Alpha 7 Nicotinic Acetylcholine Receptor Signaling Inhibits Inflammasome Activation By Preventing Mitochondrial Dna Release,
2014
Northwell Health
Alpha 7 Nicotinic Acetylcholine Receptor Signaling Inhibits Inflammasome Activation By Preventing Mitochondrial Dna Release, B. Lu, K. Kwan, Y. A. Levine, P. S. Olofsson, H. Yang, J. H. Li, S. Joshi, H. C. Wang, U. Andersson, S. S. Chavan, K. J. Tracey
Journal Articles
The mammalian immune system and the nervous system coevolved under the influence of cellular and environmental stress. Cellular stress is associated with changes in immunity and activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, a key component of innate immunity. Here we show that alpha 7 nicotinic acetylcholine receptor (alpha 7 nAchR)-signaling inhibits inflammasome activation and prevents release of mitochondrial DNA, an NLRP3 ligand. Cholinergic receptor agonists or vagus nerve stimulation significantly inhibits inflammasome activation, whereas genetic deletion of alpha 7 nAchR significantly enhances inflammasome activation. Acetylcholine accumulates in macrophage cytoplasm after adenosine triphosphate (ATP) stimulation …
Genes And Schizophrenia: From A Festschrift Seminar Honoring William T. Carpenter Jr, Md,
2014
Hofstra Northwell School of Medicine
Genes And Schizophrenia: From A Festschrift Seminar Honoring William T. Carpenter Jr, Md, Anil Malhotra
Journal Articles
Recent data have begun to elucidate the genetic architecture of schizophrenia, as well as provide new insights into the relationships of specific genetic factors across diagnostic boundaries, with specific symptom domains, and in the prediction of antipsychotic treatment response. Not surprisingly, work conducted at the Maryland Psychiatric Research Center (MPRC), led by Dr William Carpenter, has helped to guide the thinking behind much of this work, as well as contributed valuable data toward these efforts. In this article, I will briefly summarize some of the major findings emerging from these lines of research and highlight the role of the Dr …
The Relationship Of Neurocognition And Negative Symptoms To Social And Role Functioning Over Time In Individuals At Clinical High Risk In The First Phase Of The North American Prodrome Longitudinal Study,
2014
Hofstra Northwell School of Medicine
The Relationship Of Neurocognition And Negative Symptoms To Social And Role Functioning Over Time In Individuals At Clinical High Risk In The First Phase Of The North American Prodrome Longitudinal Study, E. C. Meyer, Ricardo Carrion, Barbara Cornblatt, J. Addington, K. S. Cadenhead, T. D. Cannon, T. H. Mcglashan, D. O. Perkins, M. T. Tsuang, L. J. Seidman, +3 Additional Authors
Journal Articles
OBJECTIVES: Impaired social, role, and neurocognitive functioning are preillness characteristics of people who later develop psychosis. In people with schizophrenia, neurocognition and negative symptoms are associated with functional impairment. We examined the relative contributions of neurocognition and symptoms to social and role functioning over time in clinically high-risk (CHR) individuals and determined if negative symptoms mediated the influence of cognition on functioning. METHODS: Social, role, and neurocognitive functioning and positive, negative, and disorganized symptoms were assessed in 167 individuals at CHR for psychosis in the North American Prodrome Longitudinal Study Phase 1 (NAPLS-1), of whom 96 were reassessed at 12 …
The Relationship Between Fasting Serum Glucose And Cerebral Glucose Metabolism In Late-Life Depression And Normal Aging,
2014
Hofstra Northwell School of Medicine
The Relationship Between Fasting Serum Glucose And Cerebral Glucose Metabolism In Late-Life Depression And Normal Aging, C. M. Marano, C. I. Workman, C. H. Lyman, E. Kramer, C. R. Hermann, Y. L. Ma, V. Dhawan, T. Chaly, D. Eidelberg, G. S. Smith
Journal Articles
