Social cognition [corrected] and neurocognition: effects of risperidone, olanzapine, and haloperidol.

OBJECTIVE: This study examined the short-term effects of first- and second-generation antipsychotic medications on social cognition and basic cognition. METHOD: One hundred patients with schizophrenia or schizoaffective disorder participated in an 8 week, double-blind study of risperidone, olanzapine, and haloperidol. Participants were administered multiple measures of social cognition, basic cognition, and clinical symptoms at baseline, the end of week 4, and the end of week 8. Seventy-three patients completed the baseline assessment and at least one other assessment. Data were analyzed with mixed-effects analyses of covariance. For data reduction, the social cognitive measures were clustered into a summary score, and the cognitive measures were clustered into two summary scores: general cognitive ability and processing speed. RESULTS: There were no treatment-related differences on any of the three summary scores. Social cognition did not show within-group changes over time either by itself or after control for the cognitive clusters. One cognitive score (general cognitive ability) increased during the study period for all three medication groups. CONCLUSIONS: The present study included a rather thorough assessment of social cognition and did not find any evidence of between-group or within-group effects of antipsychotic medication on social cognition.

Effects of olanzapine, risperidone and haloperidol on prepulse inhibition in schizophrenia patients: a double-blind, randomized controlled trial.

Prepulse inhibition (PPI), whereby the startle eyeblink response is inhibited by a relatively weak non-startling stimulus preceding the powerful startle eliciting stimulus, is a measure of sensorimotor gating and has been shown to be deficient in schizophrenia patients. There is considerable interest in whether conventional and/or atypical antipsychotic medications can "normalize" PPI deficits in schizophrenia patients. 51 schizophrenia patients participated in a randomized, double-blind controlled trial on the effects of three commonly-prescribed antipsychotic medications (risperidone, olanzapine, or haloperidol) on PPI, startle habituation, and startle reactivity. Patients were tested at baseline, Week 4 and Week 8. Mixed model regression analyses revealed that olanzapine significantly improved PPI from Week 4 to Week 8, and that at Week 8 patients receiving olanzapine produced significantly greater PPI than those receiving risperidone, but not haloperidol. There were no effects of medication on startle habituation or startle reactivity. These results support the conclusion that olanzapine effectively increased PPI in schizophrenia patients, but that risperidone and haloperidol had no such effects. The results are discussed in terms of animal models, neural substrates, and treatment implications.

Social cognition in schizophrenia: relationships with neurocognition and negative symptoms.

Despite the growing importance of social cognition in schizophrenia, fundamental issues concerning the nature of social cognition in schizophrenia remain unanswered. One issue concerns the strength of the relationships between social cognition and key features of the disorder such as neurocognitive deficits and negative symptoms. The current study employed structural equation modeling to examine three key questions regarding the nature of social cognition in schizophrenia: 1) Are social cognition and neurocognition in schizophrenia better modeled as one or two separate constructs? 2) Are social cognition and negative symptoms in schizophrenia better modeled as one or two separate constructs?, and 3) When social cognition, neurocognition, and negative symptoms are included in a single model, is social cognition more closely related to neurocognition or to negative symptoms? In this cross sectional study, one hundred outpatients with schizophrenia or schizoaffective disorder were administered measures of social cognition, neurocognition, and negative symptoms. A two-factor model that represented social cognition and neurocognition as separate constructs fit the data significantly better than a one-factor model, suggesting that social cognition and neurocognition are distinct, yet highly related, constructs. Likewise, a two-factor model that represented social cognition and negative symptoms as separate constructs fit the data significantly better than a one-factor model, suggesting that social cognition and negative symptoms are distinct constructs. A three-factor model revealed that the relationship between social cognition and neurocognition was stronger than the relationship between social cognition and negative symptoms. The current findings start to provide insights into the structure of social cognition, neurocognition, and negative symptoms in schizophrenia.

Social Cognition and Neurocognition: Effects of Risperidone, Olanzapine, and Haloperidol.

Objective: This study examined the short-term effects of first- and second-generation antipsychotic medications on social cognition and basic cognition. Method: One hundred patients with schizophrenia or schizoaffective disorder participated in an 8 week, double-blind study of risperidone, olanzapine, and haloperidol. Participants were administered multiple measures of social cognition, basic cognition, and clinical symptoms at baseline, the end of week 4, and the end of week 8. Seventy-three patients completed the baseline assessment and at least one other assessment. Data were analyzed with mixed-effects analyses of covariance. For data reduction, the social cognitive measures were clustered into a summary score, and the cognitive measures were clustered into two summary scores: general cognitive ability and processing speed. (The effects on thinking of risperidone and olanzapine can be found at NCT00108368, www.clinicaltrials.gov.) Results: There were no treatment-related differences on any of the three summary scores. Social cognition did not show within-group changes over time either by itself or after control for the cognitive clusters. One cognitive score (general cognitive ability) increased during the study period for all three medication groups. Conclusions: The present study included a rather thorough assessment of social cognition and did not find any evidence of between-group or within-group effects of antipsychotic medication on social cognition.

Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes.

OBJECTIVE: Most controlled studies comparing second-generation and conventional antipsychotics have focused on the acute treatment of schizophrenia. The authors compared symptom outcomes, side effects, and social adjustment in stable schizophrenia outpatients who received 2 years of maintenance treatment with risperidone or haloperidol. METHOD: This was a 2-year, randomized, double-blind comparison of 6 mg of risperidone versus haloperidol in 63 patients with stabilized DSM-IV schizophrenia. Study patients also received 15 months of standard behavioral skills training or enhanced training with a case manager who promoted patients' use of their skills in the community. RESULTS: The risk of psychotic exacerbations and the risk of leaving the study were similar for both drug treatment groups. However, patients who received both risperidone and the enhanced community-based skills training were more likely to remain in the study than those in the other treatment groups. Patients demonstrated significant improvement in score on the Brief Psychiatric Rating Scale over time with both medications. There were no between-group differences in cluster scores for thought disturbance, hostile-suspiciousness, and withdrawal-retardation. A significant between-group difference favoring risperidone was found for the anxious-depression cluster. Risperidone resulted in significantly greater reductions in tremor and akathisia and greater improvements in most items on the SCL-90-R. CONCLUSIONS: When compared with patients given a low dose of haloperidol, risperidone-treated patients experienced similar improvements in positive and negative symptoms and similar risks of psychotic exacerbations. However, risperidone-treated patients appeared to feel subjectively better, as indicated by less anxiety and depression and fewer extrapyramidal side effects.

Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative.

We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P<.05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P<.10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.