Biomedical subjects

Yechiel Levkovitz

Publications and source records attributed to Yechiel Levkovitz.

15 recordsLinked to original sources

PubMed2006

The neuroanatomical basis of affective mentalizing in schizophrenia: comparison of patients with schizophrenia and patients with localized prefrontal lesions.

Patients with schizophrenia show impaired emotional and social behavior, such as misinterpretation of social situations and lack of Theory of Mind (ToM). However, the neuroanatomical basis of impaired ToM and its nature in schizophrenia is still largely unknown. Based on previous findings, the present study suggests that impaired social cognition observed in schizophrenic patients may be similar to that observed in patients with prefrontal (PFC) damage due to impaired 'affective ToM' abilities, rather than to a general impairment in ToM. We examined the behavioral and neural mechanisms that underlie the social and communicative impairments observed in patients with schizophrenia and with PFC damage, by looking at differential patterns of ToM impairment in these individuals. The performance of 24 patients with schizophrenia was compared to the responses of patients with localized lesions in the ventromedial (VM) or dorsolateral PFC, patients with non-frontal lesions, and healthy control subjects. Patients with schizophrenia and those with VM lesions were impaired on 'affective ToM' tasks but not in cognitive ToM conditions. It was concluded that the pattern of mentalizing impairments in schizophrenia resembled those seen in patients with lesions of the frontal lobe, particularly with VM damage, providing support for the notion of a disturbance of the fronto-limbic circuits in schizophrenia.

Adolescent↗

PubMed2006

Dissociation of cognitive from affective components of theory of mind in schizophrenia.

Patients suffering from schizophrenia show impaired emotional and social behavior, such as misinterpretation of social situations and lack of theory of mind. However, there is conflicting evidence regarding their ability to perform on theory of mind tasks. Based on previous findings with patients suffering from prefrontal damage, the present study suggests that the behavioral deficit of schizophrenic patients may be due to impaired 'affective theory of mind' abilities, rather than to a general impairment in theory of mind. To test this hypothesis we assessed the ability of 22 schizophrenic patients and 55 age-matched healthy controls, to judge first and second order affective vs. cognitive mental state attribution, based on eye gaze. The relationships between negative and positive symptoms of schizophrenia, and affective and cognitive theory of mind were also assessed. Results indicated that while healthy controls made fewer errors on affective as compared to cognitive theory of mind conditions, schizophrenic patients showed a less prominent trend. Although the pattern of reaction time did not differ significantly between groups, the patients made significantly more errors in the affective conditions, as compared to controls. Furthermore, correlation analysis indicated that impaired affective theory of mind in these patients correlated with their level of negative symptoms. These results indicate that individuals with high level of negative symptoms of schizophrenia may demonstrate selective impairment in their ability to attribute affective mental states. These findings offer new insight into the affective facets of social behavior that may underlie the profound behavioral disturbances observed in schizophrenia.

Adult↗

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

Learned irrelevance is disrupted in first-episode but not chronic schizophrenia patients.

Learned irrelevance (LIrr) is a pre-exposure effect in which uncorrelated presentations of a conditioned stimulus (CS) and an unconditioned stimulus (US) retard subsequent CS-US association. LIrr is closely related to the phenomenon of latent inhibition (LI). LI refers to the retarding effects of inconsequential stimulus pre-exposure on subsequent conditioning to that stimulus, and is considered to reflect the organism's capacity to ignore irrelevant stimuli. LI is disrupted in schizophrenia patients, due to faster learning of the association between the preexposed CS and the US. A new within-subject target-recognition LIrr procedure was applied. The target was either cued by a priming signal or appeared at random, and priming signals were novel or preexposed cues. Schizophrenia patients were compared to age- and sex-matched control subjects. Normal subjects (n = 24) have shown robust LIrr, namely, faster cue-target associations of novel compared to preexposed cues. Schizophrenia patients at the early stages of their first episode (n = 7) showed LIrr disruption, namely, cue-target associations to preexposed cues were as fast as for novel cues. Chronic patients during an acute phase (n = 18) did not show LIrr as they failed to learn the cue-target association. In addition to the LIrr paradigm the same subjects were tested in a covert-orientation task. No differences were observed between the groups on this task. The possible advantages of the new LIrr paradigm are discussed.

Adult↗

PubMed2005

Gender differences in electroconvulsive therapy: a retrospective chart review.

