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
The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis
Beck K, Hindley G, Borgan F, Ginestet C, McCutcheon R, Brugger S, Driesen N, Ranganathan M, D'Souza D, Taylor M, Krystal J, Howes O. The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis. BJPsych Open 2021, 7: s237-s237. PMCID: PMC8771247, DOI: 10.1192/bjo.2021.634.Peer-Reviewed Original ResearchBrief Psychiatric Rating ScaleEffects of ketaminePlacebo conditionPositive symptomsKetamine administrationKetamine effectsHealthy participantsHealthy volunteersNegative symptomsTherapeutic useAcute ketamine administrationAcute ketamine challengeMagnitude of symptomsStudy-level dataSub-group analysisPsychiatric Rating ScaleSchizophrenia-like symptomatologySchizophrenia-like symptomsMean change scoresNegative Syndrome ScalePositive psychotic symptomsSignificant increaseEffect sizeBolus dosesKetamine challenge
2020
Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia
Beck K, Hindley G, Borgan F, Ginestet C, McCutcheon R, Brugger S, Driesen N, Ranganathan M, D’Souza D, Taylor M, Krystal JH, Howes OD. Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia. JAMA Network Open 2020, 3: e204693. PMID: 32437573, PMCID: PMC7243091, DOI: 10.1001/jamanetworkopen.2020.4693.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScalePlacebo conditionPositive symptomsNegative symptomsHealthy participantsMean differenceKetamine administrationPANSS scoresHealthy volunteersPsychotomimetic symptomsTherapeutic useAcute ketamine administrationAcute ketamine challengePlacebo-controlled studyEffect sizeMagnitude of symptomsStudy-level dataPsychiatric Rating ScaleMeta-Analyses (PRISMA) guidelinesPreferred Reporting ItemsAssociation of ketamineNegative Syndrome ScaleSignificant increaseAcute administrationBolus doses
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 cigarettesAttenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242
Ranganathan M, DeMartinis N, Huguenel B, Gaudreault F, Bednar MM, Shaffer CL, Gupta S, Cahill J, Sherif MA, Mancuso J, Zumpano L, D’Souza D. Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242. Molecular Psychiatry 2017, 22: 1633-1640. PMID: 28242871, DOI: 10.1038/mp.2017.6.Peer-Reviewed Original ResearchConceptsKetamine-induced impairmentVerbal learningAMPAR potentiatorsHopkins Verbal Learning TestN-methyl-D-aspartate receptorsVerbal Learning TestDissociative Symptoms ScaleKetamine-induced deficitsPsychotomimetic effectsMemory taskImmediate recallLearning TestCogState batteryMemory deficitsNegative Syndrome ScaleTreatment periodCognitive symptomsNMDAR functioningNMDAR antagonist ketamineNonhuman primatesNegative symptomsCognitive impairmentMemoryIsoxazolepropionic acid (AMPA) receptorsPathophysiology of schizophrenia
2016
Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO
Girgis RR, Slifstein M, D’Souza D, Lee Y, Periclou A, Ghahramani P, Laszlovszky I, Durgam S, Adham N, Nabulsi N, Huang Y, Carson RE, Kiss B, Kapás M, Abi-Dargham A, Rakhit A. Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO. Psychopharmacology 2016, 233: 3503-3512. PMID: 27525990, PMCID: PMC5035321, DOI: 10.1007/s00213-016-4382-y.Peer-Reviewed Original ResearchConceptsDopamine D3 receptorD2 receptorsD3 receptorsReceptor occupancyPartial agonistPositive symptomsD2 receptor partial agonistNegative symptomsPositron emission tomography scanDose-occupancy relationshipD2 receptor occupancyWeeks of dosingEmission tomography scanWeeks of treatmentExposure-response analysisReceptor partial agonistCerebrospinal fluid samplesDopamine D2 receptorsReward-related behaviorsD2 receptor ligandsTomography scanD2 antagonismPatientsDay 1Low doses
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 outcomeRelationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans
Driesen NR, McCarthy G, Bhagwagar Z, Bloch M, Calhoun V, D'Souza DC, Gueorguieva R, He G, Ramachandran R, Suckow RF, Anticevic A, Morgan PT, Krystal JH. Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans. Molecular Psychiatry 2013, 18: 1199-1204. PMID: 23337947, PMCID: PMC3646075, DOI: 10.1038/mp.2012.194.Peer-Reviewed Original ResearchConceptsFunctional connectivityNegative symptomsGamma-aminobutyric acid (GABA) neuronsNMDA receptor antagonist ketamineAspartate glutamate receptor antagonistContinuous ketamine infusionGlutamate receptor antagonistsNMDA-R antagonistsCortical functional connectivityNMDA-R antagonist ketamineSchizophrenia-like symptomsHealthy human subjectsNegative Syndrome ScaleBrain functional connectivityPrimary samplesRegion-specific mannerFunctional magnetic resonanceKetamine infusionReceptor antagonistPathological increaseSyndrome ScaleSymptomsPreclinical researchKetamineBrain oscillations
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 ScaleSchizophreniaTrialsGlycine treatment of the risk syndrome for psychosis: Report of two pilot studies
Woods SW, Walsh BC, Hawkins KA, Miller TJ, Saksa JR, D'Souza DC, Pearlson GD, Javitt DC, McGlashan TH, Krystal JH. Glycine treatment of the risk syndrome for psychosis: Report of two pilot studies. European Neuropsychopharmacology 2012, 23: 931-940. PMID: 23089076, PMCID: PMC4028140, DOI: 10.1016/j.euroneuro.2012.09.008.Peer-Reviewed Original ResearchConceptsPilot studyRisk syndromeSyndrome patientsNegative symptomsShort-term pilot studyEffect sizeAdjunctive antipsychotic medicationOpen-label studyPatients meeting criteriaNMDA receptor functionDurability of effectPsychosis risk symptomsGlycine site agonistsGroup effect sizesWeeks of evaluationAntipsychotic medicationSyndrome subjectsPromising effect sizesTreatment needsLarge effect sizesMeeting criteriaCognitive impairmentReduced symptomsReceptor functionSymptomsNicotine 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 dayLower β2*-Nicotinic Acetylcholine Receptor Availability in Smokers With Schizophrenia
D'Souza DC, Esterlis I, Carbuto M, Krasenics M, Seibyl J, Bois F, Pittman B, Ranganathan M, Cosgrove K, Staley J. Lower β2*-Nicotinic Acetylcholine Receptor Availability in Smokers With Schizophrenia. American Journal Of Psychiatry 2012, 169: 326-334. PMID: 22193533, PMCID: PMC3881431, DOI: 10.1176/appi.ajp.2011.11020189.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptor availabilityNicotinic acetylcholine receptorsReceptor availabilityNegative symptomsAcetylcholine receptorsNicotinic acetylcholine receptor systemHealthy tobacco smokersAcetylcholine receptor systemDevelopment of medicationsSingle photon emissionIA-85380Agonist radiotracerTobacco smokersCigarette smokingAvailability of receptorsSmoking abstinenceNicotine actionPostmortem studiesFrontal cortexSmokersSmokingVivo findingsParietal cortexReceptor systemSymptoms
2010
Armodafinil as adjunctive therapy in adults with cognitive deficits associated with schizophrenia: a 4-week, double-blind, placebo-controlled study.
Kane JM, D'Souza DC, Patkar AA, Youakim JM, Tiller JM, Yang R, Keefe RS. Armodafinil as adjunctive therapy in adults with cognitive deficits associated with schizophrenia: a 4-week, double-blind, placebo-controlled study. The Journal Of Clinical Psychiatry 2010, 71: 1475-81. PMID: 20816042, DOI: 10.4088/jcp.09m05950gry.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntipsychotic AgentsBenzhydryl CompoundsBenzodiazepinesCentral Nervous System StimulantsCognition DisordersDouble-Blind MethodDrug Therapy, CombinationFemaleHumansIsoxazolesMaleMiddle AgedModafinilOlanzapinePaliperidone PalmitatePsychiatric Status Rating ScalesPyrimidinesRisperidoneSchizophreniaTreatment OutcomeConceptsAdjunctive armodafinilAdjunctive therapyFinal visitNegative symptomsTotal scoreIsomer of modafinilTolerability of armodafinilPlacebo-controlled studyPrimary efficacy measureSecondary outcome measuresPANSS total scoreSANS total scoreNegative symptom scoresNegative Syndrome ScaleDaily placeboStable dosesAdverse eventsOral risperidoneSymptom scoresEfficacy measuresSchizophrenia (MATRICS) Consensus Cognitive BatteryOutcome measuresStable schizophreniaSD changeArmodafinil
2006
Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia
D'Souza DC, Gil RB, Madonick S, Perry EB, Forselius-Bielen K, Braley G, Donahue L, Tellioglu T, Zimolo Z, Gueorguieva R, Krystal JH. Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia. Neuropsychopharmacology 2006, 31: 2767-2775. PMID: 16985503, DOI: 10.1038/sj.npp.1301207.Peer-Reviewed Original ResearchConceptsEffects of alcoholHealthy subjectsBlood alcohol levelsPositive psychotic symptomsSmall transient increaseSelf-medication hypothesisPerceptual alterationsAlcohol administrationMotor functionAlcohol dosesElevated riskPsychotic symptomsLifetime exposureSchizophrenia patientsSchizophrenia symptomsEuphoric effectsNegative symptomsAlcohol levelsAlcohol useStimulatory effectSubjective effectsTransient increaseSchizophreniaStimulatory responseAlcohol responsesThe vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia
Krystal JH, D’Souza D, Gallinat J, Driesen N, Abi-Dargham A, Petrakis I, Heinz A, Pearlson G. The vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia. Neurotoxicity Research 2006, 10: 235-252. PMID: 17197373, DOI: 10.1007/bf03033360.Peer-Reviewed Original ResearchConceptsSubstance abuse riskSubstance abuseSubstance abuse disordersAbuse riskSubstances of abuseNicotinic cholinergicPatient groupDopaminergic inputAbused substancesAbuse disordersSchizophrenic patientsDysphoric effectsAbuse liabilityHigh dosesLow dosesNegative symptomsReceptor functionAltered responseSchizophreniaSchizophrenic individualsRiskReward processingSubjective distressImpulsive behaviorDosesGreater vulnerability to the amnestic effects of ketamine in males
Morgan CJ, Perry EB, Cho HS, Krystal JH, D’Souza D. Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology 2006, 187: 405-414. PMID: 16896964, DOI: 10.1007/s00213-006-0409-0.Peer-Reviewed Original ResearchConceptsAmnestic effectsProcessing of wordsGeneral cognitive functioningGreater performance decrementsGreater subjective senseGender differencesObjectivesThe current studyGreater vulnerabilityCognitive measuresCognitive differencesCognitive functioningPerceptual alterationsPerformance decrementsNMDA-R functionAttention dataMemory impairmentSubjective senseNegative symptomsCurrent studyFunctioningHVLTKetamine studiesAnxietyMemoryKetamine administration
2005
Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function
Krystal JH, Perry EB, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A, Cooper TB, MacDougall L, Abi-Saab W, D’Souza D. Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function. JAMA Psychiatry 2005, 62: 985-995. PMID: 16143730, DOI: 10.1001/archpsyc.62.9.985.Peer-Reviewed Original ResearchAbsence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine
Cho HS, D’Souza D, Gueorguieva R, Perry EB, Madonick S, Karper LP, Abi-Dargham A, Belger A, Abi-Saab W, Lipschitz D, Bennet A, Seibyl JP, Krystal JH. Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine. Psychopharmacology 2005, 179: 136-143. PMID: 15682309, DOI: 10.1007/s00213-004-2066-5.Peer-Reviewed Original ResearchConceptsHealthy human subjectsBehavioral sensitizationReceptor antagonistN-methyl-D-aspartate (NMDA) glutamate receptor antagonistBehavioral effectsHuman subjectsGlutamate receptor antagonistsNMDA receptor antagonistConclusionsThe current dataEvidence of sensitizationRetrospective studyKetamine administrationOutcome measuresNegative symptomsObjectivesThe purposePrevious exposureFirst exposureKetamineSensitizationAntagonistExposurePerceptual alterationsCurrent dataSeparate studiesSubjects
2004
Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects
Krystal JH, Abi-Saab W, Perry E, D’Souza D, Liu N, Gueorguieva R, McDougall L, Hunsberger T, Belger A, Levine L, Breier A. Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology 2004, 179: 303-309. PMID: 15309376, DOI: 10.1007/s00213-004-1982-8.Peer-Reviewed Original ResearchConceptsGroup II metabotropic glutamate receptor agonistMetabotropic glutamate receptor agonistHealthy human subjectsNMDA glutamate receptor antagonistGlutamate receptor agonistsGlutamate receptor antagonistsTest dayCognitive effectsPerceptual changesKetamine infusionReceptor antagonistReceptor agonistDysphoric moodMemory impairmentBehavioral consequencesSignificant dose-related improvementGroup II mGluR agonistReceptor functionHuman subjectsMemoryNegative symptomsDose-related improvementNMDA receptor functionPreliminary evidenceDisruptive effectsThe 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