פרופ' יוסף לוין

The rate of consanguineous marriages among parents of schizophrenic patients in the Arab Bedouin population in Southern Israel.

Dobrusin M, Weitzman D, Levine J, Kremer I, Rietschel M, Maier W, Belmaker RH.

Beersheva Mental Health Center, Ben Gurion University of the Negev, Beersheva, Israel.

Consanguinity may contribute to the incidence of schizophrenia in offspring despite the usually accepted polygenic model of schizophrenia inheritance. Bedouin Arab families in southern Israel have a high rate of cousin marriages as do families throughout most Arab societies. We studied consanguinity in the parents of schizophrenic patients admitted in a defined catchment area of southern Israel, compared to a control group of parents of all infants born to Bedouin mothers in this catchment area. There was a small but significant increase in the rate of cousin marriages among the parents of schizophrenia patients compared to parents of infant controls. These results are consistent with claims that inbreeding can contribute to the incidence of schizophrenia even as a polygenic illness. However, the absence of a better matched control group limits confidence in the results.

PMID: 18609440 [PubMed - as supplied by publisher]

No association between global leukocyte DNA methylation and homocysteine levels in schizophrenia patients.

Bromberg A, Levine J, Nemetz B, Belmaker RH, Agam G.

Faculty of Health Sciences, Stanley Research Center, Ben-Gurion University of the Negev & Beersheva Mental Health Center, Beersheva, Israel.

Meta-analysis recently suggested that a 5 muM increase in homocysteine is associated with a 70% higher risk for schizophrenia. Elevated homocysteine is reported to alter macromolecule methylation. We studied whether elevated plasma homocysteine levels in schizophrenia are associated with altered leukocyte global DNA methylation. DNA was extracted from peripheral blood leukocytes of 28 schizophrenia patients vs. 26 matched healthy controls. Percent of global genome DNA methylation was measured using the cytosine-extension method. Homocysteine levels were higher in schizophrenia patients than in controls. No difference in global DNA methylation between schizophrenia patients and control subjects was found (74.0%+/-14.8 vs. 69.4+/-22.0, p=0.31). A significant interaction between diagnosis and smoking on DNA methylation was obtained (F=6.8, df=1,47, p=0.032). Although leukocytes may be a useful cell model to evaluate epigenetic changes such as global DNA methylation in brain, future studies should compare global DNA methylation in peripheral tissue vs. brain in laboratory animals.

PMID: 18276118 [PubMed - indexed for MEDLINE]

Elevated serum homocysteine levels in male patients with PTSD.

Levine J, Timinsky I, Vishne T, Dwolatzky T, Roitman S, Kaplan Z, Kotler M, Sela BA, Spivak B.

Department of Psychiatry, Ben Gurion University of the Negev, Beersheva, Israel. yossilevine@gmail.com

It has been suggested that an elevated serum or plasma homocysteine level may be a risk factor for neuropsychiatric conditions such as Alzheimer's disease, schizophrenia, and depression. Because depression is closely related to anxiety disorders, and because it has been suggested that stress may be associated with an elevated homocysteine level, we studied whether serum homocysteine levels are elevated in patients with posttraumatic stress disorder (PTSD). Total serum homocysteine levels in 28 male patients with PTSD were compared to those of 223 healthy controls. The effect of PTSD on the serum homocysteine level was significant (F=42.96, P<.0001). In a regression model for the PTSD patients, the duration of PTSD was found to predict serum homocysteine levels (t=2.228, P=.035). Our results suggest that elevated levels of homocysteine in male patients with PTSD may be related to pathophysiological aspects associated with the chronicity of this disorder. 2007 Wiley-Liss, Inc.

PMID: 17994587 [PubMed - in process]

The prevalence of neuroleptic drug-induced tardive movement subsyndromes among schizophrenic and schizoaffective patients residing in the southern region of Israel.

Lerner V, Libov I, Kaptsan A, Miodownik C, Dwolatzky T, Levine J.

Division of Psychiatry, Ministry of Health Mental Health Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.

The aim of the current study was to assess the prevalence of tardive movement disorders (TMD) among a group of institutionalized schizophrenic and schizoaffective patients in southern region of Israel. Chronic schizophrenic and schizoaffective inpatients of a psychiatric hospital and its affiliated hostels were screened for the presence of TMD subsyndromes. Twenty percent (107 patients) of 523 patients with schizophrenia and schizoaffective disorder exhibited TMD. Of those with TMD, 36% had only one subsyndrome, whereas 64% had a combination of several TMD subsyndromes. With regard to patients with TMD, the most frequent TMD subsyndrome was tardive tremor (TT). TT appeared more often in males compared to females and at a younger age (44.3+/-8 vs. 54.3+/-11 years, P<0.04). TD appearing in combination with other TMD subsyndromes was significantly more prevalent among females than in males (57% vs. 35%; P<0.02). TMD generally appears in a combined fashion. Further prospective studies from different geographical areas are recommended.

