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S V Catts

Publications and source records attributed to S V Catts.

At least 19 recordsLinked to original sources

Disturbed communication in schizophrenia: the role of poor pragmatics and poor mind-reading.

BACKGROUND: Disturbed speech in schizophrenia may reflect pragmatic deficits of expressive language. Pragmatic comprehension deficits also occur in schizophrenia. This study investigated whether poor 'mind-reading' (i.e. a general difficulty with inferring and monitoring other people's thoughts) causes pragmatic language impairments of both expression and comprehension in patients with schizophrenia. METHOD: Mind-reading (or theory of mind) was tested in patients with schizophrenia and in healthy controls using a false-belief picture-sequencing task. Pragmatic comprehension skills were assessed using a test of non-literal speech interpretation. Clinical ratings of formal thought disorder (FTD) indexed the expressive language deficits of patients. To control for possible contributory effects of executive dysfunction, inhibitory control was tested using capture picture-sequences and executive-planning was tested using the Tower of London task. RESULTS: False-belief picture-sequencing, understanding of irony and understanding of metaphors were all selectively impaired in the patients. Poor mind-reading (indexed by high error rate in sequencing false-belief stories) was associated with poor understanding of irony, but was unrelated to poor understanding of metaphors. Whereas poor appreciation of irony and poor mind-reading were associated with high ratings of positive formal thought disorder, high ratings of negative formal thought disorder were associated with poor understanding of metaphors and executive dysfunction. CONCLUSIONS: Whereas poor mind-reading may contribute to positive aspects of formal thought disorder and impaired appreciation of irony in patients with schizophrenia; negative features of formal thought disorder and poor understanding of metaphors appear better explained by abnormal semantics. Overall, the findings of this study support the view that the functional basis of formal thought disorder in schizophrenia is not unitary.

Adolescent↗

Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene?

This paper reviews the six published incidence studies of the relative risk of cancer in patients with schizophrenia compared with the general population. These studies used: incidence data, register case ascertainment, and controlled for age and sex. It is concluded that schizophrenia is associated with a lower risk of developing cancer. The role of apoptosis (programmed cell death) in cancer and brain development is briefly described. The possibility is explored that increased apoptosis may account for neurodevelopmental abnormalities as well as tumour resistance associated with schizophrenia. The authors propose that p53, a tumour suppressor gene central to regulation of apoptosis, should be investigated as a candidate susceptibility gene in schizophrenia.

Apoptosis↗

Schizotypy: phenotypic marker as risk factor.

OBJECTIVE: To evaluate measures of schizotypy as familial risk factors for schizophrenia with the aim of making recommendations for assessing schizotypy as part of screening procedures for identifying people at risk of schizophrenia. METHOD: Published studies using self-report and interview-based measures of schizotypy to assess relatives of patients with schizophrenia are reviewed. A parent study is reported evaluating the diagnostic accuracy of parental schizotypy as assessed by three questionnaire-based measures: the Chapman Perceptual Aberration and Physical Anhedonia Scales, and the Eysenck Psychoticism Scale. Group scores for these self-report ratings of 23 parent-pairs of patients with schizophrenia, 20 parent-pairs of patients with chronic nonpsychotic psychiatric disorder, and 19 parent-pairs of healthy comparison subjects are compared. RESULTS: Consistent with published evidence that self-report measures of psychosis-proneness and schizotypy do not consistently reflect familial risk factors that are specific for schizophrenia, scores on questionnaire measures of schizotypy did not distinguish the parents of patients with schizophrenia from the parents in the other two groups. CONCLUSIONS: Interview-based assessments of schizotypy better assess familial risk factors than self-report measures of schizotypy. Questionnaire measures of schizotypy should be supplemented by interview-based assessments when screening for individuals at risk of schizophrenia.

Adolescent↗

Superior temporal gyral volumes and laterality correlates of auditory hallucinations in schizophrenia.

