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B Lerer

Publications and source records attributed to B Lerer.

At least 73 records · Page 4Linked to original sources
PubMed1997

In vivo cyclic AMP responses in rat brain are not modified by chronic electroconvulsive shock.

In vivo microdialysis was used to determine the effects of chronic electroconvulsive shock (ECS), given daily for 10 days, on the cyclic AMP (cAMP) responses to noradrenaline (NA) and to forskolin in the cortex of freely-moving conscious rats. Microdialysis probes were inserted on the final day of ECS administration, and cAMP responses measured the following day. Chronic ECS did not modify the responses to either NA or forskolin. These results differ markedly from those previously obtained with incubated slices of rat brain. It is concluded that care is needed in interpreting results obtained by either ex vivo or in vitro methods.

Adrenergic alpha-Agonists↗
PubMed1997

Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects.

Only in the past decade has a role of heredity in substance abuse been established as a result of extensive twin and family studies. More recently, several candidate genes have been investigated for their possible role in alcoholism and cocaine abuse. Specific genetic factors in opioid substance abuse have not been investigated in man, although animal studies suggest that quantitative trait loci (QTLs) can be identified that predispose mice both to morphine and alcohol preference. Central dopaminergic pathways figure prominently in drug-mediated reinforcement suggesting that dopamine receptors are likely candiadates for association with substance abuse in man. In addition, we recently reported an association between a human personality trait, Novelty Seeking and the long alleles (represented chiefly by the 7-repeat) of the D4 dopamine receptor (D4DR) exon III polymorphism. The personality trait of Novelty Seeking is also more pronounced in substance abusers, who score higher in this dimension than control subjects. The twin role of dopamine receptors in mediating Novelty Seeking and drugreinforcement prompted us to examine a group of Israeli heroin addicts for prevalence of the D4DR repeat polymorphism. We now show that the 7-repeat allele is significantly over-represented in the opioid-dependent cohort and confers a relative risk of 2.46. To our knowledge this is the first report of an association between a specific genetic polymorphism and opioid addiction.

Adult↗
PubMed1997

Evidence suggestive of a locus on chromosome 5q31 contributing to susceptibility for schizophrenia in German and Israeli families by multipoint affected sib-pair linkage analysis.

Suggestive evidence for a potential susceptibility locus for schizophrenia at 5q31 was obtained in two family samples. Sample I consisted of 14 families with schizophrenia and revealed for the marker IL9 a lod score of 1.8 by two point lod score analysis. Sample II comprised 44 families including four from sample I and was ascertained in order to employ affected sib-pair analysis by identity by descent. A lod score of 1.8 around the marker D5S399 was obtained by multipoint analysis. The lod score remained positive, but decreased to 1.27 when the four families from sample I were excluded in order to use sample II as a statistically independent replication sample. We propose a susceptibility locus for schizophrenia with probably minor contribution in the pedigrees under investigation.

Chromosomes, Human, Pair 5↗
PubMed1997

Concurrent treatment of nonresistant major depression with desipramine and lithium: a double-blind, placebo-controlled study.

The objective of this study was to compare the onset, rate of antidepressant (AD) response, and treatment outcome of depressed patients treated for 5 weeks with either the concomitant administration of the tricyclic AD desipramine (DMI) and lithium carbonate (Li) or with DMI alone. In this double-blind, placebo-controlled study, 31 nonpsychotic, mild to moderately depressed outpatients (DSM-III-R unipolar or bipolar major depression) were randomly assigned to 5 weeks of treatment with DMI plus Li (N = 16) or DMI plus placebo (N = 15). Drug dosages were adjusted to achieve therapeutic plasma levels. Clinical state was rated weekly by the Hamilton Rating Scale for Depression, the Clinical Global Impression Scale, a Visual Analogue Self-Report Scale, and an adverse-effect form. Twenty-seven patients completed the study, 12 in the DMI-Li group and 15 in the DMI-placebo group. Four patients dropped out due to adverse events, all from the DMI-Li group. Both groups responded well to treatment, without a significant difference between them in the rate of response of final outcome. Sixty-seven percent (10/15) of the patients taking DMI only and 75% (9/12) of the patients taking DMI plus Li met our response criteria. The combination of DMI and Li was associated with significantly more adverse effects than DMI alone. Concurrent treatment with Li did not demonstrate an enhancement of either DMI's efficacy or its onset of action in these patients, suggesting that this strategy may not confer any additional benefit compared with DMI alone in mild to moderately depressed patients who are not preselected for nonresponse to an AD during their current depressive episode.

