Medicine and Health Sciences Commons^™

Variability And Magnitude Of Brain Glutamate Levels In Schizophrenia: A Meta And Mega-Analysis., Kate Merritt, Robert A Mccutcheon, André Aleman, Sarah Ashley, Katherine Beck, Wolfgang Block, Oswald J N Bloemen, Faith Borgan, Christiana Boules, Juan R Bustillo, Aristides A Capizzano, Jennifer M Coughlin, Anthony David, Camilo De La Fuente-Sandoval, Arsime Demjaha, Kara Dempster, Kim Q Do, Fei Du, Peter Falkai, Beata Galińska-Skok, Jürgen Gallinat, Charles Gasparovic, Cedric E Ginestet, Naoki Goto, Ariel Graff-Guerrero, Beng-Choon Ho, Oliver Howes, Sameer Jauhar, Peter Jeon, Tadafumi Kato, Charles A Kaufmann, Lawrence S Kegeles, Matcheri S Keshavan, Sang-Young Kim, Bridget King, Hiroshi Kunugi, J Lauriello, Pablo León-Ortiz, Edith Liemburg, Meghan E Mcilwain, Gemma Modinos, Elias Mouchlianitis, Jun Nakamura, Igor Nenadic, Dost Öngür, Miho Ota, Lena Palaniyappan, Christos Pantelis, Tulsi Patel, Eric Plitman, Sotirios Posporelis, Scot E Purdon, Jürgen R Reichenbach, Perry F Renshaw, Francisco Reyes-Madrigal, Bruce R Russell, Akira Sawa, Martin Schaefer, Dikoma C Shungu, Stefan Smesny, Jeffrey A Stanley, James Stone, Agata Szulc, Reggie Taylor, Katharine N Thakkar, Jean Theberge, Philip G Tibbo, Thérèse Van Amelsvoort, Jerzy Walecki, Peter C Williamson, Stephen J Wood, Lijing Xin, Hidenori Yamasue, Philip Mcguire, Alice Egerton

Department of Medicine Publications

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on …

Data-Driven Neuroanatomical Subtypes In Various Stages Of Schizophrenia: Linking Cortical Thickness, Glutamate, And Language Functioning, Liangbing Liang

Electronic Thesis and Dissertation Repository

The considerable variation in the spatial distribution of cortical thickness changes has been used to parse heterogeneity in schizophrenia. We aimed to recover a ‘cortical impoverishment’ subgroup with widespread cortical thinning. We applied hierarchical cluster analysis to cortical thickness data of three datasets in different stages of psychosis and studied the cognitive, functional, neurochemical, language and symptom profiles of the observed subgroups. Our consensus-based clustering procedure consistently produced a subgroup characterized by significantly lower cortical thickness. This ‘cortical impoverishment’ subgroup was associated with a higher symptom burden in a clinically stable sample and higher glutamate levels with language impairments in …

Cancer Incidence And Stage At Diagnosis Among People With Psychotic Disorders: Systematic Review And Meta-Analysis., Jared C Wootten, Joshua C Wiener, Phillip S Blanchette, Kelly K. Anderson

Epidemiology and Biostatistics Publications

Research regarding the incidence of cancer among people with psychotic disorders relative to the general population is equivocal, although the evidence suggests that they have more advanced stage cancer at diagnosis. We conducted a systematic review and meta-analysis to examine the incidence and stage at diagnosis of cancer among people with, relative to those without, psychotic disorders. We searched the MEDLINE, EMBASE, PsycINFO, and CINAHL databases. Articles were included if they reported the incidence and/or stage at diagnosis of cancer in people with psychotic disorders. Random effects meta-analyses were used to determine risk of cancer and odds of advanced stage …

Cancer Incidence And Stage At Diagnosis Among People With Recent-Onset Psychotic Disorders: A Retrospective Cohort Study Using Health Administrative Data From Ontario, Canada., Jared C Wootten, Lucie Richard, Phillip S Blanchette, Joshua C. Wiener, Kelly K. Anderson

Epidemiology and Biostatistics Publications

OBJECTIVE: Prior evidence on the relative risk of cancer among people with psychotic disorders is equivocal. The objective of this study was to compare incidence and stage at diagnosis of cancer for people with psychotic disorders relative to the general population.