BACKGROUND: Previous studies have reported significant correlations, indicating an emerging relationship, between severity of auditory hallucinations and reduced size of temporal lobe cortical regions implicated in language processing. The present study used high-resolution magnetic resonance imaging (MRI) scanning, along with assessment of functional lateralization via a dichotic listening task (DLT), to extend these findings. METHODS: Thirty patients with schizophrenia and a history of auditory hallucinations participated in the study. All were completely right-handed. Eleven subjects were currently hallucinating at the time of the study. Volumetric T1-weighted MRI scans were obtained and regions of interest were manually traced using the BRAINS package (Andreasen et al 1993). Whole brain, bilateral temporal lobe, and anterior superior temporal gyrus volumes were calculated. Subjects completed a binaural consonant-vowel DLT. RESULTS: Increased severity of hallucinatory experience was significantly associated with smaller left anterior superior temporal gyrus volumes. Current hallucinators demonstrated a reduction in right ear advantage on the DLT. CONCLUSIONS: The results suggest that auditory hallucinations are subserved by a trait-like dysfunction in language-related neural networks, of which the superior temporal cortex forms one component. The findings are also consistent with theories proposing abnormal lateralization in the etiology of auditory hallucinations.

Adult↗

Effects of prepulses and d-amphetamine on performance and event-related potential measures on an auditory discrimination task.

RATIONALE: Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimotor gating, that is the processing of the startle stimulus (S2) is inhibited by the interfering processing of a closely preceding prepulse (S1). It has been demonstrated that PPI is disrupted in a variety of mental disorders and that several neurotransmitter systems, including dopamine, participate in the modulation of sensorimotor gating. Previous studies have also shown that a task-relevant S1 enhances PPI in healthy subjects but not in schizophrenic patients. These findings indicate an influence of attentional processes on sensorimotor gating and an impairment of this modulation in schizophrenia. OBJECTIVE: Assuming a dopamine-mediated suppression of S1 processing as a mechanism of resource management and selective attention, which might be impaired in certain mental disorders, the present study investigated the effects of the indirect dopaminergic agonist d-amphetamine on prepulse-altered S2 discrimination and event related potentials (ERPs). METHODS: Twelve healthy volunteers were tested in a double-blind, placebo-controlled experimental design. Here, S2 is the target in a difficult Go/NoGo auditory discrimination task. RESULTS: Confirming our previous results, S2 processing is "accentuated" by a weak acoustic prepulse in healthy subjects, thus leading to a lower rate of errors of omission but also to more false alarms (i.e. a liberal response bias). This performance change correlated with a prepulse-induced increase in the amplitude of the P3 ERP towards non-targets ("prepulse-induced non-target positivity"; PINTP). In addition, the results of the present study show that under prepulse conditions amphetamine disrupts "S2 accentuation" associated with a dose-related reduction of the P2 component of the S1 response and a plasma level related reduction of PINTP. CONCLUSIONS: These data suggest an involuntary attentional shift towards S1 processing with increasing dopamine-release similar to that observed in patients with schizophrenia or OCD. It is concluded that sensory gating alters selective attention via dopaminergic modulation.

Acoustic Stimulation↗

Changes in auditory selective attention and event-related potentials following oral administration of D-amphetamine in humans.

The effect of d-amphetamine on selective attention in humans was investigated by measuring event-related potentials (ERPs) during a complex auditory selective attention task (CSAT). The CSAT required subjects to make a button press response to infrequent target tones presented amongst tones that varied in pitch (high vs. low), location (left vs. right ear) and duration (51 ms vs. 102 ms). Healthy subjects completed the CSAT under three conditions: placebo, 10 mg and 20 mg d-amphetamine, at least one week apart. D-amphetamine produced a significant dose response increase in hit-rate and decrease in reaction time without changing false alarm rate. D-amphetamine reduced late PN to location irrelevant stimuli and pitch irrelevant stimuli in both the attended and unattended location. The effect of d-amphetamine was interpreted as a decrease in the maintenance of the attentional trace to irrelevant stimuli. However, these changes were accompanied by some evidence of processing of stimulus features in the unattended location. These results suggest that d-amphetamine improves selective attention, and decreases the maintenance of attention to irrelevant stimuli.

