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
2018
Dose-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 engagementPotentiationSchizophrenia
2017
Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia
Hamilton HK, D'Souza DC, Ford JM, Roach BJ, Kort NS, Ahn KH, Bhakta S, Ranganathan M, Mathalon DH. Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia. Schizophrenia Research 2017, 191: 87-94. PMID: 28711472, PMCID: PMC5745273, DOI: 10.1016/j.schres.2017.06.040.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptor agonistAcetylcholine receptor agonistReceptor agonistHealthy volunteersN-methyl-D-aspartate receptor antagonistPathophysiology of schizophreniaAuditory processing abnormalitiesProfile of effectsMMN amplitudeNicotine preventsNicotine administrationReceptor hypofunctionNMDAR hypofunctionNMDAR antagonistsReceptor antagonistMismatch negativity (MMN) event-related potential (ERP) componentPresent doseNicotinic agonistsSchizophrenia patientsCigarette useKetamineDeviant typesNeurophysiological effectsSecondary analysisMMN abnormalities
2015
Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine
Ahn KH, Sewell A, Elander J, Pittman B, Ranganathan M, Gunduz-Bruce H, Krystal J, D'Souza DC. Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine. Neuropsychopharmacology 2015, 40: 2822-2831. PMID: 25953357, PMCID: PMC4864658, DOI: 10.1038/npp.2015.132.Peer-Reviewed Original ResearchConceptsGABA deficitHealthy subjectsPsychotomimetic effectsIntravenous infusionSchizophrenia patientsPANSS positive symptoms subscaleDouble-blind crossover designStriatal dopamine releasePositive symptom subscaleAdministration of drugsDose of AMPHPartial inverse agonistSubclinical responsePharmacokinetic interactionsSubthreshold doseDopamine releaseBenzodiazepine receptorsSymptom subscalesCrossover designCADSS scoresPositive symptomsAMPHInverse agonistSubjective effectsTest day
2011
Glutamatergic Modulation of Auditory Information Processing in the Human Brain
Gunduz-Bruce H, Reinhart RM, Roach BJ, Gueorguieva R, Oliver S, D'Souza DC, Ford JM, Krystal JH, Mathalon DH. Glutamatergic Modulation of Auditory Information Processing in the Human Brain. Biological Psychiatry 2011, 71: 969-977. PMID: 22036036, PMCID: PMC3290754, DOI: 10.1016/j.biopsych.2011.09.031.Peer-Reviewed Original ResearchConceptsN-acetylcysteineAuditory mismatch negativityReceptor antagonistN-methyl-D-aspartate receptor antagonistAspartate glutamate receptor antagonistOral N-acetylcysteinePlacebo-controlled studyGlutamate receptor antagonistsEffects of ketamineInfusion of salineMismatch negativityTest dayMMN amplitudeCystine-glutamate exchangerAuditory information processingP300 event-related potentialGlutamatergic modulationCognitive enhancing agentsEvent-related potentialsKetamine effectsHealthy volunteersHealthy humansSchizophrenia patientsPositive symptomsKetamine
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
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 responses
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
Nicotine effects on brain function and functional connectivity in schizophrenia
Jacobsen LK, D'Souza DC, Mencl WE, Pugh KR, Skudlarski P, Krystal JH. Nicotine effects on brain function and functional connectivity in schizophrenia. Biological Psychiatry 2004, 55: 850-858. PMID: 15050867, DOI: 10.1016/j.biopsych.2003.12.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceAttentionBrainBrain MappingBrief Psychiatric Rating ScaleCase-Control StudiesFemaleHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedNeuropsychological TestsNicotineNicotinic AgonistsReaction TimeRegression AnalysisSchizophreniaSmokeTask Performance and AnalysisVerbal LearningConceptsTask performanceFunctional connectivityFunctional magnetic resonance imaging (fMRI) scanningBrain regionsN-back taskMultiple cognitive domainsNetwork of regionsDifficult task conditionsAnterior cingulate cortexAttention loadMemory loadSelective attentionCognitive domainsTask conditionsCognitive functionCingulate cortexThalamocortical functional connectivityNicotine effectsCognitive dysfunctionBrain functionSchizophrenia patientsControl subjectsSchizophrenic subjectsMagnetic resonance imaging (MRI) scanningMental illness
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 paradigmAbnormalities