METHOD: We constructed a retrospective cohort of people with a first diagnosis of non-affective psychotic disorder and a comparison group from the general population using linked health administrative databases in Ontario, Canada. The cohort was followed for incident diagnoses of cancer over a 25-year period. We used Poisson and logistic regression models to compare cancer incidence and stage at …

Incidence Of Cancer And Stage At Diagnosis Among People With Recent-Onset Psychotic Disorders, Jared C. Wootten

Electronic Thesis and Dissertation Repository

Evidence on cancer incidence in people with psychotic disorders, compared to the general population, is equivocal, although those with psychotic disorders so have more advanced stage of cancer at the time of diagnosis. The objective of this thesis was to compare cancer incidence and stage at diagnosis for people with psychotic disorders, relative to the general population. Our systematic review did not observe a significant difference in overall cancer incidence among people diagnosed with psychotic disorders (RR = 1.08, 95% CI: 1.00 to 1.16), however people with psychotic disorders were more likely to be present with advanced stage cancer at …

Risk Stratification For Treatment Decisions In People At Ultra-High Risk For Psychosis: A Cost-Effectiveness Analysis, Olajumoke Marissa Ologundudu

Electronic Thesis and Dissertation Repository

People with psychotic disorders have long-term negative health outcomes and contribute large health system costs. Intervening among those at ultra-high risk (UHR) for psychosis may prevent or mitigate risk for psychotic disorder; however, it is unclear if we should treat all UHR individuals or only those above a certain risk threshold. The objectives were to systematically review the literature on the cost-effectiveness of UHR programs, and to conduct an economic evaluation of a risk stratification strategy, where treatment decisions are based on the probability of transitioning to psychotic disorder. Our systematic review found that UHR programs are potentially cost-effective. The …

Sensory Filtering Disruption Caused By Poly I:C - Timing Of Exposure And Other Experimental Considerations., Faraj L Haddad, Lu Lu, Kelly J Baines, Susanne Schmid

Anatomy and Cell Biology Publications

Maternal immune activation (MIA) in response to infection during pregnancy has been linked through various epidemiological and preclinical studies to an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia in exposed offspring. Sensory filtering disruptions occur in both of these disorders and are typically measured using the acoustic startle response in both humans and rodents. Our study focuses on characterizing the baseline reactivity, habituation and prepulse inhibition (PPI) of the acoustic startle response following exposure to MIA. We induced MIA using polyinosinic: polycytidylic acid (poly I:C) at gestational day (GD) 9.5 or 14.5, and we …

Glutamate And Dysconnection In The Salience Network: Neurochemical, Effective Connectivity, And Computational Evidence In Schizophrenia, Roberto Limongi, Peter Jeon, Michael Mackinley, Tushar Das, Kara Dempster, Jean Théberge, Robert Bartha, Dickson Wong, Lena Palaniyappan

Medical Biophysics Publications

Background: Functional dysconnection in schizophrenia is underwritten by a pathophysiology of the glutamate neurotransmission that affects the excitation-inhibition balance in key nodes of the salience network. Physiologically, this manifests as aberrant effective connectivity in intrinsic connections involving inhibitory interneurons. In computational terms, this produces a pathology of evidence accumulation and ensuing inference in the brain. Finally, the pathophysiology and aberrant inference would partially account for the psychopathology of schizophrenia as measured in terms of symptoms and signs. We refer to this formulation as the 3-level hypothesis. Methods: We tested the hypothesis in core nodes of the salience network (the dorsal …

Deviant Cortical Sulcation Related To Schizophrenia And Cognitive Deficits In The Second Trimester, Michael Lloyd Mackinley, Priyadharshini Sabesan, Lena Palaniyappan

Brain and Mind Institute Researchers' Publications

Aberrant cortical development, inferred from cortical folding, is linked to the risk of schizophrenia. Cortical folds develop in a time-locked fashion during fetal growth. We leveraged this temporal specificity of sulcation to investigate the timing of the prenatal insult linked to schizophrenia and the cognitive impairment seen in this illness. Anatomical MRI scans from 68 patients with schizophrenia and 72 controls were used to evaluate the sulcal depth of five major invariable primary sulci representing lobar development (calcarine sulcus, superior temporal sulcus, superior frontal sulcus, intraparietal sulcus and inferior frontal sulcus) with formation representing the distinct developmental periods. A repeated-measure …

Functional Magnetic Resonance Spectroscopy In First-Episode Schizophrenia: Measuring Glutamate And Glutathione Dynamics At 7-Tesla, Peter Jeon

Electronic Thesis and Dissertation Repository

Schizophrenia is a neuropsychiatric illness without known etiology or cure. Current efforts for symptom treatment still seem to leave a large portion of affected individuals without proper symptom management, with those experiencing symptom relief still having to wrestle with potential side-effects from medication trials. There has been growing evidence suggesting that glutamate and glutathione abnormalities hold major roles in development and manifestation of schizophrenia symptoms.

