Ronit Weizman

Weight Gain Associated With Olanzapine and Risperidone in Adolescent Patients: A Comparative Prospective Study

OBJECTIVE To evaluate weight gain associated with olanzapine, risperidone, and haloperidol treatment and its clinical risk factors in adolescent patients. METHOD The study was conducted at three adolescent psychiatric departments in two mental health centers in the Tel Aviv area. All patients were Jewish Israelis. Weight and body mass index (BMI) of hospitalized adolescents treated with olanzapine (n = 21), risperidone (n = 21), or haloperidol (n = 8) were prospectively monitored on a weekly basis for the first 12 weeks of treatment. Various clinical risk factors were tested for association with weight gain. RESULTS The olanzapine and risperidone groups experienced significant weight gain between baseline and endpoint (p < .01), whereas the average weight of the haloperidol group did not change. Average weight gain was significantly higher for the olanzapine group (7.2 +/- 6.3 kg, 11.1% +/- 7.8%) than for the risperidone (3.9 +/- 4.8 kg, 6.6% +/- 8.6%) and haloperidol (1.1 +/- 3.3 kg, 1.5% +/- 6.0%) groups. Extreme weight gain (>7%) was recorded in 19 patients (90.5%), 9 patients (42.9%), and 1 (12.5%) patient, respectively Gender (males), low concern about gaining weight (females), low baseline BMI, and paternal BMI were positively correlated with weight gain, whereas previous neuroleptic history, neuroleptic dosage, response to treatment, and illness duration were not. CONCLUSIONS Olanzapine and risperidone are associated with extreme weight gain in adolescents, much higher than that reported in adults. This side effect should be taken into consideration before prescribing these medications, especially in patients at high risk.

Correlation of Suicidal and Violent Behavior in Different Diagnostic Categories in Hospitalized Adolescent Patients

OBJECTIVE To determine the relative importance of aggression and depression in adolescent suicide within different diagnostic categories. METHOD One hundred sixty-three consecutive admissions to an adolescent psychiatric inpatient unit were assessed using a semistructure diagnostic instrument, the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Scores for depression, suicidal behaviors, and violent behaviors were calculated from this assessment. RESULTS Anorexia nervosa and conduct disorder patients had the highest suicidal behavior scores. In addition, patients with conduct disorder were significantly more violent than patients with major depressive disorder, and scores on the Violent Behavior Scale correlated with suicidal symptoms but not with depressive symptoms. CONCLUSION Aggression may be as important in some kinds of suicidal behaviors as is depression. Thus it seems that there are hypothetically at least two types of suicidal behaviors during adolescence: a wish to die (depression) and a wish not to be here for a time (impulse control). The first type of suicidal behavior characterizes that seen in disorders with prominent depression such as major depressive disorder and anorexia nervosa, and the second characterizes disorders of impulse control such as conduct disorder.

Biochemical, Physiological, and Pathological Aspects of the Peripheral Benzodiazepine Receptor

The PBR is a mitochondrial protein composed of at least two subunits, an approximately 30-kDa subunit that contains the site for BZs and an approximately 18-kDa subunit that binds isoquinoline carboxamide derivatives. Porphyrins and diazepam binding inhibitor are putative endogenous ligands for these receptors, which are under neural and hormonal control. Alterations in the density of PBR seem to be a sensitive indicator of stress: up-regulation after acute stress and down-regulation induced by repeated stress. PBR-specific ligands are involved in the control of cell proliferation and differentiation, and their binding is increased in some cancer tumors. Numerous studies in various endocrine organs have revealed that PBR are located in specific regions or tissues in the organs. Furthermore, PBR densities in various organs subject to hormonal control are regulated by organotropic hormones. At least in some cases, BZ ligands do not exert a specific effect in an organ, but rather modulate the well-documented effects of that particular hormone. To the best of our knowledge, BZ ligand action in peripheral tissues is dependent on recognition of PBR, which may suggest a receptor-mediated action.

Association between obsessive-compulsive disorder and polymorphisms of genes encoding components of the serotonergic and dopaminergic pathways

Obsessive-compulsive disorder (OCD) is a severe and disabling anxiety disorder with a marked genetic contribution. Pharmacological data indicated involvement of the serotonergic and dopaminergic systems. We studied the association between OCD and six candidate genes encoding important components of the serotonergic and dopaminergic pathways in 75 biologically unrelated patients and 172 ethnically matched controls (Ashkenazi and non-Ashkenazi Jews). Polymorphisms in the following genes were studied: tryptophan hydroxylase (TPH), serotonin 2A receptor (HTR2A), serotonin 2C receptor (HTR2C), serotonin transporter (5-HTT), dopamine receptor D4 (DRD4), and dopamine transporter (DAT1). The genotypic and allelic distribution of all polymorphisms tested did not show statistically significant differences between patients and controls. Our results suggest that these polymorphisms do not play a major role in the genetic predisposition to OCD, although a minor contribution cannot be ruled out.

