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M Kotler

Publications and source records attributed to M Kotler.

At least 19 recordsLinked to original sources
PubMed2004

Clozapine in the treatment of obsessive-compulsive symptoms in schizophrenia patients: a case series study.

INTRODUCTION: Obsessive-compulsive (OC) symptoms have been observed in a substantial proportion of schizophrenic patients. There are some reports describing the appearance de novo or reemergence of preexisting OC symptoms under clozapine (CLZ) therapy. However, there are also reports describing a positive effect of CLZ therapy in OC schizophrenic patients. It seems that comorbid OC symptoms are common among CLZ-treated refractory schizophrenic patients and are likely to be an integral part of their illness. The complex nature of the treatment response in this group of schizophrenic patients is as yet unclear. The effects of CLZ on OC symptoms may vary, with evidence of improvement in some and worsening among others. METHODS: The present case series study describes our experience with CLZ as a sole agent (n = 10) or in combination with serotonin reuptake inhibitors (n = 5), in schizophrenic patients with prominent OC symptomatology. RESULTS: Systematic analysis of clinical features of our patients, as well as findings in the literature to date, led us to suggest some factors that may predict response to CLZ treatment in treatment-resistant schizophrenic patients with prominent OC symptoms: 1) schizophrenic patients who began to exhibit OC symptoms within the course of the psychotic process need and might to be successfully treated with CLZ alone; 2) when OC symptomatology preceded the development of schizophrenic process, CLZ monotherapy is inefficient and may even worsen OC symptoms; therefore, it should be treated concomitantly with specific anti-obsessive agents; 3) in both groups there is a definite dose-related pro-obsessive influence of CLZ when it is given in high doses. DISCUSSION: Further controlled investigations in a larger cohort of OC schizophrenic patients are needed to substantiate our hypothesis. OCD:Obsessive-compulsive disorder OCS:Obsessive-compulsive symptoms SRI:Serotonin reuptake inhibitors

Adult↗
PubMed2002

Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA).

Monoamine oxidase A (MAO A) is located on the X chromosome and metabolizes biogenic amines including dopamine, norepinephrine and serotonin. A functional promoter-region polymorphism of this gene has been described that has been studied in a number of mental illnesses but not in attention deficit hyperactivity disorder (ADHD). In the current study, we examined the MAO A promoter-region polymorphism initially in 133 triads and observed preferential transmission of the long alleles from 74 heterozygote mothers to ADHD probands (chi(2) = 4.37, P = 0.036, df = 1). We also examined the role of this polymorphism in a computerized continuous performance test, the TOVA. Significant differences were observed on errors of commission (chi(2) = 7.021, P = 0.008) and patients carrying the long MAO A allele made significantly more such errors. Errors of commission are a measure of impulsivity. However, following Ritalin (methylphenidate) administration the association between this polymorphism and errors of commission was markedly attenuated and no longer significant at the P < 0.05 level. We also analyzed the provisional association by the case-control design. A significant difference in allele frequency was observed between 110 male probands vs 202 male controls (Pearson chi(2) = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype chi(2) = 21.28; P = 0.0032, 3 df and allele chi(2) = 30.88, P= 0.0007, 2 df). All three complementary approaches employed (family-based, case-control and quantitative trait design) suggest a role for the MAO A promoter-region polymorphism in conferring risk for ADHD in our patient population.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

The short DRD4 repeats confer risk to attention deficit hyperactivity disorder in a family-based design and impair performance on a continuous performance test (TOVA).

One particular candidate gene, the dopamine D4 receptor (DRD4), has been the focus of intense study regarding ADHD since the original investigation by La Hoste et al, an observation confirmed by a recent metaanalysis. However, two previous studies from Israel failed to observe this association. We have now recruited an additional sample and, overall, in the combined sample of 178 triads we observe using the transmission disequilibrium test, preferential transmission of the short allele. Additionally, we now report the effect of the DRD4 repeat region on the Test Of Variables of Attention (TOVA), a widely used computerized continuous performance test. Probands with the short exon III repeat performed significantly worse on the TOVA measured both by errors of commission and response time variable. Intriguingly, a 'dose effect' was observed. Increasing repeat size is accompanied by a reduced number of errors of commission and a significant difference is observed between the 2 vs 7 repeats. On the whole, our results lend credence to the notion that the relationship between the DRD4 receptor and ADHD is complex and may be reflecting linkage disequilibrium between the 7 or long DRD4 exon III repeats and a 'true' risk allele in this gene or a neighboring locus.

