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Biomedical subjects

Ronit Weizman

Publications and source records attributed to Ronit Weizman.

At least 19 recordsLinked to original sources

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.

Acute Disease↗

Decreased circulatory levels of neuroactive steroids in behaviourally more extremely affected rats subsequent to exposure to a potentially traumatic experience.

This study examined the effects of stress exposure on plasma levels of corticosterone, dehydroepiandrosterone (DHEA) and its sulphate derivative DHEA-S in relation to behavioural responses. The magnitude of anxiety-like behaviours on the elevated plus-maze and of non-habituated exaggerated startle reactions were assessed in rats exposed to stress compared to controls. Individuals displaying extreme behavioural changes were termed extreme behavioural response (EBR), as opposed to minimal behavioural response (MBR) in both paradigms performed consecutively. Significantly increased circulating corticosterone levels and decreased DHEA levels were found 7 d post-exposure only in EBR individuals, not in their MBR counterparts. DHEA-S levels were reduced in both EBR and MBR stress-exposed rats compared to controls. This suggests that concomitantly decreased circulatory levels of DHEA and elevated corticosterone levels may be associated with an extreme (pathological) response to stress, whilst maintenance of normal levels of both steroids may be associated with minimal response, denoting resilience.

Acoustic Stimulation↗

Behavioral effects of opioid subtypes compared with benzodiazepines in the staircase paradigm.

Opioid abuse is frequently associated with the abuse of benzodiazepines (BZ). Despite the fact that benzodiazepines and opioids act at totally separate receptor sites and through different biochemical and pharmacological mechanisms, they obviously interact with each other at some level. The present study was designed to investigate the behavioral effects of agents with activity on the opioid system and with the benzodiazepine receptor complex in the staircase paradigm. The benzodiazepine agonist lorazepam was used as a reference drug and showed a benzodiazepine effect: it reduced the rearing activity in mice in a dose-dependent manner, at doses that did not suppress climbing. Dissociation between the rearing and climbing behavior was not obtained with the administration of the opioid benzodiazepine, tifluadome, although tifluadome was antagonized by the BZ antagonist, flumazenil and not by naloxone, an opioid antagonist. An administration of opioids that act on the different subtype receptors morphine, U50 and SNC80, induced a dose dependent decrease in both the rearing and climbing activity, meaning no behavioral dissociation. Naloxone was found to have an antagonistic effect on morphine and U50-488H (micro and kappa subtype receptors, respectively), but no antagonistic effect on the delta subtype receptor agonist, SNC80. The administration of nalorphine to mice had no effect on both the rearing and climbing, in the staircase paradigm. When combining naloxone with the mentioned nalorphine, results showed the same effect, which was achieved with all the other opiates. This data, once again, supports the validity of the mouse staircase test for the identification of anxiolytic agents with a GABA(A) receptor complex-mediated activity, and for the ability to differentiate between diverse effects of the different opioids.

Animals↗

Low-dose mirtazapine: a new option in the treatment of antipsychotic-induced akathisia. A randomized, double-blind, placebo- and propranolol-controlled trial.

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 > or = 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.

Adult↗

Obsessive-compulsive disorder in elderly schizophrenia patients.

Obsessive-compulsive disorder (OCD) has been identified in a substantial proportion of adult schizophrenia patients. Although symptoms of both disorders may persist into senescence, the prevalence of OCD in elderly schizophrenia patients has not yet been explicitly evaluated. We evaluated the prevalence of OCD in 50 elderly patients consecutively hospitalized for acute exacerbation of DSM-IV schizophrenia or schizoaffective disorder. The severity of schizophrenia and OCD symptoms was assessed using appropriate clinical rating scales. Eight (16%) of the 50 participants also met DSM-IV criteria for OCD. Schizophrenia patients with and without OCD did not differ significantly in demographic and clinical variables. In half of the schizophrenia-OCD group late onset OCD was observed, while in the remaining schizophrenia-OCD patients, early-onset OCD persisted into senescence, suggesting distinct mechanisms of occurrence. We conclude that OCD is not rare in elderly schizophrenia patients. Identification of this potentially treatable condition is imperative to provide adequate care.

