Medicine and Health Sciences Commons^™

Dopamine Perturbation Of Gene Co-Expression Networks Reveals Differential Response In Schizophrenia For Translational Machinery, Mark Z. Kos, Jubao Duan, Alan R. Sanders, Lucy Blondell, Eugene I. Drigalenko, Melanie A. Carless, Pablo V. Gejman, Harald H. H. Goring

School of Medicine Publications and Presentations

The dopaminergic hypothesis of schizophrenia (SZ) postulates that positive symptoms of SZ, in particular psychosis, are due to disturbed neurotransmission via the dopamine (DA) receptor D2 (DRD2). However, DA is a reactive molecule that yields various oxidative species, and thus has important non-receptor-mediated effects, with empirical evidence of cellular toxicity and neurodegeneration. Here we examine non-receptor-mediated effects of DA on gene co-expression networks and its potential role in SZ pathology. Transcriptomic profiles were measured by RNA-seq in B-cell transformed lymphoblastoid cell lines from 514 SZ cases and 690 controls, both before and after exposure to DA ex vivo (100 μM). …

Understanding The Association Between Negative Symptoms And Performance On Effort-Based Decision-Making Tasks: The Importance Of Defeatist Performance Beliefs, L Felice Reddy, William P Horan, Deanna M Barch, Robert W Buchanan, James M Gold, Stephen R Marder, Jonathan K Wynn, Jared Young, Michael F Green

2010-2019 OA Pubs

Effort-based decision-making paradigms are increasingly utilized to gain insight into the nature of motivation deficits. Research has shown associations between effort-based decision making and experiential negative symptoms; however, the associations are not consistent. The current study had two primary goals. First, we aimed to replicate previous findings of a deficit in effort-based decision making among individuals with schizophrenia on a test of cognitive effort. Second, in a large sample combined from the current and a previous study, we sought to examine the association between negative symptoms and effort by including the related construct of defeatist beliefs. The results replicated previous …

Identification Of Chst9 As A Candidate Gene For Schizophrenia From Whole Genome Sequencing, Christopher Sharp, Jingchun Chen, Marvi Moreno, Mahtab Hamid, Francisco Servin, Bita Bashy, Travis Mize

LSAMP Poster Presentations

Recent results imply that rare variants contribute to the risk of schizophrenia. We conducted whole genome sequencing for 99 subjects from 20 Chinese families (parents and at least two siblings with a schizophrenia diagnosis and one unaffected sibling). Of the 9 frameshift mutations identified in more than 2 families, one was at chromosome 10:125780762 on the Carbohydrate Sulfotransferase 15 (CHST15) gene and another at chromosome 18:24722723 on the Carbohydrate Sulfotransferase 9 (CHST9) gene. We observed these deletions in 4 affected persons of two families from whole. At least two types of mutations (one or three bases insertion) have been identified …

Cariprazine For Acute And Maintenance Treatment Of Adults With Schizophrenia: An Evidence-Based Review And Place In Therapy, Leslie L. Citrome

NYMC Faculty Publications

Cariprazine is an oral antipsychotic approved in the US and EU for the treatment of schizophrenia. Cariprazine differs from other antipsychotics in that it is a dopamine D3- and D2-receptor partial agonist, with tenfold higher affinity for D3 receptors than for D2 receptors. Cariprazine is metabolized in two steps by CYP3A4 to didesmethyl-cariprazine (DDCAR). DDCAR has a long half-life of 1-3 weeks and is the predominant circulating active moiety. Efficacy and safety in persons with acute schizophrenia were assessed in four similarly designed, short-term, randomized, placebo-controlled clinical trials in nonelderly adults, with three studies considered positive and yielding a number …

Efficacy And Safety Of Varenicline For Smoking Cessation In Schizophrenia: A Meta-Analysis, Saeed Ahmed, Sanya Virani, Vijaya P. Kotapati, Ramya Bachu, Mahwish Adnan, Ali M. Khan

School of Medicine Publications and Presentations

Objective: Smoking represents a major public health problem among patients with schizophrenia. To this end, some studies have investigated the efficacy of varenicline for facilitating smoking cessation in schizophrenia patients. The present review seeks to synthesize the results of these studies as well as document the reported side effects of using this medication.

