Continued cannabis use and outcome in first-episode psychosis: data from a randomized, open-label, controlled trial.

OBJECTIVE: Cannabis use has been found to increase the risk of psychosis. It is unclear whether, after a first psychotic episode has occurred, continued cannabis use is associated with poor functional outcome of psychosis. METHOD: As part of a randomized, open-label, controlled trial, the association of cannabis use and measures for psychopathology and social role functioning after 2 years of follow-up and for the recently proposed outcome measures of symptomatic remission, functional remission, and clinical recovery was explored in a group of 124 patients suffering from nonaffective first-episode psychosis (diagnosed according to DSM-IV and included from a catchment area in the Netherlands of 3.1 million inhabitants from October 2001 through December 2002). Other patient characteristics that were expected to be independently associated with outcome, among them alcohol and other drug use, were assessed at baseline. RESULTS: Continued cannabis use was not associated with symptomatic or functional remission or clinical recovery. After 2 years, cannabis use was related to certain aspects of social role functioning (economic and social activities; explained variance 5.6% and 8.4%, respectively) but not to psychopathology (Positive and Negative Syndrome Scale Positive, Negative, or General symptoms). CONCLUSIONS: Our findings support the notion that continued cannabis use after the onset of a first-episode psychosis is correlated with worse social outcome and should be discouraged whenever possible, but its role in outcome is modest in comparison to other factors. TRIAL REGISTRATION: Nederlands Trial Register: http://www.trialregister.nl (ID: NTR 374).

Neurocognition and recovery in first episode psychosis.

Cognitive functioning has been found to be a predictor of functional outcome of schizophrenia. It is unclear, however, whether clinical recovery can be predicted by scores on specific cognitive domains. The predictive value of specific neurocognitive domains and other clinical variables for symptomatic and functional outcome and clinical recovery after a 2-year follow-up is explored in a group of 51 patients with non-affective first-episode psychosis. A comprehensive neurocognitive battery was administered 18 and 41weeks after inclusion. Other patient characteristics, which were expected to independently predict clinical recovery, were assessed at baseline. Several neurocognitive tests, especially tests measuring speed of processing, and among others, Duration of Untreated Psychosis (DUP), were significant predictors of clinical recovery. Poor neuropsychological performance accurately predicted non-recovery, but improved neuropsychological performance did not accurately predict recovery. This study confirms previous findings of an association between neurocognition and outcome, but the results also suggest that in order to accurately predict recovery, the role of other factors needs to be investigated.

Abnormal externally guided movement preparation in recent-onset schizophrenia is associated with impaired selective attention to external input.

Several theories propose that the primary cognitive impairment in schizophrenia concerns a deficit in the processing of external input information. There is also evidence, however, for impaired motor preparation in schizophrenia. This provokes the question whether the impaired motor preparation in schizophrenia is a secondary consequence of disturbed (selective) processing of the input needed for that preparation, or an independent primary deficit. The aim of the present study was to discriminate between these hypotheses, by investigating externally guided movement preparation in relation to selective stimulus processing. The sample comprised 16 recent-onset schizophrenia patients and 16 controls who performed a movement-precuing task. In this task, a precue delivered information about one, two or no parameters of a movement summoned by a subsequent stimulus. Performance measures and measures derived from the electroencephalogram showed that patients yielded smaller benefits from the precues and showed less cue-based preparatory activity in advance of the imperative stimulus than the controls, suggesting a response preparation deficit. However, patients also showed less activity reflecting selective attention to the precue. We therefore conclude that the existing evidence for an impairment of externally guided motor preparation in schizophrenia is most likely due to a deficit in selective attention to the external input, which lends support to theories proposing that the primary cognitive deficit in schizophrenia concerns the processing of input information.

Effects and side effects of antipsychotic treatment in schizophrenia: pros and cons of available self-rating scales.