Evidence exists for late-life depression (LLD) as both a prodrome of and risk factor for Alzheimer's disease (AD). The underlying neurobiological mechanisms are poorly understood. Impaired peripheral glucose metabolism may explain the association between depression and AD given the connection between type 2 diabetes mellitus with both depression and AD. Positron emission tomography (PET) measures of cerebral glucose metabolism are sensitive to detecting changes in neural circuitry in LLD and AD. Fasting serum glucose (FSG) in non-diabetic young (YC; n=20) and elderly controls (EC; n=12) and LLD patients (n = 16) was correlated with PET scans of cerebral glucose metabolism …
The Content Of Attenuated Psychotic Symptoms In Those At Clinical High Risk For Psychosis,
2014
Zucker School of Medicine at Hofstra/Northwell
The Content Of Attenuated Psychotic Symptoms In Those At Clinical High Risk For Psychosis, C. Marshall, E. Denny, K. S. Cadenhead, T. D. Cannon, Barbara Cornblatt, T. H. Mcglashan, D. O. Perkins, L. J. Seidman, M. T. Tsuang, J. Addington, +2 Additional Authors
Journal Articles
Recent research has started to focus on identifying individuals who are at clinical high risk of developing psychosis as a means to try and understand the predictors and mechanisms involved in the progress to a full psychotic episode. The aim of the current study was to provide an initial description and prevalence rates of specific content found within attenuated positive symptoms. The Content of Attenuated Positive Symptoms (CAPS) codebook was used by independent raters to determine the presence of content within a sample of written vignettes. Krippendorff's alpha was used to determine inter-rater reliability. Overall, the majority of items fell …
Bdnf Val66met Polymorphism And Antipsychotic-Induced Tardive Dyskinesia Occurrence And Severity: A Meta-Analysis,
2014
Northwell Health
Bdnf Val66met Polymorphism And Antipsychotic-Induced Tardive Dyskinesia Occurrence And Severity: A Meta-Analysis, I. Miura, Jianping Zhang, M. Nitta, T. Lencz, John Kane, Anil Malhotra, H. Yabe, Christoph Correll
Journal Articles
Background: Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD. Methods: Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNF Val66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess the effects of BDNF Val66Met polymorphism on TD occurrence. Additionally, pooled standardized mean differences (Hedges'g) were calculated to assess the effects on Abnormal Involuntary Movement Scale (AIMS) total score. Results: Out of 699 potentially eligible …
Excess Of Homozygosity In The Major Histocompatibility Complex In Schizophrenia,
2014
Northwell Health
Excess Of Homozygosity In The Major Histocompatibility Complex In Schizophrenia, S. Mukherjee, S. Guha, M. Ikeda, N. Iwata, Anil Malhotra, I. Pe'er, A. Darvasi, T. Lencz
Journal Articles
Genome-wide association studies (GWAS) in schizophrenia have focused on additive allelic effects to identify disease risk loci. In order to examine potential recessive effects, we applied a novel approach to identify regions of excess homozygosity in an ethnically homogenous cohort: 904 schizophrenia cases and 1640 controls drawn from the Ashkenazi Jewish (AJ) population. Genome-wide examination of runs of homozygosity identified an excess in cases localized to the major histocompatibility complex (MHC). To refine this signal, we used the recently developed GERMLINE algorithm to identify chromosomal segments shared identical-by-descent (IBD) and compared homozygosity at such segments in cases and controls. We …
Matrics Cognitive Consensus Battery (Mccb) Performance In Children, Adolescents, And Young Adults,
2014
Northwell Health
Matrics Cognitive Consensus Battery (Mccb) Performance In Children, Adolescents, And Young Adults, G. C. Nitzburg, P. Derosse, K. E. Burdick, B. D. Peters, C. B. Gopin, Anil Malhotra
Journal Articles