Methods: An electronic search was performed using five major databases: PubMed, Scopus, EMBASE, Web of Science, and Cochrane Library. Included in the current analysis were randomized clinical trials (RCTs) that have investigated the effect of varenicline in promoting smoking cessation in patients with schizophrenia. Risk of …

Schizophrenia In Digeorge Syndrome: A Unique Case Report, Sukaina Rizvi, Ali M. Khan, Hina Saeed, Akeem M. Aribara, Alexis Carrington, Alexa Griffiths, Abdul Mohit

School of Medicine Publications and Presentations

Herein we present the unique case of a 21-year-old African American woman who presented with psychotic features and the incidental finding of basal ganglia calcifications on computed tomography (CT) scan of the head. She was initially presumed to have Fahr’s syndrome in the context of idiopathic bilateral basal ganglia calcifications and psychotic features. Genetic testing performed revealed the deletion of 22q11.2, thus establishing the diagnosis of DiGeorge syndrome. This case highlights the importance of noticing subtle physical exam findings along with laboratory findings as this led to the diagnosis of DiGeorge syndrome for this patient. This case is unique in …

Relapse Prevention: A Cost-Effectiveness Analysis Of Brexpiprazole Treatment In Adult Patients With Schizophrenia In The Usa, Myrlene Aigbogun, Sizhu Liu, Siddesh Kamat, Christophe Sapin, Amy Duhig, Leslie L. Citrome

NYMC Faculty Publications

Objective: This study used a decision-analytic framework to assess the cost-effectiveness of brexpiprazole vs comparator branded therapies for reducing relapses and hospitalizations among adults with schizophrenia from a US payer perspective. Methods: An economic model was developed to assess patients with stable schizophrenia initiating treatment with brexpiprazole (1-4 mg), cariprazine (1-6 mg), or lurasidone (40-80 mg) over a 1-year period. After 6 months, patients remained on treatment or discontinued due to relapse, adverse events, or other reasons. Patients who discontinued due to relapse or adverse events were assumed to have switched to other therapy, and those who discontinued due to …

Blocking Nmdar Disrupts Spike Timing And Decouples Monkey Prefrontal Circuits: Implications For Activity-Dependent Disconnection In Schizophrenia, Jennifer L. Zick, Rachael K. Blackman, David A. Crowe, Bagrat Amirikian, Adele L. Denicola, Theoden I. Netoff, Matthew V. Chafee

Faculty Authored Articles

We employed multi-electrode array recording to evaluate the influence of NMDA receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as they performed a cognitive control task measuring specific deficits in schizophrenia. Systemic, periodic administration of an NMDAR antagonist (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike correlation in simultaneously recorded neuron pairs. We employed transfer entropy analysis to measure effective connectivity between prefrontal neurons at lags consistent with monosynaptic interactions and found that effective connectivity was persistently reduced following exposure to the NMDAR antagonist. These results suggest that a disruption of spike timing and effective connectivity …

Multinational Comparative Cross-Sectional Survey Of Views Of Medical Students About Acceptable Terminology And Subgroups In Schizophrenia, Shanaya Rathod, Muhammad Irfan, Rachna Bhargava, Narsimha Pinninti, Joseph Scott, Haifa Mohammad Algahtani, Zhihua Guo, Rishab Gupta, Pallavi Nadkarni, Farooq Naeem, Fleur Howells, Katherine Sorsdahi, Kerensa Thorne, Victoria Osman-Hicks, Sasee Pallikadavath, Peter Phiri, Hannah Carr, Lizi Graves, David Kingdon

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

AIM: The aim of this study was to inform thinking around the terminology for 'schizophrenia' in different countries.

