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Biomedical subjects

Yuly Bersudsky

Publications and source records attributed to Yuly Bersudsky.

14 recordsLinked to original sources
PubMed2007

Lithium's effect in forced-swim test is blood level dependent but not dependent on weight loss.

The effects of lithium in models of depression are often inconsistent. We aimed to replicate a regimen that induces robust antidepressant effects in the forced-swim test. Mice were treated with three different doses of lithium chloride (LiCl) 0.25, 0.4 or 0.5% in food and the forced-swim test or open field test was performed on day 15. We yoked control mice to food deprivation to test whether lithium-induced food deprivation could cause the lithium effects in the forced-swim test. Treatment with LiCl doses leading to blood levels of 1.3 and 1.4 mmol/l led to highly significant reduction in immobility time in the forced-swim test, but the dose leading to a blood level of 0.8 mmol/l was not different from controls in immobility time. Mice yoked to lithium-induced food deprivation showed no difference in the forced-swim test compared with controls. In conclusion these results suggest that lithium effects in mice in the forced-swim test are dose dependent but not owing to lithium-induced weight loss.

Animals↗
PubMed2006

SMIT1 haploinsufficiency causes brain inositol deficiency without affecting lithium-sensitive behavior.

Two leading hypotheses to explain lithium action in bipolar disorder propose either inositol depletion or inhibition of GSK-3 as mechanisms of action. Behavioral effects of lithium are mimicked in Gsk-3beta+/- mice, but the contribution of inositol depletion to these behaviors has not been tested. According to the inositol depletion hypothesis, lithium-sensitive behavior is secondary to impaired phosphatidylinositol synthesis caused by inositol deficiency. By disrupting the sodium myo-inositol transporter1 gene, SMIT1, we show that depletion of brain myo-inositol in SMIT1+/- mice has no effect on lithium-sensitive behavior. These findings, taken together with our previous work showing that SMIT-/- mice have an even greater depletion of inositol in brain with no reduction in phosphatidylinositol levels, are difficult to reconcile with the current formulation of the inositol depletion hypothesis.

Animals↗
PubMed2006

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

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.

Adult↗
PubMed2006

Ethnic origin of alcoholics admitted to an Israeli treatment center.

Jews have a low rate of alcohol use and abuse as reported in several different countries. In Israel over the last 10 years there has been a rising rate of alcoholism. We studied consecutive new admissions to our inpatient alcohol center, and an age and sex matched comparison group of patients consecutively admitted with schizophrenia for whether each of their four grandparents was Jewish, or non-Jewish. A significantly higher percentage of alcohol-related admissions were immigrants from the Former Soviet Union (FSU) than among schizophrenics. Among the alcohol-related admissions from the FSU, there were significantly fewer Jewish grandparents than among schizophrenia patients from the FSU. These data could support the concept that biological Jewish ethnicity has a protective effect against alcohol abuse, but are also consistent with cultural transmission of Jewish attitudes toward alcohol use.

Alcoholism↗
PubMed2006

Inositol deficiency diet and lithium effects.

OBJECTIVES: A major hypothesis explaining the therapeutic effect of lithium (Li) in mania is depletion of inositol via inhibition of inositol monophosphatase. However, inositol is also present in the diet. Restriction of dietary inositol could theoretically enhance the effects of Li. METHODS: We used dietary inositol restriction in animal studies and also devised a palatable diet for humans that is 90% free of inositol. RESULTS: Dietary inositol restriction significantly augmented the inositol-reducing effect of Li in rat frontal cortex. Li reduced inositol levels by 4.7%, inositol-deficient diet by 5.1%, and Li plus inositol-deficient diet by 10.8%. However, feeding with the inositol-deficient diet did not enhance the behavioral effect of Li in the Li-pilocarpine seizure model. Fifteen patients participated in an open clinical study of the inositol-deficient diet: six rapid cycling bipolar patients responding inadequately to Li or valproate in different phases of illness; two Li-treated bipolar outpatients with residual symptomatology, and seven inpatient Li-treated bipolar patients in non-responding acute mania. The diet had a major effect in reducing the severity of affective disorder in 10 of the patients within the first 7-14 days of treatment. CONCLUSION: These results suggest that dietary inositol restriction may be useful in some bipolar patients, but controlled replication is necessary.

Adult↗
PubMed2005

Lymphocyte G-protein receptor kinase (GRK)3 mRNA levels in bipolar disorder.

Linkage studies in bipolar disorder were positive for markers in the region of chromosome 22q12.1 including the gene coding for G-protein receptor kinase (GRK)3. Two of six variants of the GRK3 5'-UTR/promoter were reported to be associated with bipolar disorder. GRK3 protein levels in lymphoblastoid cell lines derived from bipolar patients originating from families with linkage to chromosome 22q11 were reported to be decreased compared to those of control subjects and correlated with disease severity. We compared GRK3 mRNA levels in fresh lymphocytes from 31 bipolar patients vs. 26 control subjects, using real-time RT-PCR. No overall difference was found between patients and controls. However, GRK3 mRNA levels were markedly and significantly reduced in the subgroup of patients with no family history of a major psychiatric disorder compared with patients with family history.