Background: Neurodevelopmental models of schizophrenia suggest that cognitive deficits may be observed during childhood and adolescence, long before the onset of psychotic symptoms. Elucidating the trajectory of normal cognitive development during childhood and adolescence may therefore provide a basis for identifying specific abnormalities related to the development of schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB), which was designed for use in clinical trials targeting cognitive deficits most common in schizophrenia, may provide a mechanism to understand this trajectory. To date, however, there is no performance data for the MCCB in healthy children and adolescents. The present study sought to establish …
Comparative Effectiveness Of Risperidone Long-Acting Injectable Vs First-Generation Antipsychotic Long-Acting Injectables In Schizophrenia: Results From A Nationwide, Retrospective Inception Cohort Study,
2014
Hofstra Northwell School of Medicine
Comparative Effectiveness Of Risperidone Long-Acting Injectable Vs First-Generation Antipsychotic Long-Acting Injectables In Schizophrenia: Results From A Nationwide, Retrospective Inception Cohort Study, J. Nielsen, S. O. Jensen, R. B. Friis, J. B. Valentin, Christoph Correll
Journal Articles
Objective: To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI). Methods: Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinician's/patient's choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. Results: Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI …
Sentia: A Systematic Online Monitoring Registry For Children And Adolescents Treated With Antipsychotics,
2014
Hofstra Northwell School of Medicine
Sentia: A Systematic Online Monitoring Registry For Children And Adolescents Treated With Antipsychotics, I. Palanca-Maresca, B. Ruiz-Antoran, G. Centeno-Soto, S. Jimenez-Fernandez, L. Garcia-Murillo, A. Siles, S. Villagra, H. Blasco-Fontecilla, L. Iruela-Cuadrado, Christoph Correll, +2 Additional Authors
Journal Articles
INTRODUCTION: Despite drastic increases in antipsychotic prescribing in youth, data are still limited regarding their safety in this vulnerable population, necessitating additional tools for capturing long-term, real world data. METHODS: We present SENTIA (SafEty of NeurolepTics in Infancy and Adolescence; https://SENTIA.es), an online registry created in 2010 to track antipsychotic adverse effects in Spanish youthsociodemographic, diagnostic and treatment characteristics, past personal medical/psychiatric history, healthy lifestyle habits and treatment adherence. Additionally, efficacy and adverse effect data are recorded including the Children's Global Assessment Scale; Clinical Global Impressions scale for Severity and Improvement, the Safety Monitoring Uniform Report Form, Simpson-Angus Scale, Abnormal …
Quetiapine Versus Aripiprazole In Children And Adolescents With Psychosis - Protocol For The Randomised, Blinded Clinical Tolerability And Efficacy Of Antipsychotics (Tea) Trial,
2014
Hofstra Northwell School of Medicine
Quetiapine Versus Aripiprazole In Children And Adolescents With Psychosis - Protocol For The Randomised, Blinded Clinical Tolerability And Efficacy Of Antipsychotics (Tea) Trial, A. K. Pagsberg, P. Jeppesen, D. G. Klauber, K. G. Jensen, D. Ruda, M. Stentebjerg-Olesen, P. Jantzen, S. Rasmussen, Christoph Correll, B. Fagerlund, +19 Additional Authors
Journal Articles
Background: The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. Methods/Design: The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naive or treated for a limited period are, 1:1 randomised to a 12-week, double-blind intervention …
Age-Related Differences In White Matter Tract Microstructure Are Associated With Cognitive Performance From Childhood To Adulthood,
2014
Northwell Health
Age-Related Differences In White Matter Tract Microstructure Are Associated With Cognitive Performance From Childhood To Adulthood, B. D. Peters, T. Ikuta, P. Derosse, M. John, K. E. Burdick, P. Gruner, D. M. Prendergast, Philip Szeszko, Anil Malhotra
Journal Articles