OBJECTIVES: The objective of this study was to investigate: (1) whether medical students view alternative terminology (psychosis subgroups), derived from vulnerability-stress models of schizophrenia, as acceptable and less stigmatising than the term schizophrenia; (2) if there are differences in attitudes to the different terminology across countries with different cultures and (3) whether clinical training has an impact in reducing stigma.

DESIGN: This is a cross-sectional survey that examined the attitudes of medical students towards schizophrenia and the alternative subgroups.

SETTING: The study …

Synaptic Phospholipids As A New Target For Cortical Hyperexcitability And E/I Balance In Psychiatric Disorders, Carine Thalman, Guilherme Horta, Lianyong Qiao, Heiko Endle, Irmgard Tegeder, Hong Cheng, Gregor Laube, Torfi Sigurdsson, Maria Jelena Hauser, Stefan Tenzer, Ute Distler, Junken Aoki, Andrew J. Morris, Gerd Geisslinger, Jochen Röper, Sergei Kirischuk, Heiko J. Luhmann, Konstantin Radyushkin, Robert Nitsch, Johannes Vogt

Internal Medicine Faculty Publications

Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition …

Association Between A Single Nucleotide Polymorphism In Neuregulin-1 And Schizophrenia In Pakistani Patients, Haider Ali Naqvi, Shafqat Huma, Hira Waseem, Kashaf Aqeel Zaidi, Hina Saeed Zuberi, Syed Hani Abidi

Department of Biological & Biomedical Sciences

Objective: To determine the association of single-nucleotide polymorphism8nrg433E1006 in the neuregulin-1 gene associated with schizophrenia.
Methods: This case-control study was conducted at the Fountain House, Lahore, and the psychiatric clinics at the Aga Khan University, Karachi, from 2010 to 2013.The total genomic deoxyribonucleic acid was isolated and single-nucleotide polymorphism8nrg433E1006 was screened by nested polymerase chain reaction followed by sequencing. These sequences, from patients and controls, were aligned with the human neuregulin-1-glial growth factor 2 gene sequence, which served as a reference sequence. The single nucleotide polymorphism genetic algorithm was characterised at position 433 in the neuregulin-1 gene by …

Effort-Related Decision Making In Comt Variant Mice: Pharmacological Studies And Genetic Susceptibility To Motivational Dysfunction, Suzanne Cayer

Honors Scholar Theses

Effort-related decision making tasks in animals can model motivational symptoms in humans, which are a set of symptoms spanning a multitude of neuropsychiatric disorders, such as major depressive disorder and the negative symptoms of schizophrenia. The present studies aimed to evaluate the effort-related effects of the Val158Met polymorphism of human catechol-methyltransferase (COMT), by testing mice carrying either the human COMT Val (n=8) or Met allele (n=8) with Wild-Type control mice (n=15) by using concurrent FR2 and FR4/pellet choice tasks in a touchscreen operant conditioning apparatus. The Val158Met polymorphism has been repeatedly associated with neuropsychiatric disorders, and the Val allele has …

"My Bitterness Is Deeper Than The Ocean": Understanding Internalized Stigma From The Perspectives Of Persons With Schizophrenia And Their Family Caregivers., Yin-Ling Irene Wong, Dexia Kong, Lufei Tu, Rosemary Frasso Phd, Msc, Cph

College of Population Health Faculty Papers

Background: It is estimated that 8 million of the Chinese adult population had a diagnosis of schizophrenia. Stigma associated with mental illness, which is pervasive in the Chinese cultural context, impacts both persons with schizophrenia and their family caregivers. However, a review of the literature found a dearth of research that explored internalized stigma from the perspectives of both patients and their caregivers.