BACKGROUND: There is a growing interest in gender differences of different psychiatric disorders, especially major depression. We sought a possible gender difference related to electroconvulsive therapy (ECT). METHODS: This retrospective study compared 20 male and 23 female depressed adult patients treated by ECT. We compared their findings on gender differences to those of 12 female and 4 male bipolar patients and 11 male and 19 female schizophrenic patients, all treated in the same ECT setting. RESULTS: Depressed female patients underwent significantly fewer antidepressant drug trials than males before being referred to ECT (t41=2.09, P<0.05). A similar gender difference was found in the treatment of patients suffering from schizophrenia: female patients underwent fewer pharmacological antipsychotic trials than males before being referred to ECT (t28=3.11, P<0.01). ECT was significantly more effective in female patients than in male patients suffering from schizophrenia (U=38, P<0.05). LIMITATIONS: This is a retrospective pilot study whose results are based on subjective evaluations. CONCLUSION: The findings of this study may support a gender difference both in referral and in the outcome of ECT. CLINICAL RELEVANCE: there might be a need to consider lowering the number of pre-ECT drug trials for depressed males and to consider ECT as a viable therapeutic option for schizophrenic females.

Major Depressive Disorder↗

PubMed2005

Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines: evidence for p-c-Jun, cytochrome c, and caspase-3 involvement.

Several antidepressants, mainly selective serotonin-reuptake inhibitors (SSRIs) and some tricyclic antidepressants (TCAs), have been shown to possess potent apoptotic activity in different cell lines. Our aim was to screen and select those agents with significant activity and elucidate the molecular pathway underlying this process in rat glioma and human neuroblastoma cell lines. We studied the effect of different antidepressants on apoptotic markers, including: cell viability, DNA fragmentation, cytochrome c (Cyt c) release from mitochondria, and caspase-3- like activity. In addition, the involvement of MAPK genes, c-Jun, and ERK was determined. Paroxetine and fluoxetine, SSRIs, clomipramine, a TCA, but not imipramine or mianserin (an atypical antidepressant), caused apoptosis in both cell lines, as assessed by flow cytometry of propidium iodide-stained C6 cells and typical fluorescence microscopy in glioma cells. These apoptotic changes were preceded by rapid increase in p-c-Jun levels, Cyt c release from mitochondria, and increased caspase-3-like activity. Assessment of paroxetine cytotoxicity in primary mouse brain and neuronal cultures showed significantly lower sensitivity to the drug's proapoptotic activity. These results strongly suggest that selected antidepressants induce apoptosis in neuronal and glial cell lines. Activation of p-c-Jun and subsequent increased Cyt c mitochondrial release participate in the apoptotic mechanism of the antidepressant. The high sensitivity to these drugs of the cancer cell, compared with primary brain tissue, suggests the potential use of these agents in the treatment of brain-derived tumors.

Animals↗

PubMed2005

Ethical dilemmas in psychotherapy: comparison between patients, therapists and laypersons.

BACKGROUND: The attitudes of patients towards ethical dilemmas in psychotherapy have been reported in only a few studies. AIMS OF THE STUDY: We investigated whether the attitudes of patients undergoing psychotherapy to confidentiality and boundaries are different from those of therapists and laypersons. METHODS: Clinical vignettes describing ethical dilemmas of confidentiality and boundaries were presented to 103 patients undergoing psychotherapy (patient group), 93 psychotherapists of different professional backgrounds (professional group), and 55 staff and students from the fields of law and the humanities (lay group). Patients were asked how they think therapists should act in the situations presented and therapists were asked how they should behave in such situations. RESULTS: In general, the patient group showed a greater tendency to view their therapists as breaching confidentiality than the professional and lay groups. Regarding boundaries, the majority of psychotherapists were against initiating any sexual relationship with current patients, former patients, students or supervisees, whereas both patients and laypersons showed a less stringent attitude; these differences were statistically significant. The vast majority of therapists (96.7%) disapproved of accepting money in advance compared to only 31.1% in the patients group and 54.4% of the lay group. Analysis of the patients group by gender did not reveal any significant relationships. CONCLUSIONS: (1) Patients have different ethical codes from therapists and laypersons regarding the issues of confidentiality. (2) Patients and lay persons are less strict than therapists regarding issues of boundaries.

Adult↗

PubMed2004

Use of topical application of lidocaine-prilocaine cream to reduce injection-site pain of depot antipsychotics.

This study took place in Israel and examined the use of a local topical anesthetic cream to ameliorate the pain at the injection site caused by depot antipsychotic medications. Fifteen consecutive outpatients who had schizophrenia and who were under treatment with depot antipsychotic medications were enrolled in this randomized, double-blind, placebo-controlled crossover study. The patients received either lidocaine-prilocaine cream or a placebo one hour before the injection. The degree of pain at the injection site was quantified by the patients' use of a visual analogue scale five minutes after the injection. The application of the lidocaine-prilocaine cream led to a significant reduction of pain compared with the placebo.

