2024
Psychopharmacological Treatment of Schizophrenia
Singh N, Ganesh S, D'Souza D. Psychopharmacological Treatment of Schizophrenia. 2024 DOI: 10.1016/b978-0-323-95702-1.00177-9.Peer-Reviewed Original ResearchAntipsychotic drugsPositive symptoms of schizophreniaPharmacological treatment of schizophreniaTreatment-resistant schizophreniaPharmacological treatmentSymptoms of schizophreniaTreatment of schizophreniaAcute psychotic episodeNeuroleptic malignant syndromeNegative symptomsPositive symptomsExtrapyramidal symptomsPsychotic episodeCognitive deficitsCognitive symptomsMalignant syndromeSchizophreniaPrevent relapseSide effectsMaintenance treatmentLong-actingDopamineAssociated with significant side effectsMedication adherenceProportion of patients
2023
Cannabis Causes Positive, Negative, and Cognitive Symptoms and Produces Impairments in Electrophysiological Indices of Information Processing
Martin A, Ranganathan M, D’Souza D. Cannabis Causes Positive, Negative, and Cognitive Symptoms and Produces Impairments in Electrophysiological Indices of Information Processing. 2023, 156-166. DOI: 10.1017/9781108943246.017.Peer-Reviewed Original ResearchMental illnessMental health teamsHealth policy implicationsHigh-potency cannabisStages of neurodevelopmentPotential adverse effectsHealth teamsImpact of exposureCognitive symptomsCannabis dependenceAdverse effectsCannabisSynthetic cannabinoidsIllnessPsychosisCannabinoidsElectrophysiological indicesNew research findingsAssociationComplex associationSymptomsPutative modelNeurodevelopmentSchizophreniaImpairmentThe Acute Effects of Cannabinoids in Patients with Psychotic Illness
Ganesh S, Henquet C, Sewell R, Kuepper R, Ranganathan M, D’Souza D. The Acute Effects of Cannabinoids in Patients with Psychotic Illness. 2023, 225-239. DOI: 10.1017/9781108943246.023.Peer-Reviewed Original ResearchMental illnessMental health teamsHealth policy implicationsHigh-potency cannabisStages of neurodevelopmentPotential adverse effectsAcute effectsHealth teamsPsychotic illnessImpact of exposureCannabis dependenceAdverse effectsIllnessCannabisCannabinoidsSynthetic cannabinoidsPsychosisNew research findingsAssociationComplex associationPatientsNeurodevelopmentPutative modelSchizophreniaRandomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia
Surti T, Ranganathan M, Johannesen J, Gueorguieva R, Deaso E, Kenney J, Krystal J, D'Souza D. Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia. Schizophrenia Research 2023, 256: 36-43. PMID: 37141764, PMCID: PMC10257994, DOI: 10.1016/j.schres.2023.04.010.Peer-Reviewed Original ResearchConceptsGlycine transporter 1Cytochrome P450 2D6 extensive metabolizersGlyT1 inhibitorsWeeks of washoutWeeks of CTMedication adherenceReceptor hypofunctionImpaired neuroplasticityPharmacodynamic variabilityNMDAR functionExtensive metabolizersTreatment periodPsychotic symptomsStable outpatientsCognitive impairmentGlyT1 occupancyTransporter 1CTNeuroplasticityCognitive training strategiesSchizophreniaComputerized CTCognitive performanceAugmentation studiesGreater improvement
2022
Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users
Johnson E, Colbert S, Jeffries P, Tillman R, Bigdeli T, Karcher N, Chan G, Kuperman S, Meyers J, Nurnberger J, Plawecki M, Degenhardt L, Martin N, Kamarajan C, Schuckit M, Murray R, Dick D, Edenberg H, D’Souza D, Di Forti M, Porjesz B, Nelson E, Agrawal A. Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users. Schizophrenia Bulletin 2022, 49: 778-787. PMID: 36545904, PMCID: PMC10154717, DOI: 10.1093/schbul/sbac196.Peer-Reviewed Original ResearchConceptsCannabis useAlcohol use disorderCognitive difficultiesSchizophrenia polygenic risk scoresFirst cannabis useDaily cannabis useCannabis usersSocial withdrawalUnusual experiencesCannabis involvementPolygenic risk scoresExpected directionGenetic riskUse disordersIndependent replication sampleLike experiencesGenetic liabilityCannabisSchizophreniaPolygenic riskPolygenic liabilityReplication sampleExperienceAnalytic sampleDisorders
