Medicine and Health Sciences Commons^™

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Measuring Brain Serine With Proton Magnetic Resonance Spectroscopy At 3.0 Tesla, Homa Javadzadeh

Electronic Thesis and Dissertation Repository

Proton magnetic resonance spectroscopy (MRS) non-invasively measures regional human brain chemistry in vivo, providing concentration estimates for several metabolites in a pre-selected region of interest. MRS has been applied to investigations of disease-related metabolic and neurochemical alterations in schizophrenia since the early 90’s.

The objective of this research is to implement a metabolite-selective MRS method to quantify endogenous concentrations of human brain serine. Serine is a naturally-occurring amino acid and an important co-modulator of the N-Methyl D-aspartic Acid (NMDA) glutamate receptor. Glutamate abnormalities have been implicated in the pathophysiology of schizophrenia, especially its so-called negative and cognitive symptoms, which can …

Recruiting And Retaining Individuals With Serious Mental Illness And Diabetes In Clinical Research: Lessons Learned From A Randomized, Controlled Trial., Stephanie W. Kanuch M.Ed., Kristin A. Cassidy Ma, Neal Dawson Md, Melanie Athey Ms, Edna Fuentes-Casiano Mssw, Martha Sajatovic Md

Journal of Health Disparities Research and Practice

Abstract: Recruitment and retention of individuals with serious mental illness (SMI) and comorbid diabetes mellitus (DM) in research studies can be challenging with major impediments being difficulties reaching participants via telephone contact, logistic difficulties due to lack of transportation, ongoing psychiatric symptoms, and significant medical complications. Research staff directly involved in recruitment and retention processes of this study reviewed their experiences. The largest barriers at the macro, mediator, and micro levels identified in this study were inclement weather, transportation difficulties, and intermittent and inaccessible telephone contact. Barrier work-around practices included using the health system’s EHR to obtain current phone numbers, …

Systematically Characterizing Dysfunctional Long Intergenic Noncoding Rnas In Multiple Brain Regions Of Major Psychosis, Jing Hu, Jinyuan Xu, Lin Pang, Hongying Zhao, Feng Li, Yulan Deng, Ling Liu, Yujia Lan, Xinxin Zhang, Chun Xu

Health & Biomedical Sciences Faculty Publications and Presentations

Schizophrenia (SZ) and bipolar disorder (BD) are severe neuropsychiatric disorders with serious impact on patients, together termed “major psychosis”. Recently, long intergenic non-coding RNAs (lincRNAs) were reported to play important roles in mental diseases. However, little was known about their molecular mechanism in pathogenesis of SZ and BD. Here, we performed RNA sequencing on 82 postmortem brain tissues from three brain regions (orbitofrontal cortex (BA11), anterior cingulate cortex (BA24) and dorsolateral prefrontal cortex (BA9)) of patients with SZ and BD and control subjects, generating over one billion reads. We characterized lincRNA transcriptome in the three brain regions and identified 20 …

The Genetic And Environmental Etiology Of Schizophrenia In Palau, Elora James, William Byerley, Md, Christopher U. Kitalong, Phd

Journal of Health Disparities Research and Practice

Schizophrenia is a chronic, severe, and disabling brain disorder that has been affecting people throughout the world. There is an established worldwide 1% average prevalence of schizophrenia; however there are high degrees of variability between different regions. Palau, an oceanic nation located in Micronesia, has an abnormally high prevalence rate of schizophrenia at 1.99%. When separated by gender, women have abnormal prevalence rate of 1.24%, while the men have a high prevalence rate of 2.77%, which is over twice the average worldwide. There has been a plethora of research conducted over the years to determine the genetic and environmental etiology …

Update On Schizophrenia And Bipolar Disorder: Focus On Cariprazine, Rona Jeannie Roberts, Lillian Jan Findlay, Peggy El-Mallakh, Rif S. El-Mallakh

Nursing Faculty Publications

Schizophrenia and bipolar disorder are severe psychiatric disorders that are frequently associated with persistent symptoms and significant dysfunction. While there are a multitude of psychopharmacologic agents are available for treatment of these illnesses, suboptimal response and significant adverse consequences limit their utility. Cariprazine is a new, novel antipsychotic medication with dopamine D2 and D3 partial agonist effects. Its safety and efficacy have been investigated in acute psychosis of schizophrenia, bipolar mania, bipolar depression, and unipolar depression. Efficacy has been demonstrated in schizophrenia and mania. It is unclear if cariprazine is effective in depression associated with unipolar or bipolar illness. Adverse …