Methods: We integrated data from standardized scales and narratives from semi-structured interviews obtained from eight family-dyads. Interview narratives about stigma were analyzed using directed content analysis and compared with responses from Chinese versions of the Internalized Stigma …

A Computational Assessment Of Target Engagement In The Treatment Of Auditory Hallucinations With Transcranial Direct Current Stimulation, Won Hee Lee, Nigel I. Kennedy, Marom Bikson, Sophia Frangou

Publications and Research

We use auditory verbal hallucinations (AVH) to illustrate the challenges in defining and assessing target engagement in the context of transcranial direct current stimulation (tDCS) for psychiatric disorders. We defined the target network as the cluster of regions of interest (ROIs) that are consistently implicated in AVH based on the conjunction of multimodal meta-analytic neuroimaging data. These were prescribed in the New York Head (a population derived model) and head models of four single individuals. We appraised two potential measures of target engagement, tDCS-induced peak electric field strength and tDCS-modulated volume defined as the percentage of the volume of the …

Sensory, Motor And Process Skills As Compared To Symptom Severity In Adult Patients With Schizophrenia, Lola Halperin

Occupational Therapy Faculty Publications

Schizophrenia is a serious mental illness affecting millions of Americans. It is characterized by positive and negative symptoms; cognitive impairments; and sensory, motor, and process skill deficits; as well as compromised motor learning, functional difficulties, and diminished quality of life. Neuroscientists attribute the above deficits to abnormal brain development, exaggerated synaptic pruning, and neurodegenerative processes, causing disrupted connectivity and diminished plasticity in the brain, neurotransmitter dysfunction, and impaired sensory processing.

Presently, there is no cure for schizophrenia. Numerous medications and rehabilitation modalities exist; however, many of the affected individuals continue to struggle daily. Recovery of these individuals implies symptom management …

Interaction Between Pre-Treatment Drug Use And Heterogeneity Of Psychiatric Diagnosis Predicts Outcomes In Outpatients With Co-Occurring Disorders., Oladunni Oluwoye, Katherine Hirchak, Emily Leickly, Jordan Skalisky, Sterling M Mcpherson, Debra Srebnik, John M Roll, Richard K Ries, Michael G Mcdonell

Articles, Abstracts, and Reports

We examined whether the interaction of baseline stimulant use, assessed by urine drug tests, and type of serious mental illness (SMI) diagnosis predicted stimulant use in a trial of contingency management (CM). The interaction between baseline stimulant use and SMI diagnoses was significant in the overall sample (p=0.002) when controlling for the main effects of treatment condition, baseline stimulant use, and SMI diagnosis. Similar results were also found within the CM sample. Individuals with bipolar disorder were more or less likely, depending on their baseline stimulant-drug test results, to use stimulants during treatment compared to those with other SMI diagnoses.

Morbidity Burden And Community-Based Palliative Care Are Associated With Rates Of Hospital Use By People With Schizophrenia In The Last Year Of Life: A Population-Based Matched Cohort Study, Katrina Spilsbury, Lorna Rosenwax, Kate Brameld, Brian Kelly, Glenn Arendts

Health Sciences Papers and Journal Articles

Objective: People with schizophrenia face an increased risk of premature death from chronic diseases and injury. This study describes the trajectory of acute care health service use in the last year of life for people with schizophrenia and how this varied with receipt of community based specialist palliative care and morbidity burden.

Method: A population-based retrospective matched cohort study of people who died from 01/01/ 2009 to 31/12/2013 with and without schizophrenia in Western Australia. Hospital inpatient, emergency department, death and community-based care data collections were linked at the person level. Rates of emergency department presentations and hospital admissions over …

The Impact Of Schizophrenia On Copd Readmission Rate Among Hospitalized South Carolinians, Emilienne Y. Watonsi

DNP Research Projects

Due to elevated readmission costs, the Affordable Care Act established the Hospital Readmission Reduction Program in 2012 to curb the 30-day readmission rates. COPD and schizophrenia are two very expensive diseases, COPD national medical costs is projected to be $49.0 billion in 2020; the cost of schizophrenia was 155.7 billion in 2013. The main objective of this study was to determine if schizophrenia is a significant predictor of 30-day readmission following hospitalization for acute exacerbation of COPD after adjusting for age, gender, anxiety, smoking status, T2DM, chronic ischemic heart disease, and GERD. Methods: A retrospective cohort design was used to …

Integration Of Routine Qa Data Into Mega-Analysis May Improve Quality And Sensitivity Of Multisite Diffusion Tensor Imaging Studies, P. Kochunov, E. W. Dickie, J. D. Viviano, J. Turner, P. B. Kingsley, N. Jahanshad, P. M. Thompson, M. C. Ryan, A. K. Malhotra, A. N. Voineskos, +6 Additional Authors

Journal Articles

No abstract provided.

