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.

Premorbid IQ in patients with functional psychosis and their first-degree relatives.

Numerous studies have found deficits in premorbid IQ in schizophrenic patients, but it is not clear whether this deficit is shared by (a) patients with other functional psychoses, and (b) relatives of these patients. Ninety-one schizophrenic patients, 66 affective psychotic patients (29 schizoaffective and 37 manic or depressed), and 50 normal control subjects were administered the National Adult Reading Test (NART) which provides an estimate of premorbid IQ. The NART was also completed by 85 first-degree relatives of schizophrenic patients and by 65 first-degree relatives of affective psychotic patients. After adjustments were made for sex, social class, ethnicity and years of education, schizophrenic patients had significantly lower premorbid IQ than their relatives, the affective psychotic patients and controls. Manic and depressed patients had significantly lower NART scores than their first-degree relatives, but schizoaffective patients did not, and neither group differed significantly from controls. There was no significant difference in premorbid IQ between patients who had experienced obstetric complications (OC+) and those who had not (OC-). Both OC+ and OC- schizophrenic patients differed significantly from their relatives, but the disparity was greatest between OC+ patients and their relatives. Relatives of OC+ schizophrenic patients had significantly higher IQ than relatives of OC- schizophrenic patients.

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.

Disruption of the Kamin blocking effect in schizophrenia and in normal subjects following amphetamine.

The Kamin blocking effect (KBE) is an established animal learning paradigm measuring selective processing, in which reduced blocking reflects allocation of greater processing resources to non-relevant information. Two KBE tasks are described below. Results from studies using the first (between-subjects) task indicate that KBE is abolished in acute schizophrenics with positive psychotic symptoms. It is also abolished in the relatives of schizophrenic subjects, although interpretation of this finding is hampered by poor performance of subjects in the control condition. The second (within-subjects) task indicated abolition of KBE in schizophrenic patients with positive psychotic symptoms. Administration of acute amphetamine to normal human subjects did not significantly disrupt performance on the first task. Whilst for the second task, although blocking was limited to placebo subjects, overall pre-exposure effects are not sufficiently strong to indicate specific drug effects.

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.

Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls.

The aim of this study was to examine the effect of repeated testing on prepulse inhibition (PPI) and habituation of the startle reflex. Fifteen healthy control subjects (eight males, mean age 30 years; seven females, mean age 29 years) were tested on three occasions across the same day separated by a minimum of 2 h. An acoustic probe of 40-msec bursts of 116 dB(A) white noise over a continuous background noise of 70 dB(A) was presented binaurally through headphones and the eye-blink component of the startle response was measured taking electromyographic recordings from the right orbicularis oculi. The test session was identical at each time point and consisted of two blocks of 12 randomly mixed trials of four pulse-alone, four 60-msec prepulse and four 120-msec prepulse trials enclosed by two blocks each of six pulse-alone trials. There was huge variation in individual response magnitude that was independent of subsequent PPI in both women and men. Women showed greater PPI in the second half of sessions with the 120-msec prepulse only; but PPI was not altered significantly in either group between sessions across the day. In general, there was good test-retest reliability of PPI especially within trial type. Normal reflex habituation occurred across sessions and this effect was preserved in sessions across the day. Latency of response was significantly reduced in a session by the 60-msec trial type compared to the 120-msec trial type, as previously reported. Our results suggest that measures of PPI and habituation of the startle response are appropriate and reliable for a within-subject, test-retest design.

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.

Neuropsychological performance and spectrum personality traits in the relatives of patients with schizophrenia and affective psychosis.

Neuropsychological deficits are found in both schizophrenic patients and their relatives, and some studies have shown similar, but less severe, deficits in affective psychotic patients and their relatives. We set out to establish: (a) whether schizophrenia spectrum personality traits are more common in the relatives of schizophrenic patients than, in the relatives of affective psychotic patients; and (b) what the relation is between spectrum personality traits and neuropsychological deficits in these relatives. Relatives were interviewed using the International Personality Disorder Examination (IPDE), and also completed the National Adult Reading Test (NART), the Trail Making Test (TMT; Parts A and B) and Thurstone's Verbal Fluency Test (TVFT). Spectrum personality traits were equally common in 129 relatives of schizophrenic patients and 106 relatives of affective psychotic patients, but the performance of the former group was inferior to that of the latter on the NART and the TVFT. Relatives with high paranoid traits had lower NART scores than relatives without such personality traits; similarly, those with high schizoid traits took longer to complete the TMT, part B, than those without such traits; and relatives with high schizotypal traits generated significantly fewer words on the TVFT than those without such traits. We conclude that relatives of schizophrenic and affective psychotic patients share a propensity to schizophrenia spectrum traits, but relatives of the former have poorer neuropsychological performance. Furthermore, there exists an association between neuropsychological deficits and spectrum traits in both groups of relatives; in particular those with high paranoid traits have lower IQ scores than their less paranoid counterparts.

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.

A controlled trial of cognitive-behavioural and behavioural treatment of anorexia nervosa.

This study was undertaken to investigate whether a cognitive-behavioural treatment procedure was superior to a standard behavioural treatment, in the outpatient therapy of patients with anorexia nervosa. The two treatments were also compared with a control treatment procedure consisting of routine outpatient management. Each group consisted of eight subjects. All the groups showed some improvement, but the findings did not provide support for the prediction that cognitive-behavioural treatment, designed specifically to manipulate both attitudes and behaviour, was superior to the other types of treatment. The implications of the findings are considered.

Comparison of current levels of performance and scores based on change as diagnostic discriminators among the elderly.

Elderly in residential care were classified as probably 'normal' and probably 'organic' by a community screening questionnaire. Performance on a test of verbal learning was assessed at baseline and after two years. The initial and follow-up scores on this test, the changes shown during follow-up and the discrepancies between follow-up score and predicted follow-up performance (estimated from baseline score) were related to this classification. Against expectation, scores based on change did not discriminate better than current levels of performance at baseline or follow-up.

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.