Distinct Response Inhibition Patterns in Obsessive Compulsive Disorder Patients and Pathological Gamblers.

Background: Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are common disorders. The cognitive models of OCD and PG focus on abnormalities in response inhibition. Although, these functions have been studied in different PG and OCD samples, no study has compared the response inhibition in both. Methods: Medication-naïve OCD (n = 61) and PG subjects (n = 109) and healthy controls (n = 131) performed CPT and Go/NoGo tasks. Results: Compared to healthy controls (HC), PG and OCD groups underperformed on speed and exhibited larger time variability on the CPT and Go/NoGo task. Only in OCD patients, a positive correlation between omission errors and response time (RT) was observed in the CPT. At the Go/NoGo task, a negative correlation between false alarms and RT (a fast-errors trade-off) was significant only in the PG group. The HC group had greater sensitivity values (d') than the OCD and PG groups in the Go/NoGo task. The PG group displayed lower d' values and more conservative response criterion in the CPT. In addition, only the OCD group expressed a high switching cost compared to both the PG and HC groups in terms of the RT and d' values. Conclusions: Both the PG and OCD groups demonstrated impaired response inhibition compared to the HC group. On several measures, the OCD and PG groups showed comparable impairments, and in others these were distinct. Thus, it appears that distinct neurocognitive patterns are involved in performance of the CPT and the Go/NoGo tasks among OCD and PG subjects whose cognitive status is currently under intensive investigation.

Functional and structural neural indices of risk aversion in obsessive-compulsive disorder (OCD).

Obsessive-compulsive disorder (OCD) patients suffer from risk aversion, which may be mediated by their exaggerated response to threat and diminished response to reward. In this study, 13 OCD patients and 13 healthy matched controls underwent functional magnetic resonance imaging (fMRI) while playing an interactive risky choice game encompassing distinct intervals of threat and reward; as well as anatomical diffusion tensor imaging (DTI). Compared to healthy controls OCD patients were reluctant to make risky choices during the game. Furthermore, they displayed higher amygdala activation to threat; lower nucleus accumbens (Nacc) activation to reward and reduced functional connectivity of the amygdala and Nacc to two frontal regions, the orbito-frontal cortex (OFC) and the dorsal anterior cingulate cortex (dACC), respectively. OCD patients also displayed reduced structural integrity in clusters within the uncinate and cingulum fiber tracts. Finally, these deficits in limbic-frontal connectivity pathways, both at the functional and structural level, were associated with severity of OCD symptoms, as well as with each other. Our results thus suggest that risk aversion in OCD is mediated by abnormal limbic responses to threatening and rewarding stimuli, as well as by deficient functional and structural limbic-frontal connectivity. Such deficiency characterization may aid in identifying neural predictors for treatment response and localizing individual targets for direct neural intervention treatments.

Age-of-onset of schizophrenic and obsessive-compulsive symptoms in patients with schizo-obsessive disorder.

Obsessive-compulsive symptoms (OCS) are prevalent, persistent, clinically significant phenomena in schizophrenia. To facilitate the understanding of their temporal interrelationship, we assessed age-of-onset of schizophrenic and obsessive-compulsive symptoms among 133 patients admitted to Tirat Carmel Mental Health Center (Israel) during the years 1999-2010 who met DSM-IV criteria for both schizophrenic disorder and obsessive-compulsive disorder (OCD). The mean age-of-onset of the first clinically significant OCS was significantly earlier than the mean age-of onset of the first psychotic symptoms. An earlier onset of OCS was detected in men, but not in women. In sixty-four of 133 patients OCS preceded the first psychotic symptoms, in 37 patients OCS followed them, and in 32 patients OCS and psychotic symptoms occurred simultaneously. A sub-analysis of 52 first-episode schizophrenia patients revealed that OCS emerged approximately 3 years earlier than psychotic symptoms. Notably, schizo-obsessive patients had earlier mean age-of-onset of first psychotic symptoms than a comparative group of 113 non-OCD schizophrenia patients matched for age, gender and number of hospitalization. Earlier emergence of OCS than schizophrenic symptoms in schizo-obsessive patients suggests that they are independent of psychosis and are not consequent to schizophrenia. In addition, the presence of OCS seems to modify clinical features of schizophrenia accounting for earlier onset of first psychotic symptoms, however a replication of these findings is needed.

