Thought Disorder in Schizophrenia and Bipolar Disorder Probands, Their Relatives, and Nonpsychiatric Controls.

Thought disorder (TD) has long been associated with schizophrenia (SZ) and is now widely recognized as a symptom of mania and other psychotic disorders as well. Previous studies have suggested that the TD found in the clinically unaffected relatives of SZ, schizoaffective and bipolar probands is qualitatively similar to that found in the probands themselves. Here, we examine which quantitative measures of TD optimize the distinction between patients with diagnoses of SZ and bipolar disorder with psychotic features (BP) from nonpsychiatric controls (NC) and from each other. In addition, we investigate whether these same TD measures also distinguish their respective clinically unaffected relatives (RelSZ, RelBP) from controls as well as from each other. We find that deviant verbalizations are significantly associated with SZ and are co-familial in clinically unaffected RelSZ, but are dissociated from, and are not co-familial for, BP disorder. In contrast, combinatory thinking was nonspecifically associated with psychosis, but did not aggregate in either group of relatives. These results provide further support for the usefulness of TD for identifying potential non-penetrant carriers of SZ-risk genes, in turn enhancing the power of genetic analyses. These findings also suggest that further refinement of the TD phenotype may be needed in order to be suitable for use in genetic studies of bipolar disorder.

Tailoring the definition of the clinical schizophrenia phenotype in linkage studies.

The delineation of schizophrenia-related symptomatology is critical to informative clinical phenotyping in linkage studies. A minority of first-degree relatives of schizophrenia and schizoaffective probands (RelSZSA) qualifies for a clinical diagnosis in the schizophrenia spectrum. Schizotypal personality disorder (SPD) is a key component of this spectrum, largely because of its relatively specific familial aggregation in relatives. The criteria for SPD were not developed for the purpose of identifying RelSZSA, however, and SPD is not a homogeneous clinical disorder, potentially introducing false positives and false negatives into affectedness classifications. In this study we used logistic regression (LR) to identify the combination of clinical signs and symptoms that maximized the discrimination between nonpsychotic first-degree RelSZSA (n=241) and controls (n=161). Three variables contributed significantly to optimizing this distinction: no close friends or confidants other than family members, social isolation and irritability. The combination of deviant LR scores and schizophrenia-spectrum psychotic disorders had greater sensitivity for identifying RelSZSA, 23.7%, than SPD and schizophrenia-spectrum psychotic disorders, 16%. Importantly, the diagnosis of SPD and deviant LR scores were not significantly correlated. Most individuals with deviant LR scores did not meet criteria for a diagnosis of SPD and only a minority of those who were diagnosed with SPD had deviant LR scores. Since misclassification of gene carriers as non-gene carriers in linkage analyses increases the risk of false negatives, it may be advantageous to tailor the definition of the clinical phenotype to those aspects of social-interpersonal dysfunction that optimize the discrimination of RelSZSA from controls.

Double-blind, placebo-controlled, multicenter trial of selegiline augmentation of antipsychotic medication to treat negative symptoms in outpatients with schizophrenia.

OBJECTIVE: The authors' goal was to test the efficacy of selegiline augmentation of antipsychotic medication in outpatients with schizophrenia who had negative symptoms of moderate or greater severity. METHOD: A 12-week, double-blind, placebo-controlled, multicenter trial of oral selegiline augmentation of antipsychotic medication was carried out. Outpatients were chosen who did not manifest severe positive symptoms at baseline, who did not meet criteria for coexisting major depression, and who had been maintained on a stable regimen of antipsychotic medication. RESULTS: Negative symptoms were found to be significantly more improved in the patients who received selegiline, and global improvement scores reinforced the impression that selegiline augmentation was beneficial. CONCLUSIONS: These findings support further investigation of low-dose selegiline augmentation of antipsychotic medication in outpatients with schizophrenia who have at least a moderate burden of negative symptoms.

Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.

CONTEXT: Extracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated. OBJECTIVE: To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder. DESIGN AND SETTING: Double-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States. PARTICIPANTS: Adult outpatients (n = 340) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20. INTERVENTIONS: Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks. MAIN OUTCOME MEASURES: Change in the HAM-D total score from baseline to 8 weeks; rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores. RESULTS: On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression parameter estimate for mean (SE) change in HAM-D total score from baseline to week 8 (with a greater decline indicating more improvement) was -9.20 (0.67) (95% confidence interval [CI], -10.51 to -7.89) for placebo vs -8.68 (0.68) (95% CI, -10.01 to -7.35) for H perforatum (P =.59) and -10.53 (0.72) (95% CI, -11.94 to -9.12) for sertraline (P =.18). Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum-treated patients (P =.21) and 24.8% of sertraline-treated patients (P =.26). Sertraline was better than placebo on the CGI improvement scale (P =.02), which was a secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo. CONCLUSION: This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.

Convulsive Therapy in the Treatment of Mania: McLean Hospital 1973-1986.

The authors completed a retrospective chart review of the records of all patients identified with diagnoses of mania and schizoaffective disorder, manic type, who underwent electroconvulsive therapy between the years 1973 and 1986 at McLean Hospital. Ten of 18 manic patients (56%) and 3 of 9 schizoaffective patients (33%) experienced meaningful clinical benefit. The authors report the correlation of treatment and patient factors with outcome and review the literature on the convulsive therapy of mania.