PMID: 17665807 [PubMed - in process]

Lack of efficacy of 5 grams daily of creatine in schizophrenia: a randomized, double-blind, placebo-controlled trial.

Kaptsan A, Odessky A, Osher Y, Levine J.

Faculty of Health Sciences, Department of Psychiatry, Ben Gurion University of the Negev and the Beersheva Mental Health Center, Beersheva, Israel.

OBJECTIVE: Creatine plays a pivotal role in brain energy homeostasis and has been tried in the treatment of neurologic, neuromuscular, and atherosclerotic disease with a paucity of side effects. Creatine monohydrate supplementation may enhance cognitive functions in healthy subjects. Several independent lines of evidence suggest the possible involvement of altered cerebral energy metabolism in schizophrenia. Creatine effects on brain energy metabolism and its possible cognitive-enhancing properties raise the possibility of developing a new therapeutic strategy in schizophrenia by focusing on treating metabolic hypoactive brain areas including frontal regions. METHOD: Twelve schizophrenia patients (DSM-IV criteria) were enrolled into a treatment study with creatine or placebo, and each treatment was administered for 3 months (dosage, 3-5 grams per day) in a randomized, double-blind crossover design. Ten patients completed the study, which was conducted from November 2004 through February 2006. Rating scales included the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, scales for the assessment of side effects, and a cognitive battery. RESULTS: Creatine treatment was not superior to placebo in improving the scores of PANSS, CGI, or the neurocognitive measures administered. Side effects of creatine treatment were few. CONCLUSION: Three months of creatine administration failed to detect any efficacy in treating symptoms of schizophrenia, but further research is suggested. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00140192.

Publication Types:

· Randomized Controlled Trial

· Research Support, Non-U.S. Gov't

PMID: 17592912 [PubMed - indexed for MEDLINE]

Exposure to nitrous oxide may be associated with high homocysteine plasma levels and a risk for clinical depression.

Levine J, Chengappa KN.

Publication Types:

· Case Reports

· Letter

PMID: 17414264 [PubMed - indexed for MEDLINE]

High-dose vitamin B6 decreases homocysteine serum levels in patients with schizophrenia and schizoaffective disorders: a preliminary study.

Miodownik C, Lerner V, Vishne T, Sela BA, Levine J.

Division of Psychiatry, Ministry of Health, Mental Health Center, Faculty of Health Sciences Ben-Gurion University of the Negev, Be'er-Sheva, Israel.

Vitamin B6 plays an essential role in the normal functioning of the central nervous system. Normal homocysteine (Hcy) serum level is maintained by remethylation of Hcy to methionine by enzymes that require folic acid and vitamin B12 and by catabolism to cysteine by a vitamin B6-dependent enzyme. These findings may be consistent with the hypothesis that the vitamin B6 status may influence plasma Hcy levels. The aims of this preliminary study were (1) to determine whether a correlation exists between Hcy and vitamin B6 levels in patients with schizophrenia and schizoaffective disorders and (2) to investigate whether treatment with high-dose vitamin B6 may reduce Hcy levels in these patients. METHODS: In this preliminary study, we enrolled 11 patients with schizophrenia or schizoaffective disorders (7 men and 4 women; mean age +/- SD, 50 +/- 12 years) receiving high doses of vitamin B6 treatment (1200 mg/d) for 12 weeks. Blood samples for the assessment of pyridoxal-5-phosphate and Hcy serum levels were obtained at baseline and after 12 weeks of treatment. RESULTS: Age was significantly positively correlated with Hcy levels at baseline (r = 0.392, P = 0.004). All other parameters, including diagnosis, disease duration, and pyridoxal-5-phosphate serum level, were not correlated with Hcy serum levels at baseline. After vitamin B6 treatment, Hcy serum levels significantly decreased (14.2 +/- 3.4 vs. 11.8 +/- 2.0 micromol/L, respectively, t = 2.679, P = 0.023); this decrease being statistically significant in men but not in women. CONCLUSIONS: High doses of vitamin B6 lead to a decrease in Hcy serum level in male patients with schizophrenia or schizoaffective disorder.

Publication Types:

· Clinical Trial

PMID: 17272965 [PubMed - indexed for MEDLINE]

Plasma homocysteine levels in female patients with eating disorders.

Levine J, Gur E, Loewenthal R, Vishne T, Dwolatzky T, van Beynum IM, Sela BA, Vered I, Yosef G, Stein D.

Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel. yossilevine@gmail.com

OBJECTIVE: To examine plasma homocysteine, vitamin B(12), and folate levels in females with restricting and bingeing/purging eating disorders (EDs). METHOD: Adolescent and adult female patients were compared to appropriate control groups with regard to plasma homocysteine levels. RESULTS: The plasma homocysteine level of the adult ED patients was higher than that of controls for all age groups examined. In adolescents, no significant difference was found comparing ED patients younger than 16 years of age to control data, whereas in the 16-20 year age group, the plasma homocysteine level was significantly higher among the ED group, regardless of the type of ED. Vitamin B(12) and folate levels were within normal limits in all ED groups. CONCLUSION: Elevated plasma homocysteine levels were found in adult and older adolescent female ED patients (but not in younger adolescents) compared to controls. This finding is not related to deficiencies in vitamin B(12) or folate.

PMID: 17262817 [PubMed - indexed for MEDLINE]

Naive theory impairment in schizophrenia: is it domain-specific?

Bonshtein U, Leiser D, Levine J.

Child Guidance Unit, Western Galilee Hospital, Nahariya, Israel.

The ability to represent mental states of self and others to account for behavior is called theory of mind (ToM). This study examined whether ToM deficit in schizophrenia patients is a specific deficit in the cognitive component of interpersonal skills or a more global deficit, involving impaired information processing skills. Schizophrenia inpatients (N = 41) were compared with a control group of healthy subjects (N = 22) and to nonschizophrenia psychiatric patients (24 with affective disorders, seven with other psychosis) over a range of ToM tasks and another naive theory (theory of biology; ToB). Psychiatric inpatients as a whole showed significant deficit compared with the control group of healthy subjects in ToM tasks. The schizophrenia patients showed significantly larger deficits compared with patients suffering from affective disorder, while the performance of patients with nonschizophrenia psychosis was intermediate. In contrast, no difference was observed in the performance of the different groups on the ToB tasks. The fact that a deficit was found in ToM but not in ToB suggests a specific deficit in a cognitive component of interpersonal skills in schizophrenia rather than a general deficit in information processing skills. Naive theories deficits in schizophrenia seem to be domain-dependent.

PMID: 17041287 [PubMed - indexed for MEDLINE]

Observed effects of creatine monohydrate in a patient with depression and fibromyalgia.

Amital D, Vishne T, Rubinow A, Levine J.

Publication Types:

· Case Reports

· Letter

PMID: 17012702 [PubMed - indexed for MEDLINE]

Therapist-patient sexual relations: results of a national survey in Israel.

Aviv A, Levine J, Shelef A, Speiser N, Elizur A.

The Program of Psychotherapy, School of Continuing Medical Education and Abarbanel Mental Health Center, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. alexaviv@gmail.com

BACKGROUND: Studies focusing on Patient-Therapist sexual relations have been carried out mainly in the U.S. This study comes to broadly explore this phenomenon in Israel. METHOD: An indirect questionnaire was sent to all 1,817 psychiatrists, psychologists and social workers who are members of the Israeli Psychiatric Association, Psychologists Association and Psychotherapy Association, respectively. RESULTS: 29% of the responding therapists reported that at least one of their patients had experienced sexual relations with the most recent, former therapist. LIMITATION: The design of our survey made it impossible for us to conduct a follow-up after termination of therapy and to differentiate intercourse from nonintercourse sexual exploitation. CONCLUSIONS: Similar numbers of the gender of the exploiting therapist and exploited patients were obtained for both the indirect current Israeli study and previous U.S. studies. This may suggest that such parameters are influenced by common norms regarding the relationships between men and women of both societies, and from the psychotherapeutic dyadic situation.

PMID: 16910374 [PubMed - indexed for MEDLINE]

Open study of creatine monohydrate in treatment-resistant posttraumatic stress disorder.

Amital D, Vishne T, Roitman S, Kotler M, Levine J.

Publication Types:

· Clinical Trial

· Comparative Study

· Letter

· Research Support, Non-U.S. Gov't

PMID: 16841637 [PubMed - indexed for MEDLINE]

Comment on:

· Am J Psychiatry. 2005 Jan;162(1):162-7.

Osteoporosis and schizophrenia.

Levine J, Belmaker RH.

Publication Types:

· Comment

· Letter

PMID: 16513888 [PubMed - indexed for MEDLINE]

Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia.

Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I, Osher Y, Bersudsky Y, Belmaker RH.

Stanley Research Center and Beersheva Mental Health Center, Ben Gurion University of the Negev, Beersheva, Israel.