Age of Onset↗

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.

Adult↗

COMT Val158Met polymorphism in schizophrenia with obsessive-compulsive disorder: a case-control study.

This is the first study of a possible molecular genetic basis for schizophrenia with obsessive-compulsive disorder (OCD). We performed a case-control association study of the catechol-O-methyltransferase (COMT) Val158Met polymorphism in schizophrenia-OCD patients, OCD and healthy controls. One hundred and thirteen schizophrenia-OCD patients, 79 OCD patients and 171 control subjects were genotyped for the Val(158)Met polymorphism in the COMT gene. There was no significant difference in allele and genotype distribution of the COMT gene between schizophrenia-OCD patients and healthy controls. The low-activity Met allele and Met/Met genotype were more frequent in OCD men than in schizophrenia-OCD and control individuals. This difference, however, was not statistically significant following correction for multiple comparisons. These results do not support the hypothesis that the COMT Val158Met gene polymorphism is associated with liability to schizophrenia-OCD.

Case-Control Studies↗

Familiality in a five-factor model of schizophrenia psychopathology: findings from a 16-month follow-up study.

We sought to examine stability associations between family history and variability of schizophrenia symptoms repeatedly examined during a naturalistic follow-up study. The Positive and Negative Syndrome Scale, the Insight and Treatment Attitudes Questionnaire, and the Abnormal Involuntary Movement Scale were administered to 69 patients with familial and 79 patients with sporadic schizophrenia, at hospital admission and at stabilization stage (about 16 months later). Analysis of covariance was applied to identify the association of symptom factors with familiality of schizophrenia. We found that schizophrenia patients with positive family histories had significantly higher dysphoric, activation and negative factors. However, familiality of activation and negative factors were dependent on additional variables such as age of onset (both factors), baseline ratings, insight, and side effects (negative factor). No significant association of family history with intensity of positive and autistic preoccupation factors was found. Familial schizophrenia is characterized by higher severity of dysphoric mood factors that may represent impaired emotional reactivity. It is suggested that dysphoric mood may be a useful phenotype for molecular genetic studies of schizophrenia with positive family history.

Adolescent↗

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.

Adult↗

The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.

Histamine antagonism has been implicated in antipsychotic drug-induced weight gain. Betahistine, a histamine enhancer with H1 agonistic/H3 antagonistic properties (48 mg t.i.d.), was coadministered with olanzapine (10 mg/day) in three first-episode schizophrenia patients for 6 weeks. Body weight was measured at baseline and weekly thereafter. Clinical rating scales were completed at baseline and at week 6. All participants gained weight (mean weight gain 3.1+/-0.9 kg) and a similar pattern of weight gain was observed: an increase during the first 2 weeks and no additional weight gain (two patients) or minor weight loss (one patient) from weeks 3 to 6. None gained 7% of baseline weight, which is the cut-off for clinically significant weight gain. Betahistine was safe and well tolerated and did not interfere with the antipsychotic effect of olanzapine. Our findings justify a placebo-controlled evaluation of the putative weight-attenuating effect of betahistine in olanzapine-induced weight gain.

Adult↗

Switching elderly chronic psychotic patients to olanzapine.

