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
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 levelsDifferential Cognitive Performance in Females and Males with Regular Cannabis Use
Martin A, D’Souza D, Newman SD, Hetrick WP, O’Donnell B. Differential Cognitive Performance in Females and Males with Regular Cannabis Use. Journal Of The International Neuropsychological Society 2021, 27: 570-580. PMID: 34261548, PMCID: PMC8830784, DOI: 10.1017/s1355617721000606.Peer-Reviewed Original ResearchConceptsRegular cannabis useCannabis useCognitive measuresPsychomotor speedBiological sexHopkins Verbal Learning TestDifferential cognitive performanceNon-using peersVerbal Learning TestMeasures of intelligenceWechsler Abbreviated ScaleDigit symbol testGreatest group differencesVerbal learningDigit spanLearning TestCognitive performanceAbbreviated ScaleNeurocognitive deficitsCognitive deficitsSymbol testCannabis exposurePsychomotor performanceGroup differencesCognition
2019
Characterizing psychosis-relevant phenomena and cognitive function in a unique population with isolated, chronic and very heavy cannabis exposure
D'Souza DC, Ganesh S, Cortes-Briones J, Campbell MH, Emmanuel MK. Characterizing psychosis-relevant phenomena and cognitive function in a unique population with isolated, chronic and very heavy cannabis exposure. Psychological Medicine 2019, 50: 2452-2459. PMID: 31615592, DOI: 10.1017/s0033291719002721.Peer-Reviewed Original ResearchConceptsSchizotypal Personality QuestionnaireCognitive performanceCannabis exposureTests of attentionComputerized cognitive batteryVisuo-spatial processingHigher SPQ scoresSubstance use/misuseWorse cognitive performanceHeavy cannabis exposureLarge effect sizesUse/misuseCognitive flexibilityVerbal memoryCognitive batteryCognitive functioningPsychomotor speedSPQ scoresCognitive functionCognitive deficitsCannabis usersPersonality QuestionnaireCannabis useUse of cannabisEarly cannabis
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 stateSchizophrenia
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
2014
Gone to Pot – A Review of the Association between Cannabis and Psychosis
Radhakrishnan R, Wilkinson ST, D’Souza D. Gone to Pot – A Review of the Association between Cannabis and Psychosis. Frontiers In Psychiatry 2014, 5: 54. PMID: 24904437, PMCID: PMC4033190, DOI: 10.3389/fpsyt.2014.00054.BooksPsychotic disordersFamily historyEmergence of psychosisPolymorphisms of COMTPublic health policySymptoms of schizophreniaTrigger relapsePsychosis outcomesHigh riskEpidemiological studiesAcute exposurePsychotomimetic symptomsPsychophysiological abnormalitiesPersistent effectsCognitive deficitsCannabis useHealth policyCannabinoidsSymptomsGenetic factorsCannabisChildhood traumaDisordersStandard criteriaWarrants serious considerationGoing 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 utility
2012
Feasibility, Safety, and Efficacy of the Combination of D-Serine and Computerized Cognitive Retraining in Schizophrenia: An International Collaborative Pilot Study
D'Souza DC, Radhakrishnan R, Perry E, Bhakta S, Singh NM, Yadav R, Abi-Saab D, Pittman B, Chaturvedi SK, Sharma MP, Bell M, Andrade C. Feasibility, Safety, and Efficacy of the Combination of D-Serine and Computerized Cognitive Retraining in Schizophrenia: An International Collaborative Pilot Study. Neuropsychopharmacology 2012, 38: 492-503. PMID: 23093223, PMCID: PMC3547200, DOI: 10.1038/npp.2012.208.Peer-Reviewed Original ResearchConceptsCognitive retrainingCognitive deficitsVerbal Working MemoryCognitive remediation strategiesAttention/vigilanceBasic information processingIndividual test performanceGlobal cognitive indexWorking memoryD-serineCognitive indicesCombination of pharmacotherapyTest performanceInformation processingMulticenter international clinical trialParallel group designSchizophrenia subjectsCollaborative pilot studyInternational clinical trialsUS samplePreliminary findingsCombination pharmacotherapySchizophreniaClinical trialsOutcome measuresDose-Related Behavioral, Subjective, Endocrine, and Psychophysiological Effects of the κ Opioid Agonist Salvinorin A in Humans
Ranganathan M, Schnakenberg A, Skosnik PD, Cohen BM, Pittman B, Sewell RA, D'Souza DC. Dose-Related Behavioral, Subjective, Endocrine, and Psychophysiological Effects of the κ Opioid Agonist Salvinorin A in Humans. Biological Psychiatry 2012, 72: 871-879. PMID: 22817868, PMCID: PMC3638802, DOI: 10.1016/j.biopsych.2012.06.012.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, InhalationAdultCardiovascular SystemCognitionCross-Over StudiesDiterpenes, ClerodaneDose-Response Relationship, DrugDrug MonitoringElectroencephalographyEuphoriaFemaleHallucinogensHumansHydrocortisoneIllicit DrugsMalePerceptionProlactinPsychiatric Status Rating ScalesPsychoses, Substance-InducedReceptors, Opioid, kappaSensationConceptsSA administrationSalvinorin APopular recreational drugElectroencephalogram spectral powerPrimary active ingredientPsychotomimetic effectsReceptor agonismOpiate receptorsEndocrine effectsHealthy subjectsSelective agonistHealthy individualsPerceptual alterationsPlasma cortisolEuphoric effectsCognitive deficitsRecreational drugsVital signsCounterbalanced studyEffect of SAYoung adultsAdverse effectsPsychophysiological effectsIndividual variabilityAdministrationNicotine Fails to Attenuate Ketamine-Induced Cognitive Deficits and Negative and Positive Symptoms in Humans: Implications for Schizophrenia