2021
Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia
Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME, Cho YT, Fonteneau C, Gil R, Girgis R, Gur RE, Gur RC, Grinband J, Kantrowitz J, Kohler C, Krystal J, Murray J, Ranganathan M, Santamauro N, Van Snellenberg J, Tamayo Z, Wolf D, D’Souza D, Srihari V, Gueorguieva R, Patel P, Forselius-Bielen K, Lu J, Butler A, Fram G, Afriyie-Agyemang Y, Selloni A, Cadavid L, Gomez-Luna S, Gupta A, Radhakrishnan R, Rashid A, Aker R, Abrahim P, Nia A, Surti T, Kegeles L, Carlson M, Goldberg T, Gangwisch J, Benedict E, Govil P, Brazis S, Mayer M, de la Garrigue N, Fallon N, Baumvoll T, Abeykoon S, Perlman G, Bobchin K, Elliott M, Schmidt L, Rush S, Port A, Heffernan Z, Laney N, Kantor J, Hohing T, Gray D, Lieberman J. Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia Bulletin 2021, 48: 199-210. PMID: 34423843, PMCID: PMC8781338, DOI: 10.1093/schbul/sbab095.Peer-Reviewed Original ResearchConceptsCortical dopamine neurotransmissionPositive allosteric modulationImportant therapeutic targetPF-06412562Dopaminergic receptorsD1R stimulationDA levelsTolerable dosesLevel of stimulationDopamine neurotransmissionReceptor stimulationTherapeutic targetPartial agonistCognitive deficitsBiased agonismFull agonismTarget engagementAllosteric modulationNew drugsStimulationPoor bioavailabilitySchizophreniaOptimal stimulationDrugsExpression levelsAnalysis of circulating exosomes reveals a peripheral signature of astrocytic pathology in schizophrenia
Ranganathan M, Rahman M, Ganesh S, D’Souza D, Skosnik PD, Radhakrishnan R, Pathania S, Mohanakumar T. Analysis of circulating exosomes reveals a peripheral signature of astrocytic pathology in schizophrenia. The World Journal Of Biological Psychiatry 2021, 23: 33-45. PMID: 33821753, DOI: 10.1080/15622975.2021.1907720.Peer-Reviewed Original ResearchConceptsHealthy controlsSex-matched healthy controlsBlood-brain barrierNovel peripheral biomarkersPlasma-derived exosomesAstroglial pathologyWestern blot analysisPeripheral biomarkersSynaptophysin levelsBrain barrierPeripheral signatureAstrocytic pathologyGFAP concentrationsSchizophrenia patientsExosomal protein expressionNeuropsychiatric disordersNeurodegenerative disordersProtein immunopositivitySchizophreniaProtein expressionGroup differencesDisordersPatientsScarce dataConcentration of exosomes
2019
In vivo 5-HT6 and 5-HT2A receptor availability in antipsychotic treated schizophrenia patients vs. unmedicated healthy humans measured with [11C]GSK215083 PET
Radhakrishnan R, Matuskey D, Nabulsi N, Gaiser E, Gallezot JD, Henry S, Planeta B, Lin SF, Ropchan J, Huang Y, Carson RE, D'Souza DC. In vivo 5-HT6 and 5-HT2A receptor availability in antipsychotic treated schizophrenia patients vs. unmedicated healthy humans measured with [11C]GSK215083 PET. Psychiatry Research Neuroimaging 2019, 295: 111007. PMID: 31760336, DOI: 10.1016/j.pscychresns.2019.111007.Peer-Reviewed Original ResearchConceptsHealthy male controlsPositron emission tomographyMultilinear analysis 1Antipsychotic treatmentLower BPFrontal cortexReceptor availabilityAge-matched healthy male controlsDifferent second-generation antipsychoticsSteady-state troughPeak serum levelsSecond-generation antipsychoticsPotential therapeutic targetMale patientsSerum levelsHealthy humansTherapeutic targetSchizophrenia patientsTime-activity curvesMale controlsCognitive impairmentEmission tomographyVentral striatumPatientsSchizophreniaO11.2. CHARACTERIZING CANNABINOID INDUCED ACUTE PERSISTENT PSYCHOSIS (CIAPP) AS A POSSIBLE SUBTYPE OF SCHIZOPHRENIA USING DEEP LEARNING