Cytokine production in major depressed patients before and after clomipramine treatment

Cytokine production by peripheral blood mononuclear cells (PBMC) was assessed in 10 major depressed patients (5 men and 5 women) before and after 4 weeks of clomipramine treatment and in age- and gender-matched healthy controls. A significant reduction in interleukin-1B (IL-1B), interleukin-2 (IL-2) and interleukin-3-like activity (IL-3-LA) was observed in untreated depressed patients when compared to controls. IL-1B and IL-3-LA synthesis was significantly increased after drug treatment. The suppression of cytokine production by PBMC in depressed patients may be attributed to the depression per se, or it may be related to depression-associated hyperactivity of the hypothalamic-pituitary-adrenal axis. The mode of interaction between depression and cellular immune function and the mediators responsible for the reduced cytokine production need to be studied further.

Obsessive-Compulsive Disorder in Schizophrenia

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 antipsychotic s 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.

Modulatory effect of agents active in the presynaptic dopaminergic system on the striatal dopamine transporter

We have investigated the effects of agents active in the presynaptic dopaminergic system on the characterization of the rat striatal dopamine transporter. The dopamine transporter was characterized by high-affinity [3H]GBR 12935 (1-[2-diphenylmethoxy)-ethyl]-4-(3-phenylpropyl)-piperazine) binding to a membrane preparation and by [3H]dopamine uptake into striatal synaptosomes. Subchronic treatment with reserpine (2.5 mg/kg, 4 days), a monoamine depletor, caused a significant decrease in both [3H]GBR 12935 binding (20%) and [3H]dopamine uptake (51%). In contrast, amantadine (a dopamine releaser) treatment (20 mg/kg, 21 days) induced an increase (28%) in the maximal number of [3H]GBR 12935 sites. Chronic levo-dopa (dopamine precursor) treatment combined with carbidopa (50 mg/kg and 5 mg/kg respectively, 21 days) as well as benztropine (dopamine uptake inhibitor) treatment (10 mg/kg, 21 days) did not affect the striatal dopamine transporter characteristics. The present results showed that the striatal dopamine transporter is sensitive to changes in dopaminergic neurotransmission caused by agents that do not interact directly with the dopamine carrier.

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.

Humoral-endorphin blood levels in autistic, schizophrenic and healthy subjects

Basal morning humoral (H)-endorphin blood levels were assessed in ten autistic patients, 12 chronic schizophrenic patients and 11 healthy control subjects. Four autistic patients and four schizophrenic patients were drug free for at least 6 months while all other psychiatric patients were under treatment with antidopaminergic agents. Significantly reduced opioid levels were observed in the autistic group (827±103 vs 1121±75 pg-eq/ml, P<0.025), although the difference was actually only 26% of the control mean. A similar tendency toward low H-endorphin levels was also observed in the schizophrenic patients; however this difference was not significant (919±129 vs 1121±75 pg-eq/ml; NS). No significant difference was obtained between subjects suffering from the two psychiatric disorders (827±103 vs 919±129 pg-eq/ml; NS). Various interpretations of the decreased secretion of H-endorphin are discussed.

Neurocognitive Correlates of Anxiety Disorders in Children:: A Preliminary Report

Children with anxiety disorders have been suggested to possess a specific cognitive scheme that underscores negative information and leads to the formation of a negative view of themselves and of the world. The aim of the present study was to assess the neuropsychological processes of children and adolescents with anxiety disorders, as compared to healthy matched controls. Nineteen children (6-18 years) with anxiety disorders and 14 age-matched healthy controls participated in the study. Both groups scored within normal range on the Wechsler Intelligence Scale for Children-Revised (WISC-R). All children underwent neuropsychological assessment with the California Verbal Learning Test (CVLT) (Verbal Processing), the Rey-Osterrieth Complex Figure test (ROCF) (Nonverbal Processing), and the Wisconsin Card Sorting Test (WCST) (Executive Functions). The anxiety group scored lower than the control group on all measures of the CVLT and had a significantly greater number of errors, perseverative responses, and incorrect answers after negative feedback on the WCST. No differences were detected for the ROCF. We conclude that in children and adolescents, anxiety disorders may be associated with lowered linguistic abilities and cognitive flexibility, as measured by neuropsychological paradigms. Anxiety does not appear to be associated with nonverbal processes.