Alterations Of Mglur5 And Its Endogenous Regulators Norbin, Tamalin And Preso1 In Schizophrenia: Towards A Model Of Mglur5 Dysregulation, Natalie Matosin, Francesca Fernandez-Enright, Samantha J. Fung, Jeremy S. Lum, Martin Engel, Jessica L. Andrews, Xu-Feng Huang, Cynthia S. Weickert, Kelly A. Newell

Xu-Feng Huang

Knockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and pharmacological animal studies support this hypothesis, but no studies have explored mGluR5 dysfunction at the molecular level in the postmortem schizophrenia brain. We assessed mGluR5 mRNA and protein levels in the dorsolateral prefrontal cortex (DLPFC) using a large cohort of schizophrenia and control subjects (n = 37/group), and additionally measured protein levels of recently discovered mGluR5 endogenous regulators, Norbin (neurochondrin), Tamalin (GRASP-1), and Preso1 (FRMPD4), which regulate mGluR5 localization, …

Altered Il-2, Il-6 And Il-8 Serum Levels In Schizophrenia Patients With Tardive Dyskinesia, Hui-Mei An, Yun Long Tan, Jing Shi, Zhi-Ren Wang, Jair C. Soars, Jing Qin Wu, Fu-De Yang, Xu-Feng Huang, Xiang Yang Zhang

Xu-Feng Huang

Immune deregulation has been postulated to be one of the mechanisms underlying the pathogenesis of tardive dyskinesia (TD). We hypothesized that interleukins would have a link with TD in schizophrenia patients. In this study, the serum IL-2, IL-6 and IL-8 levels were examined by enzyme-linked immunosorbent assay (ELISA) in schizophrenia patients with TD (n = 48) and without TD (n = 45), and healthy controls (n = 44). The psychopathological symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS). The severity of TD was evaluated using Abnormal Involuntary Movement Scale (AIMS). The results showed that serum …

Alterations Of Mglur5 And Its Endogenous Regulators Norbin, Tamalin And Preso1 In Schizophrenia: Towards A Model Of Mglur5 Dysregulation, Natalie Matosin, Francesca Fernandez-Enright, Samantha J. Fung, Jeremy S. Lum, Martin Engel, Jessica L. Andrews, Xu-Feng Huang, Cynthia S. Weickert, Kelly A. Newell

Xu-Feng Huang

Knockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and pharmacological animal studies support this hypothesis, but no studies have explored mGluR5 dysfunction at the molecular level in the postmortem schizophrenia brain. We assessed mGluR5 mRNA and protein levels in the dorsolateral prefrontal cortex (DLPFC) using a large cohort of schizophrenia and control subjects (n = 37/group), and additionally measured protein levels of recently discovered mGluR5 endogenous regulators, Norbin (neurochondrin), Tamalin (GRASP-1), and Preso1 (FRMPD4), which regulate mGluR5 localization, …

Alterations Of Mglur5 And Its Endogenous Regulators Norbin, Tamalin And Preso1 In Schizophrenia: Towards A Model Of Mglur5 Dysregulation, Natalie Matosin, Francesca Fernandez-Enright, Samantha J. Fung, Jeremy S. Lum, Martin Engel, Jessica L. Andrews, Xu-Feng Huang, Cynthia S. Weickert, Kelly A. Newell

Xu-Feng Huang

Knockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and pharmacological animal studies support this hypothesis, but no studies have explored mGluR5 dysfunction at the molecular level in the postmortem schizophrenia brain. We assessed mGluR5 mRNA and protein levels in the dorsolateral prefrontal cortex (DLPFC) using a large cohort of schizophrenia and control subjects (n = 37/group), and additionally measured protein levels of recently discovered mGluR5 endogenous regulators, Norbin (neurochondrin), Tamalin (GRASP-1), and Preso1 (FRMPD4), which regulate mGluR5 localization, …

An Analysis Of Metabotropic Glutamate Receptors 2/3 And 5 In Schizophrenia, Major Depression And Bipolar Disorder From The Stanley Neuropathology Consortium, N Matosin, E Frank, F Fernandez, C Deng, J Wong, Xu-Feng Huang, K A. Newell

