The noradrenergic (NE) system mediates cognitive dysfunction in schizophrenia patients, and the NE transporter represents a putative target for cognitive enhancing therapy. In a double-blind placebo-controlled study we evaluated the effect of add-on reboxetine (4 mg/day), a selective norepinephrine reuptake inhibitor (NRI), co-administered with atypical antipsychotic olanzapine (10 mg/day) on cognitive functioning in DSM-IV schizophrenia patients. The Automated Neuropsychological Assessment Metrics battery and Wisconsin Card Sorting Test were used to assess selective cognitive functions at baseline and endpoint (6 weeks). Clinical assessment was also performed. No between-group differences were found in neurocognitive tests, suggesting that reboxetine did not significantly change patients' cognitive performance compared to placebo. Reboxetine was well-tolerated and did not interfere with the therapeutic effect of olanzapine. Long-term studies using higher reboxetine dosages and alternative NRIs (e.g., atomoxetine) are needed to determine the role of NRIs as cognitive enhancers in patients with schizophrenia and other disorders associated with cognitive impairments.

A substantial proportion of schizophrenia patients also exhibits obsessive-compulsive symptoms (OCS). We sought to determine whether the revealed symptom dimensions in OCD exist in schizophrenia patients with comorbid OCD. One hundred and ten patients who met DSM-IV criteria for both schizophrenia and OCD were recruited. Exploratory factor analysis of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) checklist was conducted. The inter-relationship between the resulting factors and schizophrenia symptom dimensions, as assessed by the Schedule for the Assessment of Positive (SAPS) and Negative (SANS) Symptoms, was examined. The principal component analysis of 13 Y-BOCS checklist categories yielded a five-factor solution and accounted for 58.7% of the total variance:(1) aggressive, sexual, religious obsessions and counting,(2) symmetry and ordering/hoarding compulsions,(3) contamination and cleaning,(4) somatic obsession and repeating compulsion,(5) hoarding obsession and checking/repeating compulsions. The Y-BOCS symptom dimensions did not correlate with schizophrenia symptom dimensions. The five symptom dimensions are comparable to those revealed in "pure" OCD, and suggest the involvement of universal mechanisms in the pathogenesis of OCD regardless of the presence of schizophrenia.

In this study we compared 15 patients with DSM-IV obsessive-compulsive disorder (OCD) and schizotypal personality disorder (SPD) and 31 non-SPD OCD patients. OCD-SPD patients had poorer insight, more negative symptoms, lower functioning, more antipsychotic augmentation and more first-degree relatives with schizophrenia-spectrum disorders. A distinct clinical phenotype of OCD associated with SPD should be considered when investigating etiopathogenetic mechanisms.

Obsessive-compulsive symptoms (OCS) have been revealed in a substantial proportion of schizophrenia patients. We sought to evaluate insight into OCS in schizo-obsessive patients. We evaluated insight into OCS and awareness of schizophrenia, using the Brown Assessment of Beliefs Scale (BABS) and the Scale to Assess Unawareness of Mental Disorder (SUMD), respectively. Fifty-seven inpatients that met DSM-IV criteria for both schizophrenia and OCD were recruited. To determine a possible modifying effect of OCS on the awareness of schizophrenia, we included a comparison group of non-OCD schizophrenia patients (N = 80). Nine (15.8%) schizo-obsessive patients revealed lack of insight into OCS, whereas a majority (48 patients, 84.2%) exhibited good or fair insight. In the schizo-obsessive group, insight into OCS positively correlated with awareness of schizophrenia but not with awareness of delusions. Roughly 40% of the schizo-obsessive and non-OCD schizophrenia patients revealed unawareness of schizophrenia. Our findings indicate that OCS in schizophrenia represent an identifiable dimension of psychopathology independent of core schizophrenia symptoms.

Obsessive-compulsive disorder is a prevalent and clinically significant phenomenon in schizophrenia patients. Both schizophrenia and obsessive-compulsive disorder (OCD) are considered to be neurodevelopmental disorders sharing dysfunctional frontal-subcortical circuitry. Using the Neurological Evaluation Scale (NES), the authors assessed neurological soft signs in 59 patients who met DSM-IV criteria for both schizophrenia and OCD. The two schizophrenia groups (with and without OCD) scored higher than the comparison group but did not significantly differ from one another on any of the NES subscales. The first-episode patients in both groups scored similarly to patients with repeated hospitalizations on all NES subscales. Notably, the OCD patients scored similarly to the two schizophrenia groups on the NES motor sequencing subscale. The author's findings support the notion that neurological soft signs are independent markers of brain dysfunction detectable early in the course of schizophrenia. However, they are of limited value as a putative endophenotype in a search for specific etiological mechanisms underlying a schizo-obsessive subgroup of schizophrenia.