BACKGROUND: An elevated homocysteine level is reported to be a risk factor for several diseases, including Alzheimer's and cerebrovascular disease. Recently, several studies have reported that homocysteine levels are elevated in many schizophrenic patients. Homocysteine levels can be lowered by oral folic acid, B-12, and pyridoxine. METHODS: Forty-two schizophrenic patients with plasma homocysteine levels >15 micromol/L were treated with these vitamins for 3 months and placebo for 3 months in a study with a randomized, double-blind, placebo-controlled, crossover design. RESULTS: Homocysteine levels declined with vitamin therapy compared with placebo in all patients except for one noncompliant subject. Clinical symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale declined significantly with active treatment compared with placebo. Neuropsychological test results overall, and Wisconsin Card Sort (Categories Completed) test results in particular, were significantly better after vitamin treatment than after placebo. CONCLUSIONS: A subgroup of schizophrenic patients with hyperhomocysteinemia might benefit from the simple addition of B vitamins.

Publication Types:

· Clinical Trial

· Randomized Controlled Trial

· Research Support, Non-U.S. Gov't

PMID: 16412989 [PubMed - indexed for MEDLINE]

High serum homocysteine levels in young male schizophrenic and schizoaffective patients with tardive parkinsonism and/or tardive dyskinesia.

Lerner V, Miodownik C, Kaptsan A, Vishne T, Sela BA, Levine J.

Division of Psychiatry, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Be'er Sheva, 84170 Israel.

BACKGROUND: The pathogenesis of neuroleptic-induced tardive movement disorders (TMD), including tardive parkinsonism and tardive dyskinesia (TD), has not yet been established. An elevated serum level of total homocysteine has been implicated as a risk factor for various neuropathologic states and some movement disorders. The aim of our study was to determine whether there is an association between serum total homocysteine level and the presence of TMD among schizophrenic and schizoaffective patients. METHOD: This study was conducted in Be'er Sheva Mental Health Center from August 2002 to May 2004. Fifty-eight patients with schizophrenia or schizoaffective disorder (DSM-IV) and TMD for at least 1 year (38 men, 20 women; age range, 28-73 years) were compared to a control group of 188 patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder without TMD (123 men, 65 women; age range, 19-66 years) regarding serum total homocysteine levels. RESULTS: Men with TMD (demonstrating tardive parkinsonism and/or TD) had significantly higher mean serum total homocysteine levels compared to sex- and age group-matched controls. The difference between groups was almost entirely attributable to the homocysteine levels of young male patients (age group, 19-40 years old) with TMD. CONCLUSION: High serum total homocysteine level may constitute a risk factor for certain variants of TMD, especially in young schizophrenic or schizo-affective male patients. Further prospective studies are needed to clarify these findings.

Publication Types:

· Comparative Study

PMID: 16401157 [PubMed - indexed for MEDLINE]

High homocysteine serum levels in young male schizophrenia and bipolar patients and in an animal model.

Levine J, Sela BA, Osher Y, Belmaker RH.

Ben Gurion University, Beersheva, Israel.

Elevated plasma homocysteine has been found to be a risk factor for Alzheimer's disease as well as cerebral vascular disease, suggesting that some risk factors can accelerate or increase the severity of several CNS disease processes. We screened plasma total homocysteine levels of 193 schizophrenic patients vs. 762 controls for plasma homocysteine levels. The effect of schizophrenia was marked (p<0.0001) and mean homocysteine level was 16.3+/-12 (S.D.) microM in schizophrenic patients vs. 10.6+/-3.6 (S.D.) microM in healthy controls. The increase was almost entirely in young male schizophrenic patients. It seemed important to determine if this finding is already present in newly admitted schizophrenic patients. Serum homocysteine levels were studied in 184 consecutively admitted schizophrenic patients and 305 control subjects. Homocysteine levels were markedly increased in this population of newly admitted schizophrenic patients, especially in young males. However, no difference was found for CSF homocysteine levels between schizophrenia patients and controls. We also examined homocysteine levels in 41 euthymic outpatients with bipolar disorder. Functional deterioration in patients was rated as 'present' or 'absent' by consensus of two treating clinicians. Young male bipolar patients were found to have higher homocysteine levels than controls. Among the male subjects, bipolar patients showing deterioration had homocysteine levels which were significantly higher than other patients. We attempted to develop a model of homocysteine neurotoxicity in mice. Mice were fed homocysteine in water at a dose of 200 mg/kg per mouse per day. Independent samples of animals were studied at 2 to 6 months with behavioral tests including apomorphine-induced stereotypy and spatial learning and memory in the Morris Water Maze. Homocysteine levels were elevated up to 800% at months 5 and 6 by this procedure. No homocysteine-induced defects were found in any behavioral test until month 5 when mild but statistically significant abnormalities in the Morris Water Maze were detected.