The purpose of this study was to examine whether elderly chronic schizophrenia or schizoaffective disorder patients would clinically improve if switched to olanzapine from previous neuroleptic treatment. Twenty-one hospitalized patients, aged 6088 yr, with a diagnosis of chronic schizophrenia or schizoaffective disorder who were being treated with typical neuroleptic medication were switched to olanzapine. The Positive and Negative Symptom Scale (PANSS), Geriatric Depression Scale (GDS) and Clinical Global Impression Severity (CGI-S) Scale were completed while patients were on their previous medication regimen and again 6 months after the last patient had been started on olanzapine. The mean duration of treatment was 289 d (S.D.=139). Three patients discontinued the medication. Mean end dose of olanzapine was 12.9 mg (S.D.=5.7). Paired sample t tests were used to test change on PANSS Positive, Negative and Total scales, CGI, GDS and body weight. PANSS (Positive, p=0.002; Negative, p=0.003; General, p=0.003; and Total, p=0.000) and CGI (p=0.000) but not the GDS (p=0.67) demonstrated statistically significant improvement. There was no significant change in body weight (p=0.61). Elderly patients with aggravation of chronic schizophrenia showed improvement after being switched to olanzapine with no weight gain. Clinically meaningful change was observed in positive and negative psychotic symptomatology but not in depressive symptoms.

Aged↗

Obsessive-compulsive disorder in schizophrenia: clinical characteristics and treatment.

There is a considerable overlap of schizophrenia and obsessive-compulsive disorder (OCD) in the structural and functional brain abnormalities involved, role of the dopamine/serotonin neurotransmitter systems, and some demographic and clinical characteristics. Although OCD co-occurs in a substantial proportion of schizophrenia patients, a systematic evaluation of the clinical features and treatment of this population is lacking. This review critically evaluates findings of recent studies pertaining to the rate of occurrence of OCD or obsessive-compulsive symptoms (OCS) in schizophrenia and the clinical characterisation of the schizo-obsessive subtype. Specifically, interrelationships between obsessive-compulsive and schizophrenic symptoms in terms of temporal relationships and their association with specific schizophrenia subtypes and the effect of OCS on the severity of schizophrenia symptoms are addressed. In the absence of evidence-based data, tentative therapeutic approaches in this difficult-to-treat patient subgroup are suggested. These include monotherapy with atypical antipsychotic agents or a combination of either typical or atypical antipsychotics with SSRIs or clomipramine. The clinical characteristics of antipsychotic-induced OCS/OCD are also presented to facilitate identification and management of this rare but clinically significant adverse effect. Finally, future directions of research in schizophrenia-OCD comorbidity relevant to clinical practice are discussed.

Antipsychotic Agents↗

Age-related differences in the side effect profile of citalopram.

The authors evaluated the autonomic and cardiovascular side effects of citalopram with particular emphasis on their relation to the age of treated patients. The data that formed the basis for the U.S. Food and Drug Administration approval of citalopram were provided by Lundbeck (Copenhagen, Denmark). This database included placebo-controlled short- and long-term studies in major depressed patients. The list of side effects comprised all "heart rate and rhythm disorders" as well as "autonomic nervous system disorders" that had been reported by at least 5% more than that reported for the placebo group of subjects. The database encompassed 1344 subjects treated with citalopram (20-60 mg/day) for a period of no less than 6 weeks. Statistically significant age-related distribution was found for five side effects: bradycardia, nausea, diarrhea, sweating and headache. Bradycardia was more prevalent in elderly (>65 years) patients as compared to the younger population (2.4% vs. 0.2%, P<.05), whereas gastrointestinal side effects, sweating and headache were less prevalent in the elderly. The age-related differences in the side effect profile may be attributable to altered sensitivity of the serotonergic system.

Adolescent↗

Effect of the 5-HT2 antagonist mianserin on cognitive dysfunction in chronic schizophrenia patients: an add-on, double-blind placebo-controlled study.

UNLABELLED: Preponderance of serotonin 5-HT2A antagonism over dopamine D2 blockade exerted by atypical antipsychotics may contribute to their cognitive-enhancing effect. In a double-blind placebo-controlled study we examined the effect of add-on mianserin (15 mg/day), an agent with marked 5-HT2A antagonism, on cognitive functioning in 30 chronic hospitalized DSM-IV schizophrenia patients stabilized on typical antipsychotics. The Automated Neuropsychological Assessment Metrics (ANAM) battery was used to assess learning, memory and sustained attention; Wisconsin Card Sorting Test (WCST) to assess executive function at baseline and endpoint (4 weeks). Clinical assessment included appropriate rating scales. The mianserin group overperformed the placebo group on selective ANAM memory/learning tests, reflected in moderate-to-high effect size values. No between-group differences were revealed in WCST and clinical ratings. CONCLUSIONS: Improved performance on selective neurocognitive tests with addition of the 5-HT2A antagonist mianserin to typical antipsychotics indicates a possible role of the 5-HT system in cognitive-enhancing effects. The effect of flexible doses of mianserin on cognitive deficits in a broader schizophrenia population merits further investigation.