RATIONALE: Search for safe and effective strategies to diminish weight gain associated with second generation antipsychotics (SGAs) is imperative. In the present study, we sought to replicate our preliminary findings, which indicated that coadministration of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain. MATERIALS AND METHOD: Fifty-nine patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in this randomized double-blind study. Reboxetine (4 mg/day; 31 patients) or placebo (29 patients) was coadministered with olanzapine (10 mg/day) for 6 weeks. Analysis was by intention-to-treat. RESULTS: Nine patients in each group prematurely discontinued the trial. Olanzapine/reboxetine-treated patients showed a significantly lower increase in body weight (mean = 3.31 kg, SD = 2.73) than their olanzapine/placebo-treated counterparts (mean = 4.91 kg, SD = 2.45). Significantly fewer olanzapine/reboxetine-treated patients gained at least 7% of their initial weight, the cutoff for clinically significant weight gain (6 [19.4%] of 31 patients vs 13 [46.4%] of 28 patients). Seven (22.6%) olanzapine/reboxetine-treated patients compared to only one patient (3.6%) in the olanzapine/placebo group revealed no weight change or even modest weight loss. Appetite increase was significantly lower in the olanzapine/reboxetine than olanzapine/placebo group and was correlated with attenuation of weight gain. Reboxetine addition was safe and well tolerated. CONCLUSIONS: The results confirm that coadministration of reboxetine promotes a clinically meaningful attenuation of olanzapine-induced weight gain in schizophrenia patients. If substantiated in long-term studies, along with behavioral management and diet counseling, reboxetine may have a clinical utility in controlling SGA-induced weight gain.

OBJECTIVE: To validate a complex association between schizophrenia and obsessive-compulsive disorder (OCD). METHOD: We used the Structured Clinical Interview for DSM-IV Axis I disorders to compare the rate of OCD spectrum and additional Axis I disorders in 100 patients who met criteria for both schizophrenia and OCD, non-OCD schizophrenia (n = 100), and OCD (n = 35). RESULTS: There was a robust between-group difference in the number of patients with one or more OCD spectrum disorders (schizo-obsessive n = 30, compared with schizophrenia n = 8; P = 0.001), that is, higher rates of body dysmorphic (8% compared with 0%) and tic (16% compared with 4%) disorders. No difference was revealed in affective, anxiety, and substance use disorders. We found comparable rates of OCD spectrum disorders in the schizo-obsessive and OCD groups (30% and 42.8%, respectively; P = 0.32). CONCLUSION: Preferential aggregation of OCD spectrum disorders in the schizo-obsessive group supports this unique clinical association. Whether a schizo-obsessive interface represents comorbidity or a specific subtype of schizophrenia warrants further investigation.

BACKGROUND: Evidence indicates that obsessive-compulsive disorder (OCD) co-occurs with schizophrenia and bipolar disorder (BD) at a higher rate than in the general population. The inflated rate of comorbidity may result from chronic illness, antipsychotic therapy or treatment-seeking behavior. To control for these factors we evaluated the prevalence of OCD in patients with first-episode acute mania who met DSM-IV criteria for BD-I, and compared them with our previously reported group of first-episode schizophrenia patients. METHOD: Fifty-six BD-I patients with a first-episode of acute mania were screened for OCD and additional comorbid disorders using the Structured Clinical Interview for DSM-IV Axis-I disorders and appropriate rating scales. RESULTS: Only one patient (1.8%) met DSM-IV criteria for OCD, and two (3.6%) met criteria for sub-threshold OCD. In contrast, there was a substantial aggregation of substance use disorders 32.1%(N=8), anxiety disorders, other than OCD 26.8%(N=15) and eating disorders 14.3%(N=8). LIMITATIONS: Small sample size, cross-sectional nature of the assessments and the inclusion of only BD-I patients. CONCLUSION: The rate of OCD in first-episode BD-I patients did not differ significantly from that found in the general population and was substantially lower than in previously reported first-episode schizophrenia patients (1.8% vs. 14%). We suggest that a preferential association of OCD with schizophrenia early in the course of illness represents a pathophysiological linkage between the two disorders, and putatively a specific schizo-obsessive subtype. In contrast, OCD in BD-I may stand for "true" comorbidity. Large-scale parallel comparative evaluations of comorbidity in BD-I and schizophrenia may contribute to the search for specific pathophysiological mechanisms of distinct comorbid-related subsets in either disorder.

BACKGROUND: Preliminary evidence indicates a beneficial effect of serotonin 2A (5-HT(2A)) receptor antagonists in antipsychotic-induced akathisia (AIA). We investigated the antiakathisia effect, safety, and tolerability of low-dose mirtazapine, an agent with marked 5-HT(2A) antagonism. METHODS: In a 7-day double-blind trial, 90 antipsychotic-treated patients meeting DSM-IV criteria for AIA were randomly assigned to mirtazapine (n = 30; 15 mg), propranolol (n = 30; 80 mg), or placebo (n = 30). Primary outcome measures were between-group differences in Barnes Akathisia Scale (BAS) global scores and in the proportion of responders (reduction of >/= 2 points on BAS). Analysis was by intention to treat. RESULTS: Twenty-four patients (26.6%) who were assigned treatment did not complete the study (7 mirtazapine, 8 propranolol, 9 placebo), due to lack of response (n = 19) and adverse events (n = 5). Both mirtazapine and propranolol significantly reduced AIA severity (BAS:-34% mirtazapine and -29% propranolol vs. placebo -11%; p =.012 and p =.023, respectively). Thirteen (43.3%) mirtazapine and 9 (30.0%) propranolol-treated patients versus 2 (6.7%) placebo-treated patients responded (the corresponding odds ratios 10.7 [95% confidence interval (CI), 2.1-53.3] and 6.0 [95% CI, 1.1-30.7]). Five (16.7%) of 30 propranolol-treated patients and none in the mirtazapine and placebo groups (p =.0195 for both) prematurely discontinued the study due to clinically significant hypotension or bradycardia. CONCLUSIONS: The comparable efficacy and better tolerability of low-dose mirtazapine versus propranolol, the current first-line treatment for AIA, position mirtazapine as a favorable candidate for the treatment of acute AIA and may improve current therapeutic practices.