Publication Types:

· Comparative Study

· Review

PMID: 16115716 [PubMed - indexed for MEDLINE]

Nutritional and life style determinants of plasma homocysteine in schizophrenia patients.

Stahl Z, Belmaker RH, Friger M, Levine J.

Stanley Research Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.

Recently, homocysteine levels have been reported to be elevated in young male schizophrenic patients. Since smoking, obesity, low folate or low vitamin B12 and various medications can increase homocysteine levels, we studied these variables and other clinical variables in 258 schizophrenic patients. A multiple linear regression for plasma homocysteine was performed on variables that were significantly related to plasma homocysteine. Variables predicting homocysteine levels in schizophrenic patients include gender, plasma folate levels, plasma vitamin B12 levels, mean red blood cell corpuscular volume and diastolic blood pressure. Only 24% of the variance in male patients was explained by the model. The reason for elevated plasma homocysteine in some schizophrenic populations remains unclear.

Publication Types:

· Research Support, Non-U.S. Gov't

PMID: 15820418 [PubMed - indexed for MEDLINE]

CSF homocysteine is not elevated in schizophrenia.

Levine J, Agam G, Sela BA, Garver DL, Torrey EF, Belmaker RH.

Stanley Research Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.

Homocysteine is a neurotoxic amino acid originally found to be an independent risk factor for cardiovascular and cerebral vascular disease and more recently suggested to be a risk factor for Alzheimer's disease. Several authors have observed high plasma homocysteine levels among schizophrenia patients. We reported that such high levels characterize young male schizophrenia patients.We now studied two groups of schizophrenia patients (N=41) and controls (N=29) for CSF homocysteine levels. No difference was found for CSF homocysteine levels between schizophrenia patients and controls (p=.041 for Study A and p=.52 for Study B).

Publication Types:

· Comparative Study

PMID: 15657644 [PubMed - indexed for MEDLINE]

Effect of intraperitoneal acetyl-L-carnitine (ALCAR) on anxiety-like behaviours in rats.

Levine J, Kaplan Z, Pettegrew JW, McClure RJ, Gershon S, Buriakovsky I, Cohen H.

Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Acetyl-L-carnitine (ALCAR) is an acetyl derivative of carnitine, an endogenous molecule synthesized in vivo and supplemented by diet (mainly via meat and dairy products). Several parallel, double-blind, placebo-controlled studies have demonstrated that ALCAR treatment produces beneficial effects in geriatric depression. Since most antidepressants also have anti-anxiety effects we examined whether ALCAR shows anti-anxiety effects in a rat model of anxiety. Compared to a saline-injected control group, chronic administration of ALCAR at doses of 10 and 100 mg/kg (tested 24 h after the last dose administration) showed no effects, whereas doses of 50 and 75 mg/kg significantly reduced anxiety-like behaviours in the elevated plus-maze. Acute ALCAR (100 mg/kg), on the other hand (tested 6 h after administration), demonstrated anxiogenic effects. Our data suggest that chronic ALCAR administration may produce an inverted U-shaped curve of dose-dependent changes in anxiety-like behaviour. The precise mechanism by which ALCAR decreases anxiety-like behaviour after peripheral administration remains to be determined.

Publication Types:

· Comparative Study

PMID: 15383157 [PubMed - indexed for MEDLINE]

GSK-3beta in cerebrospinal fluid of schizophrenia patients.

Kozlovsky N, Regenold WT, Levine J, Rapoport A, Belmaker RH, Agam G.

Stanley Research Center, Department of Clinical Biochemistry, Faculty of Health Sciences, Ben Gurion University of the Negev and Mental Health Center, Beersheva, Israel.

Cerebrospinal fluid contains proteins and metabolites of brain origin and was extensively studied in psychiatry in the 1970's with few definitive results. We have recently found 40% reduced protein levels of GSK-3beta in schizophrenia in postmortem prefrontal cortex, but our attempt to develop a diagnostic marker using peripheral lymphocyte GSK-3beta was not successful. In this study we aimed to find whether the reduction in brain GSK-3beta is reflected in CSF of schizophrenia patients. We report a significant reduction in CSF GSK-3beta protein levels in six schizophrenia patients compared to seventeen healthy subjects. Our results corroborate other studies in which CSF protein levels reflect the alteration found in these proteins in schizophrenia patients' postmortem brain.

PMID: 15254796 [PubMed - indexed for MEDLINE]

Homocysteine levels in newly admitted schizophrenic patients.

Applebaum J, Shimon H, Sela BA, Belmaker RH, Levine J.

Beer-Sheba Mental Health Center, Stanley Research Center, Ben Gurion University of the Negev, Beersheva, Israel.