Adult↗
PubMed2005

Phenytoin: an anti-bipolar anticonvulsant?

Phenytoin, a classical anticonvulsant has been little studied in bipolar disorder. We completed a trial of phenytoin in mania and schizoaffective disorder, manic type. Thirty-nine patients entered a 5-wk double-blind controlled trial of haloperidol+phenytoin vs. haloperidol+placebo; 30 patients completed at least 3 wk; 25 completed 5 wk. Significantly more improvement was observed in those patients receiving phenytoin. Phenytoin has not previously been studied prophylactically in bipolar patients. Bipolar patients were studied who had at least one episode per year in the previous 2 yr despite ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13) before entering the study. Phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. Thirty observation periods of 6 months each were studied for 23 patients. Three patients had relapse on phenytoin and nine had relapse on placebo. There was a significant prophylactic effect of phenytoin in bipolar disorder [Cox's F test for comparing survival in two groups: F(6, 18)=3.44, p=0.02]. This study suggests prophylactic effects of add-on phenytoin in bipolar illness. However, the number of patients was small and confirmation is necessary. Lamotrigine has recently been reported to have antidepressant effects. In the past, small studies showed antidepressant effects for carbamazepine and valproate. To determine if such effects could be a class property of other voltage-activated sodium channel blockers such as phenytoin, we performed a double-blind controlled trial of phenytoin vs. fluoxetine in unipolar depression. Thirty-three depressed patients entered the study, and 28 completed at least 3 weeks and were included in data analyses. Weekly Hamilton Depression Scales for 6 wk showed no difference between fluoxetine and phenytoin. Clearly pharmaceutical company funding for clinical trials or advertising for phenytoin is minimal and this must be taken into account in evaluating literature on phenytoin vs. other drugs. The present data suggests that effects on affective disorder may be common to many anticonvulsants.

Anticonvulsants↗
PubMed2005

Clotiapine compared with chlorpromazine in chronic schizophrenia.

OBJECTIVES: Clotiapine is a classic neuroleptic with a chemical structure similar to clozapine. It was said that patients unresponsive to other neuroleptics respond to clotiapine although it causes extrapyramidal syndromes (EPS) like other typical neuroleptics. We conducted a study of clotiapine vs. chlorpromazine in severe chronic active psychotic hospitalized schizophrenia patients. METHODS: The design was double-blind crossover of clotiapine vs chlorpromazine. No washout was necessary from previous neuroleptic treatment, and flexible overlap with the study medication was individualized for each patient. Patients were treated after reaching neuroleptic monotherapy for 3 months with clotiapine and 3 months with chlorpromazine, in random order. Medication was supplied in identical capsules of 100 mg chlorpromazine or 40 mg of clotiapine. Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) were rated every 2 weeks and Nurse's Observation Scale for Inpatient Evaluation (NOSIE) every month. RESULTS: Fifty-eight patients were randomized. Forty-three patients completed at least one phase of the study, and thirty-three completed both phases. Because of the small number of hostel patients and the very high dropout rate in the hostel patients, data analysis was done separately for inpatients and hostel patients. Clotiapine was significantly superior to chlorpromazine in 26 inpatients completing the crossover, on the PANSS, NOSIE and CGI. Clotiapine was also superior to chlorpromazine in an analysis of the parallel inpatient groups in the first three months before the crossover. CONCLUSION: Some classic neuroleptic compounds may have superiority to chlorpromazine in a "clozapine-like" manner, despite a typical profile for EPS.

Adult↗
PubMed2005

Schizophrenia and second language acquisition.

Language acquisition involves brain processes that can be affected by lesions or dysfunctions in several brain systems and second language acquisition may depend on different brain substrates than first language acquisition in childhood. A total of 16 Russian immigrants to Israel, 8 diagnosed schizophrenics and 8 healthy immigrants, were compared. The primary data for this study were collected via sociolinguistic interviews. The two groups use language and learn language in very much the same way. Only exophoric reference and blocking revealed meaningful differences between the schizophrenics and healthy counterparts. This does not mean of course that schizophrenia does not induce language abnormalities. Our study focuses on those aspects of language that are typically difficult to acquire in second language acquisition. Despite the cognitive compromises in schizophrenia and the manifest atypicalities in language of speakers with schizophrenia, the process of acquiring a second language seems relatively unaffected by schizophrenia.

Adult↗
PubMed2005

Controlled double-blind trial of phenytoin vs. fluoxetine in major depressive disorder.