INTRODUCTION: To support clinical practice as well as clinical research, self-rating scales have been developed to evaluate the effects and side effects of antipsychotic treatment. The aim of this study is to compare the psychometric properties and other characteristics of frequently used self-rating scales, and also to study their relationship to subjective quality of life. METHOD: Four self-rating scales designed to evaluate the treatment effects of antipsychotics were identified through a MEDLINE and cross-references search: The Drug Attitude Inventory (DAI-10), The Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), Subjective Well-being to Neuroleptics (SWN) and the recently developed Subjects' Reaction to Antipsychotics questionnaire (SRA). Three hundred and twenty patients with schizophrenia who were treated with antipsychotics completed these questionnaires, including a quality of life instrument, the WHO-QoLBREF. RESULTS: The self-rating scales differed in scope, number of items and subscales (total and subscale scores), but showed an acceptable internal reliability (Cronbach's alphas varying between .64 and .93) except for the DAI-10 (.52), and all were easy to complete (in less than 20 min). They did not strongly correlate with each other, except for the LUNSERS and SRA undesired experiences subscale (r=.68, p<.01). All correlations with quality of life were statistically significant, but were especially so for the SWN (.78, p<.01). CONCLUSION: Clinicians interested in the experience of the effects and side effects of antipsychotic medication in their patients are well advised to carefully consider the pros and cons of the available rating scales. They differ with respect to their internal reliability, concurrent and conceptual validity, as well as with respect to desired and undesired effects, aspects of quality of life, and attribution to medication. The choice also depends on its intended use, whether in clinical practice or in research or in both.

Predictive value of cognition for different domains of outcome in recent-onset schizophrenia.

The aim of this study was to see whether and how cognition predicts outcome in recent-onset schizophrenia in a large range of domains such as course of illness, self-care, interpersonal functioning, vocational functioning and need for care. At inclusion, 115 recent-onset patients were tested on a cognitive battery and 103 patients participated in the follow-up 2 years after inclusion. Differences in outcome between cognitively normal and cognitively impaired patients were also analysed. Cognitive measures at inclusion did not predict number of relapses, activities of daily living and interpersonal functioning. Time in psychosis or in full remission, as well as need for care, were partly predicted by specific cognitive measures. Although statistically significant, the predictive value of cognition with regard to clinical outcome was limited. There was a significant difference between patients with and without cognitive deficits in competitive employment status and vocational functioning. The predictive value of cognition for different social outcome domains varies. It seems that cognition most strongly predicts work performance, where having a cognitive deficit, regardless of the nature of the deficit, acts as a rate-limiting factor.

Cognitive self-therapy for chronic depression and anxiety: a multi-centre randomized controlled study.

BACKGROUND: Non-professional treatment programmes are presumed to relieve the extensive need for care of anxiety and depression disorders. This study investigates the effectiveness of cognitive self- therapy (CST) in the treatment of depression or generalized anxiety disorder. METHOD: Patients (n=151) were randomized to receive CST or treatment as usual (TAU) in a trial lasting for 18 months, measuring symptoms (SCL-90; main outcome), social functions, quality of life and utilization of care. RESULTS: Patients in both conditions improved significantly, but no difference was found between the conditions. Reduction of symptoms, improvement of social functions and medical utilization were maintained at the end of the 18 months. Medical care utilization (therapist contact and hospitalization) was lower for CST than for TAU. No suicides occurred. CONCLUSIONS: Cognitive self-therapy is likely to decrease the need for care of chronic depression and anxiety disorders, but it has not been proven to be more effective than treatment as usual.

Negative association between a history of obstetric complications and the number of neurological soft signs in first-episode schizophrenic disorder.

We examined the relationship between a history of obstetric complications (OCs) and the number of neurological soft signs (NSS) in a group of 132 patients experiencing their first episode of psychosis. We measured NSS by means of a comprehensive standardized assessment and gained information on a selection of nine OCs from the patient's mother. Contrary to our expectations we found significantly more NSS in the group of patients without a history of OCs. This effect was independent of medication in the group of patients with a schizophrenic disorder, but not in the entire group. It is possible that the patients with a history of OCs carry fewer genes for schizophrenia (and NSS) and 'needed' the OCs to develop schizophrenia.

Deviant strategy on The Modified Six Elements Test in patients with schizophrenia.

