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Biomedical subjects

B Lerer

Publications and source records attributed to B Lerer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis.

The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6S271), with a maximum lod score of 2.2 occurring near D6S274, located in 6p22. However, we obtained a lod score of -2 at D6S296, the locus found by others to provide the greatest linkage evidence. At D6S274, we report a positive lod score as do Straub et al. (individually non-significant). A combined total lod of 3.6-4.0 suggests the possibility of a susceptibility locus in this region. However, methodological differences between our studies makes a firm conclusion difficult.

Chromosome Mapping↗
PubMed1995

Antidepressant and cognitive effects of twice- versus three-times-weekly ECT.

OBJECTIVE: The purpose of this study was to determine which of the two commonly used schedules of ECT administration, twice or three times weekly, is clinically optimal in terms of antidepressant efficacy and cognitive effects. METHOD: In this double-blind study, 52 consenting, medication-free patients with major depressive disorder, endogenous subtype (Research Diagnostic Criteria), were randomly assigned to bilateral, brief-pulse, constant-current ECT administered over 4 weeks at a rate of three times weekly or twice weekly with the addition of one simulated ECT (anesthesia and muscle relaxant only) per week. Outcome measures were the Hamilton Depression Rating Scale, Acute Cognitive Effects Battery, and Chronic Cognitive Effects Battery. RESULTS: Hamilton depression scale scores were significantly improved by both schedules, with no difference in outcome either 1 week or 1 month after the end of the ECT series. However, the rate of response to ECT three times a week was significantly faster and was related to the rate of real ECT administration. Cognitive effects were more prominent with ECT three times a week. CONCLUSIONS: ECT twice a week is an effective schedule for clinical practice and is potentially advantageous in view of a therapeutic outcome identical to that of ECT three times a week and less severe cognitive effects. ECT three times a week may be specifically indicated when early onset of clinical effect is of primary importance.

Adult↗
PubMed1995

A prospective study of lithium continuation therapy in depressed patients who have responded to electroconvulsive therapy.

Twenty-eight of 34 patients with major depression who completed a course of electroconvulsive therapy (ECT) and were classified as responders were administered lithium carbonate (Li) continuation therapy in the context of an open, prospective study. Twenty-four patients were followed for 6 months or until relapse; four patients dropped out of follow-up while still in remission. The probability of completing 6 months without relapse (by survival analysis, including the patients who dropped out as censored observations) was 65%. The eight patients who relapsed into depression all did so within 13 weeks. They were characterized by a shorter duration of their index depressive episode, a greater likelihood of having suffered an additional depressive episode in the preceding 12 months, and failure of an adequate trial of antidepressant medication before the ECT course. Novel pharmacological strategies may be needed in the post-ECT continuation therapy of patients who have a prior history of relapse and are demonstrably resistant to antidepressant medication.

Combined Modality Therapy↗
PubMed1995

Effects of electroconvulsive therapy on plasma GABA.

There are no published data on the effects of seizures on indices of gamma-aminobutyric acid (GABA) function in human subjects. In study 1, the effects of electroconvulsive therapy (ECT) on free plasma GABA were studied in 39 inpatients with major depressive disorder. Acutely after ECT, free plasma GABA was significantly reduced for up to 1 h after seizure termination, and this finding replicated strongly in a subgroup of six patients who received a second course of ECT. In a second study at a different site that compared sham ECT and real ECT in seven patients, some doubt was raised about the replicability of the acute effect of ECT on GABA levels. Nonetheless, the strength of the findings in the larger study 1 sample suggests that, unlike virtually all other biochemical indices, free plasma GABA may be reduced acutely after ECT. This acute decrease could reflect decreased levels of GABA in brain extracellular space or decreased brain turnover. In study 1, compared with ECT nonresponders, ECT responders had higher GABA levels at both baseline and after a course of ECT. Because plasma GABA levels are known to be low in a subset of patients with major depression, the higher GABA levels observed in clinical responders before and after the ECT course indirectly suggest that patients least abnormal in GABA levels may show superior clinical response. This also suggests that low plasma GABA is not a state marker for depression.

Adult↗
PubMed1995

Two-year trial of maintenance neuroleptic dose reduction in schizophrenic out-patients: predictors of relapse.