Adult↗
PubMed1997

Schizophrenia, chronic hospitalization and the 5-HT2C receptor gene.

Frequency of a polymorphism in the coding region of the 5-hydroxytryptamine2C (5-HT2C) receptor gene (HTR2C Xq24) was not significantly different in 122 unrelated Israeli schizophrenia patients compared with 180 control subjects matched for gender and ethnicity. However, proportion of time spent in hospital since the first admission was significantly greater in patients hemi- of homozygous for the 5-HT2Cser allele than in patients carrying other genotypes (p = 0.006). The 5-HT2Cser genotype conferred a 3.3-fold increased risk for lifetime hospitalization exceeding 10 years. Genetically determined variation in the 5-HT2C receptor may influence the clinical course and phenotypic expression of schizophrenia.

Adult↗
PubMed1997

Post-traumatic stress disorder and depression. An analysis of comorbidity.

BACKGROUND: We examined psychiatric morbidity following war-related psychic trauma, with a special focus on the depressive comorbidity of post-traumatic stress disorder (PTSD). METHOD: Subjects consisted of 60 Israeli veterans who sought psychiatric treatment 4-6 years after having been exposed to war trauma. PTSD and psychiatric comorbidity were diagnosed using the Structured Interview for PTSD and the Schedule for Affective Disorders and Schizophrenia. RESULTS: Both lifetime (100%) and current (87%) PTSD were the most prevalent disorders. Comorbidity was extensive, with major depressive disorder (MDD) most prevalent (95% lifetime, 50% current), followed by anxiety disorders, minor affective disorders, and alcoholism or drug misuse. CONCLUSIONS: Within post-traumatic psychiatric and MDD are the most prevalent disorders. In addition it appears that PTSD, although related to post-traumatic MDD beyond a mere sharing of common symptoms, is at the same time differentiated from it as an independent diagnostic category.

Adult↗
PubMed1997

"Failure to thrive" in elderly depressed patients: a new concept or a different name for an old problem?

With increasing frequency one may encounter the term "failure to thrive (FTT)" as applied to elderly patients. FTT in elderly patients is characterized by an insidious deterioration in their self-care abilities, loss of weight, loss of interest in social activities, a gradual decline in physical and/or cognitive function, and increased dependency on family members. The deterioration is beyond the expected, age-associated, "normal" decline. Depression is considered to be only one of the possible causes of FTT in the elderly. However, we suggest that the term, "FTT," as applied to elderly, depressed patients, does not appear to have intrinsic clinical value in that it describes a situation which represents an extreme form of the depressed syndrome rather than a separate clinical entity. It seems that early recognition of FTT would lead to appropriate supportive treatment being instituted before an advanced level of deterioration is reached. However, early diagnosis of the depression should have the same result and should lead to appropriate antidepressant treatment combined with vigorous nutritional intervention as well. The clinical problem which may lead to a delay in treatment of "FTT" affected elderly depressed patients is not a failure to diagnose "FTT" but a failure to diagnose depression.

Aged↗
PubMed1997

Serum neuroleptic levels during reduced dose fluphenazine decanoate maintenance therapy.

Forty-one remitted and chronically psychotic schizophrenic out-patients completed a two-year clinical trial during which they were assigned, on the basis of their clinically determined maintenance dosages, to one of two reduced, fixed-dose fluphenazine decanoate (FD) regimens: 35 mg/4 wks (19 patients) or 10 mg/4 wks (22 patients). Eighty-one percent of chronically psychotic patients, who represented 74% of the high dose group, relapsed, in comparison with only 38% of remitted patients (p < .001), who represented 86% of the low dose group. During this study serum neuroleptic levels were assessed, using the radioreceptor assay, before the administration of each FD injection and whenever a patient relapsed. Overall, 334 serum neuroleptic activity measurements were performed. Serum neuroleptic levels were detectable in all patients and were higher, although not significantly, in the 35 mg/4 wks group. The dichotomous clinical outcome of chronically psychotic and remitted patients occurred within the framework of essentially similar serum neuroleptic levels. These findings suggest that: 1) serum neuroleptic levels can be monitored during low dose FD treatment, 2) the poor maintenance therapy outcome of chronically psychotic patients cannot be accounted for by inadequate neuroleptic bioavailability, 3) a majority of remitted FD maintained patients retain their clinical response at serum neuroleptic levels lower than those initially attained at steady state.

