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B Lerer

Publications and source records attributed to B Lerer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Potential linkage for schizophrenia on chromosome 22q12-q13: a replication study.

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al. [1994: Am J Med Genet 54:36-43], we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Zmax = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a nonparametric method, sib pair analysis, a P value of 0.068 corresponding to a lod score of 0.48 was obtained for this marker. This finding, together with those of Pulver et al. [1994: Am J Med Genet 54:36-43] and Coon et al. [1994: Am J Med Genet 54:72-79], is suggestive of a genetic factor in this region, predisposing for schizophrenia in a subset of families. Further studies using nonparametric methods should be conducted in order to clarify this point.

Chromosomes, Human, Pair 22↗
PubMed1995

Genetic linkage analysis of schizophrenia using chromosome 11q13-24 markers in Israeli pedigrees.

It is generally agreed that there is a genetic component in the etiology of schizophrenia which may be tested by the application of linkage analysis to multiply-affected families. One genetic region of interest is the long arm of chromosome 11 because of previously reported associations of genetic variation in this region with schizophrenia, and because of the fact that it contains the locus for the dopamine D2 receptor gene. In this study we have examined the segregation of schizophrenia with microsatellite dinucleotide repeat DNA markers along chromosome 11q in 5 Israeli families multiply-affected for schizophrenia. The hypothesis of linkage under genetic homogeneity of causation was tested under a number of genetic models. Linkage analysis provided no evidence for significant causal mutations within the region bounded by INT and D11S420 on chromosome 11q. It is still possible, however, that a gene of major effect exists in this region, either with low penetrance or with heterogeneity.

Chromosome Mapping↗
PubMed1995

Constitutive heterochromatin of chromosome 1 and Duffy blood group alleles in schizophrenia.

Cytogenetic analysis was carried out in unrelated schizophrenic patients, unrelated controls and patients and family members in multiplex families. The size distribution of chromosome 1 heterochromatic region (1qH, C-band variants) among 21 unrelated schizophrenic patients was different from that found in a group of 46 controls. The patient group had 1qH variants of smaller size than the control group (P < 0.01). Incubation of phytohemagglutinin-treated blood lymphocytes with 5-azacytidine (which causes decondensation and extension of the heterochromatin) led to a lesser degree of heterochromatin decondensation in a group of patients than in the controls (7 schizophrenic, 9 controls, P < 0.01). The distribution of phenotypes of Duffy blood group system [whose locus is linked to the 1qH region (Donahue et al.: Proc Natl Acad Sci USA 61:949-955, 1968; Rouleau et al.: Genomics 7:313-318, 1990)] among 28 schizophrenic patients was also different from that in the general population. Cosegregation of schizophrenia with a 1qH (C-band) variant and Duffy blood group allele was observed in one of six multiplex families. The overall results suggest that alterations within the Duffy/1qH region are involved in schizophrenia in some cases. This region contains the locus of D5 dopamine receptor pseudogene 2 (1q21.1), which is transcribed in normal lymphocytes (Takahashi et al.: FEBS Lett 314:23-25, 1992).

Adolescent↗
PubMed1995

Onset and time course of antidepressant action: psychopharmacological implications of a controlled trial of electroconvulsive therapy.

Onset and time course of antidepressant effect were examined in 47 patients with major depressive disorder who had been randomly assigned to twice weekly bilateral, brief pulse electroconvulsive therapy plus one simulated treatment per week (ECTx2) or to a three times weekly schedule of administration (ECTx3). Rapid improvement was observed in the ECTx3 group in whom the number of real ECTs to 30% reduction on the Hamilton Depression Scale (HAM-D) was 3.2 +/- 1.90, administered over 7.3 +/- 4.43 days and to 60% reduction, 5.9 +/- 3.09 real ECTs over 13.7 +/- 7.21 days. Among the responders in both groups combined, 24.3 +/- 29.58% of the overall improvement in HAM-D was contributed by the first real ECT, 60.9 +/- 28.13% by the first four real ECTs and 91.6 +/- 25.82% by the first eight. Although 85.3% of the responders had reached 60% HAM-D improvement after eight ECTs, a clinically significant minority (14.7%) responded later in the course (ECT 9-12). However, response was predictable on the basis of symptomatic improvement (30% on the HAM-D) by the sixth real ECT. Thirty-three out of 34 responders would have been correctly identified by this criterion and only 2 out of 13 non-responders mis-identified (P < 0.000001). Once achieved, the antidepressant effect was stable, without continuation pharmacotherapy, until 1 week after the last treatment and on lithium carbonate (Li) or Li plus clomipramine for a further 3 weeks. These findings confirm the clinical impression that ECT is a rapidly effective treatment for major depression with a shorter latency than generally reported for antidepressant drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Complex effects of age and gender on hypothermic, adrenocorticotrophic hormone and cortisol responses to ipsapirone challenge in normal subjects.

The effects of a challenge dose of the 5-HT1A agonist, ipsapirone (0.3 mg per kg body weight), or placebo on body temperature and on adrenocorticotrophic hormone (ACTH) and cortisol release, were examined in 30 normal subjects (14 males, 19-74 years and 16 females, 22-69 years) using a randomized, double blind design. Irrespective of age or gender, ipsapirone induced a significant reduction in body temperature relative to placebo and a significant increase in ACTH and cortisol release. Maximal temperature reduction by ipsapirone was significantly blunted in older subjects and was inversely related to age. There was no gender difference in the hypothermic response to ipsapirone. ACTH and cortisol responses showed an opposite impact of aging in males and females. Whereas both responses diminished with age in male subjects, they increased with age in females. The cortisol response of older females was significantly larger than that of all the other subjects. Adverse effects of ipsapirone were also more marked in elderly females and were correlated with ACTH and cortisol responses. These findings should be taken into consideration in the use of ipsapirone and other 5-HT1A agonists as challenge procedures for studying central serotonergic function in depression and other disorders. Careful matching of control and experimental subjects is indicated so as to avoid spurious results which reflect the effects of age and gender rather than the pathophysiology of the disorders being investigated.

Adrenocorticotropic Hormone↗
PubMed1995

Frequency of positive family history in bipolar patients in a catchment-area population.

1. Major family studies of bipolar disorder report the frequency of affective disorder among probands' relatives, but do not usually report the frequency of a positive family history among probands. A single previous study was not population based. 2. The Division of Psychiatry of Ben Gurion University provides virtually all psychiatric services for a catchment area of 300,000 people. The authors reviewed the charts of all 236 treated bipolar I patients in 1991, and interviewed 177 of them with a modified FH-RDC. 3. 48% of probands had a family history of mental illness. 4. However, the present methods of ascertainment may have been insufficiently sensitive.

Bipolar Disorder↗
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↗