Impaired executive functioning is found in a considerable proportion of schizophrenia patients. Neuropsychological tests are originally designed to measure the behavior of neurological patients and may therefore miss psychiatry-related cognitive deficits. Qualitative information on tests for executive functioning is important in psychiatric populations. The Modified Six Elements Test (MSET) is a planning test that consists of 6 tasks, for which subjects have limited time and have to obey to switching rules. This study concerns a qualitatively different approach schizophrenia patients use on the MSET, and its relationship with cognitive measures. MSET scores and strategies of schizophrenia patients were compared to those of healthy controls, closed-head-injury patients, and peripheral injury patients. Also, schizophrenia patients and healthy controls were compared on verbal memory and vigilance. Schizophrenia patients finish fewer assignments on the MSET, receive a lower profile score compared to healthy controls, and use a different strategy on the test compared to the other groups. They also perform below healthy controls on the tests for verbal memory and vigilance. Use of the different strategy in schizophrenia patients was related to impaired cognitive functioning. An interesting strategy used by schizophrenia patients on the MSET appears to be indicative of impaired cognitive functioning. This strategy may be a compensatory strategy to spare cognitive resources. It could also be the result of a concrete interpretation of the test instructions.

Niacin skin flushing in schizophrenic and depressed patients and healthy controls.

This study compares the skin reactions to the niacin flushing test of 16 schizophrenic patients with those of 17 depressed patients and 16 healthy controls. Methyl nicotinate (niacin) in a concentration of 0.1 M was applied to the forearm for 5 min. Significant differences could be observed between the group of schizophrenic patients (less flushing) in comparison to the other groups. There were no statistical differences in niacin flushing between patients with depression and healthy controls. Gender, age and the use of antipsychotic agents did not appear to be confounders. The differences in flushing within the group of schizophrenic patients were striking, however. Most patients showed little or no flushing, but some patients reacted strongly. Although the three groups could be differentiated by the niacin flushing test, to develop a reliable clinical application of this test, further research is necessary.

A randomized open-label comparison of the impact of olanzapine versus risperidone on sexual functioning.

The objective of this study was to compare sexual functioning in patients treated with olanzapine or risperidone. This open-label trial included 46 patients randomized to olanzapine (5-15 mg/d) or risperidone (1-6 mg/d) for 6 weeks. We used sexual dysfunction was assessed by a semistructured interview based on the items of the UKU side effect rating scale. Three olanzapine-treated patients (12.0%), compared with 11 risperidone-treated patients (52.4%), reported sexual dysfunctions (p = .008) in the semistructured interview. Only 4 patients (8.7%) spontaneously reported sexual dysfunction. The mean dose was 9.4 mg/d for olanzapine and 3.4 mg/d for risperidone. The mean (+/-SD) prolactin levels (ng/mL) in olanzapine-and risperidone-treated patients were 25.1 (+/- 23.5) and 43.5 (+/- 26.1), respectively. Less sexual dysfunction occurred in the group treated with olanzapine compared with the risperidone group. Direct questioning about sexual functioning is necessary to avoid underestimating the frequency of sexual side effects in patients with schizophrenia and related psychotic disorders.

Evaluation of the subjects' response to antipsychotics questionnaire.

The present study reports on the development of a new self-administered instrument to assess patients' responses to antipsychotic medication. The Subjects' Response to Antipsychotics (SRA) Questionnaire is a 74-item instrument with eight scales (Recovery, Weight Gain, Sexual Anhedonia, Sedation, Affective Flattening, Extrapyramidal Side-Effects, Diminished Sociability and Increased Sleep), and a total adverse responses score including additional items. Psychometric aspects were examined in a study of 320 inpatients and outpatients showing good internal consistency, reproducibility and external validity. Concordance with other instruments claiming to measure the subjective response is low, suggesting that the instruments measure different concepts. The SRA Questionnaire appears to be a reliable and efficient way of measuring patients' subjective responses to antipsychotic medication.

The 2-year stability of neurological soft signs after a first episode of non-affective psychosis.

We examined the 2-year stability of neurological soft signs (NSS) in 29 patients after a first episode of psychosis. The numbers of NSS at inclusion and at 2 years follow-up were similar, but there was a significant increase in the numbers of NSS in the sub-group of patients whose dosage of antipsychotic medication had increased over time.

Measuring the executive functions in schizophrenia: the voluntary allocation of effort.