Administration, Topical↗

PubMed2004

Characterization of phenothiazine-induced apoptosis in neuroblastoma and glioma cell lines: clinical relevance and possible application for brain-derived tumors.

In this study we aimed to (1). screen phenothiazines for cytotoxic activity in glioma, neuroblastoma, and primary mouse brain tissue; and (2). determine the mechanism of the cytotoxic effect (apoptosis, necrosis) and the roles of calmodulin inhibition and sigma receptor modulation. Rat glioma (C6) and human neuroblastoma (SHSY-5Y) cell lines were treated with different phenothiazines. All agents induced a dose-dependent decrease in viability and proliferation, with the highest activity elicited by thioridazine. Sensitivity to thioridazine of glioma and neuroblastoma cells was significantly higher (p < 0.05) than that of primary mouse brain culture (IC50 11.2 and 15.1 microM vs 41.3 microM, respectively). The N-mustard fluphenazine induced significantly lower cytotoxicity in glioma cells, compared to fluphenazine. The sigma receptor selective ligand (+)-SK&F10047 increased viability slightly while combined with fluphenazine; SK&F10047 did not alter fluphenazine activity. Flow cytometry of propidium iodide (PI)-stained glioma cells treated with thioridazine, fluphenazine, or perphenazine (6-50 microM) resulted in a concentration-dependent increase of fragmented DNA up to 94% vs 3% in controls by all agents. Thioridazine (12.5 microM)-treated glioma cells costained with PI and Hoechst 33342 revealed a red fluorescence of fragmented nuclei in treated cells and a blue fluorescence of intact control nuclei. After 4-h exposure to thioridazine (25 and 50 microM), a 25- to 30-fold increase in caspase-3 activity in neuroblastoma cells was noted. Overall, the marked apoptotic effect of phenothiazines in brain-derived cancer cells, and the low sensitivity of primary brain tissue suggest the potential use of selected agents as therapeutic modalities in brain cancer.

Animals↗

PubMed2004

Are psychotherapists consistent in their ethical attitude to patient confidentiality?

BACKGROUND: The issue of confidentiality often causes an ethical dilemma for the psychotherapist. AIMS OF THE STUDY: We investigated if therapists are consistent in their attitude to confidentiality or judge each case on its own merit. METHODS: A questionnaire consisting of a series of clinical vignettes representing different ethical dilemmas in confidentiality in psychotherapy was completed by 93 therapists of different professional backgrounds and by a control group of 55 students from the fields of law and the humanities. RESULTS: Subjects in both groups were inconsistent in their attitude to confidentiality in two-thirds of cases, and most of the participants based their decisions on the particular history and circumstances of each case. CONCLUSION: The rules guiding psychotherapists for the disclosure of confidential information are unclear. These findings failed to pinpoint a common denominator to explain the manner in which professionals handle information that may demand a break of confidentiality.

Attitude of Health Personnel↗

PubMed2003

Hyperglycemia from olanzapine treatment in adolescents.

The increasing use of olanzapine for treating adolescent patients has brought with it greater awareness of the recognized side effects of this medication, especially weight gain. Of the reports of glucose dysregulation related to olanzapine therapy, only a few pertain to adolescents. We present five cases: two youths who consequently suffered from overt diabetes and three who responded with glucose dysregulation. According to the Naranjo probability scale, the relation of this phenomenon to olanzapine therapy is "probable." We consider the findings of the presented case series as justification for regular metabolic follow-up for apparently healthy adolescents receiving olanzapine therapy.

Adolescent↗

PubMed2003

Effect of L-tryptophan on memory in patients with schizophrenia.

SUMMARY: ABSTRACT It has been well established that patients with schizophrenia have impaired cognitive abilities on neuropsychological tasks related to memory. Previous studies also suggest a central role for serotonin in memory. This double-blind crossover study aimed to explore the effect of l-tryptophan, a serotonin precursor, on a variety of memory tasks in schizophrenic patients. Antipsychotic-treated schizophrenic patients in remission (N = 21) were randomly treated with l-tryptophan or placebo and then evaluated at three consecutive points on clinical measures (including Positive and Negative Syndrome Scale for Schizophrenia, Clinical Global Impression, and Extrapyramidal Symptoms Rating Scale) and by neuropsychological tests (including Digit-Span, Paired Association, Rey-Osterich Complex Figure Test, Digit Symbol, Number Facility Test, and the Rivermead Behavioral Memory Tests. Compared with placebo, l-tryptophan had a beneficial effect on memory functions but not on the patients' psychotic state or on the side effects of medications. These preliminary results suggest the possibility of using serotonin precursor to enhance memory function in schizophrenia.