Adolescent↗
PubMed2001

A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes.

Dopamine is a major neurotransmitter in the central nervous system, and its receptors are associated with a number of neuropathological disorders such as Parkinson's disease and schizophrenia. Although the precise pathophysiology of schizophrenia remains unknown, the dopaminergic hypothesis of the illness assumes that the illness results from excessive activity at dopamine synapses in the brain. Because, at present, the diagnosis of schizophrenia relies on descriptive behavioral and symptomatic information, a peripheral measurable marker may enable a simpler, more rapid, and more accurate diagnosis and monitoring. In recent years, human peripheral blood lymphocytes have been found to express several dopamine receptors (D(3), D(4), and D(5)) by using molecular biology techniques and binding assays. It has been suggested that these dopamine receptors found on lymphocytes may reflect receptors found in the brain. Here we demonstrate a correlation between the D(3) dopamine receptor on lymphocytes and schizophrenia and show a significant elevation of at least 2-fold in the mRNA level of the D(3), but not of the D(4), dopamine receptor in schizophrenic patients. This increase is not affected by different antipsychotic drug treatments (typical or atypical). Moreover, nonmedicated patients exhibit the same pattern, indicating that this change is not a result of medical treatment. We propose the D(3) receptor mRNA on blood lymphocytes as a marker for identification and followup of schizophrenia.

Adult↗
PubMed2001

Family-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder.

Low serotonin activity has been associated in both animal and human studies with measures of impulsivity, aggression, and disinhibited behaviors. Recently, a common 44-bp deletion in the promoter region of the serotonin transporter (5-HTTLPR) that results in reduced transcription and lower transporter protein levels was described. Toward unraveling a possible role of the 5-HTTLPR polymorphism in childhood disruptive behaviors, we examined this gene in attention deficit hyperactivity disorder (ADHD), a heterogeneous childhood disorder in which three phenotypes are recognized by DSM IV criteria: inattentive (type I), hyperactive-impulsive (type II), and combined type (type III). By using the haplotype relative risk design, a group of 98 triads (both parents and proband child) were tested for a possible association between 5-HTTLPR and ADHD. A significant decrease in the short/short 5-HTTLPR genotype was observed in the ADHD type III combined group (10.29% vs. 30.88%) compared with the HRR-derived control group (likelihood ratio = 9.62, P = 0.008, n = 68 triads). Similar results were observed when allele frequencies were compared (likelihood ratio = 3.81, P = 0.05, n = 136 alleles). These first findings should be interpreted cautiously until replicated in independently recruited clinical samples.

Adolescent↗
PubMed2001

Analysis of neurosteroid levels in attention deficit hyperactivity disorder.

Neurosteroids are important neuroactive substrates with demonstrated involvement in several neurophysiological and disease processes. Attention deficit hyperactivity disorder (ADHD) has been associated with dysregulation of the catecholaminergic and serotonergic systems, however its relationship to irregularities or changes in neurosteroid levels remains unknown. We examined the relationship between blood levels of dehydroepiandrosterone (DHEA), its principal precursor pregnenolone and its principal metabolite dehydroepiandrosterone sulphate (DHEAS) in 29 young male subjects aged 7-15 years with DSM-IV criteria of ADHD. Subjects were evaluated by a specially designed scale, following which patients were divided into two groups according to severity of symptomatology. Results indicated significant inverse correlations between clinical symptomatology and levels of DHEA and pregnenolone in the total group. These inverse correlations were particularly evident in the less severe group of subjects. Levels of DHEA and DHEAS were inversely correlated with the hyperactivity subscale. Furthermore, using median blood levels as a cut-off indicator, higher blood levels of DHEA and DHEAS were associated with fewer ADHD symptoms, in particular hyperactivity symptomatology. Our findings suggest a possible protective effect of various neurosteroids on the expression of ADHD symptomatology.

Adolescent↗
PubMed2001

Olanzapine-induced leukopenia with human leukocyte antigen profiling.