Ganesh S, Vidya K, Tikka S, Raj J, Gahalout R, Skosnik P, Luddy C, Goyal N, Ram D, D’Souza D, Cortes-Briones J. O11.2. CHARACTERIZING CANNABINOID INDUCED ACUTE PERSISTENT PSYCHOSIS (CIAPP) AS A POSSIBLE SUBTYPE OF SCHIZOPHRENIA USING DEEP LEARNING. Schizophrenia Bulletin 2019, 45: s194-s194. PMCID: PMC6455269, DOI: 10.1093/schbul/sbz021.258.Peer-Reviewed Original Research
2018
Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study
Breier A, Buchanan RW, D'Souza D, Nuechterlein K, Marder S, Dunn W, Preskorn S, Macaluso M, Wurfel B, Maguire G, Kakar R, Highum D, Hoffmeyer D, Coskinas E, Litman R, Vohs JL, Radnovich A, Francis MM, Metzler E, Visco A, Mehdiyoun N, Yang Z, Zhang Y, Yolken RH, Dickerson FB. Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study. Schizophrenia Research 2018, 206: 291-299. PMID: 30478008, DOI: 10.1016/j.schres.2018.11.002.Peer-Reviewed Original ResearchConceptsHSV-1Double-blind efficacy trialHerpes simplex virus 1 (HSV-1) infectionEarly phase schizophreniaSimplex virus 1 infectionVirus-1 infectionPathophysiology of schizophreniaPrimary endpointValacyclovir treatmentNegative subjectsRecent trialsVISTA studyEfficacy trialsLetter-Number Sequencing TestNegative groupPositive groupSevere formHerpes virusPositive symptomsMore impairmentTreatment resultsUS sitesCognitive deficitsNon-activated stateSchizophreniaDose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects
D’Souza D, Carson RE, Driesen N, Johannesen J, Ranganathan M, Krystal JH, Ahn K, Bielen K, Carbuto M, Deaso E, D’Souza D, Ranganathan M, Naganawa M, Ranganathan M, D’Souza D, Nabulsi N, Zheng M, Lin S, Huang Y, Carson R, Driesen N, Ahn K, Morgan P, Suckow R, He G, McCarthy G, Krystal J, Johannesen J, Kenney J, Gelernter J, Gueorguieva R, Pittman B. Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects. Biological Psychiatry 2018, 84: 413-421. PMID: 29499855, PMCID: PMC6068006, DOI: 10.1016/j.biopsych.2017.12.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzabicyclo CompoundsBrainCognitive DysfunctionDose-Response Relationship, DrugDouble-Blind MethodFemaleGlycine Plasma Membrane Transport ProteinsHumansImidazolesKetamineLong-Term PotentiationMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedPositron-Emission TomographySchizophreniaYoung AdultConceptsHealthy control subjectsLong-term potentiationSchizophrenia patientsControl subjectsCognitive impairmentClinical trialsGlyT1 occupancyN-methyl-D-aspartate receptor functionGlycine transporter-1 inhibitorKetamine-induced disruptionKetamine-induced effectsFunctional magnetic resonance imagingMagnetic resonance imagingPositron emission tomographyMemory-related activationF-MKSubstudy 1Schizophrenia subjectsResonance imagingReceptor functionCortical regionsEmission tomographyTarget engagementPotentiationSchizophreniaChapter 4 Psychotomimetic and Cognitive Effects of Δ9-Tetrahydrocannabinol in Laboratory Settings
Cahill J, Gupta S, Cortes-Briones J, Radhakrishnan R, Sherif M, D'Souza D. Chapter 4 Psychotomimetic and Cognitive Effects of Δ9-Tetrahydrocannabinol in Laboratory Settings. 2018, 75-128. DOI: 10.1016/b978-0-12-804791-0.00004-5.Peer-Reviewed Original ResearchHuman laboratory studiesCognitive effectsFunctional magnetic resonance imagingDeleterious cognitive effectsCannabis use disorderArray of outcomesPsychophysiological correlatesNeural noiseWider clinical implicationsEEG measuresRisk of psychosisΔ9-tetrahydrocannabinolUse disordersLaboratory settingPsychotic disordersMethodological strengthsClinical implicationsElectroencephalographyCannabisSchizophreniaSingle Photon Emission Computerized TomographyPhoton Emission Computerized TomographyHealthy humansPsychosisMagnetic resonance imaging