Administration, Oral↗

The effect of decreased catecholamine transmission on ERP indices of selective attention.

This study examines the effect of decreased catecholamine transmission on event-related potential (ERP) indices of selective attention. Intravenous clonidine (1.5 micrograms/kg Catapres), droperidol (15 micrograms/kg Droleptan), or placebo were administered to healthy adult males prior to performance of a multidimensional auditory selective attention task (SAT) in which dichotically presented sequences of tone pips varied on dimensions of location (left or right ear), pitch (high or low), and duration (short or long). Subjects were required to make a button press response to infrequent "target" stimuli that matched a prespecified stimulus on the three dimensions. ERPs were recorded during the task. Clonidine led to a significant increase of processing negativity (PN) over 200-400 ms at the irrelevant location. Droperidol led to a significant increase in reaction time (RT), a significant decrease in hit rate, and an attenuation of PN over the 200- to 400-ms and 400- to 700-ms epochs. Neither substance led to a significant change in P3 amplitude. The role of catecholamines in the selective attention subprocesses of "tuning" and "switching" is discussed.

Adrenergic alpha-Agonists↗

Molecular biological investigations into the role of the NMDA receptor in the pathophysiology of schizophrenia.

OBJECTIVE: There is increasing acceptance that schizophrenia is associated with a generalised disorder in cortical neurodevelopment. The aim of this paper is to review the evidence that this disorder may be accounted for by abnormalities in mechanisms mediated by the main family of excitatory neuroreceptors in cortical brain systems, the N-methyl-D-aspartate (NMDA) glutamatergic receptors. METHOD: The neurobiological evidence is presented for an abnormality in cortical development related to synaptic pathology in schizophrenia. The unique functions of the NMDA receptor in information processing are described, especially its role in learning and memory, and in neural plasticity and brain development. It is argued that the cellular and molecular mechanisms which underlie learning and memory also govern normal brain development. Studies examining abnormalities in glutamatergic transmission in schizophrenia are reviewed. RESULTS: There is a substantial literature in support of the possibility that NMDA receptor abnormalities may be involved in the neurodevelopmental predisposition to schizophrenia, as well as in symptom production. CONCLUSIONS: Research to determine the role of the NMDA receptor in the pathophysiology of schizophrenia is warranted and now feasible. To be successful, this research will require the application of molecular biology techniques to postmortem brain tissue studies, in addition to traditional histochemical approaches.

Cerebral Cortex↗

Increased production of interleukin-2 (IL-2) but not soluble interleukin-2 receptors (sIL-2R) in unmedicated patients with schizophrenia and schizophreniform disorder.

This study investigated immune activation, as measured by production of interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R) from stimulated lymphocytes, in schizophrenia and schizophreniform disorder. The study included 13 neuroleptic-free patients, 13 medicated patients and 13 age- and sex-matched control subjects. Production of IL-2 and sIL-2R by peripheral blood mononuclear cells (PBMCs) was measured after in vitro stimulation with phytohaemagglutinin (PHA). Patients' symptoms were rated on the Scales for Assessment of Positive (SAPS) and Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS). IL-2 production by stimulated lymphocytes was significantly elevated in neuroleptic-free patients compared with both medicated patients and control subjects. IL-2 production was inversely correlated with the SAPS subscales of bizarre behaviour and formal thought disorder. The pattern of increased IL-2 production is in contrast to previous findings in patients with schizophrenia. Significant associations with clinical rating scores suggest that IL-2 production may vary in different biological subgroups of schizophrenia and schizophreniform disorder.

Adult↗

Replication of a P50 auditory gating deficit in Australian patients with schizophrenia.

