Medicine and Health Sciences Commons^™

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 …

Bayesian Prediction Intervals For Assessing P-Value Variability In Prospective Replication Studies, Olga A. Vsevolozhskaya, Gabriel Ruiz, Dmitri Zaykin

Biostatistics Faculty Publications

Increased availability of data and accessibility of computational tools in recent years have created an unprecedented upsurge of scientific studies driven by statistical analysis. Limitations inherent to statistics impose constraints on the reliability of conclusions drawn from data, so misuse of statistical methods is a growing concern. Hypothesis and significance testing, and the accompanying P-values are being scrutinized as representing the most widely applied and abused practices. One line of critique is that P-values are inherently unfit to fulfill their ostensible role as measures of credibility for scientific hypotheses. It has also been suggested that while P-values …

Molecular Cause And Functional Impact Of Altered Synaptic Lipid Signaling Due To A Prg-1 Gene Snp, Johannes Vogt, Jenq-Wei Yang, Arian Mobascher, Jin Cheng, Yunbo Li, Xingfeng Liu, Jan Baumgart, Carine Thalman, Sergei Kirischuk, Petr Unichenko, Guilherme Horta, Konstantin Radyushkin, Albrecht Stroh, Sebastian Richers, Nassim Sahragard, Ute Distler, Stefan Tenzer, Lianyong Qiao, Klaus Lieb, Oliver Tüscher, Harald Binder, Nerea Ferreiros, Irmgard Tegeder, Andrew J. Morris, Sergiu Gropa, Peter Nürnberg, Mohammad R. Toliat, Georg Winterer, Heiko J. Luhmann, Jisen Huai, Robert Nitsch

Gill Heart & Vascular Institute Faculty Publications

Loss of plasticity‐related gene 1 (PRG‐1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg‐1 (R345T/mutPRG‐1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss‐of‐PRG‐1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG‐1^+/− mice, which are animal correlates of human PRG‐1^+/mut carriers, showed an altered cortical network …

Special Ops: Vulnerable Populations And Tobacco Treatment, Chizimuzo T.C. Okoli, Audrey Darville

Nursing Presentations

• Reasons for Smoking among individuals with co-morbid substance use (SUD)and/or psychiatric disorders (PD)

• Smoking cessation treatment for individuals with co-morbid substance use (SUD) and/or psychiatric disorders (PD)

• Smoking among the Homeless population

Outcomes Of A Tailored Smoking Cessation Program For Individuals With A Substance Use And/Or Psychiatric Disorder, Chizimuzo T.C. Okoli, Milan Khara

Nursing Presentations

BACKGROUND: Tobacco use remains a significant cause of morbidity and mortality globally. Although there has been a steady decline in the overall smoking prevalence in North America during the last decade some subsets of the population continue to smoke at high rates, particularly individuals with a history of substance use disorders (SUD) and/or psychiatric disorders (PD). Studies suggest that individuals with SUD’s and PD’s often have disproportionately higher smoking-related mortality. Studies further suggest that in clinical samples an estimated 75% of individuals with PD and up to 90% of individuals with PD concurrently smoke. This high prevalence of smoking among …

An Evidence-Based Approach To Address Tobacco Dependence Treatment In Mental Health And Addictions Settings, Chizimuzo T.C. Okoli

Nursing Presentations

Purpose: To examine the program completion and smoking cessation outcomes of a tobacco dependence treatment program for individuals with a history of substance use (SUD) and/or psychiatric disorders (PD). Despite the steady decline in the overall smoking prevalence in North America during the last decade some subsets of the population continue to smoke at high rates, particularly individuals with a SUD and/or PD. Among clinical samples, an estimated 75% of individuals with SUD and up to 90% of individuals with PD concurrently smoke. Such findings have prompted the need for tailored tobacco dependence treatment approaches in this population.

Methods: The …

Smoking Cessation Outcomes Among Individuals With Substance Use And/Or Psychiatric Disorders, Milan Khara, Chizimuzo T.C. Okoli

Nursing Faculty Publications

Objectives: The population of individuals with substance use (SUD) and/or psychiatric disorders (PD) has a high prevalence of smoking and a consequent increase in tobacco-related morbidity and mortality when compared to the general population. The aim of this study is to examine the outcomes of a program in a real-life setting which takes a tailored approach to smoking cessation among individuals with SUD and/or PD.

Methods: A retrospective chart review of tailored tobacco dependence treatment was performed on individuals with histories of SUD and/or PD attending a Tobacco Dependence Clinic (TDC) program in Vancouver, British Columbia, Canada. Participants of the …

Outcomes Of A Tailored Tobacco Treatment Approach For Individuals With Substance Use Disorders And/Or Psychiatric Disorders, Chizimuzo T.C. Okoli, Milan Khara

Nursing Presentations

Summary of Key Findings

• Smoking abstinence at end of program:
• Intent to treat analysis: 31% (167/540)
• Among program completers: 41% (167/406)

• Significant predictors of abstinence:
• Having a history of an anxiety disorder is predictive of being less likely to quit smoking when compared to having no history of a psychiatric disorder.
• Having a lower CO level at program enrolment was a significant predictor of being more likely to quit.
• Attending the TDC program for a longer duration was a significant predictor of being more likely to quit.

Trauma, Psychiatric Disorders, Substance Use, And Smoking Among Women, Chizimuzo T.C. Okoli, Nancy Poole, Natalie Hemsing, Karin O'Leary

Chizimuzo T.C. Okoli

Despite decreasing smoking rates among women in the general population, there remain subgroups of women characterized by high nicotine dependence, who remain less able to quit.

One subgroup of women who continue to smoke at rates higher than the general population are those who: have past experiences of trauma, are vulnerable to psychiatric disorders and have substance use problems/addictions.

However, the prevalence of the co-occurrence of trauma, psychiatric disorders, and substance use problems/ addictions, with smoking among women has not previously been synthesized.

The purpose of this study is to conduct a comprehensive review to identify the prevalence of smoking …

Treatment Outcomes From The Tdc: A Look At Smoking Cessation Among Patients With Co-Occurring Substance Use And Psychiatric Disorders, Chizimuzo T.C. Okoli

Chizimuzo T.C. Okoli

Summary of Key Findings

• Smoking abstinence at end of program:
• Intent to treat analysis: 32.2% (83/258)
• Among program completers: 41.3% (83/201)

• Significant predictors of abstinence:
• Having an alcohol, heroin (or other opioid) or marijuana use history was a significant predictor of being less likely to quit smoking when compared to having no history of substance use disorder.
• Having a lower CO level at program enrolment was a significant predictor of being more likely to quit
• Attending the TDC program for a longer duration was a significant predictor of being more likely to quit.