Olanzapine is an atypical antipsychotic medication frequently used in the management of psychotic states. While it has proved to be safe compared to clozapine with regard to haematotoxicity, because it has only been available for a few years, full documentation of its haematological side-effects remains incomplete. We report a case of olanzapine-induced leukopenia with associated neutropenia. Since clozapine-induced haematotoxicity has been associated with characteristic human leukocyte antigen (HLA) groups, HLA typing was determined in this patient. Following failure with typical antipsychotic medication, the patient received 10 mg/day of olanzapine. Three weeks later, he developed fever and a significant decrease in leukocyte count. Olanzapine was immediately discontinued. HLA typing was determined. The white cell count returned to normal and the fever, most probably secondary to the low white cell count, subsided with antibiotic treatment. HLA typing results were: A1 24, B7, B35, DRB1*15, DRB1*11, DRB3*01-03, DRB5*01-02. Olanzapine may induce serious leukopenia and neutropenia. HLA typing in this single patient demonstrated a distinct haplotype compared to that previously observed in clozapine-induced haematoxicity.

Clozapine↗
PubMed2001

Anger, impulsivity, social support, and suicide risk in patients with posttraumatic stress disorder.

An emerging literature suggests that posttraumatic stress disorder (PTSD) patients are at an increased risk for suicide. The objective of this study was: a) to reexamine the relationship between PTSD and suicide by comparing suicide risks of persons with PTSD, to persons with anxiety disorder and to matched controls; and b) to examine the relationship between anger, impulsivity, social support and suicidality in PTSD and other anxiety disorders. Forty-six patients suffering from PTSD were compared with 42 non-PTSD anxiety disorder patients and with 50 healthy controls on measures of anger, impulsivity, social support, and suicide risk. Persons with PTSD had the highest scores on the measures of suicide risk, anger, and impulsivity and the lowest scores on social support. Multivariate analysis revealed that in the PTSD group, impulsivity was positively correlated with suicide risk and anger was not. PTSD symptoms of intrusion and avoidance were only mildly correlated with suicide risk at the bivariate level but not at the multivariate level. For the PTSD and anxiety disorder groups, the greater the social support, the lower the risk of suicide. For the controls, social support and impulsivity were not related to suicide risk, whereas anger was. These findings suggest that persons with PTSD are at higher risk for suicide and that in assessing suicide risk among persons with PTSD, careful attention should be paid to levels of impulsivity, which may increase suicide risk, and to social support, which may reduce the risk.

Adolescent↗
PubMed2001

Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study.

OBJECTIVE: The authors' goal was to conduct a double-blind trial of vitamin B(6) in the treatment of tardive dyskinesia in patients with schizophrenia. METHOD: Fifteen inpatients with schizophrenia who met research diagnostic criteria for tardive dyskinesia were randomly assigned to treatment with either vitamin B(6) or placebo for 4 weeks in a double-blind crossover paradigm. The Extrapyramidal Symptom Rating Scale was used to assess patients weekly. RESULTS: Mean scores on the parkinsonism and dyskinetic movement subscales of the Extrapyramidal Symptom Rating Scale were significantly better in the third week of treatment with vitamin B(6) than during the placebo period. CONCLUSIONS: Vitamin B(6) appears to be effective in reducing symptoms of tardive dyskinesia.

Adult↗
PubMed2001

Association of autonomic dysfunction and clozapine. Heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication.

BACKGROUND: Antipsychotic medications cause a wide range of adverse effects and have been associated with sudden death in psychiatric patients. AIMS: To supply power spectral analysis of heart rate variability as a tool to examine the arrythmogenic effects of neuroleptics. METHOD: Heart rate analysis was carried out in patients with schizophrenia on standard doses of neuroleptic monotherapy -- 21 were on clozapine, 18 on haloperidol and 17 on olanzapine -- and in 53 healthy subjects. RESULTS: Patients with schizophrenia on clozapine had significantly higher heart rate, lower heart rate variability and lower high-frequency and higher low-frequency components compared with patients on haloperidol or olanzapine and matched control subjects. Prolonged QTc intervals were more common in patients than controls. CONCLUSIONS: Patients treated with neuroleptic medications, especially clozapine, showed autonomic dysregulation and cardiac repolarisation changes. Physicians should be aware of this adverse reaction.

Adult↗
PubMed2001

Abnormal sympathovagal balance in men with fibromyalgia.