INTRODUCTION: Executive functioning reflects not only what a patient does, but also how he does it or whether he does it at all [Lezak MD. The problem of assessing executive functions. Int. J. Psychol. 17 (1982) 281]. Standard test procedures strongly prompt subjects to certain behavior, so that initiative and the amount of voluntary effort one is willing to invest are therefore not being adequately assessed. METHODS: We developed the Cognitive Effort Test (CET); a test for executive functioning specifically aimed at measuring subject's free initiatives, and the amount of effort they invest voluntarily. It is a complex planning task, and performance is being judged by three subscales: Initiative, Planning, and Workload. 36 schizophrenia patients and 30 healthy controls were tested with the CET, and a battery of other cognitive tests (executive functioning, memory, attention and psychomotor speed) was added to investigate construct and divergent validity. Negative symptoms were also recorded (predictive validity). RESULTS: Patients scored below controls on Planning and Workload, but not on Initiative. The CET was significantly related to other tests for cognition but not to negative symptoms. CET Planning and Workload predicted group membership (patients-controls) better than the other tests for executive functioning combined. CONCLUSION: The CET appears to be a clinically useful test that measures an aspect of schizophrenia that is not being assessed by existing tests, presumably the voluntarily allocation of effort.

Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels.

OBJECTIVE: The atypical antipsychotic risperidone significantly raises plasma prolactin levels in patients, but clozapine, olanzapine, and quetiapine do not. The differences in neuroendocrine response may be connected with the metabolism of the medications. The authors examined the contributory role of risperidone's active metabolite 9-hydroxy-risperidone by measuring plasma concentrations of risperidone, 9-hydroxy-risperidone, and prolactin. METHOD: Blood samples taken from 25 patients with psychotic disorders following 6 weeks of treatment with risperidone (mean dose=3 mg/day) were examined. Mean plasma concentrations of risperidone, 9-hydroxy-risperidone, and prolactin were 4.6, 19.4, and 49.3 ng/ml, respectively. RESULTS: The oral dose of risperidone correlated significantly with plasma concentrations of risperidone, 9-hydroxy-risperidone, active moiety, and prolactin. The plasma concentration of 9-hydroxy-risperidone, but not of risperidone, correlated significantly with increases in plasma prolactin. CONCLUSIONS: These data suggest that the 9-hydroxy metabolite plays a predominant role in risperidone's effect on prolactin release.

What is measured by verbal fluency tests in schizophrenia?

INTRODUCTION: Schizophrenia patients perform below the norm on verbal fluency tests. The causes for this are unknown, but defective memory, executive functioning and psychomotor speed may play a role. METHOD: We examined 50 patients with schizophrenia and related disorders, and 25 healthy controls with a cognitive test battery containing tests for verbal memory, executive functioning and psychomotor speed, and a categorical fluency test. RESULTS: Patients obtained significantly lower test results than the controls on most cognitive measures including the verbal fluency test. During the fluency test, they formed as many clusters, and switched as often between clusters as the controls did, but they generated fewer words per cluster. Interestingly, in the control group, fluency performance was predicted by memory and executive functioning, but not by psychomotor speed. In patients, verbal fluency was predicted by psychomotor speed, but not by memory or executive functioning. DISCUSSION: We conclude that psychomotor speed could be a crucial factor in cognition, and its influence on cognitive test performance should be considered in schizophrenia research. Furthermore, these data illustrate the importance of qualitative analysis of cognitive impairments in schizophrenia patients, as traditional cognitive tests often only provide quantitative information.

A randomized open-label study of the impact of quetiapine versus risperidone on sexual functioning.

OBJECTIVE: To compare sexual functioning in patients treated with quetiapine or risperidone. METHODS: This open-label study included patients with schizophrenia or a related psychotic illness who were randomized to quetiapine (200-1200 mg/d) or risperidone (1-6 mg/d) for 6 weeks. Sexual dysfunction was assessed by a semistructured interview, the Antipsychotics and Sexual Functioning Questionnaire (ASFQ), based upon the Utvalg for Kliniske Undersogelser (UKU). RESULTS: Four of 25 quetiapine-treated patients (16%) and 12 of 24 risperidone-treated patients (50%) reported sexual dysfunction (chi 2 = 6.4; df = 1; P = 0.006) on the ASFQ. Six patients (11.7%; 4 on risperidone, 2 on quetiapine) spontaneously reported sexual dysfunction. The mean+/-SD dose was 580+/-224 mg/d for quetiapine and 3.2 +/- 1.3 mg/d for risperidone. Mean +/- SD prolactin levels in quetiapine- and risperidone-treated patients were 13.8 +/- 17.9 and 57.7 +/- 39.7 ng/mL, respectively. CONCLUSION: Sexual dysfunction was less common in patients treated with quetiapine than with risperidone. Direct questioning about sexual functioning is necessary to avoid underestimating the frequency of sexual side effects in patients with schizophrenia and related psychotic disorders.