Xu-Feng Huang

Purpose: Metabotropic glutamate receptors (mGluRs) are proposed novel therapeutic targets for a variety of brain disorders such as schizophrenia (SZ), bipolar disorder (BP) and major depression (MD). Despite their potential, the involvement of these receptors in these pathological processes is uncertain. This information is crucial to understand the efficiency of drugs that target these receptors. Methods: Using post-mortem human brains, mGluR2/3 and mGluR5 binding densities were measured in the anterior cingulate cortex of SZ, BP, MD and matched controls (CT) (n=15/group) by receptor autoradiography. Results: Whilst preliminary analyses indicated no diagnostic effect in mGluR2/3 or mGluR5 binding densities, mGluR2/3 binding …

Facing Our Demons: Psychiatric Perspectives On Exorcism Rituals, Joel R. Sanford

The Hilltop Review

Belief in possession by malevolent spirits exists in many cultures and religions throughout the world, and such beliefs often serve as explanations for a variety of psychological and emotional afflictions. Traditional remedies in these cases often involve exorcism rituals, which are believed to expel spirits from a person's mind and/or body. Some of the cases commonly attributed to involuntary spirit possession are diagnosed within the psychiatric community as schizophrenia or some sort of dissociative disorder and treated with psychotherapy and/or medicine. For some in the psychiatric community, exorcisms and their use by patients are viewed as problematic due to their …

Is Adherence Therapy An Effective Adjunct Treatment For Patients With Schizophrenia Spectrum Disorders? A Systematic Review And Meta-Analysis, Richard Gray, Daniel Bressington, Ada Ivanecka, Sheila Hardy, Martin Jones, Michael Schulz, Suparpit Von Bormann, Jacquie White, Kathryn H. Anderson, Wai-Tong Chien

School of Nursing Faculty Publications

Background: Poor adherence to medication in schizophrenia spectrum disorders leads to inadequate symptom control. Adherence therapy (AT) is an intervention that seeks to reduce patients’ psychiatric symptoms by enhancing treatment adherence. We aimed to systematically review the trial evidence of the effectiveness of AT on improving clinical outcomes in these patients.

Method: Systematic review and meta-analysis of published RCTs. We included studies testing AT as an adjunct intervention against treatment as usual or a comparator intervention in the general adult psychiatric population. The primary outcome of interest was improvement in psychiatric symptoms.

Results: We included six studies …

Medial Prefrontal And Anterior Insular Connectivity In Early Schizophrenia And Major Depressive Disorder: A Resting Functional Mri Evaluation Of Large-Scale Brain Network Models, Jacob Penner, Kristen A. Ford, Reggie Taylor, Betsy Schaefer, Jean Theberge, Richard W. J. Neufeld, Elizabeth A. Osuch, Ravi S. Menon, Nagalingam Rajakumar, John M. Allman, Peter C. Williamson

Anatomy and Cell Biology Publications

Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients …

Managing Agitation Associated With Schizophrenia And Bipolar Disorder In The Emergency Setting, Scott Zeller, Leslie Citrome

NYMC Faculty Publications

INTRODUCTION: Patient agitation represents a significant challenge in the emergency department (ED), a setting in which medical staff are working under pressure dealing with a diverse range of medical emergencies. The potential for escalation into aggressive behavior, putting patients, staff, and others at risk, makes it imperative to address agitated behavior rapidly and efficiently. Time constraints and limited access to specialist psychiatric support have in the past led to the strategy of "restrain and sedate," which was believed to represent the optimal approach; however, it is increasingly recognized that more patient-centered approaches result in improved outcomes. The objective of this …

Explicit Time Deficit In Schizophrenia: Systematic Review And Meta-Analysis Indicate It Is Primary And Not Domain Specific., V Ciullo, G Spalletta, C Caltagirone, Re Jorge, F Piras

Faculty Publications

Although timing deficits are a robust finding in schizophrenia (SZ), the notion of a genuine time perception disorder in SZ is still being debated because distortions in timing might depend on neuropsychological deficits that are characteristics of the illness. Here we used meta-analytic methods to summarize the evidence of timing deficits in SZ and moderator analyses to determine whether defective timing in SZ arises from nontemporal sources or from defective time perception. PubMed Services, PsycNET, and Scopus were searched through March 2015, and all references in articles were investigated to find other relevant studies. Studies were selected if they included …

Book Review On Disease Monograph: Bronchial Asthma, Shashi Tiwari

Indian Journal of Research in Homoeopathy

No abstract provided.