Magnetic resonance spectroscopy (MRS) provides a non-invasive means to observe in-vivo brain chemistry, including glutamate and glutathione. By adding a functional component to an MRS paradigm (fMRS), such as the color-word Stroop task, it is …

Inviting Hallucinatory Percepts During Speech-Listening To Detect Cognitive Changes In Early Psychosis, Ana-Bianca Popa

Electronic Thesis and Dissertation Repository

Treatment outcomes for people with schizophrenia are more favourable if treatment starts early in the course of the disorder. Current detection methods lack specificity and do not make use of cognitive markers. We presented individuals experiencing a first episode of psychosis (FEP) and matched control participants with acoustically degraded meaningful and matched nonsense sentences to examine the degree to which people reported words that were not actually presented. Intrusion errors were counted when reported words were unrelated to words in the original sentence. Intelligibility (measured as words reported correctly) did not differ between groups but intrusion errors were more frequent …

Cannabinoid Transmission In The Basolateral Amygdala Modulates Prefrontal Cortex And Ventral Hippocampal Activity, Brian J. Pereira

Electronic Thesis and Dissertation Repository

The cannabinoid system is important for maintaining neuron-to-neuron communication within the mammalian brain. One of the most commonly used substances to alter the cannabinoid system is cannabis. Individuals who are exposed to cannabis report having dissociable effects; both positive and negative. High amounts of THC have been commonly associated with the negative effects of cannabis, whereas CBD can be used to counter these. Pre-clinical evidence suggests that the combination of the two compounds can produce a therapeutic benefit for individuals who are susceptible to the effects of THC. The present study investigates whether the combination of THC+CBD can prevent electrophysiological …

Adolescent Cannabinoid Exposure Induces A Persistent Sub-Cortical Hyper-Dopaminergic State And Associated Molecular Adaptations In The Prefrontal Cortex., Justine Renard, Laura G Rosen, Michael Loureiro, Cleusa De Oliveira, Susanne Schmid, Walter J Rushlow, Steven R Laviolette

Brain and Mind Institute Researchers' Publications

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. …

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 …

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 …

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 …

Addressing Very Short Stimulus Encoding Times In Modeling Schizophrenia Cognitive Deficit, Colleen D. Cutler

Electronic Thesis and Dissertation Repository

It is well known that encoding times in persons with schizophrenia are longer than those of normal controls. Neufeld and others have argued that this is the consequence of additional subprocesses being executed during the encoding process in the case of schizophrenia. In general they expressed an encoding time as the sum of $k^{\prime}$ independent exponentially-distributed subprocesses, each executed with rate $v$. A troubling consequence of their application of this model to real data was that under some circumstances some individuals appeared to encode instantaneously. This was accommodated in Neufeld et al. by placing a Poisson distribution on …

Nicotine Receptors Mediating Sensorimotor Gating And Its Enhancement By Systemic Nicotine, Farena Pinnock, Daniel Bosch, Tyler Brown, Nadine Simons, John R. Yeomans, Cleusa Deoliveira, Susanne Schmid

Anatomy and Cell Biology Publications

Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10–1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the …

Activation Of Mglur2/3 Receptors In The Ventral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By A Systemic Nmda Receptor Antagonist, Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid

Anatomy and Cell Biology Publications

Prepulse inhibition (PPI) of acoustic startle is an operational measure of sensorimotor gating, which is disrupted in schizophrenia. NMDA receptor (NMDAR) antagonist induced PPI disruption has become an important pharmacological model for schizophrenia; however, knowledge of the underlying mechanism remains incomplete. This study examines the role of NMDAR in the caudal pontine reticular nucleus (PnC) and the medial prefrontal cortex (mPFC) in NMDARs antagonist induced PPI deficits, as well as the NMDA receptor subtypes involved. We administered the NMDA antagonist MK-801 locally into the caudal pontine reticular formation (PnC), where the PPI mediating pathway converges with the primary startle pathway, …

Beyond Early Intervention, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Antipsychotics And Outcome In Schizophrenia, Amresh Srivastava, Anukant Mital

Psychiatry Presentations

No abstract provided.

