Medicine and Health Sciences Commons^™

Drugging The Histone Acetyltransferase Ep300 Modulates Alternative Splicing At Schizophrenia Risk Genes, Shravani Malay

Theses and Dissertations

Purpose. We will evaluate the effects of drugging the epigenetic histone acetyltransferase (HAT) enzyme p300, encoded by the schizophrenia risk gene EP300, on genome-wide gene expression in neural cells. We hypothesize that drugging p300 will affect gene expression and alternative splicing of other schizophrenia risk genes. Our motivation is to identify potential new epigenetic treatment avenues for schizophrenia.

Methods. Prior to my joining the lab, an experiment was conducted using the novel p300 HAT inhibitor, A-485, to modulate genomic regulation in a neural cell line (SH-SY5Y). SH-SY5Y cells were exposed to 10μM of A-485 or vehicle (DMSO) for 24 …

Design And Synthesis Of Substituted N,3,3-Triphenylpropanamide And 1-Benzhydryl-N-Phenylazetidine-3-Carboxamide Analogs And Their Biological Evaluation, Michael Dorogan

Theses and Dissertations

As D₁R agonism has significant implications in the treatment of cognitive deficits, we sought to develop novel D₁R PAMs, through the derigidification of BMS D₁R PAM hit compound. While we were able to synthesize derigidified analogs of the BMS hit compound, derigidification did not produce active D₁R ligands.

Patterns Of Cilia Gene Dysregulations In Major Psychiatric Disorders, Wedad Alhassen, Siwei Chen, Marquis Vawter, Brianna Kay Robbins, Henry Nguyen, Thant Nyi Myint, Yumiko Saito, Anton Schulmann, Surya M. Nauli, Olivier Civelli, Pierre Baldi, Amal Alachkar

Pharmacy Faculty Articles and Research

Primary cilia function as cells' antennas to detect and transduce external stimuli and play crucial roles in cell signaling and communication. The vast majority of cilia genes that are causally linked with ciliopathies are also associated with neurological deficits, such as cognitive impairments. Yet, the roles of cilia dysfunctions in the pathogenesis of psychiatric disorders have not been studied. Our aim is to identify patterns of cilia gene dysregulation in the four major psychiatric disorders: schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BP), and major depressive disorder (MDD). For this purpose, we acquired differentially expressed genes (DEGs) from the …

Assessing The Effect Of Chronic Dopamine Receptor 2 Blockade As A Potential Model Of Secondary Negative Symptoms In Rats Using The Fr5/Chow Feeding Choice Task, Cyrene Nicholas

Honors Scholar Theses

Haloperidol, a dopamine (DA) D2 receptor antagonist, is an antipsychotic drug which is commonly used to treat schizophrenia and other psychiatric disorders. These disorders are often characterized by elevated striatal dopamine, which is speculated to have a role in producing positive symptoms such as hallucinations, delusions, and paranoia, as well as symptoms related to motivational salience and reward prediction. Individuals with schizophrenia also exhibit negative symptoms, such as amotivation, anergia, fatigue, and apathy among others. While some negative symptoms of schizophrenia are inherent to the pathophysiology, other negative symptoms are hypothesized to be partially induced by chronic exposure to antipsychotic …

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 …

Evaluating Prescribing Patterns Of Long-Acting Injectable Antipsychotics At A Community Health System, Chelsea L Ferguson Pharmd, Jamie Gaul Pharmd, Bcps, Jared Netley Pharmd

Parkview Pharmacy Department

2017 ASHP Midyear Clinical Meeting / Orlando, Florida / Poster 10-084

Poster Presentation

Objective: Describe prescribing patterns for long-acting injectable antipsychotics and identify knowledge gaps in prescribing within our health system.

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 …

Differential Effects Of Acute Amphetamine And Phencyclidine Treatment And Withdrawal From Repeated Amphetamine Or Phencyclidine Treatment On Social Interaction And Social Memory In Rats, Ming Li, Wei He, Rebecca Munro

Department of Psychology: Faculty Publications

Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals …

Do Atypical Antipsychotics Differ In Determining Long-Term Outcome Of First Episode Schizophrenia? A Naturalistic Outcome Study In India, Amresh Srivastava, Nilesh Shah, Megan Johnston, Larry Stitt, Meghana Thakar, Gurusamy Chinnasamy, Anukant Mital

Amresh Srivastava

Antipsychotic medications form the mainstream of treatment in schizophrenia. These drugs have several short term as well long term advantage. It is not known if atypical antipsychotics have the long-term effect in improving outcome and meeting expectations (1,2,3). The present study examined usage and association of antipsychotics drugs with clinical outcome a long-term naturalistic study.

Up-Regulation Of Neuronal Calcium Sensor-1 (Ncs-1) In The Prefrontal Cortex Of Schizophrenic And Bipolar Patients, Phil Ok Koh, Ashiwel S. Undieh, Robert Levenson, Patricia S. Goldman-Rakic, Michael S. Lidow

Publications and Research

The delineation of dopamine dysfunction in the mentally ill has been a long-standing quest of biological psychiatry. The present study focuses on a recently recognized group of dopamine receptor- interacting proteins as possible novel sites of dysfunction in schizophrenic and bipolar patients. We demonstrate that the dorsolateral prefrontal cortex in schizophrenia and bipolar cases from the Stanley Foundation Neuropathology Consortium display significantly elevated levels of the D2 dopamine receptor desensitization regulatory protein, neuronal calcium sensor-1. These levels of neuronal calcium sensor-1 were not influenced by age, gender, hemisphere, cause of death, postmortem period, alcohol consumption, or antipsychotic and mood stabilizing …