Adding Insult To Injury: Childhood And Adolescent Risk Factors For Psychosis Predict Lower Fractional Anisotropy In The Superior Longitudinal Fasciculus In Healthy Adults,
2014
Northwell Health
Adding Insult To Injury: Childhood And Adolescent Risk Factors For Psychosis Predict Lower Fractional Anisotropy In The Superior Longitudinal Fasciculus In Healthy Adults, P. Derosse, T. Ikuta, B. D. Peters, K. Karlsgodt, P. Szeszko, A. K. Malhotra
Journal Articles
Although epidemiological studies provide strong support for demographic and environmental risk factors in psychotic disorders, few data examine how these risk factors relate to the putative aberrant neurodevelopment associated with illness. The present study examined how the accumulation of risk factors including low IQ, low parental socioeconomic status (SES), history of adolescent cannabis use and childhood trauma, and high levels of subclinical psychotic-like experiences (PLEs) contributed to aberrant neurodevelopmental outcomes in 112 otherwise healthy adults recruited from the community. Participants were studied with diffusion tensor imaging (DTI), and voxel-wise statistical analysis of fractional anisotropy (FA) using tractbased spatial statistics (TBSS) …
The Relation Between Childhood Maltreatment And Psychosis In Patients With Schizophrenia And Non-Psychiatric Controls,
2014
Northwell Health
The Relation Between Childhood Maltreatment And Psychosis In Patients With Schizophrenia And Non-Psychiatric Controls, P. Derosse, G. C. Nitzburg, B. Kompancaril, A. K. Malhotra
Journal Articles
Several lines of evidence suggest that childhood maltreatment is associated with an increased risk for both psychotic disorders and subclinical psychotic-like experiences in the general population. Few studies, however, have sought to examine whether the strength of this relationship is comparable across patient and non-patient groups. The present study sought to compare the strength of the association between childhood maltreatment and self-reported psychotic symptoms in 447 healthy adult volunteers and 184 stable outpatients with schizophrenia or schizoaffective disorder. Strong positive correlations between childhood maltreatment and self-reported symptoms were observed in both groups. Although patients scored significantly higher than controls on …
Reliability Of Functional Magnetic Resonance Imaging Activation During Working Memory In A Multi-Site Study: Analysis From The North American Prodrome Longitudinal Study,
2014
Hofstra Northwell School of Medicine
Reliability Of Functional Magnetic Resonance Imaging Activation During Working Memory In A Multi-Site Study: Analysis From The North American Prodrome Longitudinal Study, J. K. Forsyth, C. E. Bearden, J. Addington, B. Goodyear, K. S. Cadenhead, H. Mirzakhanian, B. A. Cornblatt, D. M. Olvet, M. L. Qiu, T. D. Cannon, +13 Additional Authors
Journal Articles
Multi-site neuroimaging studies offer an efficient means to study brain functioning in large samples of individuals with rare conditions; however, they present new challenges given that aggregating data across sites introduces additional variability into measures of interest. Assessing the reliability of brain activation across study sites and comparing statistical methods for pooling functional data are critical to ensuring the validity of aggregating data across sites. The current study used two samples of healthy individuals to assess the feasibility and reliability of aggregating multi-site functional magnetic resonance imaging (fMRI) data from a Sternberg-style verbal working memory task. Participants were recruited as …
Disease Variants In Genomes Of 44 Centenarians,
2014
Hofstra Northwell School of Medicine
Disease Variants In Genomes Of 44 Centenarians, Y. Freudenberg-Hua, J. Freudenberg, D. Oschwald, E. Christen, J. Koppel, B. Greenwald, R. B. Darnell, S. Germer, G. Atzmon, P. Davies, +5 Additional Authors
Journal Articles
To identify previously reported disease mutations that are compatible with extraordinary longevity, we screened the coding regions of the genomes of 44 Ashkenazi Jewish centenarians. Individual genome sequences were generated with 30x coverage on the Illumina HiSeq 2000 and single-nucleotide variants were called with the genome analysis toolkit (GATK). We identified 130 coding variants that were annotated as "pathogenic" or "likely pathogenic" based on the ClinVar database and that are infrequent in the general population. These variants were previously reported to cause a wide range of degenerative, neoplastic, and cardiac diseases with autosomal dominant, autosomal recessive, and X-linked inheritance. Several …
Extension And Refinement Of The Predictive Value Of Different Classes Of Markers In Adni: Four-Year Follow-Up Data,
2014
Northwell Health
Extension And Refinement Of The Predictive Value Of Different Classes Of Markers In Adni: Four-Year Follow-Up Data, J. J. Gomar, C. Conejero-Goldberg, P. Davies, T. E. Goldberg, Initi Alzheimer's Dis Neuroimaging
Journal Articles
