J.S.E. Hellewell

Thought disorder in schizophrenia is associated with both executive dysfunction and circumscribed impairments in semantic function.

BACKGROUND Formal thought disorder (FTD) has long been regarded as a key sign of schizophrenia but little is known about its origins or aetiology. One suggestion is that it is directly related to disordered language functioning; a second is that it is a reflection of poor neurocognitive functioning. A current model posits that it is related to a combination of executive dysfunction and impaired semantic processing. METHOD To examine these alternative ideas, a heterogeneous group of 30 patients, all carrying a diagnosis of schizophrenia, and 18 non-patient controls completed a series of neurocognitive and psycholinguistic tests, and a clinical review that, inter alia, permitted assessment of thought disorder (TD) using the Thought, Language and Communication Scale (TLC). RESULTS Patients generally performed at a lower level on most components of the test battery, but there was little evidence of a relationship between TD and syntactic psycholinguistic function. However, schizophrenic patients manifesting higher levels of TD performed at a lower level on tests sensitive to executive dysfunction and semantic impairments. CONCLUSIONS The origins of TD seem more closely linked to deficits in executive functioning and semantic processing than to impairments in other language functions or general cognition.

Patients' subjective experiences of antipsychotics: Clinical relevance

The subjective experience of patients with schizophrenia who are receiving antipsychotic medication has been a neglected research area, as has the satisfaction of patients with their drug treatments. This is unfortunate, as satisfaction with treatment appears to be related strongly to the readiness of patients to take their medication as prescribed, and thereby to outcome. Patients’ perceptions of their treatment do not appear to be related strongly to severity of illness or symptom ratings, although there are associations between perceptions of treatment and adverse effects.Surveys of patient experience with typical antipsychotics have tended to indicate high levels of dissatisfaction and perceived adverse effects. There have been a number of surveys of patients’ perceptions of treatment with the atypical antipsychotics. These tend to accord with the expectation that a relative freedom from adverse effects with the atypical antipsychotics will be reflected in enhanced levels of satisfaction and perceived well-being.In general, these studies share a number of weaknesses, including small sample sizes, bias in selection of respondents, open treatment and lack of suitable comparator groups. In addition, many have adopted a cross-sectional, rather than longitudinal, approach and have relied on nonvalidated and perhaps idiosyncratic rating measures. Recently, there have been studies of better methodological quality. These, too, have indicated that patients regard the newer treatments more positively than the older regimens. In addition, there is now evidence that the various new-generation antipsychotics may be evaluated differently by patients.

Verbal memory impairment in schizophrenia: no sparing of short-term recall

Verbal memory function was assessed in 27 schizophrenic patients and 19 healthy control subjects matched for premorbid IQ and age using a test battery comprising measures of short-term, long-term and source memory. Patients were also rated for positive and negative symptoms. Results indicated that the patient group evinced poorer performance on all tests of short-term memory, and most tests of long-term memory, and that these differences remained when current IQ was introduced as a covariate. Within the patient group, overall verbal memory performance was associated only with a negative symptoms. Results are discussed in the context of a generalised neuropsychological deficit in schizophrenia.

Oxcarbazepine (Trileptal) in the treatment of bipolar disorders: a review of efficacy and tolerability

Oxcarbazepine, although structurally similar to carbamazepine, is metabolised very differently. As a consequence, oxcarbazepines pharmacokinetic profile is comparatively less complex, and a more predictable, linear relationship between oxcarbazepine and blood levels is apparent. Furthermore, hepatic enzyme induction is considerably less with oxcarbazepine. Unlike carbamazepine, oxcarbazepine does not appear to induce its own metabolism, nor is it highly protein bound. These pharmacokinetic and metabolic characteristics raise the expectation that potential for drug interactions and side effects with oxycarbazepine will be less than that reported for carbamazepine. This review compares the pharmacokinetic and metabolic profiles of the two drugs and the available efficacy and safety data of carbamazepine and oxcarbazepine, in the treatment of bipolar disorder.

Characterization of a psychophysiological model of classical fear conditioning in healthy volunteers: influence of gender, instruction, personality and placebo

Two experiments are described which evaluate the role of associative mechanisms and placebo effects on aversively conditioned skin conductance responses in groups of healthy volunteers. In both experiments, skin conductance level (SCL), variability (spontaneous fluctuations, SF) and amplitude (SCR) were recorded during a sequence of tone stimuli (80 dB, 1 s, 360 Hz). All the variables habituated during the first ten presentations of the tones. Tone 11 was immediately followed by a loud (100 dB) aversive brief (1 s) white noise UCS. The conditioning trial significantly enhanced SCRs to a further ten presentations of the tones and increased SCL and variability (SF). No enhancement of SCRs occurred when tone 11 was omitted and the UCS occurred in temporal isolation (experiment 1). Thus enhanced SCRs to tones following paired tone-noise presentation involves an associative mechanism. Increased “spontaneous” variability was shown to involve both conditioning and sensitization following the UCS. In both experiments females showed greater conditioned SCRs than males. In experiment 2 no effect of “anxiolytic” placebo could be discerned and there were no general relationships between questionnaires scores of extraversion or neuroticism with skin conductance measures in a group of 40 volunteers. The results question the role of conditionability and autonomic lability as major determinants of extraversion and neuroticism. These studies validate the use of the psychophysiological model of aversive conditioning in pharmacological studies of the mechanisms of habituation, conditioning and sensitization.