Adult↗
PubMed1996

Cerebral hypoperfusion in medication resistant, depressed patients assessed by Tc99m HMPAO SPECT.

Functional imaging studies generally show decreased cerebral metabolism and perfusion in depressed patients relative to normal controls, although the location of the deficits varies. We used Tc99m HMPAO SPECT to compare cerebral blood flow in medication resistant, depressed patients and a normal control group. HMPAO uptake ratios (adjusted for age) were significantly lower in the depressed patients in the transaxial slices 4 cm and 6 cm above the orbitomeatal line (OML) on the left side. Examining individual regions of interest (corrected for age and multiple testing), we found significantly lower perfusion in the left superior temporal, right parietal and bilateral occipital regions in the patient group. These findings are in limited agreement with previous HMPAO SPECT studies. Methodological differences between studies, particularly variability in adjusting data for age, lead to a divergence in findings. Future research should seek to standardize protocols and data analysis in order to generate comparable results.

Adult↗
PubMed1996

Acute or chronic lithium does not affect agonist-stimulated inositol trisphosphate formation in rat brain in vivo.

Rats were given lithium either acutely by s.c. injection (4 m eq kg-1) or chronically by including 0.2% LiCl in their diet for 3 weeks. Microdialysis probes were inserted into the cortex or hippocampus, using re-usable guides, and perfused with artificial CSF. Fractions were collected beginning 18 h after the end of treatment and were analysed for inositol trisphosphate (IP3). Neither acute nor chronic treatment affected basal levels of IP3 or stimulation of IP3 formation by either carbachol or noradrenaline in the hippocampus. Similarly, neither basal nor carbachol-stimulated IP3 levels in rat cortex were affected by acute Li administration. It would appear that the reductions in these parameters previously reported by other workers using brain slices were due to inositol depletion occurring at the stage of brain slice preparation. The inositol depletion hypothesis for the mechanism of action of lithium does not therefore appear to be supported by in vivo evidence.

Animals↗
PubMed1996

Brain SPECT imaging of neuropsychiatric disorders.

Brain imaging has become an integral part of the evaluation of neurological and psychiatric disorders. Functional imaging techniques, SPECT and PET, together with structural modalities, CT and MRI, are widely employed. Functional imaging studies are routinely used in the diagnostic workup of patients with well-characterized neurological disorders, such as epilepsy and brain tumors, and have a growing role in research on psychiatric disorders without known mechanisms such as depression and schizophrenia. Furthermore, many well-defined neurological disorders manifest prominent psychiatric symptomatology which may pose difficulties in differential diagnosis. This review addresses the current knowledge of SPECT findings in patients who present with psychiatric phenomena, associated with disorders at the interface of neurology and psychiatry.

Alzheimer Disease↗
PubMed1996

Genetic relationship between dopamine transporter gene and schizophrenia: linkage and association.

This study explores the genetic relationship between schizophrenia and the dopamine transporter gene (DAT) by a variety of methods. In a sample of 48 families--each family containing at least one nuclear family with a pair of affected siblings--we performed linkage analysis using the maximum likelihood (LOD score) method as well as sibpair analysis (identity by descent). In addition, we investigated a sample of 108 nuclear families--index case affected with schizophrenia/chronic schizoaffective disorder--for association using the haplotype relative risk method. Linkage between schizophrenia and DAT using two- and three-point linkage analysis was excluded with all disease models employed. No evidence for association between haplotypes of the VNTR-probe of the DAT and schizophrenia has been detected. Thus, a contribution of the DAT gene to the genetic diathesis of schizophrenia is unlikely in the families studied.

Adult↗
PubMed1996

Interrelationship of age, depression, and central serotonergic function: evidence from fenfluramine challenge studies.