We previously found a marked elevation of plasma homocysteine in young male schizophrenic patients in hospital. It seemed important to determine if this finding is already present in newly admitted schizophrenic patients. Serum homocysteine levels were studied in 184 consecutively admitted schizophrenic patients and 305 control subjects from an employee screening program. Homocysteine levels were markedly increased in this population of newly admitted schizophrenic patients, especially in young males. Newly admitted male schizophrenic patients have elevated homocysteine levels that cannot be explained on the basis of poor hospital nutrition. Smoking may raise homocysteine by 1-2 microM/L but this is not a large enough effect to explain our findings.

Publication Types:

· Research Support, Non-U.S. Gov't

PMID: 15203293 [PubMed - indexed for MEDLINE]

Elevated homocysteine levels in euthymic bipolar disorder patients showing functional deterioration.

Osher Y, Sela BA, Levine J, Belmaker RH.

Stanley Research Center, Ministry of Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.

OBJECTIVE: Previous studies have found elevated plasma homocysteine levels in schizophrenic patients. This study examined homocysteine levels in euthymic bipolar patients. METHODS: Homocysteine levels in 41 euthymic outpatients with bipolar disorder (DSM IV) were compared with 305 comparison subjects from a large employee health screening program. Homocysteine levels were assessed using high-pressure liquid chromatography by fluorescence detection following labeling of homocysteine with monobromobimane. Functional deterioration in patients was rated as 'present' or 'absent' by consensus of two treating clinicians. RESULTS: Data were analyzed by two-way (sex, patient versus control) ANCOVA, with age as the covariant. Significant effects were found for age (p < 0.001) and for sex (p < 0.001) and a significant two-way interaction was found for group by sex (p < 0.001). One-way (by group) ANCOVAs were then performed separately for each sex. For the male subjects, a main effect was found for group (p = 0.001) and for age (p < 0.001): young male bipolar patients have higher homocysteine levels than controls. Among the females, bipolar patients had homocysteine levels, which were lower than controls across all age groups (p < 0.05) with homocysteine levels increasing with age for both groups (p < 0.001). ANCOVA, which divided subjects into three groups – bipolar patients with and without functional deterioration versus comparison subjects – found a significant group by sex interaction (p < 0.05). Sheffe'post-hoc comparisons revealed that among the male subjects, bipolar patients showing deterioration had homocysteine levels which were significantly higher than those of comparison subjects, while bipolar subjects without deterioration had homocysteine levels which were almost identical to the comparison subjects. CONCLUSION: Bipolar patients who show functional deterioration have plasma levels of homocysteine, which are significantly elevated as compared with controls.

Publication Types:

· Research Support, Non-U.S. Gov't

PMID: 14996145 [PubMed - indexed for MEDLINE]

Obesity and medical illnesses in psychiatric patients admitted to a long-term psychiatric facility.

Levine J, Chengappa KN, Patel A, Vagnucci A, John V, Brar JS, Chalasani L, Parepally H, Ganguli R.

Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, PA 15213-2593, USA.

Obesity and associated medical conditions may have an impact on morbidity and even mortality in patients with psychiatric disorders. The authors present the results of a survey of the prevalence of obesity and selected medical conditions among 420 consecutively admitted psychiatric inpatients at a long-stay facility and compare these data with those reported in the literature.Female psychiatric subjects had considerably higher rates of being either overweight or obese (69%) as compared to women in the general U.S. population (51%). Male psychiatric subjects did not differ significantly from their counterparts in the general population in being overweight or obese (nearly 55%). The majority of psychiatric subjects with essential hypertension, diabetes mellitus, dyslipidemias, cardiovascular disease, or sleep apnea were either overweight or obese (72%-87%). In this cross-sectional study, no associations could be deduced between psychotropic drug classes and specific medical conditions. No specific psychiatric diagnostic category was associated with a significantly greater prevalence of any specific medical condition, except that subjects with schizoaffective disorder appeared to have a higher prevalence of type II diabetes mellitus (11.6%). Subjects with predominant substance or alcohol abuse or dependence disorders had a lower prevalence of obesity and associated medical conditions.Obesity-either independently or additively along with a sedentary lifestyle, unhealthy dietary habits, and nicotine dependence-may have a serious impact on coexisting medical comorbidity in psychiatric patients. Judicious monitoring for obesity and rapid pharmacological and nonpharmacological intervention, where appropriate, by concerned clinicians may improve several coexisting medical conditions in psychiatric patients and thereby improve patients' overall quality of life.