Predictors And Characteristics Of Response And Nonresponse: A Ten Year Follow-Up Of First Episode Schizophrenia In Mumbai, Amresh Shrivastava, Nilesh Shah, Megan Johnston, Larry Stitt, Meghana Thakar, Gurusamy Chinnasamy

Psychiatry Presentations

▪ It is not clearly known what predicts good long-term outcome in first episode schizophrenia and what the characteristics are that differentiate patients who do and do not show good response

▪ We attempted to find the characteristics and predictors of good out-come for patients who presented with severe psychopathology and were hospitalized in their first episode psychosis in a tertiary psychiatric hospital in the city of Mumbai

▪ 101 patients of first episode schizophrenia were assessed at hospitalization, and reassessed at ten years

▪ The data was analyzed on 13 outcome parameters for predictors and characteristics of good outcome, …

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

Psychiatry Presentations

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.

Should Schizoaffective Disorder Be Dropped From Dsm V, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Baseline Serum Prolactinin Drug Naïve First Episode Schizophrenia Predicts A Positive Clinical And Social Outcome At Five Years, Post Discharge Follow-Up, Amresh Srivastava, Manoj Tamhane, Meghana Thakar, Yves Bureau, Nilesh Shah

Psychiatry Presentations

Serum prolactinis an indicator of tuberoinfundibulardopamine activity. It is reported to increase in wide variety of mental illnesses. It has close relationship with antipsychotic therapy. However, its relationship with psychopathology and outcome is not clear. Serum prolactinlevel was measured in 30 male and 30 female drug naive patients of schizophrenia. Subsequently, these patients were treated with antipsychotics. The severity of psychopathology at the baseline and subsequent improvement at the end of 3 weeks and 6 weeks was assessed on modified brief psychiatric rating scale (mBPRS). Available to follow up at five years 18 males & 22 females patients were reassessed …

Identifying Schizophrenia: Paradigm Shift ‘The Uhr Research’, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

First Episode Is The Best Episode: Lessons And Limitations In Duration Of Untreated Psychosis (Dup) And Outcome In Schizophrenia, Amresh Srivastava, Larry Stitt, Meghana Thakar, Gurusamy Chinnasamy, Nilesh Shah

Psychiatry Presentations

Background: Early intervention in psychosis is an opportunity. Research ahs shown that if any thing community members can do to prevent psychosis is to report early. This has opened newer vistas for understanding the complexity of brain and behaviour in schizophrenia. At the same time it has raised the bar of expectations regarding its correlation to outcome. It finally narrows down to meaningful public campaign for awareness, which will decide success of research to clinics in schizophrenia management. Duration of untreated psychosis (DUP) has emerged as a reliable predictor of outcome and provides credence to development of early intervention services. …

Interface Of Cannabis And Early Psychosis--Priorities In Research And Service Development, Amresh Srivastava

Psychiatry Presentations

Introduction: cannabis continues to affect mental health. Its abuse is on rise globally. In Canada a rise by 30% in last ten years has been observed in high school students. Interrelationship of cannabis with psychosis and schizophrenia is a complex one. Cannabis is highly comorbid with psychosis, & related to functional disability and outcome. It poses several challenges in understanding causal relationship for comorbidity, underlying neurochemical basis and specifics of service development. Prevalence of Cannabis varies from 20 to 50% early psychosis. Objective of this paper is to review available literature to identify challenges for newer targets of research and …

Differential Characteristics Of “Good Outcome Schizophrenia” In A Long-Term Ten Years Study, Mumbai, India, Amresh Srivastava, Meghan Thakar, Nilesh Shah, Larry Stitt

Psychiatry Presentations

No abstract provided.

Outcome In Schizophrenia: The Long-Term Good Outcome In Schizophrenia Is Not Yet Good Enough, Amresh Srivastava, Meghan Thakar

Psychiatry Presentations

The illness of schizophrenia has always been a matter of concern for its nature and extent of outcome particularly for its regional and cultural differences. The concept of outcome has been evolving and this study examines the scenario of good outcome in developing countries.