Background: This study examined the predictive value of different classes of markers in the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) over an extended 4-year follow-up in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Methods: MCI patients were assessed for clinical, cognitive, magnetic resonance imaging (MRI), positron emission tomography-fluorodeoxyglucose (PET-FDG), and cerebrospinal fluid (CSF). markers at baseline and were followed on a yearly basis for 4 years to ascertain progression to AD. Logistic regression models were fitted in clusters, including demographics, APOE genotype, cognitive markers, and biomarkers (morphometric, PET-FDG, CSF, amyloid-beta, and tau). Results: The predictive model …
Apoe Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites In The Aging Brain,
2014
Northwell Health
Apoe Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites In The Aging Brain, J. J. Gomar, M. L. Gordon, P. B. Kingsley, A. M. Ulug, L. Keehlisen, S. Huet, J. J. Buthorn, J. Koppel, E. Christen, C. Conejero-Goldberg, P. Davies, T. E. Goldberg, +1 Additional Author
Journal Articles
Background: Proton magnetic resonance spectroscopy (H-1-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. Methods: We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of H-1-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures …
Independent Component Analysis Of Resting State Activity In Pediatric Obsessive-Compulsive Disorder,
2014
Hofstra Northwell School of Medicine
Independent Component Analysis Of Resting State Activity In Pediatric Obsessive-Compulsive Disorder, P. Gruner, A. Vo, M. Argyelan, T. Ikuta, A. J. Degnan, M. John, B. D. Peters, A. K. Malhotra, A. M. Ulug, P. Szeszko
Journal Articles
Obsessive-compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared with healthy volunteers and their clinical correlates. Twenty-three pediatric OCD patients and 23 healthy volunteers (age range 9-17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children's Yale Brown Obsessive Scale. Data were decomposed into 36 …
A Schizophrenia Risk Gene, Znf804a, Is Associated With Brain White Matter Microstructure,
2014
Northwell Health
A Schizophrenia Risk Gene, Znf804a, Is Associated With Brain White Matter Microstructure, T. Ikuta, B. D. Peters, S. Guha, M. John, K. H. Karlsgodt, T. Lencz, P. R. Szeszko, A. K. Malhotra
Journal Articles
Genome-wide association studies have provided strong evidence for association of the SNP rs1344706 in the ZNF804A gene with schizophrenia and bipolar disorder. Neuroimaging studies have suggested that variation at rs1344706 may be associated with neural endophenotypes such as white matter volumes and densities. However, analyses of white matter microstructure using diffusion tensor imaging (DTI) have produced conflicting results. We examined the association between rs1344706 and white matter microstructure in 107 healthy individuals using tract-based spatial statistics (TBSS). TBSS analysis showed significant association between the risk allele and lower fractional anisotropy in the corpus callosum, left forceps minor, and right parietal …
Subcortical Modulation Of Attentional Control By Second-Generation Antipsychotics In First-Episode Psychosis,
2014
Hofstra Northwell School of Medicine
Subcortical Modulation Of Attentional Control By Second-Generation Antipsychotics In First-Episode Psychosis, T. Ikuta, D. G. Robinson, J. A. Gallego, B. D. Peters, P. Gruner, J. M. Kane, M. John, S. Sevy, A. K. Malhotra, P. R. Szeszko
Journal Articles
Psychotic disorders are characterized by significant deficits in attentional control, but the neurobiological mechanisms underlying these deficits early in the course of illness prior to extensive pharmacotherapy are not well understood. Moreover, little is known regarding the symptom and brain changes associated with amelioration of attentional impairments through antipsychotic pharmacotherapy. In this study 14 male patients experiencing a first-episode of psychosis with minimal prior antipsychotic treatment completed an attentional control task while undergoing functional magnetic resonance imaging at the onset of treatment with a second generation antipsychotic (rispericlone or aripiprazole) in a double blind randomized clinical trial and then again …
Abnormal Cingulum Bundle Development In Autism: A Probabilistic Tractography Study,
2014
Northwell Health
Abnormal Cingulum Bundle Development In Autism: A Probabilistic Tractography Study, T. Ikuta, K. M. Shafritz, J. Bregman, B. D. Peters, P. Gruner, A. K. Malhotra, P. R. Szeszko
Journal Articles
There is now considerable evidence that white matter abnormalities play a role in the neurobiology of autism. Little research has been directed, however, at understanding (a) typical white matter development in autism and how this relates to neurocognitive impairments observed in the disorder. In this study we used probabilistic tractography to identify the cingulum bundle in 21 adolescents and young adults with Autism Spectrum Disorder (ASD), and 21 age- and sex-matched healthy volunteers. We investigated group differences in the relationships between age and fractional anisotropy, a putative measure of white matter integrity, within the cingulum bundle. Moreover, in a preliminary …
Long-Acting Injectable Vs Oral Antipsychotics For Relapse Prevention In Schizophrenia: A Meta-Analysis Of Randomized Trials,
2014
Northwell Health