OBJECTIVE: It is possible that there are differences in clinical manifestations between men and women with fibromyalgia syndrome (FM), especially in autonomic dysfunction; we assessed the interaction between the sympathetic and parasympathetic systems in postural change in men with FM using power spectral analysis (PSA) of heart rate variability (HRV), and investigated the pathogenesis of the orthostatic intolerance. METHODS: We studied 19 men with FM and 19 controls matched for age and sex. A high resolution electrocardiogram was obtained in supine and standing postures during complete rest. Spectral analysis of R-R intervals was done by the fast Fourier transform algorithm. RESULTS: PSA of HRV revealed that men with FM at rest are characterized by sympathetic hyperactivity and concomitantly reduced parasympathetic activity. During postural changes, male patients demonstrated an abnormal sympathovagal response. These results provide the physiological basis for the orthostatic intolerance in men with FM. CONCLUSION: This report of autonomic dysfunction in men with FM revealed an abnormal autonomic response to orthostatic stress. This abnormality may have implications regarding the symptoms of FM.

Adult↗
PubMed2001

Autonomic nervous system derangement in fibromyalgia syndrome and related disorders.

Fibromyalgia syndrome is a chronic, painful musculoskeletal disorder of unknown etiology and/or pathophysiology. During the last decade many studies have suggested autonomic nervous system involvement in this syndrome, although contradictory results have been reported. This review focuses on studies of the autonomic nervous system in fibromyalgia syndrome and related disorders, such as chronic fatigue syndrome and irritable bowel syndrome on the one hand and anxiety disorder on the other, and highlights techniques of dynamic assessment of heart rate variability. It raises the potentially important prognostic implications of protracted autonomic dysfunction in patient populations with fibromyalgia and related disorders, especially for cardiovascular morbidity and mortality.

Adult↗
PubMed2001

[Heart rate variability in schizophrenic patients treated with antipsychotic agents].

BACKGROUND: Antipsychotic medication causes a wide range of predictable adverse effects, and has long been associated with sudden unexplained and unexpected death in psychiatric patients, despite controversies surrounding the issue. In light of the evidence that sudden cardiovascular-related death is associated with neuroleptic medication, we are especially interested in examining whether measurements of the power spectral analysis (PSA) of heart rate variability (HRV) are differentially affected by various antipsychotic medications. We will also examine the cases in which PAS provides information regarding the relative safety of the various groups of drugs under investigation, in terms of their influence on the sympathetic-parasympathetic balance. AIM: The primary aim of this study is to utilize spectral analysis of heart rate variability as a tool to examine the differential arythmogenic effects of antipsychotic medications. The secondary aim was to examine the QT interval in schizophrenic patients receiving this treatment. METHOD: Standardized heart rate analysis was carried out in twenty-one schizophrenic patients receiving monotherapy with the following medications: treatment with 300-700 mg/day of clozapine, eighteen schizophrenic patients treated with 5-10 mg/day haloperidol, seventeen schizophrenic patients treated with 5-20 mg/day Olanzapine, and 53 healthy subjects. RESULTS: Our results show that schizophrenic patients treated with clozapine had significantly higher HR, lower HRV, lower high frequency (HF) and higher low frequency (LF) components compared to the patients treated with haloperidol, olanzapine, and the matched control subjects. Prolonged QTc intervals were more common in patients receiving treatment than in the control group, although the PR and QRS intervals did not differ significantly. CONCLUSIONS: The overall results showed that, patients treated with neuroleptic medication, especially clozapine, presented autonomic dysregulation and cardiac repolarization changes. Care should be taken in prescribing clozapine to patients prone to cardiovascular side effects.

Adult↗
PubMed2000

Failure to replicate an association between the catechol-O-methyltransferase polymorphism and attention deficit hyperactivity disorder in a second, independently recruited Israeli cohort.

Attention deficit hyperactivity disorder (ADHD) is a developmental syndrome expressed along three domains: inattention, hyperactive-impulsive, and combined type. Both environmental and genetic factors contribute to the etiology of this complex disease. We previously reported an association in 48 ADHD triads (both parents and proband) between the catechol-O-methyl- transferase (COMT) polymorphism (especially the high enzyme activity val allele) and the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) combined category (excluding inattention) of ADHD (however, see erratum, Am. J. Med. Genet. [Neuropsychiatr. Genet.] 96:893). In the current report, we attempted to replicate this finding in an independently recruited group of 70 nuclear families using the haplotype relative risk design. In the current investigation, no evidence for association of the COMT polymorphism and ADHD (or any of the DSM IV subtypes) was observed in either the current cohort or the expanded cohort of 118 Israeli triads. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:858-860, 2000.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Confirmation of an excess of the high enzyme activity COMT val allele in heroin addicts in a family-based haplotype relative risk study.

