Source memory errors in schizophrenia, hallucinations and negative symptoms: a synthesis of research findings.

BACKGROUND: Previous research has shown associations between source memory errors and hallucinations in patients with schizophrenia. We bring together here findings from a broad memory investigation to specify better the type of source memory failure that is associated with auditory and visual hallucinations. METHOD: Forty-one patients with schizophrenia and 43 healthy participants underwent a memory task involving recall and recognition of lists of words, recognition of pictures, memory for temporal and spatial context of presentation of the stimuli, and remembering whether target items were presented as words or pictures. RESULTS: False recognition of words and pictures was associated with hallucination scores. The extra-list intrusions in free recall were associated with verbal hallucinations whereas the intra-list intrusions were associated with a global hallucination score. Errors in discriminating the temporal context of word presentation and the spatial context of picture presentation were associated with auditory hallucinations. The tendency to remember verbal labels of items as pictures of these items was associated with visual hallucinations. Several memory errors were also inversely associated with affective flattening and anhedonia. CONCLUSIONS: Verbal and visual hallucinations are associated with confusion between internal verbal thoughts or internal visual images and perception. In addition, auditory hallucinations are associated with failure to process or remember the context of presentation of the events. Certain negative symptoms have an opposite effect on memory errors.

Hallucinations and two types of free-recall intrusion in schizophrenia.

BACKGROUND: Previous research has demonstrated that various types of verbal source memory error are associated with positive symptoms in patients with schizophrenia. Notably, intrusions in free recall have been associated with hallucinations and delusions. We tested the hypothesis that extra-list intrusions, assumed to arise from poor monitoring of internally generated words, are associated with verbal hallucinations and that intra-list intrusions are associated with global hallucination scores. METHOD: A sample of 41 patients with schizophrenia was administered four lists of words, followed by free recall. The number of correctly recalled words and the number of extra- and intra-list intrusions were tallied. RESULTS: The verbal hallucination score was significantly correlated with the number of extra-list intrusions, whereas it was unrelated to the number of correctly recalled words. The number of intra-list intrusions was significantly correlated with the global, but not with the verbal, hallucination score in the subsample of hallucinating patients. It was marginally significantly correlated with the delusion score in delusional patients. CONCLUSIONS: The data corroborate the view that verbal hallucinations are linked to defective monitoring of internal speech, and that errors in context processing are involved in hallucinations and delusions.

Interrater reliability of the Antipsychotic Non-Neurological Side-Effects Rating Scale measured in patients treated with clozapine.

The Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS) was developed to provide a comprehensive measure for rating non-neurological adverse drug reactions (ADRs) to antipsychotics. Although there were already available measures that adequately rated specific non-neurological ADRs, such as sexual side effects, a need was identified for a scale that comprehensively rated the full range of non-neurological ADRs commonly seen across the spectrum of first and second generation antipsychotic drugs, including metabolic and autonomic ADRs. This article reports on work to establish the interrater reliability of an early version and a later, more comprehensive version of the ANNSERS (versions 1 and 2, v1 and v2, respectively). The measures were administered in London centres to patients treated with clozapine. Trained clinicians rated the patients simultaneously and independently. Interrater reliability on the scores was calculated using the kappa coefficient method. The results (mean kappa coefficients of 0.77 and 0.72, respectively) indicate that substantial interrater reliability was achieved for both versions. Items for which the main basis for rating was laboratory investigations rather than patient interview were largely excluded from this study, and kappas were also not calculated for items with a low frequency (less than 10%) of endorsement. Samples of patients on other antipsychotics would be required to reliably calculate kappa coefficients for these items. In conclusion, the ANNSERS represents a clinically applicable research innovation, with good interrater reliability on clinician judged items, which is now available for the comprehensive assessment of non-neurological ADRs to antipsychotics, to aid the processes of clinical audit, research and drug discovery.

The place of partial agonism in psychiatry: recent developments.

Drugs used to treat psychiatric disorders, although effective, are often restricted by adverse events. The use of partial agonists for treating hypertension was found to limit some of the side-effects in some patients. This led to the investigation of partial agonists as a treatment modality in psychiatric disorders. Partial agonists have a lower intrinsic efficacy than full agonists leading to reduced maximum response. They can act as antagonists by competing for receptor binding with full agonists. The level of activity depends on the level of endogenous receptor activity. Buprenorphine, a partial agonist at the mu-opioid receptor, is used to treat patients with addiction and decreases the symptoms of withdrawal and risks of overdose and intoxication. The anxiolytic buspirone shows partial agonism at 5-HT(1A) receptors, and this seems to provide anxioselective effects, without inducing extrapyramidal side-effects, convulsions, tolerance or withdrawal reactions. In schizophrenia, partial dopamine agonism results in antagonistic effects at sites activated by high concentrations of dopamine and agonistic effects at sites activated by low concentrations of dopamine. This stabilizes the dopamine system to effect antipsychotic action without inducing adverse motor or hormonal events. Aripiprazole is the first 'dopamine system stabilizer', and the data are promising, with efficacy at least equivalent to that with current atypical antipsychotics but fewer of the troublesome side-effects. Partial agonists seem to provide a way to fine-tune the treatment of psychiatric disorders by maximizing the treatment effect while minimizing undesirable adverse events.