Adult↗

Efficacy of low-dose mirtazapine in neuroleptic-induced akathisia: a double-blind randomized placebo-controlled pilot study.

The nonselective serotonin (5-HT)-2A antagonists ritanserin, mianserin, and cyproheptadine were found efficacious in neuroleptic-induced akathisia (NIA). Mirtazapine is structurally and pharmacologically similar to mianserin, and the authors sought to determine its anti-NIA activity. Twenty-six neuroleptic-treated schizophrenic patients with DSM-IV diagnosis of NIA received add-on mirtazapine (15 mg/day) or placebo for 5 days in a double-blind design. Patients were assessed at baseline and days 3 and 5 with the Barnes Akathisia Scale (BAS), Positive and Negative Symptom Scale, Hamilton Rating Scale for Depression, and Simpson-Angus Scale for parkinsonism. Analysis of covariance with repeated measurements revealed significant group x time effects in favor of the mirtazapine group in both completers (n = 10 in each group) and intent-to-treat analysis (n = 13 in each group) for the BAS global subscale (F [1, 17] = 14.87, p = 0.001, and F [1, 23] = 13.24, p = 0.01, respectively) and objective subscale (F [1, 17] = 8.25, p = 0.011, and F [1, 23] = 7.35, p = 0.012, respectively) and borderline significant superiority for the BAS subjective subscale (F [1, 17] = 4.39, p = 0.051, and F [1, 23] = 4.12, p = 0.054, respectively) and distress subscale (F [1, 17] = 4.21, p = 0.056, and F [1, 23] = 3.80, p = 0.064, respectively). Significantly more mirtazapine-than placebo-treated patients (53.8% [7/13] vs. 7.7% [1/13], respectively; chi2 = 8.3, p = 0.004) met operational response criterion, a reduction of at least two points on the BAS global subscale. Mirtazapine treatment was associated with modest improvement of psychotic and parkinsonian symptoms. Mild sedation was the only side effect. Our study demonstrated that mirtazapine (15 mg/day) is an efficacious and well-tolerated therapeutic option in NIA. Marked 5HT2A/2C antagonistic activity of mirtazapine apparently accounts for its anti-NIA activity. The role of mirtazapine in the treatment of akathisia induced by atypical antipsychotic agents merits further investigation.

Adult↗

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.

Adrenergic Uptake Inhibitors↗

Obsessive-compulsive disorder in adolescent schizophrenia patients.

OBJECTIVE: The co-occurrence of obsessive-compulsive disorder (OCD) in adult patients with schizophrenia has been increasingly recognized. However, the rate of OCD comorbidity in adolescent schizophrenia patients has yet to be systematically evaluated. METHOD: The rate of DSM-IV OCD was evaluated in 50 adolescent inpatients with schizophrenia or schizoaffective disorder. The severity of schizophrenia and OCD symptoms was assessed with the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms (SANS), and Yale-Brown Obsessive Compulsive Scale. RESULTS: Thirteen schizophrenia patients (26.0%) also met the DSM-IV criteria for OCD. This subgroup scored significantly higher on the SANS subscale for affective flattening or blunting. The total SANS score positively correlated with the total Yale-Brown Obsessive Compulsive Scale score. CONCLUSIONS: A substantial proportion of adolescent schizophrenia inpatients have concomitant OCD. A prospective study is needed to evaluate the clinical course, response to treatment, and prognosis for this complex disorder.

Adolescent↗