Background: Age-related differences in white matter tract microstructure have been well established across the life span. In the present cross-sectional study, we examined whether these differences are associated with neurocognitive performance from childhood to late adulthood. Methods: Diffusion tensor imaging was performed in 296 healthy subjects aged 8 to 68 years (mean = 29.6, SD = 14.6). The corpus callosum, two projection tracts, and five association tracts were traced using probabilistic tractography. A neurocognitive test battery was used to assess speed of processing, attention, spatial working memory, verbal functioning, visual learning, and executive functioning. Linear mediation models were used to …
Antipsychotic Treatment For Children And Adolescents With Schizophrenia Spectrum Disorders: Protocol For A Network Meta-Analysis Of Randomised Trials,
2014
Hofstra Northwell School of Medicine
Antipsychotic Treatment For Children And Adolescents With Schizophrenia Spectrum Disorders: Protocol For A Network Meta-Analysis Of Randomised Trials, A. K. Pagsberg, S. Tarp, D. Glintborg, A. D. Stenstrom, A. Fink-Jensen, Christoph Correll, R. Christensen
Journal Articles
Introduction: Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative effectiveness studies in children and adolescents are limited in number and size, and only a few meta-analyses based on conventional methodologies have been conducted. Methods and analyses: We will conduct a network meta-analysis of all randomised controlled trials (RCTs) that evaluate antipsychotic therapies for EOS to determine which compounds are efficacious, and to determine the relative efficacy and safety of these treatments …
Brain White Matter Development Is Associated With A Human-Specific Haplotype Increasing The Synthesis Of Long Chain Fatty Acids,
2014
Northwell Health
Brain White Matter Development Is Associated With A Human-Specific Haplotype Increasing The Synthesis Of Long Chain Fatty Acids, B. D. Peters, A. N. Voineskos, P. R. Szeszko, T. A. Lett, P. Derosse, S. Guha, K. H. Karlsgodt, M. John, T. Lencz, A. K. Malhotra, +4 Additional Authors
Journal Articles
The genetic and molecular pathways driving human brain white matter (WM) development are only beginning to be discovered. Long chain polyunsaturated fatty acids (LC-PUFAs) have been implicated in myelination in animal models and humans. The biosynthesis of LC-PUFAs is regulated by the fatty acid desaturase (FADS) genes, of which a human-specific haplotype is strongly associated with omega-3 and omega-6 LC-PUFA concentrations in blood. To investigate the relationship between LC-PUFA synthesis and human brain WM development, we examined whether this FADS haplotype is associated with age-related WM differences across the life span in healthy individuals 9-86 years of age (n = …
Towards A Psychosis Risk Blood Diagnostic For Persons Experiencing High-Risk Symptoms: Preliminary Results From The Napls Project,
2014
Hofstra Northwell School of Medicine
Towards A Psychosis Risk Blood Diagnostic For Persons Experiencing High-Risk Symptoms: Preliminary Results From The Napls Project, D. O. Perkins, C. D. Jeffries, J. Addington, C. E. Bearden, K. S. Cadenhead, T. D. Cannon, Barbara Cornblatt, D. H. Mathalon, S. W. Woods, R. Heinssen, +4 Additional Authors
Journal Articles
INTRODUCTION: A barrier to preventative treatments for psychosis is the absence of accurate identification of persons at highest risk. A blood test that could substantially increase diagnostic accuracy would enhance development of psychosis prevention interventions. METHODS: The North American Prodrome Longitudinal Study project is a multisite endeavor that aims to better understand predictors and mechanisms for the development of psychosis. In this study, we measured expression of plasma analytes reflecting inflammation, oxidative stress, hormones, and metabolism. A "greedy algorithm" selected analytes that best distinguished persons with clinical high-risk symptoms who developed psychosis (CHR-P; n = 32) from unaffected comparison (UC) …
Early Specific Cognitive-Behavioural Psychotherapy In Subjects At High Risk For Bipolar Disorders: Study Protocol For A Randomised Controlled Trial,
2014
Hofstra Northwell School of Medicine