A previous case control study by Vandenbergh et al. [1997: Am J Med Genet 74:439-442] showed an association between the high activity catechol O-methyltransferase (COMT) polymorphism and polysubstance abuse in a group of North American subjects. In the current study we confirm these results by genotyping 38 Israeli heroin addicts and both parents using a robust family-based haplotype relative risk (HRR) strategy. There is an excess of the val COMT allele (likelihood ratio = 4.48, P = 0.03) and a trend for an excess of the val/val COMT genotype (likelihood ratio = 4.97, P = 0.08, 2 df) in the heroin addicts compared to the HRR control group. We also genotyped an additional 101 nonrelated heroin addicts and 126 control subjects using a case control design and found no significant difference in COMT val allele frequency (25.4% vs. 29.7%, likelihood ratio = 1.04, P = 0.31). A significant difference is observed in COMT allele frequency among the three principal Israeli ethnic groups (Ashkenazi Jewish, non-Ashkenazi Jewish, and Palestinian Arab) in a large group of control subjects we have so far examined (chi-square = 7.9, P = 0.019, df = 2, n = 1,422 alleles) suggesting that population stratification is responsible for our failure to observe an excess of the COMT val allele when using the case-control design.

Alleles↗
PubMed2000

Autonomic dysregulation in panic disorder and in post-traumatic stress disorder: application of power spectrum analysis of heart rate variability at rest and in response to recollection of trauma or panic attacks.

Power spectral analysis (PSA) of heart rate variability (HRV) offers reliable assessment of cardiovascular autonomic responses, providing a 'window' onto the interaction of peripheral sympathetic and parasympathetic tone. Alterations in HRV are associated with various physiological and pathophysiological processes, and may contribute to morbidity and mortality. Previous studies of posttraumatic stress disorder (PTSD) found lower resting HRV in patients compared to controls, suggesting increased sympathetic and decreased parasympathetic tone. This article describes the analysis of HRV at rest and after psychological stress in panic disorder (PD) patients, in an enlarged sample of PTSD patients, and in healthy control subjects. Standardized heart rate (HR) analysis was carried out in 14 PTSD patients, 11 PD patients and 25 matched controls. ECG recordings were made while subjects were resting ('rest 1'), while recalling the trauma implicated in PTSD, or the circumstances of a severe panic attack, as appropriate ('recall'), and again while resting ('rest 2'). Controls were asked to recall a stressful life event during recall. While both patient groups had elevated HR and low frequency (LF) components of HRV at baseline (suggesting increased sympathetic activity), PTSD patients, unlike PD patients and controls, failed to respond to the recall stress with increases in HR and LF. HRV analysis demonstrates significant differences in autonomic regulation of PTSD and PD patients compared to each other and to control subjects. HRV analysis may augment biochemical studies of peripheral measures in these disorders.

Adult↗
PubMed2000

Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study.

The DRD4 exon III repeat polymorphism has been associated in adults with Novelty Seeking personality traits and in children with attention deficit hyperactivity disorder (ADHD) in some but not all studies. In a previous report we failed to observe preferential transmission of the long DRD4 repeat in ADHD compared to the haplotype relative risk (HRR) derived control group in a group of 49 triads (both parents and ADHD child) recruited in the Jerusalem area. In the current study we independently recruited an additional group of 49 triads from a different geographical location (Petak Tikvah) in Israel but having a similar ethnic background. In contrast to previous findings from a number of groups, in the current study an excess of the long DRD4 alleles was observed in the HRR control group compared to the ADHD subjects (Likelihood ratio = 5.50, P = 0. 02). In the expanded Israeli group of 98 triads so-far examined for the DRD4 repeat polymorphism there is an excess of the long alleles in the HRR control group (Likelihood ratio = 3.81, P = 0.05). These results attest to the complexity of ADHD inheritance and the likelihood that genetic heterogeneity characterizes this disorder especially across ethnic and cultural boundaries.

Adolescent↗