Biomedical subjects

Abraham Weizman

Publications and source records attributed to Abraham Weizman.

At least 37 records · Page 2Linked to original sources

PubMed2006

DHEA, a neurosteroid, decreases cocaine self-administration and reinstatement of cocaine-seeking behavior in rats.

Dehydroepiandrosterone (DHEA), which can act as a potential antidepressant in both animals and humans, appears to lower distress involved with cocaine withdrawal. In fact, a role for neurosteroids in modulation of substance-seeking behavior is becoming increasingly clear. Therefore, we tested the effects of DHEA on the self-administration of cocaine (1 mg/kg/infusion) by rats. At maintenance, a relatively low dose of exogenous DHEA (2 mg/kg; i.p.) attenuated cocaine self-administration after several days of chronic treatment. More than 2 weeks (19 days) of daily DHEA injections were required to decrease the cocaine-seeking behavior of rats to less than 20% of their maintenance levels. DHEA does not seem to decrease cocaine self-administration by increasing the reinforcing properties of the drug, as indicated by a cocaine dose-response determination. After being subjected to extinction conditions in the presence of DHEA, rats demonstrated a minimal response to acute exposure to cocaine (10 mg/kg), which indicated a protective effect of DHEA on relapse to cocaine usage. Our results suggest a potential role for the neurosteroid DHEA in controlling cocaine-seeking behavior, by reducing both the desire for cocaine usage and the incidence of relapse.

Adjuvants, Immunologic↗

PubMed2006

Clinical characteristics of inpatient adolescents with severe obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a common disorder in adolescents, usually treated in the outpatient setting. Our aim in this study was to evaluate the clinical characteristics of adolescents with severe OCD that required hospitalization. A total of 342 patients consecutively admitted to a psychiatric adolescent inpatient unit and 87 healthy volunteers were assessed by a semistructured interview for clinical diagnosis, suicide risk factors, aggression, ego defense mechanisms, and intelligence. Patients with OCD (n=40) were compared to other four diagnostic patient groups with psychotic, affective, conduct, and eating disorders, as well as to normal controls. Adolescent inpatients with OCD experienced less separation anxiety than all the other psychiatric groups (P < .01) and were less impulsive than controls (P < .001). They differed in aggressive/impulsive traits and hospital-related behaviors from other diagnostic groups. Adolescent inpatients with OCD consist of a unique subgroup in the inpatient unit in terms of their clinical characteristics and risk factors for suicide. These characteristics should be taken into account when developing a treatment plan for these difficult-to-treat inpatients.

Adolescent↗

PubMed2006

Comparison between risperidone, olanzapine, and clozapine in the management of chronic schizophrenia: a naturalistic prospective 12-week observational study.

Risperidone, olanzapine, and clozapine are three atypical antipsychotic medications commonly used in the management of chronic schizophrenia. While they offer advantages with regard to clinical efficacy and side-effect profile, few studies have compared them in a naturalistic prospective observational manner. This study therefore investigated their comparative efficacy over 12 weeks including illness characteristics and adverse effects. One hundred thirty-one patients (76 M, 55 F) with DSMI-V schizophrenia or schizoaffective disorder were treated with risperidone (n = 38), olanzapine (n = 38), or clozapine (n = 55). All patients showed a significant decrease of Positive and Negative Syndrome Scale (PANSS)-positive scores. Decreases in tardive dyskinesia and impulsivity scores were noted with clozapine and olanzapine, respectively. No differences between the medications were noted on depression, anxiety, EPS, or overt aggression scores. Olanzapine and clozapine appeared to be more effective in females. Males showed a decreased sexual performance irrespective of the medication and those treated with risperidone and clozapine showed greater proportional reduction of overt aggression. Clozapine-treated patients showed significant increased weight, increased glucose levels, and lowered sexual performance. Risperidone patients tended to exhibit reduced cholesterol levels. Higher creatine kinase (CK) levels were noted in risperidone-treated patients. While cautious given the nature of the study design, results suggest differences in the response to various atypical antipsychotic medications regarding efficacy and side-effect susceptibility.

Adolescent↗

PubMed2006

Electroconvulsive therapy and transcranial magnetic stimulation: can they be considered valid modalities in the treatment of pediatric mood disorders?

Depression in children and adolescents is a severe and debilitating disorder and can be life-endangering. Even when it is not life-endangering, however, it has a grave impact on the quality of life of youngsters and their families, and interferes with normal growth and development. In recent years, the field of child psychiatry has become more aware of the limited applicability of data from the adult literature to children and adolescents and the limited resources that child psychiatrists have in treating depression. This awareness substantiates the need to define the place of electroconvulsive therapy and transcranial magnetic stimulation in the treatment of pediatric depression.