Diminished language lateralization in schizophrenia corresponds to impaired inter-hemispheric functional connectivity.

INTRODUCTION: A consistent brain imaging finding in schizophrenia is decreased language-asymmetry, already evident in first episode patients, thus arguing for a biomarker of the disorder. Nonetheless, its specificity to schizophrenia is questionable. Furthermore, while previous studies suggested that enhanced right hemisphere activation underlies this diminished asymmetry, the mechanism for this anomaly is yet unknown. This study aimed to examine the role of inter-hemispheric relations in such abnormality through functional connectivity analysis driven by left inferior frontal gyrus (IFG) activation. To test for disorder specificity we compared schizophrenia patients not only to healthy controls but also to patients with obsessive compulsive disorder (OCD). METHODS: Functional magnetic resonance imaging (fMRI) was applied during an auditory verb generation task in the 3 groups. Language-related activation in BA44/45 located in the IFG was used for regional estimation of brain asymmetry and for assessment of inter-hemispheric functional connectivity. RESULTS: Schizophrenia, but not OCD patients showed reduced language asymmetry in the IFG relative to healthy controls and diminished functional connectivity between the left and right IFG. Importantly, decreased inter-hemispheric functional connectivity in the IFG was related to more negative symptoms among the schizophrenia patients. CONCLUSIONS: Diminished language-related asymmetry in the IFG seems to be an early disorder specific neural marker of schizophrenia, supporting its pathogenic role. The relation of this regional abnormality to reduced inter-hemispheric functional connectivity and symptom severity supports the role of large-scale brain disorganization in schizophrenia. This may relate to the known structural abnormalities of the corpus callosum leading to functional hemispheric dysconnection.

Obsessive musical hallucinations in a schizophrenia patient: psychopathological and FMRI characteristics.

Obsessive-compulsive symptoms (OCS) are relatively common and clinically significant phenomena in schizophrenia patients, suggesting the existence of a separate schizo-obsessive subgroup of the disorder. Although a majority of schizo-obsessive patients have typical ego-dystonic OCS, a meaningful proportion exhibits diagnostically challenging psychopathological phenomena, psychotic in content and obsessive in form. We report the clinical and functional magnetic resonance imaging characteristics of a schizophrenia patient who developed auditory hallucinations with musical content and obsessive in form. We suggest that "obsessive musical hallucinations", that integrate both psychotic and obsessive-compulsive disorder (OCD)-related features, may be mediated by the brain networks believed to be involved in OCD and in auditory musical hallucinations.

Effect of the selective norepinephrine reuptake inhibitor reboxetine on cognitive dysfunction in schizophrenia patients: an add-on, double-blind placebo-controlled study.

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.

Obsessive-compulsive symptom dimensions in schizophrenia patients with comorbid obsessive-compulsive disorder.

A substantial proportion of schizophrenia patients also exhibit 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.

Clinical characteristics of schizotypal-related obsessive-compulsive disorder.

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.

Comparison of clinical characteristics, co-morbidity and pharmacotherapy in adolescent schizophrenia patients with and without obsessive-compulsive disorder.