Transdiagnostic Psychiatric Symptoms And Event-Related Potentials Following Rewarding And Aversive Outcomes, Jeffrey S. Bedwell, Geoffrey Potts, Diane C. Gooding, Benjamin J. Trachik, Chi C. Chan, Christopher C. Spencer

Psychology Faculty Publications

There is a need for a better understanding of transdiagnostic psychiatric symptoms that relate to neurophysiological abnormalities following rewarding and aversive feedback in order to inform development of novel targeted treatments. To address this need, we examined a transdiagnostic sample of 44 adults (mean age: 35.52; 57% female), which consisted of individuals with broadly-defined schizophrenia-spectrum disorders (n = 16), bipolar disorders (n = 10), other mood and anxiety disorders (n = 5), and no history of a psychiatric disorder (n = 13). Participants completed a Pavlovian monetary reward prediction task during 32-channel electroencephalogram recording. We assessed the event-related potentials (ERPs) …

Medial Prefrontal And Anterior Insular Connectivity In Early Schizophrenia And Major Depressive Disorder: A Resting Functional Mri Evaluation Of Large-Scale Brain Network Models., Jacob Penner, Kristen A Ford, Reggie Taylor, Betsy Schaefer, Jean Théberge, Richard W J Neufeld, Elizabeth A Osuch, Ravi S Menon, Nagalingam Rajakumar, John M Allman, Peter C Williamson

Brain and Mind Institute Researchers' Publications

Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed-based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with …

The Method Of Madness: A Brief Biography Of Schizophrenia, Riley Hawkins

Honor Scholar Theses

No abstract provided.

1h-Magnetic Resonance Spectroscopy In First Episode And Chronic Schizophrenia Patients, Duygu Kirtaş, Ruki̇ye Fi̇li̇z Karadağ, Meli̇ke Ceyhan Balci Şengül, Yilmaz Kiroğlu

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to compare metabolite levels of the dorsolateral prefrontal cortex (DLPFC), anterior cingulate gyrus (ACG), thalamus, and hippocampus in patients with chronic schizophrenia (CSPs) and first psychotic episode patients (FEPs) by the use of magnetic resonance spectroscopy (MRS). Materials and methods: Thirty CSPs, 20 FEPs, and 30 healthy subjects participated in this study. N-Acetylaspartate (NAA), creatine, choline (Cho), and myoinositol levels of the DLPFC, ACG, thalamus, and hippocampus were measured by 1H-MRS. Results: It was determined that the NAA/Cho ratio was lower in both the FEPs and CSPs than the healthy controls in the …

Total White Blood Cell Count, Liver Enzymes, And Metabolic Syndrome In Schizophrenia, Görkem Karakaş Uğurlu, Semra Ulusoy Kaymak, Mustafa Uğurlu, Si̇bel Örsel, Ali̇ Çayköylü

Turkish Journal of Medical Sciences

Background/aim: Metabolic syndrome (MetS) is an important clinical issue in patients with schizophrenia, but its associated factors are still ambiguous. The aim of the present study was to test whether there are any associations between MetS and white blood cell (WBC) levels, liver enzymes, or sociodemographic variables. Materials and methods: The study included 91 patients with a diagnosis of schizophrenia. We used the National Cholesterol Education Program's Third Adult Treatment Protocol criteria to evaluate MetS in patients. Schizophrenia patients with MetS were compared with those without MetS on the basis of demographic and clinical characteristics and total WBC counts. We …

What Are The Top 10 Physical Activity Research Questions In Schizophrenia?, Davy Vancampfort, Simon Rosenbaum, Michel Probst, Joanne Connaughton, Christy Du Plessis, Taisei Yamamoto, Brendon Stubbs

Physiotherapy Papers and Journal Articles

Purpose: Research has only recently started to consider the applicability of physical activity (PA) for people with schizophrenia. Although there is increasing evidence for the benefits of physical activity, this population remains generally physically inactive and sedentary. The aim of the current study is to highlight 10 pertinent physical activity research questions in people with schizophrenia.