Early Specific Cognitive-Behavioural Psychotherapy In Subjects At High Risk For Bipolar Disorders: Study Protocol For A Randomised Controlled Trial, A. Pfennig, K. Leopold, A. Bechdolf, C. U. Correll, M. Holtmann, M. Lambert, C. Marx, T. D. Meyer, G. Juckel, M. Bauer, +5 Additional Authors
Journal Articles
Background: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their …
Delineation Of Hippocampal Subregions Using T1-Weighted Magnetic Resonance Images At 3 Tesla,
2014
Northwell Health
Delineation Of Hippocampal Subregions Using T1-Weighted Magnetic Resonance Images At 3 Tesla, K. Rhindress, T. Ikuta, R. Wellington, A. K. Malhotra, P. Szeszko
Journal Articles
Although several novel approaches for hippocampal subregion delineation have been developed, they need to be applied prospectively and may be limited by long scan times, the use of high field (>3T) imaging systems, and limited reliability metrics. Moreover, the majority of MR imaging data collected to date has employed a T1-weighted acquisition, creating a critical need for an approach that provides reliable hippocampal subregion segmentation using such a contrast. We present a highly reliable approach for the identification of six subregions comprising the hippocampal formation from MR images including the subiculum, dentate gyrus/cornu Ammonis 4 (DG/CA4), entorhinal cortex, fimbria, …
Biological Insights From 108 Schizophrenia-Associated Genetic Loci,
2014
Hofstra Northwell School of Medicine
Biological Insights From 108 Schizophrenia-Associated Genetic Loci, S. Ripke, B. M. Neale, A. Corvin, J. T. R. Walters, K. H. Farh, T. Lencz, A. K. Malhotra, Consortium Psychiat Genomics, Conso Psychosis Endophenotypes Int, Consor Wellcome Trust Case-Control, +292 Additional Authors
Journal Articles
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and …
Child And Adolescent Psychiatrists' Attitudes And Practices Prescribing Second Generation Antipsychotics,
2014
Hofstra Northwell School of Medicine
Child And Adolescent Psychiatrists' Attitudes And Practices Prescribing Second Generation Antipsychotics, A. M. Rodday, S. K. Parsons, C. U. Correll, A. S. Robb, B. T. Zima, T. S. Saunders, L. K. Leslie
Journal Articles
Objective: The purpose of this study was to examine psychiatrists' attitudes and practices in prescribing second-generation antipsychotics (SGA) to children and adolescents (referred to here as "children") and identify factors associated with off-label SGA use. Methods: A survey was mailed to a national, randomly selected sample of 1600 child and adolescent psychiatrists identified by the American Medical Association. Multivariable logistic regression was used to identify factors, including psychiatrists' characteristics, practice characteristics, and psychiatrists' attitudes, that are associated with off-label SGA use (i.e., SGAs used in children with attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, or nonbipolar mood disorders). Results: …
Perceived Discrimination In Those At Clinical High Risk For Psychosis,
2014
Hofstra Northwell School of Medicine
Perceived Discrimination In Those At Clinical High Risk For Psychosis, M. M. Saleem, J. Stowkowy, K. S. Cadenhead, T. D. Cannon, B. Cornblatt, T. H. Mcglashan, D. O. Perkins, L. J. Seidman, M. T. Tsuang, S. W. Woods, +2 Additional Authors
Journal Articles
Aim: There is evidence to suggest that perceived discrimination may be associated with psychosis. Less is known about its potential impact on those at clinical high risk (CHR) for psychosis. The aim of this study was to determine the prevalence of perceived discrimination in a CHR sample and its possible relationship to attenuated positive symptoms and negative self-beliefs. Methods: Participants were 360 CHR individuals and 180 healthy controls. Assessments included a self-report measure of perceived discrimination, the Scale of Prodromal Symptoms and the Brief Core Schema Scale. Results: CHR participants reported significantly more perceived discrimination. Perceived discrimination was significantly associated …