Adolescent↗

PubMed2006

An open-label randomized comparison of olanzapine versus risperidone in the treatment of childhood-onset schizophrenia.

BACKGROUND AND PURPOSE: Childhood-onset schizophrenia (COS) is a clinically severe form of schizophrenia, which causes severe impairment to cognitive, linguistic, and social development. There are few prospective and retrospective open clinical trials of risperidone and olanzapine in COS. In this open-label, randomized, prospective study, we compared the tolerability and effectiveness of risperidone versus olanzapine in the treatment of COS patients. METHODS: The study population consisted of 25 children with COS (mean age 11.09 +/- 1.55 years). After an evaluation, patients received risperidone (0.25-4.5 mg/day, mean dose 1.62 +/- 1.02 mg/day) or olanzapine (2.5-20 mg/day, mean dose 8.18 +/- 4.41 mg/day) for 12 weeks, with weekly evaluations. RESULTS: Both groups showed comparable significant (p < 0.001) within-group improvement from baseline to endpoint (LOCF) in Positive and Negative Symptoms Scale (PANSS) total and subscale scores. Of the olanzapine-treated children, 11 (91.7%) completed the 12 weeks of the study, whereas in the risperidone-treated children only 9 (69.2%) did. No significant differences between risperidone-treated children and olanzapine-treated children were observed on Barnes Akathisia Rating Scale (BAS) and Simpson-Angus Scale (SAS) rating scales. Both treatment groups showed significant (p < 0.001) increase in weight from baseline to endpoint. CONCLUSION: Our open-label, small-scale comparative study suggests that both risperidone and olanzapine appear to be efficacious antipsychotic medications in COS, with a slight nonsignificant advantage of olanzapine in the dropout rate.

Adolescent↗

PubMed2006

Substance use, suicidality, and adolescent-onset schizophrenia: an Israeli 10-year retrospective study.

OBJECTIVE: The aim of this study was to investigate the link between the use of specific types of substances and suicidality in adolescent inpatients with schizophrenia and schizoaffective disorder. METHODS: We performed a 10-year naturalistic retrospective study of 178 adolescent inpatients diagnosed as suffering from either schizophrenia or schizoaffective disorder. A comparison was made between the suicide-attempting adolescent inpatients and the non-attempting subjects, by the use of specific types of substances, measurements of psychotic, depressive, and aggressive symptoms, and clinical data reported during their hospitalization. RESULTS: The suicide attempters reported considerably greater usage of inhalants and lysergic acid diethylamide (LSD). Alcohol and methylene-dioxy-methylamphetamine (MDMA) were also used significantly more by this group. However, no differences were found in the usage of cannabis, amphetamines, cocaine, and opiates. The suicide-attempting patients were found to have had more previous psychiatric admissions, a greater level of deliberate self-harm behavior, and a higher level of suicide ideation, but a decreased severity of psychotic symptoms. CONCLUSIONS: This study is the first report of the association between specific types of substances and suicidality in the high-risk population of adolescent psychotic inpatients. The strong association between inhalants, LSD, alcohol, and MDMA with suicidality is relevant to suicide prevention and intervention programs in adolescent-onset schizophrenia.

Adolescent↗

PubMed2006

Reboxetine versus fluvoxamine in the treatment of motor vehicle accident-related posttraumatic stress disorder: a double-blind, fixed-dosage, controlled trial.

BACKGROUND: Motor vehicle accidents (MVAs) are a leading cause of posttraumatic stress disorder (PTSD) in the general population. Alterations in norepinephrine and serotonin systems have been proposed as mechanisms involved in the pathophysiology of the condition, with treatment directed at these neurotransmitter systems. Reboxetine, a selective norepinephrine reuptake inhibitor, exhibits high affinity and selectivity for the human norepinephrine transporter. Inasmuch as PTSD may be associated with dysregulation of noradrenergic activity, the present double-blind randomized clinical trial intended to evaluate reboxetine's efficacy in the management of MVA-related PTSD and to compare its efficacy with a medication commonly used in PTSD, the selective serotonin reuptake inhibitor fluvoxamine. METHODS: Forty patients with MVA-related PTSD attending a local community mental health outpatient clinic were randomized to receive a fixed dose of either reboxetine (8 mg/d) or fluvoxamine (150 mg/d) in a double-blind fashion for a period of 8 weeks. RESULTS: At baseline and at study end point, the 2 subgroups demonstrated no statistical differences in scores on PTSD, depression, and anxiety rating scales. Both medications led to significant improvements in all clinical scales measured. Nine patients receiving reboxetine and 3 receiving fluvoxamine withdrew from the study because of side effects. CONCLUSIONS: Study observations indicate comparable efficacy of reboxetine and fluvoxamine in the management of MVA-related PTSD despite reboxetine's selective noradrenergic activity. Reboxetine appears to be at least as effective as fluvoxamine and may offer an alternative management option in this often difficult-to-treat and disabling condition. A lower and flexible reboxetine dosing schedule will be recommended for future research to improve its tolerability in PTSD patients.