PMID: 15990558 [PubMed]

Cognitive Group Therapy for Paranoid Schizophrenics: Applying Cognitive Dissonance

Levine, Joseph; Barak, Yoram; Granek, Ilana

Psychotherapy with paranoid schizophrenics is a hard and often unrewarding task. Individual and group therapies are usually supportive only and are not aimed at changing the paranoid mode of thinking. Although cognitive therapy has been applied in schizophrenic patients, it has not gained wide acceptance. Cognitive dissonance postulates that individuals experience discomfort and tension when holding two dissonant beliefs simultaneously. We here present the group therapy of six schizophrenic paranoids treated by modified cognitive group therapy implementing cognitive dissonance as the vector of change. A control group of six age- and sex-matched paranoid schizophrenics was treated by supportive group therapy. Analysis of the results, using the Positive and Negative Syndrome Scale (PANSS), during therapy and at follow-up of 4 weeks demonstrates statistically significant improvement in total PANSS score as well as in the positive symptoms subscale.

Physiological reactions to a suicide film: suicide attempters, suicide ideators, and nonsuicidal patients.

Doron A, Stein D, Levine Y, Abramovitch Y, Eilat E, Neuman M.

Shalvata Mental Health Center, Hod Hasharon, Israel.

A film about two teenagers who commit suicide was shown to three groups of psychiatric inpatients: 17 who had attempted suicide, 20 who had expressed suicidal thoughts, and 10 who were not suicidal. Anxiety before and after the film was evaluated with psychometric (anxiety rating scale) and physiological tools (heart and respiration rate, blood pressure, electromyogram). Values noted before and after screening, and the degree of change in these values, were compared. In addition, psychomotor agitation was rated at several points during the film. Most results were negative. The suicide attempters had significantly lower postscreening heart rates and a significantly lesser change in heart and respiration rates than the other two groups. The suicide attempters revealed an increase in psychomotor agitation until the discovery of the suicide and a decrease thereafter, whereas the agitation of the nonsuicidal patients continued to increase from the start to the end of the film. The study suggests that on some parameters, suicide attempters reveal less anxiety than nonsuicidal psychiatric patients following exposure to a simulated suicide. The reaction of suicide ideators falls somewhere between the two groups.

PMID: 9807776 [PubMed - indexed for MEDLINE]

Requalifying examination and employment in immigrant physicians as predictors of successful immigration to Israel.

Moldavsky D, Levin J, Elizur A.

Yehuda Abarbanel Mental Health Center, Bat Yam, Israel.

Thirty physicians who immigrated together from South America to Israel were followed during their first two years in Israel. Success in the medical requalifying examination and finding work as physicians correlated directly with permanency in Israel, and, inversely, returning to country of origin was associated with being unqualified and unemployed. Age, sex, marital status, religion and previous professional status were not associated with permanency in Israel.

PMID: 8766433 [PubMed - indexed for MEDLINE]

Cognitive Dissonance in the Treatment of Paranoid Schizophrenia

Levine, Joseph; Barak, Yoram; Caspi, Natan

Paranoid thinking is often well organized, systemized and detailed so that treating a paranoid patient is a difficult challenge. It is suggested that cognitive dissonance, once created, may cause a person to change his cognitions in order to lower or eliminate it. The treatment of a paranoid schizophrenic is presented wherein by introducing strong group pressure the patient accepted an axiom, which created dissonance with his paranoid content. This axiom was "A wise man sees more than two alternatives in any given situation." Therefore, by stepwise pacing, alternative evaluations of affect "free" situations were made by the patient using the accepted basic axiom. This technique was gradually used with the patient's paranoid content, and later on with basic characteristics underlying the paranoid system. The patient exhibited curiosity and a willingness to investigate his paranoid inner state according to the new accepted axiom, and a significant symptomatic relief was seen within a few days, in contrast to past hospitalizations where only partial response to antipsychotic medication was noted. Research is needed in order to examine the effectiveness of this mode of treatment.

A double-blind trial of carbamazepine in negative symptom schizophrenia.

Nachshoni T, Levin Y, Levy A, Kritz A, Neumann M.

Shalvata Mental Health Center, Kupat-Holim, Hod Hasharon, Israel.

Twenty-eight residual schizophrenics hospitalized in a chronic institution with a 9 to 30 year history of disease, with predominantly negative symptoms were given carbamazepine. Carbamazepine was administered in a double-blind trial and therapeutic effects were measured by the Scale for the Assessment of Negative Symptoms (SANS). Patients were also assessed for positive symptoms using the Brief Psychiatric Rating Scale (BPRS), for depression using the Hamilton Depression Scale, for extrapyramidal symptoms by the Simpson and Angus scale, to rule out these symptoms as sources of secondary negative symptoms. The study continued for 7 weeks with therapeutic carbamazepine levels achieved during the last 5 weeks. There was no significant positive effect of carbamazepine on negative symptoms.

Publication Types:

· Clinical Trial

· Randomized Controlled Trial

PMID: 7909450 [PubMed - indexed for MEDLINE]

[Negative symptoms in schizophrenia]

[Article in Hebrew]

Nachshoni T, Levy A, Levin Y, Neumann M.