Method: The International Organisation of Physical Therapy in Mental Health (IOPTMH) executed a consultation of its National Organisations (n=13) to identify the most salient questions relevant to guide clinical practice on physical activity in people with schizophrenia.

Results: We identified the following …

Neurodevelopmental Expression Profile Of Dimeric And Monomeric Group 1 Mglurs: Relevance To Schizophrenia Pathogenesis And Treatment, Jeremy Lum, Francesca Fernandez-Enright, Natalie Matosin, Jessica L. Andrews, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell

Illawarra Health and Medical Research Institute

Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically …

Molecular Evidence Of Synaptic Pathology In The Ca1 Region In Schizophrenia, Natalie Matosin, Francesca Fernandez-Enright, Jeremy Lum, Martin Engel, Jessica L. Andrews, Nils C. Gassen, Klaus V. Wagner, Mathias V. Schmidt, Kelly A. Newell

Illawarra Health and Medical Research Institute

Alterations of postsynaptic density (PSD)95-complex proteins in schizophrenia ostensibly induce deficits in synaptic plasticity, the molecular process underlying cognitive functions. Although some PSD95-complex proteins have been previously examined in the hippocampus in schizophrenia, the status of other equally important molecules is unclear. This is especially true in the cornu ammonis (CA)1 hippocampal subfield, a region that is critically involved in the pathophysiology of the illness. We thus performed a quantitative immunoblot experiment to examine PSD95 and several of its associated proteins in the CA1 region, using post mortem brain samples derived from schizophrenia subjects with age-, sex-, and post mortem …

Hoarding Among Outpatients Seeking Treatment At A Psychiatric Hospital In Singapore, Clarissa Ong, Vathsala Sagayadevan, Siau Pheng Lee, Rebecca Ong, Siow Ann Chong, Randy O. Frost, Mythily Subramaniam

Psychology: Faculty Publications

Hoarding symptoms commonly co-occur with other psychiatric disorders, such as major depressive disorder, and have been observed across cultures. Yet, few studies have examined hoarding in other disorders or in an Asian context. The present study aimed to determine: (1) the prevalence of clinically significant hoarding, (2) differences between participants with and without significant hoarding, and (3) predictors of hoarding severity in a Singaporean clinical sample. Five hundred outpatients with anxiety disorders, depressive disorders, schizophrenia, and pathological gambling completed a battery of questionnaires on hoarding, anxiety, depression, functional impairment due to clutter, and quality of life. Thirty percent of our …

Electroconvulsive Therapy Added To Non-Clozapine Antipsychotic Medication For Treatment Resistant Schizophrenia: Meta-Analysis Of Randomized Controlled Trials, W Zheng, X Cao, G Ungvari, Y Xiang, T Guo, Z Liu, Y Wang, B Forester, S Seiner, Y Xiang

Medical Papers and Journal Articles

This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement …

Cell-Specific Pgc-1Α-Dependent Transcription: Implications For Cognitive And Motor Dysfunction, Laura Mcmeekin

All ETDs from UAB

Expression and/or function of transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is reduced in a variety of both neurodegenerative and psychiatric disorders. However, it is difficult to determine the significance of decreased PGC-1α expression and/or function in disease without knowing 1) the localization of these changes, 2) what the normal function of PGC-1α is in that specific cell-type, and 3) how its role in one neuronal population is different from its role in another. PGC-1α is highly expressed in GABAergic interneurons, and although it plays a significant role in interneuron function, several reports suggest that it also plays …

Two Sudden And Unexpected Deaths Of Patients With Schizophrenia Associated With Intramuscular Injections Of Antipsychotics And Practice Guidelines To Limit The Use Of High Doses Of Intramuscular Antipsychotics, Nasratullah Wahidi, Katie M. Johnson, Allen Brenzel, Jose De Leon

Psychiatry Faculty Publications

Intravenous haloperidol has been associated with torsades de pointes (TdP). These two sudden deaths were probable adverse drug reactions (ADRs) following intramuscular (IM) antipsychotics. The autopsies described lack of heart pathology and were highly compatible with the possibility of TdP in the absence of risk factors other than the accumulation of antipsychotics with a high serum peak after the last injection, leading to death within hours. The first case was a 27-year-old African-American male with schizophrenia but no medical issues. His death was probably caused by repeated IM haloperidol injections of 10 mg (totaling 35 mg in 2 days). The …