2023
The 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 modelSchizophrenia
2021
Analysis 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 striatumPatientsSchizophrenia
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
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 ScaleSchizophreniaTrialsComorbid Alcohol, Cannabis, and Cocaine Use Disorders in Schizophrenia: Epidemiology, Consequences, Mechanisms, and Treatment
Addy P, Radhakrishnan R, Cortes J, D’Souza D. Comorbid Alcohol, Cannabis, and Cocaine Use Disorders in Schizophrenia: Epidemiology, Consequences, Mechanisms, and Treatment. FOCUS The Journal Of Lifelong Learning In Psychiatry 2012, 10: 140-153. DOI: 10.1176/appi.focus.10.2.140.Peer-Reviewed Original ResearchComorbid substance use disorderSubstance use disordersUse disordersSubstance abuseHigh rateTreatment of schizophreniaCo-occurring disordersCourse of schizophreniaCocaine use disorderSelf-medication hypothesisCombination pharmacotherapyComorbid alcoholService utilizationLow compliancePatientsSchizophreniaSubstance useDisordersTreatmentDSM definitionCliniciansEpidemiologyThorough assessmentCannabisLatest findings
2011
The acute effects of cannabinoids in patients with psychotic illness
Henquet C, Sewell A, Kuepper R, Ranganathan M, D’Souza D. The acute effects of cannabinoids in patients with psychotic illness. 2011, 198-209. DOI: 10.1017/cbo9780511706080.019.Peer-Reviewed Original ResearchMental health teamsImpact of cannabisEffects of cannabisPublic health specialistsCannabinoid systemAcute effectsHealth teamsPsychotic illnessHealth specialistsMental illnessMental healthEpidemiological factsCannabisIllnessAlcohol researchCannabis sativaNew research findingsPatientsSchizophreniaCannabinoids
2010
Probing GABA Receptor Function in Schizophrenia with Iomazenil
Ahn K, Gil R, Seibyl J, Sewell RA, D'Souza DC. Probing GABA Receptor Function in Schizophrenia with Iomazenil. Neuropsychopharmacology 2010, 36: 677-683. PMID: 21068719, PMCID: PMC3055690, DOI: 10.1038/npp.2010.198.Peer-Reviewed Original ResearchConceptsSchizophrenia patientsHealthy controlsGABA deficitHealthy subjectsBrief Psychiatric Rating ScaleGABA-deficit hypothesisPlacebo-controlled studyChronic schizophrenia patientsPathophysiology of schizophreniaPsychiatric Rating ScalePartial inverse agonistDissociative Symptoms ScaleGABA receptor functionPerceptual alterationsPsychotomimetic effectsPsychotic symptomsIomazenilBenzodiazepine receptorsPatientsSymptom ScalePharmacological inductionReceptor functionInverse agonistRating ScaleBrain imaging
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 alterationsDeficitsCannabisSubjectsAkathisiaExacerbationMazindol Augmentation of Antipsychotic Treatment for Schizophrenic Patients with Comorbid Cocaine Abuse or Dependence
Perry E, Gil R, Miles D, Brenner L, Macdougall L, Johnson R, Degen K, Gueorguieva R, Petrakis I, Krystal J, D'Souza D. Mazindol Augmentation of Antipsychotic Treatment for Schizophrenic Patients with Comorbid Cocaine Abuse or Dependence. Journal Of Dual Diagnosis 2005, 1: 37-47. DOI: 10.1300/j374v01n01_04.Peer-Reviewed Original ResearchCocaine abusePsychiatric symptomsCocaine cravingCatecholamine reuptake inhibitorCurrent antipsychotic medicationsCocaine consumptionPlacebo groupAntipsychotic pharmacotherapyReuptake inhibitorsAntipsychotic medicationAntipsychotic treatmentComorbid schizophreniaSchizoaffective patientsSubstance abuse issuesSchizophrenic patientsPatientsSchizoaffective disorderSchizophrenia patientsNatural historyMazindolPilot studyGroup therapySchizophreniaSymptomsAbuse issues
2004
Cannabinoid ‘model’ psychosis, dopamine–cannabinoid interactions and implications for schizophrenia