Developing a service to monitor and improve physical health in people with serious mental illness.

Developing effective models of identifying and managing physical health problems amongst mentally ill populations has become a more pressing issue in recent years as the prescription of Second Generation Antipsychotics (SGAs) has burgeoned. Some of the side effects commonly associated with SGAs such as weight gain and metabolic disorders have potentially devastating effects on health and well-being, increasing cardiovascular risk and the incidence of diabetes. The Well-Being Support Programme (WSP), a nurse-led service, was designed to provide a care delivery system whereby physical problems could be identified and appropriate treatment and monitoring initiated by prompt referral to suitable specialist services or general practitioners, forging strong links between primary and secondary care and ensuring that mentally ill patients with physical health problems were receiving holistic care packages. Other problems such as unhealthy lifestyles and obesity were managed by the Nurse Advisor running the programme. Interventions such as weight counselling and groups, and structured exercise programmes were beneficial in terms of encouraging healthier lifestyles, managing obesity and improving self-esteem. This paper describes the manner in which the service was set up and implemented, demonstrating an effective model for identifying and managing physical health problems in the mentally ill.

Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [123I]epidepride single photon emission tomography (SPET) study.

RATIONALE: Previous work suggests clozapine preferentially targets limbic cortical dopamine systems, which could help account for its lack of extrapyramidal side effects (EPS) and superior therapeutic efficacy. OBJECTIVES: To test the hypothesis that olanzapine, a novel atypical antipsychotic drug, occupies temporal cortical D2/D3 receptors to a greater extent than striatal D2/D3 receptors in vivo. METHODS: Nine schizophrenic patients taking either olanzapine [(n=5; mean (SD) age: 32.5 (6.5) years; daily dose: 18.3 (2.6) mg] or sertindole [(n=4; mean (SD) age: 30.3 (7.4) years; daily dose: 16 (5.6) mg] were studied with [123I]epidepride ((S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenz amide) and single photon emission tomography (SPET). An estimate of [123I]epidepride 'specific binding' to D2/D3 receptors was obtained in patients and age-matched healthy volunteers. A summary measure was generated representing striatal and temporal cortical relative %D2/D3 receptor occupancy by antipsychotic drugs. Occupancy data were compared with previously studied groups of patients receiving typical antipsychotic drugs (n=12) and clozapine (n=10). RESULTS: Mean striatal and temporal cortical %D2/D3 receptor occupancy in olanzapine-treated patients was 41.3% (SD 17.9) and 82.8% (SD 4.2), respectively. Unexpectedly low levels of striatal relative %D2/D3 receptor occupancy were seen in two patients with typical antipsychotic-drug-induced movement disorder prior to switching to olanzapine. In the temporal cortex, mean D2/D3 dopamine receptor occupancy levels above 80% were seen for all antipsychotic drugs studied. CONCLUSIONS: The atypical antipsychotic drugs olanzapine and sertindole, in common with clozapine, demonstrate higher occupancy of temporal cortical than striatal D2/D3 dopamine receptors in vivo at clinically useful doses. This could help mediate their atypical clinical profile of therapeutic efficacy with few extrapyramidal side effects. Limbic selective blockade of D2/D3 dopamine receptors could be a common action of atypical antipsychotic drugs.

Treating first episode psychosis--the service users' perspective: a focus group evaluation.

UK national guidance has prioritized developing specialist services for first episode psychosis. Such services are in the early stages of development and a definitive treatment model has yet to be established. The aim of this study was to explore service users' experiences of a first episode intervention designed along evidence-based 'best practice' guidelines and to establish specific elements seen as effective to help inform future service planning and provision. Twelve users of a specialist first episode service participated in focus groups. These were then analyzed using Interpretative Phenomenological Analysis, a specialized form of content analysis. Key elements identified by the service users included the 'human' approach as a key to the recovery process, being involved in treatment decisions, flexibility of appointments, high nurse to patient ratio, reduction in psychotic symptoms, increased confidence and independence and the provision of daily structure. To our knowledge, this is the first systematic qualitative evaluation of users' experience of a specialist first episode treatment intervention. Our findings indicate that adherence to best practice guidelines was appreciated. Regular focus groups provide a continuous audit cycle incorporating service improvements in line with government recommendations, centrally informed by the service users' and caregivers' perspective.