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Koenigsberg H.W.,James ters Medical Center
Journal of personality disorders | Year: 2010

Affective instability is a prominent feature of a wide variety of psychiatric and neurological disorders, yet it has not been systematically studied. It encompasses a number of distinct phenomena, including: (1) frequent affective category shifts, (2) disturbances in affect intensity, (3) excessively rapid emotion rise-times, (4) delayed return to emotional baseline, (5) excessive reactivity to psychosocial cues, (6) endogenously driven, random, chaotic or rapid-cycling changes, and (7) overdramatic expression. To further clarify the construct of affective instability, this article examines the manifestations of affective instability in a range of psychiatric and neurologic disorders, reviews relevant neurobiological and psychological emotion regulatory processes, and considers the psychology of affective instability.

Podolak E.,James ters Medical Center
International Journal of Adolescent Medicine and Health | Year: 2015

Suicide is a major public health problem and the 10th leading cause of death in the United States. Due to low base rates and the numerous comorbid risk factors associated with suicide, accurate prediction is difficult. This is particularly true for adolescents and young adults. In this article, some associated risk factors are discussed in the context of two high-risk populations (young adult prison inmates and young adult veterans) and several recommendations are made for conducting suicide risk assesments. General prescriptions for intervention are also outlined with the goal of reducing overly defensive practice and increasing the likelihood that high-risk individuals will receive effective intervention. Finally, several suggestions for future research are made. © 2015 by De Gruyter.

Horesh Y.,Weizmann Institute of Science | Katsel P.,Mount Sinai School of Medicine | Haroutunian V.,Mount Sinai School of Medicine | Haroutunian V.,James ters Medical Center | Domany E.,Weizmann Institute of Science
European Journal of Neurology | Year: 2011

Background: Alzheimer's disease and Schizophrenia are two common diseases of the brain with significant differences in neuropathology, etiology and symptoms. This dissimilarity in the two diseases makes a comparison of the two ideal for detecting molecular substrates that are common to brain disorders in general. Methods: In this study, we compared gene expression profiles across multiple brain areas, taken postmortem from patients with well-characterized Alzheimer's disease and Schizophrenia, and from cognitively normal control group with no neuro- or psychopathology. Results: Although the totality of gene expression changes in the two diseases is dissimilar, a subset of genes appears to play a role in both diseases in specific brain regions. We find at Brodmann area 22, the superior temporal gyrus, a statistically significant number of genes with apparently disregulated expression in both diseases. Furthermore, we found genes that differentiate the two diseases from the control across multiple brain regions, and note that these genes were usually down-regulated. Brodmann area 8, part of the superior frontal cortex, is relatively abundant with them. Conclusion: We show overwhelming statistical evidence for Alzheimer's and Schizophrenia sharing a specific molecular background at the superior temporal gyrus. We suggest that impairment of the regulation of autophagy pathway is shared, in BA 22, by the two diseases. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

Ghalib R.H.,The Texas Institute | Rustgi V.K.,Metropolitan Research | Martorell C.,The Research Institute | Everson G.T.,University of Colorado at Denver | And 16 more authors.
The Lancet Infectious Diseases | Year: 2012

Background: Several direct-acting antivirals for chronic hepatitis C virus (HCV) infection are available, but they are limited by tolerability and dosing schedules. Once-daily daclatasvir, a potent NS5A replication complex inhibitor, was generally well tolerated in phase 1 studies. We assessed daclatasvir in combination with pegylated interferon (peginterferon) and ribavirin for chronic HCV. Methods: In this double-blind, parallel-group, dose-finding, phase 2a study, treatment-naive patients with HCV genotype-1 infection (without cirrhosis) from 14 centres in the USA and France were randomly assigned (1:1:1:1) to receive peginterferon alfa-2a (180 μg per week) and ribavirin (1000-1200 mg daily) plus placebo or 3 mg, 10 mg, or 60 mg of daclatasvir taken once daily, for 48 weeks. The primary efficacy endpoint was undetectable HCV RNA at 4 weeks and 12 weeks after start of treatment (extended rapid virological response, eRVR). Analysis was of all participants who received one dose of study drug. We used descriptive analyses to compare results. This study is registered with. ClinicalTrials.gov, number. NCT00874770. Findings: 48 patients were randomly assigned (12 per group); all received at least one dose of study drug. 15 patients discontinued treatment before week 48. Five of 12 patients (42%, 80% CI 22-64%) who received 3 mg daclatasvir achieved eRVR, compared with ten of 12 (83%, 61-96%) who received 10 mg daclatasvir, nine of 12 (75%, 53-90%) who received 60 mg daclatasvir, and one of 12 (8%, 1-29%) who received placebo. Adverse events and discontinuations as a result of adverse events occurred with similar frequency across groups. Interpretation: Daclatasvir seems to be a potent NS5A replication complex inhibitor that increases the antiviral potency of peginterferon and ribavirin. Our findings support the further development of regimens containing 60 mg daclatasvir for the treatment of chronic genotype-1 HCV infection. Funding: Bristol-Myers Squibb. © 2012 Elsevier Ltd.

Hertzberg L.,Weizmann Institute of Science | Hertzberg L.,Tel Aviv University | Katsel P.,Mount Sinai School of Medicine | Roussos P.,Mount Sinai School of Medicine | And 3 more authors.
Schizophrenia Research | Year: 2015

The number of Genome Wide Association Studies (GWAS) of schizophrenia is rapidly growing. However, the small effect of individual genes limits the number of reliably implicated genes, which are too few and too diverse to perform reliable pathway analysis; hence the biological roles of the genes implicated in schizophrenia are unclear. To overcome these limitations we combine GWAS with genome-wide expression data from human post-mortem brain samples of schizophrenia patients and controls, taking these steps: 1) Identify 36 GWAS-based genes which are expressed in our dataset. 2) Find a cluster of 19 genes with highly correlated expression. We show that this correlation pattern is robust and statistically significant. 3) GO-enrichment analysis of these 19 genes reveals significant enrichment of ion channels and calcium-related processes. This finding (based on analyzing a small number of coherently expressed genes) is validated and enhanced in two ways: First, the emergence of calcium channels and calcium signaling is corroborated by identifying proteins that interact with those encoded by the cluster of 19. Second, extend the 19 cluster genes into 1028 genes, whose expression is highly correlated with the cluster's average profile. When GO-enrichment analysis is performed on this extended set, many schizophrenia related pathways appear, with calcium-related processes enriched with high statistical significance. Our results give further, expression-based validation to GWAS results, support a central role of calcium-signaling in the pathogenesis of schizophrenia, and point to additional pathways potentially related to the disease. © 2015 Elsevier B.V.

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