The purpose of this study was to examine the relationship between age-associated changes in central serotonergic function and abnormalities associated with major depression. Under randomized double-blind conditions, prolactin and cortisol responses to the serotonin-releasing agent d,l-fenfluramine hydrochloride (60 mg orally) and placebo were examined in 30 normal subjects (15 men, 15 women; age range 21-84 years) and 39 patients with major depressive disorder, endogenous subtype (14 men, 25 women; age range 29-72 years). In the normal subjects, a significant Age x Challenge x Time interaction was observed in the prolactin response (p = .03). This was primarily due to the elevated prolactin responses of the younger healthy women. Peak minus baseline (delta) prolactin responses were negatively correlated with age (women, p = .004; men, p = .06). In the depressed patients there was no age-related decline in prolactin response to fenfluramine. When depressed and healthy younger subjects were compared, delta prolactin responses to fenfluramine were significantly blunted in young patients with depression (p = .003) irrespective of the significant effect of gender (p = .01), but not in older depressed patients. Cortisol responses to fenfluramine did not reveal consistent effects of age, gender, or diagnosis. Age-related decline in central serotonergic function may make older individuals more vulnerable to depression and possibly render depressive episodes more frequent, more severe, and less amenable to treatment.

Adult↗
PubMed1996

Electroconvulsive therapy and resistant depression: clinical implications of seizure threshold.

BACKGROUND: Patients with major depressive disorder (MDD) were treated with electroconvulsive therapy (ECT) to determine (1) variability of initial seizure threshold, (2) factors that influence seizure threshold, (3) change in seizure threshold during the ECT course, and (4) relationship of seizure threshold to antidepressant effects. METHOD: Seizure threshold was measured by a stimulus titration technique during the first, eighth, and final ECT of medication-free patients who had MDD, endogenous subtype based on Research Diagnostic Criteria and were randomly assigned to three-times-weekly, bilateral, brief pulse ECT (N = 24) or twice-weekly ECT plus one simulated treatment per week (N = 23). Subsequent to the first ECT, stimulus intensity was 1.3 to 1.8 (median = 1.5) times threshold. The Hamilton Rating Scale for Depression (HAM-D) was the primary clinical outcome measure. RESULTS: Initial seizure threshold varied by 594%. Gender (p = .03), total strength of pre-ECT pharmacotherapy trials (p = .02), and age (p = .12) accounted for 23.9% of the variance. Threshold increased by 42% +/- 26% (p = .0001) from the first to the final ECT, and seizure duration decreased by 33% +/- 28% (p = .0001). Seizure duration and mean stimulus intensity were negatively associated over all treatments (r = -.49, p = .0003). Change in HAM-D score was related to duration of the current depressive episode (r = -.39, p = .006) and total strength of pre-ECT pharmacotherapy trials (r = -.39, p = .008), but not to seizure threshold or duration. CONCLUSION: (1) Initial seizure threshold for pulse bilateral ECT is highly variable and not yet amenable to accurate prediction. (2) Stimulus titration allows threshold to be determined on an individual basis and dosage for subsequent treatments to be defined. (3) Seizure duration is of limited value as a sole criterion for the adequacy of treatment when initial threshold is unknown and/or electrical doses that substantially exceed threshold are used. (4) With moderately suprathreshold bilateral ECT, a relationship of seizure threshold to antidepressant response is not demonstrable.

Adult↗
PubMed1996

Increased cerebral blood flow in depressed patients responding to electroconvulsive therapy.

UNLABELLED: Considerable data support the existence of impaired regional cerebral blood flow (rCBF) in major depression. We compare rCBF in depressed patients before and after electroconvulsive therapy (ECT) to define whether the impairment is a "state"-related property or a trait phenomenon. METHODS: Twenty patients with a major depressive disorder were studied by 99mTc-HMPAO brain SPECT, 2-4 days before and 5-8 days after a course of ECT. Three transaxial brain slices delineating anatomically defined regions of interest at approximately 4, 6 and 7 cm above the orbitomeatal line were used, with the average number of counts for each region of interest normalized to the area of maximal cerebellar uptake. RESULTS: Technetium-99m-HMPAO uptake significantly increased in patients who responded to ECT but remained unchanged in patients who did not respond to the treatment (response defined as a reduction of at least 60% on the Hamilton Depression Rating Scale). An inverse correlation was observed between severity of depression and HMPAO uptake, and clinical improvement was positively correlated with the increase in tracer uptake. CONCLUSIONS: These findings imply that reduced rCBF in depression, as reflected in brain 99mTc-HMPAO uptake, is a "state"-related property and is reversible by successful treatment. Technetium-99m-HMPAO uptake may serve as an objective state marker for depression, an an indicator of the severity of depression and as an objective means of evaluating response to treatment.

Brain↗
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↗