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Biomedical subjects

Michael Poyurovsky

Publications and source records attributed to Michael Poyurovsky.

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↗

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↗

The neuropsychological basis of competence to consent in first-episode schizophrenia: a pilot metacognitive study.

BACKGROUND: This study was designed to explore the neuropsychological basis of competence to consent to treatment in first-episode schizophrenia by evaluating its differential and joint links with cognitive versus metacognitive performance. METHODS: Twenty-one first-episode patients were assessed with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) and a metacognitive version of the Wisconsin Card Sorting Test (WCST). In addition to the standard administration of the WCST, subjects were also asked to rate their level of confidence in the correctness of each sort (prior to getting the feedback) and to choose whether they wanted each sort to be "counted" toward their overall performance score on the test. Each "ventured" sort received a bonus of 10 cents if correct but an equal penalty if wrong. RESULTS: Compromised capacity to consent was more strongly related to deficits at the metacognitive level than to cognitive deficits per se. Moreover, prediction of competence to consent significantly improved when adding the new, free-choice metacognitive measures to the conventional WCST measures but not the other way around. CONCLUSIONS: These preliminary results suggest that metacognition plays a fundamental role in capacity to consent, which might be at least equally important for decision-making competence as cognitive deficits per se.

Adult↗

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↗

The neuropsychological basis of insight in first-episode schizophrenia: a pilot metacognitive study.

The aim of the present study was to explore the neuropsychological basis of insight in first-episode schizophrenia, by evaluating its differential and joint links with cognitive vs. metacognitive performance. Thirty first-episode patients were assessed with the Scale of Unawareness of Mental Disorder (SUMD) and a metacognitive version of the Wisconsin Card Sorting Test (WCST). In addition to the standard administration of the WCST, subjects were also asked to rate their level of confidence in the correctness of each sort (prior to getting the feedback), and to choose whether they wanted each sort to be "counted" toward their overall performance score on the test. Each "volunteered" sort received a bonus of 10 cents if correct, but an equal penalty if wrong. Insight into illness had higher correlations with free-choice metacognitive indices derived from confidence ratings and volunteered sorts than with the conventional scores from the WCST. Moreover, prediction of poor insight was significantly improved when adding the new, free-choice metacognitive measures to the conventional WCST measures, but not the other way around. These preliminary results suggest that metacognition is an important mediator between basic cognitive deficits and poor insight, and might be even more relevant to poor insight than cognitive deficits per se.

Adult↗

Chronic lithium treatment affects rat brain and serum dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) levels.

Lithium (Li) is an established effective treatment for bipolar disorder. However, the molecular mechanism of its action is still unknown. Dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) are adrenal hormones also synthesized de novo in the brain as neurosteroids. Recent studies have suggested that DHEA has mood-elevating properties and may demonstrate antidepressant effects. 3(2)-Phosphoadenosine 5-phosphate (PAP) phosphatase is a novel Li-inhibitable enzyme involved in sulphation processes. In the present study we examined the impact of 10 d Li treatment on serum and brain DHEA and DHEA-S levels in rats. Our results show that Li administration lowered frontal cortex and hippocampus DHEA and DHEA-S levels, in line with our hypothesis assuming that Lis inhibition of PAP phosphatase leads to elevated PAP levels resulting in inhibition of sulphation and reduction in brain DHEA-S levels. Future studies should address the involvement of neurosteroids in the mechanism of Lis mood stabilization.

Animals↗

The effect of famotidine addition on olanzapine-induced weight gain in first-episode schizophrenia patients: a double-blind placebo-controlled pilot study.

Olanzapine treatment is associated with substantial weight gain. In this double-blind placebo-controlled study we evaluated whether the H2 antagonist famotidine may prevent/attenuate olanzapine-induced weight gain. Fourteen first-episode DSM-IV schizophrenia patients were randomly allocated to receive either famotidine (40 mg/day, n=7) or placebo (n=7) in addition to olanzapine (10 mg/day) for 6 weeks. All patients completed the trial. Patients in both groups showed a similar increase in body weight (olanzapine/famotidine: 4.8 (3.2) kg and olanzapine/placebo: 4.9 (1.6) kg, respectively; a between-group difference of 0.14 (1.3) kg). Four of seven (57.1%) patients in the olanzapine/famotidine group and three of seven (42.9%) in the olanzapine/placebo group gained at least 7% of their initial body weight, a cut-off for clinically significant weight gain. Famotidine addition was safe and well tolerated and did not interfere with olanzapine's therapeutic effect. In conclusion, famotidine (40 mg/day for 6 weeks) is not effective in preventing/attenuating weight gain in olanzapine-treated first-episode schizophrenia patients.

Adult↗

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↗

Clozapine decreases rat brain dehydroepiandrosterone and dehydroepiandrosterone sulfate levels.

We examined the influence of the atypical antipsychotic agent clozapine compared to haloperidol, on levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate ester (both gamma-aminobutyric acid(A) (GABA(A)) receptor allosteric antagonists) in the rat cortex. i.p. injections of clozapine (5 and 15 mg/kg), but not haloperidol (1 mg/kg), for 8 days decreased rat brain cortical dehydroepiandrosterone and dehydroepiandrosterone sulfate levels. These findings support the role of neurosteroids and possibly GABA(A) receptor modulation in the mechanism of action of clozapine.

Animals↗

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↗

Brain neurosteroid changes after paroxetine administration in mice.

Although it is known that selective serotonin reuptake inhibitors (SSRIs), as other antidepressants, elevate mood only after 3-4 weeks of treatment, the mechanism responsible for this delay is not understood. SSRIs have been demonstrated to alter the levels of neurosteroids such as allopregnanolone (THP) which possess anxiolytic and mood-elevating properties. We compared the effect of 9 and 21 days i.p. administration of paroxetine, a potent SSRI, on the synthesis of THP and its precursor, 5alpha-dihydroprogesterone (DHP), in the mouse cortex, hypothalamus and olfactory bulb. Cortex, olfactory bulb and hypothalamus synthesized levels of DHP were significantly raised after 9 days of paroxetine administration, whereas a significant rise in the THP synthesized level was observed only after 21 days of treatment. Peripheral synthesis of DHP, measured by the level in serum, significantly increased after 9 days, but reverted to normal values after 21 days. No increase was detected in serum THP levels either after 9 or 21 days treatment. Differences in peripheral and brain synthesis indicates independence in brain synthesis. The data indicate that paroxetine administration differentially increases [3H]DHP and [3H]THP content, depending on the duration of the treatment. Our results suggest that brain THP may be involved in the antidepressive and anxiolytic activity of paroxetine.

5-alpha-Dihydroprogesterone↗

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↗