2017
Minimal effects of prolonged smoking abstinence or resumption on cognitive performance challenge the “self-medication” hypothesis in schizophrenia
Boggs DL, Surti TS, Esterlis I, Pittman B, Cosgrove K, Sewell RA, Ranganathan M, D'Souza DC. Minimal effects of prolonged smoking abstinence or resumption on cognitive performance challenge the “self-medication” hypothesis in schizophrenia. Schizophrenia Research 2017, 194: 62-69. PMID: 28392208, PMCID: PMC5630481, DOI: 10.1016/j.schres.2017.03.047.Peer-Reviewed Original ResearchConceptsProcessing speedMultiple cognitive domainsCognitive test performancePro-cognitive effectsSelf-medication hypothesisNicotine-dependent smokersVerbal memoryVerbal recallCognitive batteryCognitive domainsExecutive functionVerbal fluencyBehavioral measuresTest batteryCognitive deficitsTest performanceSmoking cessationSmoking abstinenceNegative symptomsConflict resolutionAbstinenceCognitionDepressive symptomsSchizophreniaSmoke cigarettes
2016
Human Laboratory Studies on Cannabinoids and Psychosis
Sherif M, Radhakrishnan R, D’Souza D, Ranganathan M. Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry 2016, 79: 526-538. PMID: 26970363, DOI: 10.1016/j.biopsych.2016.01.011.BooksConceptsCannabinoid agonistsPsychotomimetic effectsAcute psychotomimetic effectsHealthy control subjectsCrossover laboratory studyEffects of ketamineHuman laboratory studiesGamma-aminobutyric acidHealthy human subjectsSelf-medication hypothesisTransient exacerbationAntipsychotic medicationControl subjectsDopamine metabolismGlutamate systemDopamine releasePsychotomimetic drugsCognitive symptomsDrug AdministrationAgonistsMagnitude of effectSymptomsSchizophreniaCannabinoidsLaboratory studies
2015
The early identification of psychosis: can lessons be learnt from cardiac stress testing?
Gupta S, Ranganathan M, D’Souza D. The early identification of psychosis: can lessons be learnt from cardiac stress testing? Psychopharmacology 2015, 233: 19-37. PMID: 26566609, PMCID: PMC4703558, DOI: 10.1007/s00213-015-4143-3.Peer-Reviewed Original ResearchConceptsCardiac stress testingCoronary artery diseaseMyocardial infarctionOutcome measuresPsychotic disordersDetection of CADManagement of schizophreniaStress testingManagement of anginaDiagnosis of schizophreniaStress testArtery diseasePsychotic episodePsychiatric disordersPredictive valueEarly identificationEarly detectionSchizophreniaPsychosisDisordersTarget populationRiskSafe stimuliRange of risksUrgent needReduced Brain Cannabinoid Receptor Availability in Schizophrenia
Ranganathan M, Cortes-Briones J, Radhakrishnan R, Thurnauer H, Planeta B, Skosnik P, Gao H, Labaree D, Neumeister A, Pittman B, Surti T, Huang Y, Carson RE, D’Souza D. Reduced Brain Cannabinoid Receptor Availability in Schizophrenia. Biological Psychiatry 2015, 79: 997-1005. PMID: 26432420, PMCID: PMC4884543, DOI: 10.1016/j.biopsych.2015.08.021.Peer-Reviewed Original ResearchConceptsHealthy control subjectsSCZ subjectsCB1R availabilityECB systemMale healthy control subjectsBody mass indexAge-matched male healthy control subjectsPathophysiology of schizophreniaPositron emission tomographyPosterior cingulate cortexPresence of abnormalitiesMass indexControl subjectsEndocannabinoid systemTobacco useReceptor availabilityCingulate cortexEmission tomography dataBrain regionsEmission tomographySelective radiotracerVivo measuresRegional volumesSchizophreniaPositron emission tomography data
2014
Going up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia.