Long-Acting Injectable Vs Oral Antipsychotics For Relapse Prevention In Schizophrenia: A Meta-Analysis Of Randomized Trials, Taishiro Kishimoto, A. Robenzadeh, C. Leucht, S. Leucht, K. Watanabe, M. Mimura, M. Borenstein, John Kane, Christoph Correll
Journal Articles
Background: While long-acting injectable antipsychotics (LAIs) are hoped to reduce high relapse rates in schizophrenia, recent randomized controlled trials (RCTs) challenged the benefits of LAIs over oral antipsychotics (OAPs). Methods: Systematic review/meta-analysis of RCTs that lasted = 6 months comparing LAIs and OAPs. Primary outcome was study-defined relapse at the longest time point; secondary outcomes included relapse at 3, 6, 12, 18, and 24 months, all-cause discontinuation, discontinuation due to adverse events, drug inefficacy (ie, relapse + discontinuation due to inefficacy), hospitalization, and nonadherence. Results: Across 21 RCTs (n = 5176), LAIs were similar to OAPs for relapse prevention at …
Psychotic Alzheimer's Disease Is Associated With Gender-Specific Tau Phosphorylation Abnormalities,
2014
Hofstra Northwell School of Medicine
Psychotic Alzheimer's Disease Is Associated With Gender-Specific Tau Phosphorylation Abnormalities, Jeremy Koppel, C. Acker, P. Davies, O. L. Lopez, H. Jimenez, M. Azose, Blaine Greenwald, P. S. Murray, C. M. Kirkwood, J. Kofler, R. A. Sweet
Journal Articles
Converging evidence suggests that psychotic Alzheimer's disease (AD + P) is associated with an acceleration of frontal degeneration, with tau pathology playing a primary role. Previous histopathologic and biomarker studies have specifically implicated tau pathology in this condition. To precisely quantify tau abnormalities in the frontal cortex in AD + P, we used a sensitive biochemical assay of total tau and 4 epitopes of phospho-tau relevant in AD pathology in a postmortem sample of AD + P and AD - P. Samples of superior frontal gyrus from 26 AD subjects without psychosis and 45 AD + P subjects with psychosis …
Cb2 Receptor Deficiency Increases Amyloid Pathology And Alters Tau Processing In A Transgenic Mouse Model Of Alzheimer's Disease,
2014
Hofstra Northwell School of Medicine
Cb2 Receptor Deficiency Increases Amyloid Pathology And Alters Tau Processing In A Transgenic Mouse Model Of Alzheimer's Disease, Jeremy Koppel, V. Vingtdeux, P. Marambaud, C. D'Abramo, H. Jimenez, M. Stauber, R. Friedman, P. Davies
Journal Articles
The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer's disease (AD). In order to investigate the impact of the CB2 receptor system on AD pathology, a colony of mice with a deleted CB2 receptor gene, CNR2, was established on a transgenic human mutant APP background for pathological comparison with CB2 receptor-sufficient transgenic mice. J20 APP (PDGFB-APPSwInd) mice were bred over two generations with CNR2(-/-) (Cnr2(tm1Dgen)/J) mice to produce a colony of J20 CNR2(+/+) and J20 CNR2(-/-)mice. Seventeen J20 CNR2(+/+) mice (12 females, 5 males) and 16 J20 CNR2(-/-) mice (11 females, 5 males) were killed at …
Positive And Negative Subclinical Symptoms And Mccb Performance In Non-Psychiatric Controls,
2014
Northwell Researcher
Positive And Negative Subclinical Symptoms And Mccb Performance In Non-Psychiatric Controls, C. Korponay, G. C. Nitzburg, Anil Malhotra, P. Derosse
Journal Articles
Considerable data support the phenomenological and temporal continuity between subclinical psychosis and psychotic disorders. In recent years, neurocognitive deficits have increasingly been recognized as a core feature of psychotic illness but there are few data seeking to elucidate the relationship between subclinical psychosis and neurocogntive deficits in non-clinical samples. The goal of the present study was to examine the relationship between subclinical positive and negative symptoms, as measured by the Community Assessment of Psychic Experiences (CAPE) and performance on the MATRICS Consensus Cognitive Battery (MCCB) in a large (n=303) and demographically diverse non-clinical sample. We found that compared to participants …
The Influence Of Neighborhood Characteristics On Police Officers' Encounters With Persons Suspected To Have A Serious Mental Illness,
2014
Northwell Health
The Influence Of Neighborhood Characteristics On Police Officers' Encounters With Persons Suspected To Have A Serious Mental Illness, S. Krishan, R. Bakeman, B. Broussard, S. L. Cristofaro, D. Hankerson-Dyson, L. Husbands, A. C. Watson, Michael Compton
Journal Articles
Objective: Police officers' decisions and behaviors are impacted by the neighborhood context in which police encounters occur. For example, officers may use greater force and be more likely to make arrests in disadvantaged neighborhoods. We examined whether neighborhood characteristics influence police encounters with individuals suspected to have a serious mental illness, addictive disorder, or developmental disability. Method: We obtained data on 916 encounters from 166 officers in six jurisdictions in Georgia, USA and abstracted geographical data pertaining to the location of these encounters from United States Decennial Census data. Encounters were nested within 163 census tracts. Officer-reported data covered general …
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 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 …