A substantial proportion of adolescent schizophrenia patients exhibit obsessive-compulsive symptoms/disorder (OCS/OCD). In the present study we sought to provide a clinical characterization of adolescent schizo-obsessive patients. A consecutive sample of 22 adolescent patients (age 13-18 years) who met DSM-IV criteria for both schizophrenia and OCD was compared with 22 non-OCD schizophrenia patients matched for age, gender and number of hospitalizations. The Structured Clinical Interview for DSM-IV Axis I psychiatric disorders (SCID-I), the Scale for the Assessment of Positive (SAPS) and Negative (SANS) Symptoms, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression (CGI) were used. We found that schizo-obsessive patients had earlier age at onset of schizophrenia symptoms, had more OCD spectrum disorders, primarily tic disorders, but did not differ in severity of schizophrenia symptoms from non-OCD schizophrenia patients. In a majority of the schizo-obsessive patients, OCS preceded or co-occurred with the onset of schizophrenia and did not correlate with schizophrenic symptoms. As expected, more schizo-obsessive patients than their non-OCD counterparts were treated with adjunctive anti-obsessive agents. These findings indicate that clinical characteristics of adolescent schizo-obsessive patients are generally similar to those previously revealed in their adult counterparts. The neurobiology underlying the co-occurrence of the OC and schizophrenia symptoms merits further evaluation.

Insight into obsessive-compulsive symptoms and awareness of illness in adolescent schizophrenia patients with and without OCD.

A substantial proportion of adolescent schizophrenia patients also has obsessive-compulsive disorder (OCD). As the reliability of OCD identification in schizophrenia has been challenged, we evaluated insight into OCD symptoms and awareness of schizophrenia, using the Brown Assessment of Beliefs Scale and the Scale to Assess Unawareness of Mental Disorder respectively, in 22 adolescent inpatients who met DSM-IV criteria for both schizophrenia and OCD. Awareness of illness was also assessed in a comparison group of 22 non-OCD adolescent schizophrenia patients. Nineteen (86.3%) schizo-obsessive patients exhibited good or fair insight into OCD, while only 3 patients revealed lack of insight. Roughly 30% of patients in the two schizophrenia groups with and without OCD exhibited unawareness of schizophrenia, indicating that the presence of OCD does not substantially modify global awareness of illness. The effect size of the correlation between insight into OCD and awareness of schizophrenia in the schizo-obsessive group was small and not statistically significant. Our findings support the notion that OCD in adolescent schizophrenia patients represent an identifiable dimension of psychopathology independent of core schizophrenia symptoms. Early identification of this potentially treatable syndrome is imperative for appropriate diagnosis and treatment of this unique subset of schizophrenia patients.

Awareness of illness and insight into obsessive-compulsive symptoms in schizophrenia patients with obsessive-compulsive disorder.

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.

Neurological soft signs in schizophrenia patients with obsessive-compulsive disorder.

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.

Attenuating effect of reboxetine on appetite and weight gain in olanzapine-treated schizophrenia patients: a double-blind placebo-controlled study.

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.

Preferential aggregation of obsessive-compulsive spectrum disorders in schizophrenia patients with obsessive-compulsive disorder.

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.

Obsessive-compulsive disorder in bipolar disorder patients with first manic episode.

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.

Familial aggregation of schizophrenia-spectrum disorders and obsessive-compulsive associated disorders in schizophrenia probands with and without OCD.

A substantial proportion of schizophrenia patients also has obsessive-compulsive disorder (OCD). To further validate the clinical validity of a schizo-obsessive diagnostic entity, we assessed morbid risks for schizophrenia-spectrum disorders and OC-associated disorders in first-degree relatives of schizophrenia probands with and without OCD. Two groups of schizophrenia probands [with OCD (n = 57) and without OCD (n = 60)] and community-based controls (n = 50) were recruited. One hundred eighty two first-degree relatives of probands with OCD-schizophrenia, 210 relatives of non-OCD schizophrenia probands, and 165 relatives of community subjects were interviewed directly [59.3% (108/182), 51.9% (109/210), and 54.5% (90/165), respectively], using the Structured Clinical Interview for Axis-I DSM-IV Disorders and Axis II DSM-III-R Personality Disorders and the remaining relatives were interviewed indirectly, using the Family History Research Diagnostic Criteria. Relatives of OCD-schizophrenia probands had significantly higher morbid risks for OCD-schizophrenia (2.2% vs. 0%; P = 0.033) and OCPD (7.14% vs. 1.90%; P = 0.014), and a trend towards higher morbid risk for OCD (4.41% vs. 1.43%; P = 0.08) compared to relatives of non-OCD schizophrenia probands. When morbid risks for OCD, OCPD, and OCD-schizophrenia were pooled together, the significant between-group difference became robust (13.74% vs. 3.33%; P = 0.0002). In contrast, relatives of the two schizophrenia groups did not differ significantly in morbid risks for schizophrenia-spectrum disorders, mood disorders, or substance abuse disorders. A differential aggregation of OC-associated disorders in relatives of OCD-schizophrenia versus non-OCD schizophrenia probands, provides further support for the validity of a putative OCD-schizophrenia ("schizo-obsessive") diagnostic entity.