Boggs DL, Carlson J, Cortes-Briones J, Krystal JH, D'Souza DC. Going up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia. Current Pharmaceutical Design 2014, 20: 5077-92. PMID: 24345265, PMCID: PMC4442779, DOI: 10.2174/1381612819666131216121019.Peer-Reviewed Original ResearchConceptsCognitive impairmentStandardized cognitive test batteryCognitive test batteryInformation processing impairmentsNicotinic medicationsProcessing impairmentsCore deficitAttentional deficitsTest batteryCognitive deficitsProximal measuresBrain functionCognitionSchizophreniaDeficitsImpairmentNumber of medicationsNicotinic acetylcholine receptorsCertain symptomsConsistent improvementClinical evidenceTreatment strategiesClinical studiesNicotinic receptorsClinical utilityChapter Fourteen Cannabis, Cannabinoids, and the Association with Psychosis
Radhakrishnan R, Addy P, Sewell R, Skosnik P, Ranganathan M, D’Souza D. Chapter Fourteen Cannabis, Cannabinoids, and the Association with Psychosis. 2014, 423-474. DOI: 10.1016/b978-0-12-418679-8.00014-9.Peer-Reviewed Original ResearchPsychotic disordersCannabis exposureComponent causesCannabinoid receptor functionDevelopment of schizophreniaHeavy cannabis exposurePublic health policyCannabinoid exposureTrigger relapsePsychophysiological deficitsCognitive symptomsReceptor functionSchizophreniaHealth policyCannabinoidsPsychosisCannabisLines of evidenceDisordersFurther studiesSymptomsBiological mechanismsExposureIndividual vulnerabilityCause
2013
In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia
Esterlis I, Ranganathan M, Bois F, Pittman B, Picciotto MR, Shearer L, Anticevic A, Carlson J, Niciu MJ, Cosgrove KP, D’Souza D. In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia. Biological Psychiatry 2013, 76: 495-502. PMID: 24360979, PMCID: PMC4019710, DOI: 10.1016/j.biopsych.2013.11.001.Peer-Reviewed Original ResearchConceptsLower β2Negative symptomsCortical regionsLower receptor availabilitySelf-medicate symptomsComparison groupLower negative symptomsHigh β2Executive controlExecutive functionNicotine cravingSex-matched comparison subjectsMood assessmentBrain regionsWorse performanceComparison subjectsDiagnosis interactionLimited brain regionsNicotinic acetylcholine receptorsSchizophreniaSingle photon emissionNAChR availabilityActive smokingTobacco smokingPoor outcome
2012
Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia
Gunduz-Bruce H, Oliver S, Gueorguieva R, Forselius-Bielen K, D'Souza DC, Zimolo Z, Tek C, Kaliora S, Ray S, Petrides G. Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia. Schizophrenia Research 2012, 143: 344-347. PMID: 23219861, DOI: 10.1016/j.schres.2012.11.008.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleTreatment-resistant schizophreniaClinical trialsNegative symptomsDouble-blind placeboAdequate blood levelsPsychiatric Rating ScaleNeurocognitive measuresAttention/executive functionBPRS totalPartial respondersPartial responseStudy entryQTc intervalBlood levelsClozapine's effectSide effectsNeurocognitive functionPatientsWeekly assessmentsClozapineNeurocognitive testsRating ScaleSchizophreniaTrials