Low dose maintenance therapy has been proposed as a pharmacological strategy for reducing exposure to neuroleptic drugs in schizophrenia. However, reliable predictors of post-dose reduction relapse, which could guide clinicians in selecting patients suitable for this type of treatment, have not yet been determined. In this study, 41 schizophrenic out-patients were assigned, on the basis of their previously clinically determined dosages, to one of two reduced maintenance fluphenazine decanoate regimes (35 mg/4 wks. or 10 mg/4 wks.) and were assessed, subsequently, for a 2-year period. Demographic, clinical and treatment characteristics of relapsers (22 patients) and non-relapsers (18 patients) were compared using univariate and multivariate tests. Four parameters: age, course of illness, duration of illness and duration since last psychiatric hospitalization, suggested, in univariate tests, significant discrimination between relapsers and non-relapsers. Stepwise discriminant function analyses defined a highly significant function (p < .01) which included only 3 predictors of relapse. In order of importance, these predictors were: (1) a history of chronic psychosis (2) male sex, and (3) an illness of short duration. Parameters such as age, baseline rating scales scores, magnitude of dose reduction and baseline maintenance dose failed to improve the ability to discriminate between relapsers and non-relapsers. Implications of these findings for clinical practice are discussed.

Adult↗
PubMed1994

[Psychiatric morbidity following psychic trauma of combat origin].

Psychiatric morbidity following trauma of combat origin was studied in 60 Israeli veterans who applied for treatment 4-6 years after the war in Lebanon. Diagnostic tools were structured interviews for psychiatric disorders. In all subjects multiple psychiatric disorders had been diagnosed, most of which developed following the traumatic experience. Post-traumatic stress disorder (PTSD) was the most prevalent condition (100%-ever; 87%-present). Comorbidity included major depression with a very high prevalence (95%-ever; 50%-present) and anxiety disorders: phobic disorder, obsessive-compulsive disorder, panic attacks and generalized anxiety (prevalence range 12-25%-ever and 8-18%-present). The prevalence of minor affective disorders (specifically alcoholism or drug abuse) was considerably less. These findings suggest a possible link between PTSD and depressive and anxiety disorders, beyond a mere sharing of common symptoms. They also support the diagnostic validity of PTSD as an independent nosologic category. In addition, the lack of specific pharmacotherapy for PTSD on the one hand and the high prevalence of depressive and anxiety comorbidity on the other, support a special focus on antidepressive and anxiolytic medication for PTSD.

Anxiety Disorders↗
PubMed1994

Platelet adenylate cyclase activity in Israeli victims of Iraqi Scud missile attacks with post-traumatic stress disorder.

Platelet adenylate cyclase activity was measured in 16 control subjects and 16 patients who developed post-traumatic stress disorder (PTSD) as a result of damage inflicted on their homes during the Iraqi Scud missile attacks on Israel which occurred during the 1991 Gulf War. There were no differences in basal, NaF-stimulated, PGE1-stimulated or forskolin-stimulated activity between controls and PTSD subjects. Epinephrine inhibition of forskolin-stimulated activity, an effect mediated by alpha 2 adrenergic receptors, was slightly but not significantly increased in the PTSD patients compared to the controls, while 5-HT induced inhibition, an effect mediated by putative 5-HT1a-like receptors, was unchanged. The relationship of these activities to measures of anxiety and depression in these patients is discussed.

Adenylyl Cyclases↗
PubMed1994

A pedigree series for mapping disease genes in bipolar affective disorder: sampling, assessment, and analytic considerations.

A series of 57 extended pedigrees with high density of bipolar affective disorder is described. Ascertainment and diagnostic procedures are documented and simulation studies to assess statistical power are carried out. The pedigrees, obtained in the US and Israel, are comprised of 1508 adult individuals with best estimate consensus diagnoses (12-71 relatives per pedigree), 490 of whom (including 401 sib pairs) meet criteria for a conservative disease definition (bipolar disorder or recurrent major depression). Cell lines have been established on 1324 of these individuals. Statistical power to detect linkage with lod score analysis, assuming autosomal dominant transmission and highly polymorphic DNA markers, is nearly 100% for alpha (proportion of linked families) = 30%, and 75% for alpha = 20%. This is the largest bipolar pedigree series reported to date; its unique features make it amenable to various gene detection techniques.

Bipolar Disorder↗
PubMed1993

Prolactin response to fenfluramine and placebo challenge following maintenance pharmacotherapy withdrawal in remitted depressed patients.

Plasma prolactin (PRL) response to fenfluramine (FF) (60 mg orally) and placebo challenge was examined in eight remitted depressed patients who were withdrawn for 14 days from maintenance pharmacotherapy with clomipramine (CMI) plus lithium carbonate (Li) (n = 6) or Li alone (n = 2), 6 months after recovering from their major depressive episode. The patients had undergone identical FF challenge tests while drug free prior to commencing treatment with electroconvulsive therapy (ECT) (n = 4) or CMI supplemented with Li (n = 4) and after completing the above treatments. PRL response to FF in the remitted, drug-free state was significantly enhanced compared to the response prior to treatment (while depressed and drug-free) and not significantly different from the response following treatment with ECT (n = 4) or CMI plus Li (n = 4) 6 months before. Other work of a similar nature supports the view that enhanced serotonergically mediated hormone release in drug-withdrawn, remitted depressives, represents a long-standing change in central serotonergic responsiveness and not a continued effect of antidepressant treatment or a manifestation of medication withdrawal.