Schizophrenic patients reportedly have a deficit in the control of sensitivity to auditory stimuli as shown by the P50 auditory evoked potential wave in a conditioning-testing paradigm that measures suppression of response to a repeated stimulus. Although this finding has been replicated by several US laboratories, one European group has not found differences between schizophrenic patients and normal control subjects. In the present study, investigators in the Schizophrenia Research Center at the Prince of Wales Hospital in Sydney, Australia, selected 22 normal control subjects, 11 acutely ill schizophrenic inpatients, and 11 clinically stable schizophrenic outpatients. Both schizophrenic groups were treated with similar doses of classical neuroleptic medications. Evoked potentials were recorded by an investigator from the US laboratory that initially reported the difference; five averages, each the response to 32 stimulus pairs, were recorded from each subject. The normal control subjects demonstrated significantly more suppression of the P50 response to the repeated stimuli than the schizophrenic groups, as previously reported. There were no significant changes in the suppression measure over the five trials. The suppression of the P50 wave by schizophrenic outpatients was somewhat greater than that by schizophrenic inpatients, but both schizophrenic groups had decreased suppression, compared with the normal subjects. The mean P50 suppression for five averages was successfully used in a logistic regression to classify subjects as normal or schizophrenic. This method was more accurate than attempts to classify subjects with only one average. The mean amplitude of the initial conditioning response did not differ between groups. Schizophrenic patients had slightly shorter mean latencies. There was no direct relationship of P50 suppression to measures of clinical psychopathology.

Adult↗

Brain potential evidence for an auditory sensory memory deficit in schizophrenia.

OBJECTIVE: The multiple disorders of selective attention found in schizophrenia could be secondary to disturbances in sensory processing. The authors investigated this possibility by using an event-related potential index of auditory sensory memory, called "mismatch negativity." METHOD: Medicated (N = 11) and neuroleptic-free (N = 11) patients with schizophrenia and patients with bipolar affective disorder (N = 11) were compared with age- and sex-matched healthy comparison subjects. Auditory stimuli were presented while the subjects were distracted with an attention-demanding visual task. Event-related potentials were elicited by infrequently occurring auditory stimuli (deviants) and by regularly presented auditory stimuli (standards), which differed slightly in duration. The difference in amplitude between the event-related potentials elicited by the deviant and standard stimuli was the mismatch negativity. RESULTS: The amplitude of the mismatch negativity was significantly lower in both groups of schizophrenic patients than in the healthy comparison subjects. Mismatch negativity amplitude was significantly correlated with ratings of negative schizophrenic symptoms but not with positive symptoms. Compared with the matched comparison subjects, the bipolar affective disorder patients did not show lower amplitude of mismatch negativity. There was a significant negative correlation between age and mismatch negativity amplitude. CONCLUSIONS: The abnormal auditory sensory memory processing indicated by low mismatch negativity amplitude in the schizophrenic patients cannot be accounted for by neuroleptic medication status. Because this abnormality was significantly related to measures of negative symptoms only, it may be a chronicity marker or reflect a predisposition to the development to schizophrenia. These findings implicate the auditory cortex in the pathophysiology of schizophrenia.

Acoustic Stimulation↗

Event-related potential indices of semantic processing in schizophrenia.

Event-related potentials (ERPs) were recorded while schizophrenic patients and healthy controls read congruous and incongruous sentences in anticipation of a memory test. The schizophrenic group performed more poorly in both recognition memory and cued recall tests. The two groups did not differ in the amplitude of the N400 component of the ERP but the difference between the ERPs to congruous and incongruous sentences persisted longer in the schizophrenic sample. The schizophrenic sample also showed reduced parietal positivity and a reduced effect of congruity on the late positive component that follows N400. Within the schizophrenic sample, measures of attentional impairment and positive thought disorder were correlated with mean amplitude of both the N400 and the subsequent positivity. The results imply that the structure and spread of activation within semantic memory is not impaired in schizophrenia. Rather, impairments appear to lie in processes required to integrate activated information with the current context.

Adolescent↗

P300 indexes thought disorder in schizophrenics, but allusive thinking in normal subjects.

