteer subjects on an auditory latent inhibition (LI) paradigm was assessed following administration of a single oral dose of d-amphetamine or placebo. It was predicted that a low (5 mg), but not a high (10 mg), dose of d-amphetamine would disrupt LI. The prediction was supported with left ear presentation of the preexposed stimulus only. When the preexposed stimulus was presented to the right ear the predicted pattern of findings was not obtained. It is concluded that the dopaminergic system is involved in the mediation of LI in man and it is speculated that the interaction between amphetamine dose and ear of presentation of the preexposed stimulus may reflect normally occurring dopaminergic hemisphere asymmetry.

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.

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 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.

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.

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.

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.

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.

Schizophrenia: a failure to control the contents of consciousness?

Frith (1979) proposed that the 'positive' symptoms of schizophrenia, i.e. hallucinations, delusions, and though disorder, could be accounted for in terms of a defect in the mechanism(s) that controls and limits the contents of consciousness. The present study was designed to test one of the predictions derived from this model; that schizophrenics should fail to inhibit alternative meanings of ambiguous words. As a means of testing this prediction the effects of semantic priming on the 'availability' of subsequent target words to consciousness were assessed, measuring recognition thresholds. The priming conditions employed were expected to either facilitate or inhibit perception of target words in the control groups, normals and depressed patients without psychotic features. A strong priming effect was obtained in the control groups, but was much weaker in the schizophrenic group; this provides some support for the model.

A psychophysical investigation of auditory functioning in schizophrenia.

The present report is of the application of Treisman's (1964) model of perceptual functioning to the study of schizophrenic hallucinations. It was hypothesized that hallucinators would perform on an auditory threshold task as if possessing a perceptual system showing high levels of spontaneous neural activity (In). Three groups were compared on the Weber functions for pure tone intensity: schizophrenic hallucinators, old people and anxiety neurotics. From these functions, estimates of In were calculated using Barlow's (1957b) method. No group differences were found. An alternative explanation of schizophrenic hallucinations, in terms of increased responsiveness to normal levels of background sensory activity, is proposed.

The use of directed masturbation training in the treatment of primary anorgasmia.

This review evaluates the evidence for the effectiveness of the use of directed masturbation training in the treatment of primary anorgasmia. Various methodological problems are discussed but it is clear that some clients can be helped by this form of therapy. As yet it is unclear which clients are likely to benefit from such a programme or what are the most important factors influencing outcome. Some social and cultural implications, including issues relating to the role of the therapist, are briefly discussed.

Illusory correlations in paranoid and non-paranoid schizophrenia.

Paranoid schizophrenics, non-paranoid schizophrenics and normals were assessed on tasks designed to demonstrate their tendency to perceive illusory correlations. It was hypothesized that paranoids would show stronger illusory correlations than normals due to the predominance of their schemata when processing information, and that non-paranoids would show weaker correlations than normals because of their impaired ability to establish conceptual categories. Results were broadly consistent with predictions.

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.

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.

The relationship between alternative assessments of self-care ability in the elderly.

The self-care performance of 126 residents of old people's homes was assessed by self-report, informant rating and performance test. Scores on all three scales were related but associations were low and gross disagreements between measures were found in almost half of the cases. The associations between self-report and the other two measures were significantly lower than those between informant and performance ratings. There was no evidence of systematic bias in self-report related to cognitive or to affective impairment. It is probable that the three scales measure different aspects of dependency.

The retention of new information in senile dementia.

Paired associate learning performance of demented patients was assessed repeatedly over six months. Patterns of change of performance for repeated and for changing items were compared. Performance on changing items progressively declined, performance on repeated items was maintained at initial levels. This difference was significant and indicates that these patients are able to retain same information over one- and two-month intervals.

'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.