Clomipramine↗
PubMed1993

5-HT-1A receptor-mediated effects of antidepressants.

1. Antidepressant (AD) drugs in general induce subsensitivity of behavioural functions associated with activation of 5-HT-1a receptors in animals. 2. Electrophysiological studies in animals in general indicate increased serotonergic transmission after AD administration, mediated partly by increased functioning of post-synaptic 5-HT-1a receptors in the hippocampus. 3. Binding studies have in general shown no change in 5-HT-1a receptor number either pre-or post-synaptically, while results of second messenger studies (inhibition of adenylate cyclase) indicate subsensitivity after AD administration. 4. Human studies also indicate subsensitivity of 5-HT-1a receptors after ADs.

Animals↗
PubMed1993

Factor analysis of schizophrenic symptoms and comparison of different rating scales.

This study examines the factor structure of persistent schizophrenic symptoms and compares factors derived from different rating scales. Forty stable chronic schizophrenic patients were assessed for positive and negative symptoms. In factor analysis, 3 factors could be detected: a negative factor which correlated with low drug dose and increased involuntary movements, a thought disturbance/paranoid factor which correlated negatively with extrapyramidal side effects and a delusion/hallucination factor which correlated negatively with involuntary movements. These findings support the existence of a negative factor but only partly the trichotomous division of schizophrenic symptoms. Positive symptom organisation is heterogeneous but thought disorder marks one clear dimension and non-paranoid delusions and hallucinations may mark another. The type of scale used has very significant effects on the findings.

Adolescent↗
PubMed1993

Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees.

The hypothesis that chromosomal region Xq27-28 harbours a gene for manic-depression has been a focus of interest in human genetics. X-linked inheritance of manic depressive illness has been re-examined in 3 multigeneration Israeli kindreds. Extension and re-evaluation of pedigree data, including new individuals, diagnostic follow-up, and analysis with DNA markers, shows greatly diminished support for linkage to Xq28. The peak lod scores in two of the pedigrees have dropped several lod units to clearly negative values at the RCP-F8-G6PD gene cluster. On the other hand, positive lod scores (Zmax = 2.09) are sustained in another pedigree at the same map location. None of the pedigrees show linkage to more proximal markers, including the Xq27 locus DXS98. Our analysis underscores the uncertainties in studying complex disorders.

Adult↗
PubMed1993

Trial of maintenance neuroleptic dose reduction in schizophrenic outpatients: two-year outcome.

BACKGROUND: An open trial was undertaken to assess the feasibility of reducing maintenance doses in a public clinical setting and to identify eventual predictors of outcome after dose reduction in schizophrenia. METHOD: Forty-one remitted and chronically psychotic schizophrenic outpatients were assigned, on the basis of their previously clinically determined maintenance dosages, to one of two reduced fluphenazine decanoate regimens: 35 mg/4 wk (19 patients) or 10 mg/4 wk (22 patients). Subsequently, patients were assessed, for a 2-year period, by means of the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, the Simpson-Angus Scale, and the Abnormal Involuntary Movement Scale. RESULTS: Chronically psychotic patients, who represented 74% of the high-dose group and only 14% of the low-dose group, had a significantly higher cumulative relapse rate (81%) than remitted patients (38%). For most remitted patients a dose of 10 mg of fluphenazine decanoate, injected every 4 weeks, was satisfactory. Both remitted and chronically psychotic patients displayed reductions in the severity of neuroleptic side effects. CONCLUSION: Maintenance dose reductions may be beneficial for many schizophrenic outpatients. Chronically psychotic and remitted patients maintained on lowered dosages differ significantly in the stability of their course of illness.

Adolescent↗
PubMed1992

Effect of clomipramine and lithium on fenfluramine-induced hormone release in major depression.

Prolactin (PRL) and cortisol responses to oral administration of d-1 fenfluramine hydrochloride (60 mg) and placebo were examined in patients with endogenous major depressive disorder on three separate occasions: prior to treatment with clomipramine (CMI), after 4 weeks of CMI administration (175-250) mg/day), and 3 weeks after addition of lithium (Li) carbonate (serum level 0.5-0.9 mmol) to the treatment regimen. CMI significantly increased baseline PRL levels which were further elevated following Li supplementation. PRL response to fenfluramine (minus elevated baseline PRL levels) but not to placebo, was significantly increased by CMI administration, reflected over the 6-hr time course examined and in peak minus baseline values. Following addition of Li, the degree of enhancement was diminished although the peak minus baseline value remained significant relative to the pretreatment response. Cortisol levels were not increased by fenfluramine and were not altered by CMI or CMI + Li administration. The effect of CMI extends previous observations regarding the action of antidepressant treatment on serotenergically mediated hormone release. Methodological considerations relevant to the effect of CMI + Li are discussed.

Adult↗