Loosening of thinking as assessed by the Object Sorting Test (OST) has been found in a percentage of normal subjects but in a higher percentage of schizophrenics, and is familially transmitted in both groups. Loosening of thinking in normal subjects is not associated with evidence of impaired function or increased psychopathology, and in recognition of this, it was termed allusive thinking rather than thought disorder. Both OST-assessed loosening and concreteness of thinking were found to be present independently in a high percentage of schizophrenics, so that both were considered to contribute to schizophrenic thought disorder. The presence of OST-assessed loosening in schizophrenics would, therefore, be predicted to correlate partially rather than totally with measures of schizophrenic thought disorder. It has been suggested that OST-assessed loosening in normal subjects is due to a genetically determined reduction in strength of an inhibitory process that limits the spread of activation of semantic associations and results in a predisposition to schizophrenia. The brain event-related potential P300, which is, in part, under genetic control, may index this inhibitory process. Therefore, it was predicted that in normal subjects, P300 would correlate with OST-assessed loosening of associations. If schizophrenic thought disorder is due to a further weakening of this inhibitory process, it can be predicted that P300 in schizophrenics correlates only weakly with OST-assessed loosening of thinking, but more strongly with schizophrenic thought disorder. In a study in which P300 was elicited using a difficult selective attention task with 15 unmedicated schizophrenics and 22 healthy subjects, all three predictions were supported.

Adult↗

Allusive thinking in parents of schizophrenics. Meta-analysis.

Romney (J. Nerv. Ment. Dis. 178:481-486, 1990) performed a meta-analysis of studies examining psychometrically assessed "thought disorder" in the relatives of schizophrenics. He concluded that thought disorder was more prevalent in the relatives of schizophrenics than control subjects. The present review focuses on only those studies that measured "allusive thinking" using the Lovibond-Rapaport Object Sorting Test in parents of schizophrenics. Even when the meta-analysis included this more limited number of studies, it demonstrated that the parents of schizophrenics were 2.42 times more likely to obtain high scores on the Object Sorting Test, confirming replication of the original McConaghy (J. Neurol. Neurosurg. Psychiatry 22:243-246, 1959) finding. This effect remained significant when the original study was excluded from the meta-analysis. The predictive strength of parental Object Sorting Test score as a familial risk factor for the development of schizophrenia is discussed.

Family↗

P300 and conceptual loosening in normals: an event-related potential correlate of "thought disorder?".

Reduced amplitude of the P300 component of the event-related potential (ERP) has frequently been reported in schizophrenic patients and their first-degree relatives. The present study examined the relationship between this ERP measure of attentional processing and loosening of associations in normal university students (termed "allusive thinking"). Among male subjects, scores reflecting increased conceptual loosening, measured using the Lovibond scoring method for the Goldstein-Scheerer Object Sorting Test (OST), were significantly correlated with smaller P300 amplitude recorded during an auditory target detection task. There was no association between OST score and either performance of the target detection task or self-reported psychopathology. It is suggested that reduced P300 amplitude could reflect altered attentional processing in individuals with a constitutional trait factor of thought disorder.

Adolescent↗

The effect of repeated testing on ERP components during auditory selective attention.

The present study examined long-term repetition effects on human auditory event-related potentials (ERPs). ERPs were recorded from subjects performing the same multidimensional auditory selective attention task on six separate occasions spaced one week apart. The task required subjects to attend to tones that varied along the dimensions of location (L), pitch (P), and duration (D) and to detect prespecified target (L + P + D +) combinations of these attributes. Processing negativity (PN) between 100-400 ms did not change in amplitude or onset latency as a function of repeated experience with the task. In contrast, two measures of "very late" PN were reduced with practice. Specifically, the location effect measured over the 400-700-ms epoch was significant only for Weeks 1 and 2, and the separation of the L + P + D- ERP from other D- ERPs, measured over the 700-1000-ms epoch, was significantly reduced from Week 1 to Week 2. A late negative component (700-1000 ms) elicited by correctly identified targets increased between Weeks 1 and 2, consistent with subjects adopting the strategy of rehearsal of the target itself rather than the L + P + D- standard. P2 amplitude increased significantly for all standards, possibly due to decreased latency jitter in later weeks. N1 latency became significantly shorter over weeks, reflecting either increasing confidence in stimulus discrimination with repeated testing or the overlapping of an unchanging N1 with an increasing P2.

Acoustic Stimulation↗