Accidents, Traffic↗

PubMed2006

Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study.

The beneficial effect of sulpiride augmentation of clozapine therapy for treatment-resistant schizophrenia patients is enhanced by its antisalivatory effect on clozapine-induced hypersalivation (CIH). Amisulpride, similar to sulpiride, is a substitute benzamide derivative with higher selective binding to the D2/D3 dopamine receptor. We hypothesized that add-on amisulpride would also be beneficial in controlling CIH. In a randomized, double-blind, placebo-controlled cross-over study, 20 clozapine-treated schizophrenia (DSM-IV criteria) inpatients with CIH were randomly initially assigned to add-on amisulpride (nine patients; 400 mg/day up-titrated from 100 mg/day over 1 week) or placebo (11 patients). Primary outcome was change in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Other measures included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression scale (CGI) and Simpson-Angus Scale (SAS). Mean NHRS indices were considerably lower with amisulpride (1.79 +/- 1.25) than with placebo (2.63 +/- 1.33) [F(1,38) = 5.36, P < 0.05]. With amisulpride treatment, there was a significant improvement on the negative symptoms subscale of the PANSS [F(3,57) = 3.76, P < 0.05], but not on the SAS, CGI or other subscales of the PANSS (all F < 1). Short-term amisulpride augmentation has a strong ameliorating effect on CIH. A long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time.

Amisulpride↗

PubMed2006

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↗

PubMed2006

Impact of gastric banding on plasma adiponectin levels.

BACKGROUND: Several endocrine abnormalities are reported in obesity. In an earlier study, we found that the changes in BMI following laparoscopic adjustable gastric banding (LAGB) were associated with changes in hormone profiles such as insulin and proinsulin. In the current study, we explored the changes in plasma adiponectin levels in morbidly obese subjects who lost abundant weight following LAGB. METHODS: 23 adult morbidly obese patients (15 females), aged 21-56 years, were studied. Blood samples were collected before, and 6 and 14 months after LAGB. The plasma adiponectin levels were determined by commercial kit (B-Bridge International, Inc). Statistical analysis was based on one-way repeated measures ANOVA, followed by Student-Newman-Keuls post-hoc test. Regression model was used to look for predictors of adiponectin change after LAGB. RESULTS: Mean BMI before surgery was 46.04+/-4.44 kg/m2, and decreased significantly by 18% 6 months after surgery to 37.67+/-4.47 kg/m2. BMI further decreased by 32% 14 months after surgery to a mean of 31.30+/-4.65 kg/m2 (P=.000). The mean adiponectin level before surgery was 3997+/-1766 microg/ml, and increased significantly by 16% to 4763+/-1776 microg/ml 6 months after surgery, and to 6336+/-3292 microg/ml (37%) 14 months after surgery. Although BMI persistently decreased, while adiponectin persistently increased, BMI did not correlate with adiponectin. CONCLUSION: In morbidly obese patients who underwent LAGB, adiponectin levels persistently increased, probably due to the reduction of visceral fat mass. Adiponectin plasma increase was correlated with proinsulin levels prior to the surgery. The interaction between adiponectin, proinsulin and BMI change in morbid obesity merits further investigation.

Adiponectin↗

PubMed2006

A six-month outcome of long-stay inpatients resettled in a hostel.

This prospective study evaluated a 6-month outcome of resettlement of long-term psychiatric inpatients to a hostel-based residence. Participants included 92 patients with DSM-IV chronic psychotic disorders, aged 18 to 65 years, hospitalized for 16.7 +/- 10.6 years. Evaluations performed at 2 weeks before their resettlement and following 6 months of hostel residence included the Positive and Negative Syndromes Scale, Montgomery and Asberg Depression Scale, Clinical Global Impression, Global Assessment of Functioning, Social Adaptive Functioning Evaluation and Social Behavior Schedule. The Nurses' Observation Scale for Inpatient Evaluation was completed regularly. Psychopathological symptoms declined and social interaction increased. Hostel-based deinstitutionalization programs are a promising alternative for long-term psychiatric inpatients.