Prospective Relationships Between Motivation And Functioning In Recovery After A First Episode Of Schizophrenia, D. Fulford, D. Piskulic, J. Addington, J. M. Kane, N. R. Schooler, K. T. Mueser

Journal Articles

No abstract provided.

Predictors Of Aggression In 3.322 Patients With Affective Disorders And Schizophrenia Spectrum Disorders Evaluated In An Emergency Department Setting, E. A. Blanco, L. M. Duque, V. Rachamallu, E. Yuen, J. M. Kane, J. A. Gallego

Journal Articles

No abstract provided.

The Genetics Of Endophenotypes Of Neurofunction To Understand Schizophrenia (Genus) Consortium: A Collaborative Cognitive And Neuroimaging Genetics Project, G. A. Blokland, E. C. Del Re, R. I. Mesholam-Gately, J. Jovicich, J. Trampush, M. S. Keshavan, L. E. Delisi, A. K. Malhotra, T. Lencz, T. L. Petryshen, +64 Additional Authors

Journal Articles

No abstract provided.

What Is The Risk-Benefit Ratio Of Long-Term Antipsychotic Treatment In People With Schizophrenia?, C. U. Correll, J. M. Rubio, J. M. Kane

Journal Articles

No abstract provided.

Initiating/Maintaining Long-Acting Injectable Antipsychotics In Schizophrenia/Schizoaffective Or Bipolar Disorder - Expert Consensus Survey Part 2, M. Sajatovic, R. Ross, S. N. Legacy, M. Byerly, J. M. Kane, F. Dibiasi, H. Fitzgerald, C. U. Correll

Journal Articles

No abstract provided.

Identifying Patients And Clinical Scenarios For Use Of Long-Acting Injectable Antipsychotics - Expert Consensus Survey Part I, M. Sajatovic, R. Ross, S. N. Legacy, C. U. Correll, J. M. Kane, F. Dibiasi, H. Fitzgerald, M. Byerly

Journal Articles

No abstract provided.

Impact Of Paliperidone Palmitate One-Month Formulation On Relapse Prevention In Patients With Schizophrenia: A Post-Hoc Analysis Of A One-Year, Open-Label Study Stratified By Medication Adherence, T. Si, N. Li, H. Lu, S. Cai, J. Zhuo, C. U. Correll, L. Zhang, Y. Feng

Journal Articles

No abstract provided.

Computational Linguistic Analysis Applied To A Semantic Fluency Task To Measure Derailment And Tangentiality In Schizophrenia, L. Pauselli, B. Halpern, S. D. Cleary, B. Ku, M. A. Covington, M. T. Compton

Journal Articles

No abstract provided.

The Early Psychosis Screener (Eps): Quantitative Validation Against The Sips Using Machine Learning, B. B. Brodey, R. R. Girgis, O. Favorov, J. Addington, D. O. Perkins, C. E. Bearden, S. W. Woods, E. F. Walker, B. A. Cornblatt, I. S. Brodey, +3 Additional Authors

Journal Articles

No abstract provided.

The Role Of Genetic Variation Of Human Metabolism For Bmi, Mental Traits And Mental Disorders, J. Hebebrand, T. Peters, D. Schijven, M. Hebebrand, C. Grasemann, T. W. Winkler, I. M. Heid, J. Antel, C. U. Correll, L. Libuda, +7 Additional Authors

Journal Articles

No abstract provided.

Tardive Dyskinesia Risk With First- And Second-Generation Antipsychotics In Comparative Randomized Controlled Trials: A Meta-Analysis, M. Carbon, J. M. Kane, S. Leucht, C. U. Correll

Journal Articles

No abstract provided.