Self-Monitoring Dysfunction and the Positive Symptoms of Schizophrenia

Frith has proposed that symptoms of alien control in schizophrenia result from a defect in a metarepresentational process leading to a failure to properly monitor self-willed intentions and actions. To examine this hypothesis, a group of 40 schizophrenic patients, all meeting DSM-III-R criteria, and rated for current symptoms on the basis of a detailed clinical interview, were compared with 36 non-patient controls, using a battery of tests which included measures of self-monitoring, general cognitive function and attention. In comparison with controls, patients were impaired on two tests of self-monitoring. These differences were preserved when measures of current IQ, attention, and recognition memory were entered as covariates. Amongst patients, self-monitoring performance was related to the severity and extent of positive symptoms. These findings provide further experimental support for the proposal that positive symptoms of schizophrenia arise as a result of deficiencies in self-monitoring.

Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans

The effects of buspirone, fluvoxamine and diazepam were investigated, using healthy volunteers, in an aversive conditioning paradigm, a putative model for conditioned anxiety. The main prediction was that buspirone, an anxiolytic agent which reduces activity in serotonin (5-hydroxytryptophan, 5-HT) neurones, would attenuate aversively conditioned skin conductance responses. Skin conductance responses were recorded to 10 neutral tones (habituation phase). Tone 11 was immediately followed by a 1-s 90-dB aversive white noise (unconditioned stimulus). The conditioning trial reinstated responding to a second presentation of the tones (extinction phase). Skin conductance response amplitude, inter-response level and spontaneous fluctuations were recorded. There were five treatment groups comprising five men and five women. One control group took placebo, another control group received nothing; there was no effect of placebo on any measure. Diazepam (2 mg, p.o.), a positive comparator, markedly reduced the amplitude of skin conductance responses at all phases of the experiment, but only in women. Buspirone (5 mg, p.o.) had the predicted effect of accelerating extinction but also of unexpectedly accelerated habituation of skin conductance responses. There was a trend to reduce spontaneous fluctuations and no effect on skin conductance level. The effects of buspirone were thus specific to responses to stimuli. Fluvoxamine (25 mg, p.o.) had similar effects to buspirone and diazepam in women. An action common to buspirone, fluvoxamine and diazepam, which may account for their shared effect on conditioned autonomic responses, is the suppression of neural activity in the dorsal raphe nucleus. It is argued that enhanced habituation must involve a different mechanism, such as enhanced 5-HTIA function in the terminal fields of the median raphe nucleus.

2-COM: an instrument to facilitate patient-professional communication in routine clinical practice.

Objective:  A simple patient‐completed self‐report instrument may facilitate patient–professional carer communication.

Effects of the 5HT antagonist cyproheptadine on neuropsychological function in chronic schizophrenia

This study tests the hypothesis that the ability of atypical neuroleptics to improve negative symptoms is due to 5HT-receptor antagonism and enhanced frontal lobe function. We investigated the effects of cyproheptadine (a 5HT2 antagonist) on neuropsychological tests of frontal lobe functions in chronic schizophrenic patients. Eighteen stable schizophrenic patients on depot neuroleptic medication participated in a 4-week double blind crossover study. Outcome measures were clinical symptoms rating scales, neuropsychological tests (verbal fluency, Stroop colour word task, trail making) and antisaccade eye movements. During the cyproheptadine phase statistically significant improvement was seen on Stroop colour word task, verbal fluency and Trail B tests. The ability to suppress reflexive eye movement to a target light in an anti saccade task was also significantly enhanced. The patients had low clinical ratings of negative symptoms and they were unaffected by cyproheptadine. The results indicate that 5HT2C receptors selectively modulate speed and motor control mechanisms related to frontal lobe functions but this was not associated with changes in symptoms.

Antipsychotic induced hyperprolactinaemia: a series of illustrative case reports

Hyperprolactinaemia is a common side-effect of many antipsychotic drugs but, in comparison to extrapyramidal side-effects, it has received little attention. Four case reports are presented which illustrate important clinical and pharmacological aspects of the syndrome. Two of the cases were caused by conventional antipsychotic drugs and two by risperidone, an atypical antipsychotic. Symptoms included gynaecomastia, galactorrhoea, amenorrhoea and sexual dysfunction. Three patients were switched to a prolactin sparing antipsychotic leading to normalization of serum prolactin and resolution of the symptoms. Patients prescribed prolactin elevating antipsychotics should, where possible, have this issue explained to them prior to commencing treatment and be screened for symptoms suggestive of hyperprolactinaemia before starting treatment and regularly thereafter.