Activities of Daily Living↗

PubMed2006

Phenothiazines induce apoptosis in a B16 mouse melanoma cell line and attenuate in vivo melanoma tumor growth.

Phenothiazines and related antipsychotics were reported to have an antiproliferative effect in several tissue cultures. The aims of this study were: a) to screen in vitro, the potential anti-cancer activity of phenothiazines in wild-type and multi-drug resistant (MDR) B16 mouse melanoma cell lines; and b) to determine the in vivo anti-tumor effect of an in vitro selected highly potent phenothiazine (thioridazine) in a murine melanoma model. The following phenothiazines were evaluated: perphenazine, fluphenazine, thioridazine trifluoperazine and chlorpromazine. All agents induced a dose-dependent decrease in cell viability in wild-type and in MDR B16 melanoma cells. Thioridazine displayed the highest antiproliferative activity. Flow cytometric analyses of 24-h treated B16 melanoma cells revealed an increase in fragmented DNA (16.3 vs 71.3% and 87.2% in controls, 25 microM and 50 microM thioridazine-treated, respectively). Apoptosis was confirmed by co-staining of thioridazine-treated B16 cells (12.5 microM) with propidium iodide and Hoechst 33342 reagents. Caspase-3 expression, a typical mediator of apoptosis, was markedly increased following a 4-h exposure of B16 cells to thioridazine (25 microM and 50 microM). This increase could be blocked by a specific caspase-3 inhibitor. In vivo studies were performed using female C57/Bl mice. Animals were inoculated with wild-type B16 cells by i.v. injection into the tail vein. Mice were treated with thioridazine (10 and 15 mg/kg x3/week i.p. or 15, and 25 mg/kg/day p.o.) and control animals received saline. Mice were monitored for 21-30 days. Body weight was recorded. After autopsy, the lung weight and number of pulmonary melanoma colonies were determined. Thioridazine administration (i.p. or p.o.) resulted in the reduction of lung tumor burden and an increase in mice survival. In conclusion, several phenothiazines, and particularly thioridazine, induced apoptosis of B16 melanoma cells and demonstrated in vivo anti-tumor activity.

Administration, Oral↗

PubMed2005

Dehydroepiandrosterone (DHEA) attenuates cocaine-seeking behavior in the self-administration model in rats.

The aim of this study was to determine the possible involvement of the neurosteroid dehydroepiandrosterone (DHEA) in cocaine-seeking behavior in a self-administration model in rats. DHEA pretreatment (continued thereafter concomitantly with cocaine self-administration) attenuated cocaine-seeking behavior and elevated the levels of dopamine and serotonin in several brain regions relevant to cocaine addiction. Chronic cocaine self-administration induced elevation in brain DHEA, its sulfate ester, DHEAS, and pregnenolone. The increased brain DHEA following cocaine self-administration may serve as a compensatory protective mechanism geared to attenuate the craving for cocaine. Such anti-craving activity is further enhanced by DHEA treatment before and during cocaine self-administration.

Affect↗

PubMed2005

Haplotype analysis of the COMT-ARVCF gene region in Israeli anorexia nervosa family trios.

Anorexia nervosa (AN) is a severe and complex psychiatric disorder with a significant genetic contribution. Previously, we found an association between AN and the 158Val/Met polymorphism of the catechol-O-methyltransferase (COMT) gene in a family-based study of 51 Israeli AN trios. In the present study, we extended the original sample to include 85 family trios [66 AN restricting (AN-R) and 19 bingeing/purging (AN-BP) subtype] and performed a family-based transmission disequilibrium test (TDT) analysis for five SNPs in the COMT and two in the adjacent ARVCF gene. Association was found between AN-R and several SNPs in the COMT-ARVCF region including the 158Val/Met polymorphism. TDT analysis of 5-SNP haplotypes in AN-R trios revealed an overall statistically significant transmission disequilibrium (P < 0.001). Specifically, haplotype B [COMT-186C-408G-472G(158Val)-ARVCF-659C(220Pro)-524T(175Val)] was preferentially transmitted (P < 0.001) from parents of AN-R patients to their affected daughters, while haplotype A [COMT-186T-408C-472A(158Met)-ARVCF-659T(220Leu)-524C(175Ala)] was preferentially (P = 0.01) not transmitted. Haplotype B was associated with increased risk (RR 3.38; 0.95CI 1.98-6.43) while haplotype A exhibited a protective effect (RR 0.40; 0.95CI 0.21-0.70) for AN-R. Preferential transmission of the risk alleles and haplotypes from the parents was mostly contributed by the fathers. No significant transmission disequilibrium of alleles or haplotypes was found for AN-BP trios. The risk and protective haplotypes may carry molecular variations in the COMT gene or its vicinity that are relevant to the pathophysiology of restrictive anorexia nervosa in the Israeli-Jewish population.

