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 …
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 …
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 …
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 = …
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, …
White Matter Changes Associated With Antipsychotic Treatment In First-Episode Psychosis,
2014
Hofstra Northwell School of Medicine
White Matter Changes Associated With Antipsychotic Treatment In First-Episode Psychosis, P. Szeszko, D. G. Robinson, T. Ikuta, B. D. Peters, J. Gallego, J. Kane, A. K. Malhotra
Journal Articles
Second-generation antipsychotics are utilized extensively in the treatment of psychotic disorders and other psychiatric conditions, but the effects of these medications on human brain white matter are not well understood. We thus investigated the effects of second-generation antipsychotics on white matter integrity using tract-based spatial statistics in patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure, and how potential changes were associated with metabolic side effects. Thirty-five (26 men/9 women) patients experiencing a first episode of psychosis received diffusion tensor imaging (DTI) exams, clinical assessments, and provided fasting blood samples at the onset of antipsychotic …
Prevalence And Correlates Of Antipsychotic Polypharmacy In Children And Adolescents Receiving Antipsychotic Treatment*,
2014
Northwell Health
Prevalence And Correlates Of Antipsychotic Polypharmacy In Children And Adolescents Receiving Antipsychotic Treatment*, N. Toteja, J. Gallego, E. Saito, T. Gerhard, A. Winterstein, M. Olfson, C. U. Correll
Journal Articles
Antipsychotic polypharmacy (APP), which is common in adults with psychotic disorders, is of unproven efficacy and raises safety concerns. Although youth are increasingly prescribed antipsychotics, little is known about APP in this population. We performed a systematic PubMed search (last update 26 January 2013) of studies reporting the prevalence of APP in antipsychotic-treated youth. Summary statistics and statistical tests were calculated at the study level and not weighted by sample size. Fifteen studies (n=58041, range 68-23183) reported on APP in youth [mean age=13.4 +/- 1.7 yr, 67.1 +/- 10.2% male, 77.9 +/- 27.4% treated with second-generation antipsychotics (SGAs)]. Data collected …
Age-Associated Alterations In Corpus Callosum White Matter Integrity In Bipolar Disorder Assessed Using Probabilistic Tractography,
2014
Hofstra Northwell School of Medicine
Age-Associated Alterations In Corpus Callosum White Matter Integrity In Bipolar Disorder Assessed Using Probabilistic Tractography, N. Toteja, P. Guvenek-Cokol, T. Ikuta, V. Kafantaris, B. D. Peters, K. E. Burdick, M. John, A. K. Malhotra, P. Szeszko
Journal Articles
OBJECTIVES: Atypical age-associated changes in white matter integrity may play a role in the neurobiology of bipolar disorder, but no studies have examined the major white matter tracts using nonlinear statistical modeling across a wide age range in this disorder. The goal of this study was to identify possible deviations in the typical pattern of age-associated changes in white matter integrity in patients with bipolar disorder across the age range of 9-62 years. METHODS: Diffusion tensor imaging was performed in 57 (20 male and 37 female) patients with a diagnosis of bipolar disorder and 57 (20 male and 37 female) …
Genome-Wide Mapping Of Ibd Segments In An Ashkenazi Pd Cohort Identifies Associated Haplotypes,
2014
Northwell Researcher
Genome-Wide Mapping Of Ibd Segments In An Ashkenazi Pd Cohort Identifies Associated Haplotypes, V. Vacic, L. J. Ozelius, L. N. Clark, A. Bar-Shira, M. Gana-Weisz, T. Gurevich, A. Gusev, S. Guha, T. Lencz, A. Orr-Urtreger, +10 Additional Authors
Journal Articles
The recent series of large genome-wide association studies in European and Japanese cohorts established that Parkinson disease (PD) has a substantial genetic component. To further investigate the genetic landscape of PD, we performed a genome-wide scan in the largest to date Ashkenazi Jewish cohort of 1130 Parkinson patients and 2611 pooled controls. Motivated by the reduced disease allele heterogeneity and a high degree of identical-by-descent (IBD) haplotype sharing in this founder population, we conducted a haplotype association study based on mapping of shared IBD segments. We observed significant haplotype association signals at three previously implicated Parkinson loci: LRRK2 (OR = …
Hospitalization Rates In Patients Switched From Oral Anti-Psychotics To Aripiprazole Once-Monthly: Final Efficacy Analysis,
2014
Hofstra Northwell School of Medicine
Hospitalization Rates In Patients Switched From Oral Anti-Psychotics To Aripiprazole Once-Monthly: Final Efficacy Analysis, John Kane, C. Zhao, B. R. Johnson, R. A. Baker, A. Eramo, R. D. Mcquade, A. R. Duca, R. Sanchez, T. Peters-Strickland
Journal Articles
Abstract Objective: To compare hospitalization rates in patients with schizophrenia treated prospectively with aripiprazole once-monthly 400 mg (AOM 400; an extended-release injectable suspension) vs the same patients' retrospective rates with their prior oral anti-psychotic therapy. Research design and methods: Multi-center, open-label, mirror-image, naturalistic study in a community setting in North America. Patients who required a change in treatment and/or would benefit from long-acting injectable anti-psychotic therapy were treated prospectively for 6 months with AOM 400. Retrospective data on hospitalization rates were obtained. Clinical trial registration: ClinicalTrials.gov: NCT01432444. Main outcome measures: The proportion of patients with >/=1 psychiatric inpatient hospitalization with …
Optimal Treatment Of Alzheimer's Disease Psychosis: Challenges And Solutions,
2014
Hofstra Northwell School of Medicine
Optimal Treatment Of Alzheimer's Disease Psychosis: Challenges And Solutions, Jeremy Koppel, Blaine Greenwald
Journal Articles
Psychotic symptoms emerging in the context of neurodegeneration as a consequence of Alzheimer's disease was recognized and documented by Alois Alzheimer himself in his description of the first reported case of the disease. Over a quarter of a century ago, in the context of attempting to develop prognostic markers of disease progression, psychosis was identified as an independent predictor of a more-rapid cognitive decline. This finding has been subsequently well replicated, rendering psychotic symptoms an important area of exploration in clinical history taking - above and beyond treatment necessity - as their presence has prognostic significance. Further, there is now …