D'Souza DC, Ahn K, Bhakta S, Elander J, Singh N, Nadim H, Jatlow P, Suckow RF, Pittman B, Ranganathan M. Nicotine Fails to Attenuate Ketamine-Induced Cognitive Deficits and Negative and Positive Symptoms in Humans: Implications for Schizophrenia. Biological Psychiatry 2012, 72: 785-794. PMID: 22717030, DOI: 10.1016/j.biopsych.2012.05.009.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAttentionCognitionCognition DisordersCross-Over StudiesDouble-Blind MethodDrug InteractionsExecutive FunctionHumansInhibition, PsychologicalKetamineMemoryMiddle AgedMotor SkillsNicotinePsychiatric Status Rating ScalesPsychomotor PerformanceReaction TimeRecognition, PsychologySchizophreniaConceptsCognitive deficitsPositive symptomsExecutive functionResponse inhibitionKetamine-induced cognitive deficitsChoice reaction time taskSpeed of processingReaction time taskReaction timeVisual memoryEmotion recognitionImmediate recallSustained attentionTime taskFeeling statesPerceptual alterationsSerial processingEffects of nicotineNegative symptomsMemoryBehavioral effectsDeficitsInteractive effectsNicotine infusionTest dayDose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans
D'Souza DC, Fridberg DJ, Skosnik PD, Williams A, Roach B, Singh N, Carbuto M, Elander J, Schnakenberg A, Pittman B, Sewell RA, Ranganathan M, Mathalon D. Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans. Neuropsychopharmacology 2012, 37: 1632-1646. PMID: 22334121, PMCID: PMC3358754, DOI: 10.1038/npp.2012.8.Peer-Reviewed Original ResearchConceptsRecent cannabis usersPerceptual alterationsERP componentsCannabis usersEvent-related potential taskSensory ERP componentsCannabis Use StatusModulation of eventsΔ9-THCProperties of cannabisContext updatingNeural correlatesP3b amplitudeTarget stimuliPsychophysiological indicesCortical processesP300b amplitudesProcessing speedCognitive deficitsPsychophysiological dataInformation processingAutomatic orientationCounterbalanced designSubjective effectsPotential tasks
2005
Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction
D’Souza D, Abi-Saab WM, Madonick S, Forselius-Bielen K, Doersch A, Braley G, Gueorguieva R, Cooper TB, Krystal JH. Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. Biological Psychiatry 2005, 57: 594-608. PMID: 15780846, DOI: 10.1016/j.biopsych.2004.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAkathisia, Drug-InducedArousalCognitionDose-Response Relationship, DrugDouble-Blind MethodDronabinolEndocrine SystemFemaleHumansInjections, IntravenousMaleMental RecallMiddle AgedMotor ActivityNeuropsychological TestsPerceptionPsychiatric Status Rating ScalesPsychotic DisordersPsychotropic DrugsSchizophreniaVerbal LearningConceptsSchizophrenia patientsAntipsychotic-treated schizophrenia patientsDelta-9-tetrahydrocannabinol effectsLong-term adverse eventsCognitive deficitsPlacebo-controlled studyDelta-9-THCTransient exacerbationAdverse eventsReceptor dysfunctionEndocrine effectsHealthy subjectsStudy participationPsychotic disordersPlasma prolactinSchizophrenia symptomsPatientsSchizophreniaCognitive effectsPerceptual alterationsDeficitsCannabisSubjectsAkathisiaExacerbation
2004
The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis
D'Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, Braley G, Gueorguieva R, Krystal JH. The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis. Neuropsychopharmacology 2004, 29: 1558-1572. PMID: 15173844, DOI: 10.1038/sj.npp.1300496.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnxietyArousalAttentionBehaviorCognitionDose-Response Relationship, DrugDouble-Blind MethodDronabinolFemaleHallucinogensHemodynamicsHumansHydrocortisoneInjections, IntravenousMaleMemory, Short-TermMental RecallPanicProlactinPsychiatric Status Rating ScalesPsychometricsPsychoses, Substance-InducedSpeechVerbal LearningConceptsCannabinoid receptor functionWord recallRecognition recallVerbal fluencyCognitive deficitsProspective safety dataNegative symptomsAbuse disordersHealthy individualsCounterbalanced studyMonths poststudyRecallPsychotomimetic effectsPsychotic disordersReceptor functionPsychosisEndogenous psychosesIndividualsDistractibilityFluencyTransient symptomsDisordersEndocrine effectsSafety dataAnxiety