Adolescent↗

PubMed2005

The relevance of neurosteroids to clinical psychiatry: from the laboratory to the bedside.

Neurosteroids are important neuroactive molecules with suggested central involvement in several neurophysiological and psychiatric disease processes. The discovery of neurosteroids followed the revelation that the brain exhibited the capacity to synthesize its own steroids in situ and thus be a potential site of steroidogenesis. In contrast to some steroids that exhibit traditional genomic steroid actions, most neurosteroids appear to regulate neuronal function by means of "non-genomic" mechanisms influencing neuronal excitability. Neurosteroids are synthesized either from CNS cholesterol or from peripheral steroid precursors and exhibit a wide range of modulatory effects on neurotransmitter receptor activity, most notably at the gamma-aminobutyric acid A (GABA(A)) receptor. Neurosteroids play an important role in neurodevelopment and neuroprotective effects, many aspects of which may have particular applicability to psychiatric disorders including various gender differences. Neurosteroids appear to be relevant to the pathophysiology and pharmacological treatment of many psychiatric disorders including the most notable mood and anxiety disorders, but also psychotic, childhood, eating, dementia, stress and postpartum disorders. It has been suggested that neurosteroids may become potential targets for pharmacological intervention in the future with further neurosteroid investigation contributing to a more comprehensive understanding of human behavior and psychopathology.

Aging↗

PubMed2005

Red cell membrane omega-3 fatty acids are decreased in nondepressed patients with social anxiety disorder.

The "phospholipid hypothesis" attributes a pathophysiologic role to the polyunsaturated fatty acid (PUFA) composition of phospholipids in depression. The aim of the present study was to determine whether the hypothesis is relevant to social anxiety disorder (SAD). The study sample consisted of 27 untreated, nondepressed patients with SAD (DSM-IV) and 22 controls. Severity of SAD was assessed with the Liebowitz Social Anxiety Scale (LSAS). Erythrocyte PUFA concentrations were measured by gas-liquid chromatography. Concentrations of most n-3 PUFAs were lower in the patients: 18:3n-3 by 32% (p < 0.002), 20:3n-3 by 34%, 20:5n-3 by 36% (all p < 0.001) and 22:6n-3 by 18% (p = 0.002). No significant differences were observed in other fatty acids. Significant inverse correlations were obtained between levels of n-3 PUFAs and LSAS scores. In conclusion, the phospholipid hypothesis may apply to SAD, thereby opening new therapeutic options. The robust relationship between low erythrocyte n-3 PUFA concentrations and SAD justifies exploration of relevant neuropathophysiological mechanisms.

Adult↗

PubMed2005

Involvement of GABAA receptor modulating neuroactive steroids in patients with social phobia.

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEA-S), neurosteroids synthesized in the brain, are weak gamma-aminobutyric acid (GABA) A receptor allosteric antagonists that may be involved in anxiety disorders. In the present study we measured the circulatory [corrected] levels of DHEA, DHEA-S, pregnenolone and cortisol in [corrected] untreated patients (n=26) diagnosed with social phobia (SP) compared with sex- and age-matched healthy controls (n=21). No significant differences in neurosteroids were observed in [corrected] untreated SP patients and [corrected] compared with healthy controls. The findings may reflect an absence of involvement of the GABA(A) modulators DHEA, DHEA-S and pregnenolone in SP.

Adult↗

PubMed2005

Platelet vesicular monoamine transporter density in untreated patients diagnosed with social phobia.

The vesicular monoamine transporter (VMAT2) is important in the storage and release of monoamines. Platelet VMAT2 was characterized using high-affinity [(3)H]dihydrotetrabenazine ([(3)H]TBZOH) binding in untreated social phobia (SP) patients (n=20) compared with sex- and age-matched healthy controls (n=15). No significant differences in VMAT2 density (B(max)) and affinity constants (K(d)) were observed.

Adult↗