Publication Types:

· Review

PMID: 8344629 [PubMed - indexed for MEDLINE]

Effects of antipsychotic drugs on memory functions of schizophrenic patients.

Eitan N, Levin Y, Ben-Artzi E, Levy A, Neumann M.

Shalvatah Mental Health Center, Hod-Hasharon, Israel.

In this research we investigated the effects of 4 antipsychotic drugs with different anticholinergic components on different memory functions of schizophrenic patients. Drugs were administered in cumulative doses and memory was tested 90 min after each drug was administered. The results show that chlorpromazine and thioridazine impaired short-term verbal memory after 6 h of sequential administration. Trifluoperazine and haloperidol improved short-term verbal memory from the third to the fifth administration. Immediate memory, long-term memory and visual short-term memory were not impaired by any drug.

Publication Types:

· Clinical Trial

· Comparative Study

· Controlled Clinical Trial

PMID: 1347670 [PubMed - indexed for MEDLINE]

[Is there a linkage between mental illness and traffic accidents?]

[Article in Hebrew]

Levin Y, Ben-Artzi E, Levy A, Neumann M.

PMID: 1752570 [PubMed - indexed for MEDLINE]

[Inter- and intrahemispheric dysfunction in schizophrenia]

[Article in Hebrew]

Ben-Artzi E, Levy A, Levin Y, Neumann M.

Publication Types:

· Review

PMID: 2010128 [PubMed - indexed for MEDLINE]

[Sudden death in psychiatric patients]

[Article in Hebrew]

Levkovitz Y, Levy A, Levin Y, Neumann M.

Publication Types:

· Review

PMID: 1980904 [PubMed - indexed for MEDLINE]

Should electroconvulsive therapy be used as an ambulatory preventive treatment?

Ezion T, Levy A, Levin Y, Neumann M.

Shalvata Mental Health Center, Kupat Holim, Hod Hasharon, Israel.

Electroconvulsive therapy (ECT) has often been withheld from patients in many instances, even when it was the preferred form of psychiatric treatment. From clinical, social, and legal points of view, it is associated with many negative connotations. This paper reviews the use of ECT as a "legitimate" form of long-term ambulatory preventive treatment for psychiatric patients who have previously received it during hospitalization. Attempts to terminate or reduce the frequency of ECT treatments may well be the cause for readmission or exacerbation of an acute attack in patients already in remission who have been discharged.

PMID: 2125033 [PubMed - indexed for MEDLINE]

The hypoparathyroid syndrome: psychiatric observations and case description.

Levine Y, Gaoni B.

Shalvata Mental Health Center, Adolescent Department, Kupat Holim, Hod Hasharon, Israel.

We present a case description of a 15-year-old youth admitted in a psychotic state to the Adolescent Department of Shalvata Mental Health Center and diagnosed as having Idiopathic Hypoparathyroidism. A review of the neurological and psychiatric manifestations accompanying Hypoparathyroid Syndrome is presented, together with several aspects we feel are relevant in reaching this particular diagnosis.

Publication Types:

· Case Reports

· Review

PMID: 2086541 [PubMed - indexed for MEDLINE]

[A hundred year's quest for objective diagnosis of schizophrenia]

[Article in Hebrew]

Trieman N, Levy A, Levin Y, Neumann M.

PMID: 3350432 [PubMed - indexed for MEDLINE]

The effect of trihexphenidyl (Artane) on memory in schizophrenic patients.

Fennig S, Levine Y, Naisberg S, Elizur A.

The anticholinergic effect of trihexphenidyl on memory function of 20 schizophrenic patients has been investigated in a double blind crossover design. Impairment of immediate memory and short term memory was evident after trihexphenidyl treatment in comparison with placebo. Sensory short term memory tested by visual tasks and remote memory showed no significant statistical differences. Our data suggested that trihexphenidyl due to its anticholinergic effect might impair memory function.

Publication Types:

· Clinical Trial

· Controlled Clinical Trial

PMID: 3299495 [PubMed - indexed for MEDLINE]

Physostigmine improves ECT-induced memory disturbances.

Levin Y, Elizur A, Korczyn AD.

Electroconvulsive therapy (ECT) induces transient confusion and amnesia. Using a double-blind crossover method we studied the influence of physostigmine on ECT-induced memory disturbances. We found that physostigmine reverse the impairment of verbal and visual short- and long-term memory after ECT. Immediate recall was neither impaired by ECT nor improved by physostigmine.

Publication Types:

· Clinical Trial

· Controlled Clinical Trial

PMID: 3574695 [PubMed - indexed for MEDLINE]