Adult↗

PubMed2002

The SSRIs drug Fluoxetine, but not the noradrenergic tricyclic drug Desipramine, improves memory performance during acute major depression.

Accumulating evidence suggests that noradrenergic and serotonergic drugs are equally effective in ameliorating the depressive symptoms of major depression. Major depression is associated also with memory impairments, but the comparative effects of the antidepressant drugs on memory are not clear. We previously found that serotonergic neurotransmission is of particular importance for some aspects of episodic memory. We set out to test whether treatment with the selective serotonergic drug Fluoxetine (Prozac) would be advantageous in this respect over treatment with the selective noradrenergic tricyclic antidepressant drug Desipramine (Deprexan). Seventeen patients with major depressive episode, randomly assigned for treatment with either Fluoxetine (n = 8) or Desipramine (n = 9), were assessed for their clinical situation and for memory performance at the beginning of treatment, after 3 weeks, and after 6 weeks of pharmacological treatment. We found that although clinically both drugs were equally effective, the improvement of memory performance in the Fluoxetine-treated patients was significantly greater compared with that of the Desipramine-treated patients. The results support the role of serotonin in memory. More studies in larger samples of patients are required, but it may be that in cases where memory impairment is a major symptom, it would be beneficial to consider serotonergic antidepressant drugs for treatment. Furthermore, in cases where, for various reasons, the treatment of choice is noradrenergic, it may be worthwhile to consider a supplementary serotonergic drug to improve memory deficits.

Acute Disease↗

PubMed2002

A dominant negative Egr inhibitor blocks nerve growth factor-induced neurite outgrowth by suppressing c-Jun activation: role of an Egr/c-Jun complex.

Members of the Egr family of transcription factors are rapidly and robustly induced by neurotransmitters and neurotrophins and have been implicated in mediating enduring changes in neuronal function elicited by these stimuli. Because we have found in previous studies that a dominant negative inhibitor of Egr action, the Egr zinc finger domain (ZnEgr), blocks NGF-induced neurite outgrowth in PC12 cells, we have used this preparation to help identify the downstream targets of Egr proteins involved in plasticity. Our investigation into the mechanism of action of ZnEgr indicates that it blocks NGF-induced neurite outgrowth by suppressing activation of c-Jun, a critical step in the signaling pathway mediating this response. Although we had assumed that ZnEgr exerts its effects by binding to the Egr response element (ERE) and thereby blocking target gene regulation by Egr proteins, this classical mode of action appears to be too slow to mediate the effects of Egr proteins on c-Jun activation. In evaluating alternative ERE-independent mechanisms of Egr (and ZnEgr) action, we found that Egr1 and c-Jun coprecipitate and that ZnEgr disrupts formation of the Egr1/c-Jun complex. Furthermore, mutations of ZnEgr that greatly impair or abolish its ability to bind to the ERE do not block its ability to suppress c-Jun activation or neurite outgrowth induced by NGF. Accordingly, our studies indicate that Egr and ZnEgr proteins regulate c-Jun activation via a novel mechanism, protein-protein interaction with c-Jun, rather than via their classical mode of action, binding to the ERE.

Cell Line↗

PubMed2002

Everyday memory and laboratory memory tests: general function predictors in schizophrenia and remitted depression.

This study was designed to compare neuropsychological memory measures ("laboratory memory tests") and an everyday memory measure in patients with schizophrenia, patients with major depression, and normal controls. Patients with schizophrenia ( N= 68) treated with typical (N = 33) or atypical ( N= 35) neuroleptics, patients with major depression (N = 30), and a control group (N = 36) were evaluated with clinical measures (Positive and Negative Syndrome Scale and Hamilton Depression Rating Scale), laboratory memory tests (Digit-Span, Paired-Associates, Rey Complex Figure Test, and Digit-Symbol), everyday memory test (RMBT), and the Global Assessment of Functioning (GAF). The schizophrenia group had a significantly lower level of performance in everyday memory and general function but not in laboratory memory tests. Verbal and everyday memory measures were correlated with general function. The diagnosis rather than current symptoms (in remission) contributed to test variance and was correlated with performance on everyday memory and general function tests. Everyday memory and verbal memory were good predictors of general function in schizophrenic and depressive patients in the remitted phase. However, the advantages of these tests over laboratory memory tests need to be further investigated in larger and more representative samples.

Adolescent↗