D'souza D, Cho H, Perry E, Krystal J. Cannabinoid ‘model’ psychosis, dopamine–cannabinoid interactions and implications for schizophrenia. 2004, 142-165. DOI: 10.1017/cbo9780511543630.012.Peer-Reviewed Original ResearchReceptor dysfunctionCannabinoid compoundsCannabis consumptionPathophysiology of psychosisPathophysiology of schizophreniaRecent pharmacological studiesPrincipal psychoactive constituentEffects of exposurePostmortem studiesNormal controlsPsychotic symptomsPsychotic disordersPharmacological studiesPsychosisPsychoactive constituentPathophysiologyΔ9-tetrahydrocannabinolSchizophreniaCannabisDysfunctionAssociationPossible mechanismPatientsSymptomsPharmacological
2003
Altered NMDA Glutamate Receptor Antagonist Response in Recovering Ethanol-Dependent Patients
Krystal JH, Petrakis IL, Limoncelli D, Webb E, Gueorgueva R, D'Souza DC, Boutros NN, Trevisan L, Charney DS. Altered NMDA Glutamate Receptor Antagonist Response in Recovering Ethanol-Dependent Patients. Neuropsychopharmacology 2003, 28: 2020-2028. PMID: 12888778, DOI: 10.1038/sj.npp.1300252.Peer-Reviewed Original ResearchConceptsEthanol-dependent patientsNMDA receptor antagonistReceptor antagonistEthanol dependenceN-methyl-D-aspartate (NMDA) glutamate receptorsDouble-blind studySelective NMDA receptor antagonistNMDA receptor functionAlcohol-dependent patientsHealthy comparison subjectsTreatment of alcoholismHealthy comparison groupExecutive cognitive functionKetamine infusionKetamine 0.5NMDA receptorsGlutamate receptorsComparison subjectsPatientsAmnestic effectsRandomized orderReceptor functionCognitive functionAntagonist responseAntagonist
2002
Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms
Abi-Saab W, Seibyl JP, D'Souza C, Karper LP, Gueorgueva R, Abi-Dargham A, Wong ML, Rajhans S, Erdos JP, Heninger GR, Charney DS, Krystal JH. Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms. Psychopharmacology 2002, 162: 55-62. PMID: 12107618, DOI: 10.1007/s00213-002-1057-7.Peer-Reviewed Original ResearchConceptsReceptor antagonismSchizophrenic patientsNeuroleptic-free schizophrenic patientsBrief Psychiatric Rating ScaleDouble-blind conditionsPsychiatric Rating ScaleTest dayRitanserin pretreatmentIntravenous infusionReceptor modulationAntipsychotic activityMale inpatientsReceptor stimulationPlasma prolactinCortisol levelsSchizoaffective disorderSchizophrenia symptomsPositive symptomsNegative symptomsRandomized orderPatientsRating ScaleBehavioral activationSymptomsRitanserin
2001
Lower prolactin bioactivity in unmedicated schizophrenic patients
Warner M, Walker A, D'Souza D, Lee D, Nasseri D, Peabody C. Lower prolactin bioactivity in unmedicated schizophrenic patients. Psychiatry Research 2001, 102: 249-254. PMID: 11440775, DOI: 10.1016/s0165-1781(01)00256-6.Peer-Reviewed Original ResearchConceptsSchizophrenic patientsControl subjectsMale control subjectsUnmedicated schizophrenic patientsTuberoinfundibular dopamine systemProlactin abnormalitiesMale patientsNeuroleptic medicationProlactin bioactivityLong-term effectsPRL valuesNormal controlsDopamine systemPRL ratioPatientsSchizophrenic groupDifferent molecular formsRIABA techniqueSubjectsMolecular formsEarlier findingsMedicationsCURRENT PERSPECTIVES ON THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA, DEPRESSION, AND ANXIETY DISORDERS
Krystal J, D'Souza D, Sanacora G, Goddard A, Charney D. CURRENT PERSPECTIVES ON THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA, DEPRESSION, AND ANXIETY DISORDERS. Medical Clinics Of North America 2001, 85: 559-577. PMID: 11349473, DOI: 10.1016/s0025-7125(05)70329-1.Peer-Reviewed Original Research
2000
Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT
Laruelle M, Abi-Dargham A, van Dyck C, Gil R, D’Souza D, Krystal J, Seibyl J, Baldwin R, Innis R. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT. Biological Psychiatry 2000, 47: 371-379. PMID: 10704949, DOI: 10.1016/s0006-3223(99)00257-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsBrain StemCarrier ProteinsCase-Control StudiesCocaineDopamineDopamine Plasma Membrane Transport ProteinsFemaleHumansIodine RadioisotopesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNeostriatumNerve Tissue ProteinsSchizophreniaSerotoninSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-PhotonConceptsAmphetamine-induced dopamine releaseStriatal dopamine transporterDopamine transporterControl subjectsDAT densityDopamine releaseNegative symptomsStriatal DAT densityDuration of illnessDopamine nerve terminalsHealthy control subjectsSerotonin transporter densityCohort of subjectsRelative deficitSingle photon emissionNeurodegenerative processesPostmortem studiesNerve terminalsSerotonin functionTrend-level associationReceptor radiotracerPatientsDopamine functionLower striatalTransporter density
1999
Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report
Boutros N, Belger A, Campbell D, D’Souza C, Krystal J. Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report. Psychiatry Research 1999, 88: 119-130. PMID: 10622348, DOI: 10.1016/s0165-1781(99)00074-8.Peer-Reviewed Original ResearchConceptsNormal control subjectsSchizophrenia patientsSensory gatingControl subjectsNormal subjectsSex-matched normal control subjectsPathophysiology of schizophreniaStimulus repetitionStable schizophrenia patientsSchizophrenia subjectsSimilar abnormalitiesPatientsPreliminary reportDysfunctionDegree of attenuationSchizophreniaLate phaseSubjectsDeviant stimuliStimulus changeIrrelevant stimuliPathophysiologyStimuliPotential paradigmAbnormalitiesNo Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia
Abi-Dargham A, Laruelle M, Krystal J, D'Souza C, Zoghbi S, Baldwin R, Seibyl J, Mawlawi O, de Erasquin G, Charney D, Innis R. No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia. Neuropsychopharmacology 1999, 20: 650-661. PMID: 10327433, DOI: 10.1016/s0893-133x(98)00107-9.Peer-Reviewed Original ResearchConceptsReceptor densitySchizophrenic patientsVivo benzodiazepine receptor bindingBDZ receptor densityMale schizophrenic patientsBenzodiazepine receptor densityPathophysiology of schizophreniaBenzodiazepine receptor bindingSingle photon emissionRegional distribution volumesPrevious postmortemGABA transmissionBDZ antagonistBDZ receptorsReceptor expressionNeurotransmitter systemsHealthy volunteersPsychotic symptomsBrain regionsDistribution volumeReceptor bindingSchizophreniaVivo studiesPatientsPossible alterationsToward a rational pharmacotherapy of comorbid substance abuse in schizophrenic patients
Krystal J, D'Souza D, Madonick S, Petrakis I. Toward a rational pharmacotherapy of comorbid substance abuse in schizophrenic patients. Schizophrenia Research 1999, 35: s35-s49. PMID: 10190224, DOI: 10.1016/s0920-9964(98)00162-5.Peer-Reviewed Original ResearchConceptsSchizophrenic patientsSubstance abuseTerms of rehospitalizationComorbid substance abuseExacerbation of symptomsHealth care expensesSelf-medication hypothesisBetter prognosisMedical illnessPharmacotherapeutic approachesRational pharmacotherapyNonschizophrenic populationsPatientsVocational functionIllicit substancesCare expensesAbuseVulnerability hypothesisRehospitalizationExacerbationMedicationsPharmacotherapyPrognosisPsychostimulantsIllness
1996
SPECT imaging of synaptic dopamine release in drug free schizophrenic patients: An experimental validation of the dopamine hypothesis of schizophrenia
Laruelle M, Abi-Dargham A, Gil R, van Dyck C, Erdos J, D'Souza D, Rosenblatt W, McCance-Katz E, Zea-Ponce Y, Zoghbi S, Baldwin R, Hoffer P, Krystal J, Charney D, Innis R. SPECT imaging of synaptic dopamine release in drug free schizophrenic patients: An experimental validation of the dopamine hypothesis of schizophrenia. Schizophrenia Research 1996, 18: 198-199. DOI: 10.1016/0920-9964(96)85619-2.Peer-Reviewed Original Research