Long-term memory deficits in schizophrenia: primary or secondary dysfunction?

Long-term memory impairment is often found in schizophrenia. The question remains whether this is caused by other cognitive deficits. One hundred eighteen first-episode patients were compared with 45 control participants on several memory tasks. The role of processing speed and central executive functions on memory performance was examined with regression analysis for all participants and for patients separately. Deficits were found in general verbal learning performance and retrieval in episodic memory and semantic memory. Processing speed reduced disease-related variance in all memory variables. Coordination, organization of information, and speed of processing were the best predictors for long-term memory deficits in patients. The amount of explained variance, however, is small, especially in general verbal learning performance.

Learning (potential) and social functioning in schizophrenia.

Cognitive dysfunction in schizophrenia has well-known functional consequences. The ability to learn (learning potential) may be an important mediator. This study examines the relationship between learning and functional status in schizophrenia patients before and after participation in a rehabilitation program. We reasoned that learning is a broad construct, encompassing controlled, effortful as well as automatic (learning by doing) mechanisms, called explicit and implicit learning, respectively. Both types of learning ability are important in daily life. The study included 44 medicated schizophrenia patients and 79 healthy controls. We included measures of implicit and explicit learning as well as measures of the cognitive domains for which significant relationships with functional outcome have been established: immediate and secondary verbal memory, card sorting and vigilance. Learning potential and the patient's 'learner status' were also assessed. The results show that learning, as assessed by measures of explicit and implicit learning and learning potential, was not associated with social functioning or rehabilitation outcome. The highest correlations between cognitive functioning and social functioning were found for more or less 'static' performance measures when they were assessed for a second time with or without instructions on how to do the test. Optimized cognitive performance (i.e. performance after instruction or training) seems to be a better predictor of complex domains of functioning than naive or everyday performance.

Cognitive deficits and social functioning in schizophrenia: a clinical perspective.

Impaired social functioning is one of the diagnostic features of schizophrenia. Cognitive functioning is also often impaired in several domains. Meta-analysis has shown a predictive value of cognition for a variety of domains related to social functioning (Green, Kern, Braff, & Mintz, 2000). The significance of these findings for clinical practice has remained largely uninvestigated, however, and is therefore taken up here. We investigated verbal memory, attention and executive functioning in 52 schizophrenia patients. Social functioning was assessed for different types of social roles. The percentages of cognitive and social impairments in our group were assessed according to clinical principles, normally used to judge an individual patient. A possible predictive relationship between cognition and social functioning was studied on the basis of these clinical criteria. A large proportion of patients showed impairments in both cognitive functioning and social functioning. However, the clinical method resulted in a successful prediction of social functioning in only 21-69% of the cases. Social functioning and cognitive functioning were impaired in a large proportion of patients, but were largely independent from each other. Since relationships between cognition and social functioning are weak, assessment procedures are inconsistent and possibly not optimally adjusted to the psychiatric population, the clinical relevance of cognitive testing in order to predict social functioning is as yet questionable.

The spectrum of subjective effects of antipsychotic medication.

BACKGROUND: This study examined the spectrum of subjective experiences which patients attribute to the use of antipsychotic medication. METHODS: We collected interview data and answers to structured questions based on a comprehensive checklist in 77 patients using various types of classical or atypical antipsychotic drugs. RESULTS: The responses of the patients could be categorized into psychological and somatic domains. The psychological domain could be subdivided into emotional, cognitive and sociability domains. The somatic set could be subdivided into activation and physiological domains. CONCLUSIONS: Our data reveal that the same effects may be experienced in either a positive or a negative way by different patients. We conclude that existing scales for measuring subjective effects of antipsychotic medication are incomplete.