Publications (367) View all
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Article: Neonatal stress modulates sickness behavior: Role for proinflammatory cytokines.
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ABSTRACT: Neonatal stress increased the duration and augmented symptoms of sickness behavior induced by influenza virus infection or endotoxin challenge in mice. Since proinflammatory cytokines were implicated in sickness behavior, the present study sought to determine the effect of neonatal stress on cytokines-induced sickness behavior and on proinflammatory cytokine secretion. Data indicate that separation of mouse pups from the dams at an early age (maternal separation, MSP) increased the duration and augmented some of the symptoms of sickness behavior induced by proinflammatory cytokines. In addition, MSP partially suppressed cytokine and corticosterone secretion in response to endotoxin administration. These data may suggest that MSP increased sensitivity to the effects of proinflammatory cytokines on sickness behavior following an immune challenge.Journal of neuroimmunology 03/2013; · 2.84 Impact Factor -
Article: In vitro catabolic effect of protoporphyrin IX in human osteoblast-like cells: possible role of the 18 kDa mitochondrial translocator protein.
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ABSTRACT: In several pathological conditions, when conversion of Protoporphyrin (PP)IX into heme is impaired, a toxic accumulation of PPIX might occur. PPIX has been found to have affinity to the mitochondrial Translocator Protein 18 kDa. Since it is known that TSPO is abundant in human osteoblast cells, thus we assumed that PPIX can affect cellular functions via interactions with TSPO in these cells. Therefore we aimed to study the metabolic responses of human osteoblast to a high (10-5M) concentration of PPIX in vitro. We found that in primary culture of human osteoblast-like cells cell numbers decreased following exposure to PPIX(10-5M). Cellular [18F]-FDG incorporation, mitochondrial mass, ATP content were suppressed, and ΔΨm collapsed. Lactate dehydrogenase activity was enhanced in culture media, indicating overall cell death, while no increase in apoptotic levels was observed. Cellular proliferation was not affected. Protein expression of TSPO, VDAC 1, and hexokinase 2 decreased, although the synthesis of mRNA for hexokinase 2 increased. Thus, PPIX(10-5M) has a cytotoxic effect on human osteoblast-like cell in vitro. Since these cells remain viable following exposure to another TSPO ligand, PK 11195 (10-5M), as observed previously by us, the mode of action of PPIX on osteoblast-like cells is not identical to that of PK 11195. Accordingly pathological accumulation of PPIX may cause necrosis of osteoblasts leading to bone mass loss. We show that this phenomenon is unrelated to iron overload.Journal of Bioenergetics 03/2013; · 2.81 Impact Factor -
Article: Additive Effects of 5-HTTLPR (Serotonin Transporter) and Tryptophan Hydroxylase 2 G-703T Gene Polymorphisms on the Clinical Response to Citalopram among Children and Adolescents with Depression and Anxiety Disorders.
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ABSTRACT: Abstract Objective: The purpose of this study was to evaluate the association between polymorphisms in two serotonin pathway genes and the clinical response to citalopram among children and adolescents with depression and/or anxiety disorders. Methods: Eighty-three children and adolescents with depression and/or anxiety disorders were treated with citalopram for 8 weeks. We assessed the association between the response to citalopram and polymorphisms in the tryptophan hydroxylase-2 (TPH2) and the serotonin transporter gene. The polymorphisms included single nucleotide polymorphisms (SNPs) in the transcriptional control region (G-703T) of the TPH2 gene and the serotonin transporter gene-linked promoter region (5-HTTLPR). Results: Fifty patients of the 83 (60.2%) achieved satisfactory response (Clinical Global Impressions - Improvement ≤2). We observed an additive effect of the two genes on the clinical response to citalopram. Patients carrying the combination of TPH2 -703G and the 5-HTTLPR L alleles were the most likely to respond (80%). In contrast, patients carrying the combination of TPH2 -703T and the 5-HTTLPR S alleles were least likely to respond (31%). The other patients (with -703G/5-HTTLPR S and -703T/5-HTTLPR L alleles) showed intermediate response (67%). Conclusions: This finding suggests that 5-HTTLPR and TPH2 genes may act in concert to modulate the clinical response to citalopram among children and adolescents with depression and/or anxiety disorders.Journal of child and adolescent psychopharmacology 03/2013; 23(2):117-22. · 2.59 Impact Factor -
Article: Reboxetine treatment for autistic spectrum disorder of pediatric patients with depressive and inattentive/hyperactive symptoms: an open-label trial.
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ABSTRACT: Reboxetine is a norepinephrine reuptake inhibitor that may be useful in treating pediatric depression as well as attention-deficit/hyperactivity disorder (ADHD). Both are often comorbid with autistic spectrum disorder (ASD). We evaluated the effectiveness of reboxetine treatment in pediatric patients with ASD with symptoms of depression and ADHD. Eleven adolescent patients with ASD (9 boys and 2 girls, aged 12.2 ± 3.6 years) with depressive and ADHD symptoms were treated with reboxetine (maximal dose, 4 mg/d) in an open-label trial during a 12-week period. The severity of depressive and ADHD symptoms was assessed by the Child Depression Rating Scale (CDRS) and Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), respectively. Significant, but modest, decreases in the severity of depressive symptoms (CDRS before vs after scores: 65.5 ± 10.8 vs 58.3 ± 8.2; paired t test, 3.1; df, 10; P =0.01) and ADHD symptoms (Attention Deficit/Hyperactivity Disorder Rating Scale before vs after: 36.4 ± 5 vs 32.8 ± 5; paired-t test, 2.94; df, 10; P = 0.015) were obtained after reboxetine treatment. The patients (n = 5) with high baseline scores of CDRS (T score >75) showed a trend toward larger response to reboxetine than those (n = 6) with low (T score <75) basal CDRS scores (Δ, 12.8 ± 5.4 vs 2.3 ± 5.2; P = 0.07).A significant positive correlation was found between the changes in the total scores of the depression and the ADHD severity (Spearman correlation r = 0.65 [95% confidence interval, 0.09-0.9]; n = 11; P = 0.029). Most of the patients (approximately 90%) reported tolerable adverse effects. Reboxetine treatment may reduce, modestly but significantly, depressive and ADHD symptoms in adolescents with ASD. High rate of adverse effects requires close monitoring.Clinical neuropharmacology 03/2013; 36(2):37-41. · 2.35 Impact Factor -
Article: Mental disorders in primary care in Israel: prevalence and risk factors.
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ABSTRACT: OBJECTIVE: Psychiatric morbidity is common among patients in primary care services and leads to disability and increased use of medical services. Comparison of primary care and community prevalence data is of interest in relation to the health services planning for mental disorders. The aim of the present study was to measure prevalence of mental disorders in six primary care clinics in Israel and to assess risk factors for these disorders. METHOD: Prevalence of mental disorders was measured in a sample of 2,948 primary care consecutive attendees, using two-stage stratified sampling with the General Health Questionnaire 12 (GHQ-12) and the Composite International Diagnostic Interview (CIDI). RESULTS: A high rate (46.3 %) of current mental disorders was found, with rates of current depressive episode, generalized anxiety disorder, somatization disorder, and neurasthenia being relatively high in comparison with rates in other countries. Low education was a risk factor for all categories of disorders, unemployment a risk factor for depressive disorders, and parenthood was protective for most categories of disorders. CONCLUSIONS: High rates of mental disorders were found in this Israeli primary care sample as compared to other countries, while in the community the rates were midrange as compared to other countries, pointing to a relatively higher use of primary care services by patients with mental disorders in Israel than in other countries.Social Psychiatry 01/2013; · 2.05 Impact Factor