Comparison of clinical characteristics and comorbidity in schizophrenia patients with and without obsessive-compulsive disorder: schizophrenic and OC symptoms in schizophrenia.

BACKGROUND: Since a substantial proportion of schizophrenia patients has symptoms of obsessive-compulsive disorder (OCD), we sought to provide a phenomenological characterization of a schizophrenia subgroup with OCD. METHOD: A consecutive sample of patients who met DSM-IV criteria for both schizophrenia and OCD (N = 55) was compared with 55 schizophrenia patients without OCD matched for age and number of hospitalizations. Structured Clinical Interview for DSM-IV Axis I psychiatric disorders (SCID-I), including a specific module for tic disorders based on DSM-IV criteria, Scales for the Assessment of Positive and Negative Symptoms, Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impressions scale, and Hamilton Rating Scale for Depression were used. RESULTS: Schizophrenia patients with OCD (N = 55) had lower positive dimension scores than schizophrenia patients without OCD (N = 55) (p =.01). Two subgroups of schizo-obsessive patients were identified: OCD independent of schizophrenia symptoms and OCD partially overlapping positive schizophrenia symptoms. Schizophrenia patients with OCD had more SCID-detectable OCD-spectrum disorder, primarily body dysmorphic disorder and chronic tic disorders. More schizophrenia patients with OCD were treated with either add-on serotonin reuptake inhibitors or clozapine. CONCLUSION: Schizophrenia patients with OCD differ from their non-OCD-schizophrenia counterparts in severity of schizophrenia symptoms, co-occurrence of OCD-spectrum disorders, and pharmacotherapy. These findings and the identification of 2 subgroups of schizo-obsessive patients support the validity of this unique clinical entity and may facilitate the establishment of diagnostic criteria for a schizo-obsessive subtype of schizophrenia.

Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study.

OBJECTIVE: Since increased norepinephrine availability may account for the weight-reducing effect of appetite suppressants, the authors hypothesized that the addition of the selective norepinephrine reuptake inhibitor reboxetine may prevent or attenuate olanzapine-induced weight gain. METHOD: Twenty-six patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in the study. In addition to 6 weeks of treatment with olanzapine, 10 mg/day, patients were randomly allocated in a double-blind design to receive either reboxetine, 4 mg/day, (N=13) or placebo (N=13). RESULTS: Ten patients in each group completed the 6-week trial. Patients given olanzapine and reboxetine demonstrated a significantly lower increase in body weight (mean=2.5 kg, SD=2.7) than those given olanzapine and placebo (mean=5.5 kg, SD=3.1). Significantly fewer patients in the olanzapine/reboxetine group (N=2 of 10) than in the olanzapine/placebo group (N=7 of 10) gained at least 7% of their initial weight, the cutoff for clinically significant weight gain. The addition of reboxetine to olanzapine treatment was safe and well tolerated by the patients. A between-group difference in the reduction of Hamilton depression scale scores was seen that favored the olanzapine/reboxetine group (mean difference=-3.1, SD=1.25). CONCLUSIONS: The selective norepinephrine reuptake inhibitor reboxetine may reduce olanzapine-induced weight gain in schizophrenia patients, and activation of the adrenergic system may attenuate weight gain induced by atypical antipsychotic agents.