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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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Positive And Negative Subclinical Symptoms And Mccb Performance In Non-Psychiatric Controls, C. Korponay, G. C. Nitzburg, Anil Malhotra, P. Derosse Jan 2014

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 …

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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 Jan 2014

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 …

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Genes And Schizophrenia: From A Festschrift Seminar Honoring William T. Carpenter Jr, Md, Anil Malhotra Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 = …

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Delineation Of Hippocampal Subregions Using T1-Weighted Magnetic Resonance Images At 3 Tesla, K. Rhindress, T. Ikuta, R. Wellington, A. K. Malhotra, P. Szeszko Jan 2014

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, …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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) …

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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 Jan 2014

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 = …

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Mantle Cell Lymphoma With In Situ Or Mantle Zone Growth Pattern: A Study Of Five Cases And Review Of Literature, P. Hsu, T. Yang, S. Sheikh-Fayyaz, J. Brody, J. Bandovic, S. Roy, J. Laser, J. E. Kolitz, C. Devoe, X. Zhang Jan 2014

Mantle Cell Lymphoma With In Situ Or Mantle Zone Growth Pattern: A Study Of Five Cases And Review Of Literature, P. Hsu, T. Yang, S. Sheikh-Fayyaz, J. Brody, J. Bandovic, S. Roy, J. Laser, J. E. Kolitz, C. Devoe, X. Zhang

Journal Articles

We present two rare cases of in situ mantle cell lymphoma ("in situ MCL") and three cases of MCL with mantle zone growth pattern (MCL-MZGP). The patients include four males and one female, with a median age of 66 years (range, 52 to 86 years). Two present with isolated lymphadenopathy and three with multiple lymphadenopathy. At presentation, the complete blood count (CBC) and serum lactate dehydrogenase (LDH) are normal in all cases. Histologic examination reveals an in situ pattern in two cases and a mantle zone growth pattern in three cases. The staging bone marrow biopsies show minimal involvement by …

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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 Jan 2014

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 …

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Optimal Treatment Of Alzheimer's Disease Psychosis: Challenges And Solutions, Jeremy Koppel, Blaine Greenwald Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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 …

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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 Jan 2014

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) …

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