BACKGROUND: Phenytoin was the first non-sedative anticonvulsant introduced and is still the anticonvulsant most widely used worldwide in neurology. Given the efficacy of the anticonvulsant lamotrigine in the depressed phase of bipolar disorder, a critical theoretical question is whether other anticonvulsants used in treating bipolar disorder might be similarly effective. We therefore undertook a controlled trial of phenytoin versus fluoxetine in major depressive disorder. METHOD: Data were collected from July 2001 to July 2003. Thirty-three subjects entered the study. All patients met DSM-IV criteria for major depressive disorder and scored a minimum of 18 on the 24-item Hamilton Rating Scale for Depression (HAM-D) at baseline. After a 3-day washout of any previous medications, patients were randomly assigned to fluoxetine or phenytoin in identical capsules. Each capsule contained phenytoin 100 mg or fluoxetine 7 mg plus cornstarch. Patients started with 1 tablet daily and increased every other day until they were taking 1 tablet 3 times daily with meals. Blood phenytoin levels were taken after 1 week, 3 weeks, and 6 weeks, and dosage was adjusted to achieve blood levels of 10 to 20 microg/mL, to a maximum dose of 4 capsules per day or a minimum dose of 2 capsules per day. Fluoxetine patients were assigned dummy blood phenytoin levels by the control psychiatrist such that the treating physician would raise the number of capsules to at least 3 per day (20 mg of fluoxetine). RESULTS: Thirty-three patients entered the study, and 28 (N = 14 in each treatment group) completed at least 3 weeks and were included in the data analysis. Patients who dropped out after week 3 (3 patients) were included in the study as last value carried forward. There was no difference between treatment groups in overall rate of response or speed of response. CONCLUSION: The absence of a placebo arm in our study allows for the possibility that neither treatment was more effective than placebo. However, the exclusion of past fluoxetine nonresponders and the minimum HAM-D score at baseline of 18 make this possibility unlikely.

Adult↗
PubMed2005

Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study.

INTRODUCTION: Epidemiologic studies have suggested that consumption of cold water fish oils may have some protective function against depression. This proposition is supported by a series of biochemical and pharmacologic studies that have suggested that fatty acids may modulate neurotransmitter metabolism and cell signal trans-duction in humans and that abnormalities in fatty acid and eicosanoid metabolism may play a causal role in depression. Aware of the critical need for antidepression treatments that might not carry the risk of precipitating a manic episode in bipolar patients, we decided to conduct an open-label add-on trial of eicosapentaenoic acid (EPA) in bipolar depression. METHOD: Twelve bipolar I outpatients with depressive symptoms diagnosed by DSM-IV were treated with 1.5 to 2 g/day of the omega-3 fatty acid EPA for up to 6 months. The study was conducted between September 2001 and January 2003. RESULTS: Eight of the 10 patients who completed at least 1 month of follow-up achieved a 50% or greater reduction in Hamilton Rating Scale for Depression scores within 1 month. No patients developed hypomania or manic symptoms. No significant side effects were reported. LIMITATIONS: This study is limited both by the open-label design and by the small sample size. As in all previous reported studies, patients in this study were treated in an outpatient setting, so that the most severely depressed bipolar patients (requiring hospitalization) are not represented. CONCLUSIONS: Although the ultimate utility of omega-3 fatty acids in bipolar depression is still an open question, we believe that these initial results are encouraging, especially for mild to moderate bipolar depression, and justify the continuing exploration of its use.

Adult↗
PubMed2003

Impaired heart rate variability in euthymic bipolar patients.

BACKGROUND: Power spectral analysis of heart rate variability (HRV) has recently been shown to be a reliable non-invasive test for quantitative assessment of the central sympathovagal interaction that modulates cardiovascular autonomic function. METHODS: We studied 39 euthymic bipolar patients and 39 controls, matched for age and sex. A high-resolution electrocardiogram was obtained during complete rest. Spectral analysis of R-R intervals was performed by the fast Fourier transform algorithm. RESULTS: Euthymic bipolar patients at rest are characterized by markedly low HRV, independent of specific drug treatments. CONCLUSION: While these results of autonomic stability in euthymic bipolar patients are counter-intuitive, the findings may be important in understanding pathophysiology of bipolar affective illness.

Adolescent↗
PubMed2002

GSK-3 parameters in lymphocytes of schizophrenic patients.

Glycogen synthase kinase-3 (GSK-3) is a highly conserved serine/threonine protein kinase that is involved in the signal transduction cascades of multiple cellular processes. GSK-3 has two isoforms, designated alpha and beta. GSK-3beta protein levels and GSK-3 enzyme activity have been reported to be reduced by over 40% in postmortem frontal cortex of schizophrenic patients. GSK-3 is also present in peripheral tissue such as lymphocytes. In this study we aimed to find whether the reduction in brain GSK-3beta measures is reflected in peripheral tissue of schizophrenic patients. Fresh lymphocytes from schizophrenic patients showed no difference in GSK-3 alpha and GSK-3beta mRNA levels, GSK-3beta protein levels, or total GSK-3 (alpha+beta) enzyme activity compared with findings in control subjects. In addition, lymphocyte-derived cell lines from schizophrenic patients did not differ in their GSK-3beta protein levels from levels in normal control subjects. The results rule out the use of lymphocyte GSK-3 as a marker for central GSK-3 abnormalities in schizophrenia.

Adult↗