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
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
Reduced 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
2008
The effects of cannabinoids on serum cortisol and prolactin in humans
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J, D’Souza D. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology 2008, 203: 737. PMID: 19083209, PMCID: PMC2863108, DOI: 10.1007/s00213-008-1422-2.Peer-Reviewed Original ResearchConceptsPlasma prolactin levelsPlasma cortisol levelsProlactin levelsNeuroendocrine effectsCannabis exposureHealthy controlsNeuroendocrine functionHormonal levelsCortisol levelsFrequent usersChronic cannabis exposureHealthy control subjectsDose-related increaseEffects of cannabinoidsBaseline hormonal levelsDose-related effectsDevelopment of toleranceLimited dose-response dataDose-dependent mannerBlunted increaseMultiple dosesControl subjectsSerum cortisolHormone levelsPlasma cortisolPreliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans
D’Souza D, Pittman B, Perry E, Simen A. Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans. Psychopharmacology 2008, 202: 569. PMID: 18807247, PMCID: PMC2791800, DOI: 10.1007/s00213-008-1333-2.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorBDNF levelsBrain-derived neurotrophic factor levelsNeurotrophic factor levelsSerum BDNF levelsΔ9-THCEffects of cannabinoidsΔ9-THC administrationSpatial memory impairmentBasal BDNF levelsResultsΔ9-THCPlacebo administrationPrincipal active componentNeurotrophic factorControl subjectsPsychotomimetic effectsHealthy controlsCannabinoid effectsIntravenous administrationAltered neurodevelopmentPreclinical studiesHigh riskConsequence of exposureChronic exposureMemory impairment
2006
Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects
Neumeister A, Carson R, Henry S, Planeta-Wilson B, Binneman B, Maguire RP, Luckenbaugh DA, D'Souza C, Krystal JH, Frost JJ. Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects. Journal Of Clinical Psychopharmacology 2006, 26: 595-599. PMID: 17110816, DOI: 10.1097/01.jcp.0000245558.14284.aa.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntipsychotic AgentsBehaviorBrainBrain MappingCluster AnalysisCross-Over StudiesDouble-Blind MethodFemaleFluorodeoxyglucose F18GlycineHumansInfusions, IntravenousMagnetic Resonance ImagingMaleNeuropsychological TestsPositron-Emission TomographyRadiopharmaceuticalsReference ValuesSerineConceptsN-methyl-D-aspartate receptor functionReceptor functionRegional cerebral metabolic rateAdministration of glycineCerebral metabolic effectsMagnetic resonance imaging studyPositron emission tomography studyHealthy control subjectsNMDA receptor functionCerebral metabolic rateEmission tomography studiesTest dayHealthy human subjectsResonance imaging studySignificant reductionPositron emission tomographyDorsolateral prefrontal cortexIntravenous glycinePlacebo infusionCerebral metabolismPatient populationControl subjectsGlycine administrationGlycine infusionIntravenous administration
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
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 findingsMedications
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 paradigmAbnormalities[123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia
Verhoeff N, Soares J, D’Souza C, Gil R, Degen K, Abi-Dargham A, Zoghbi S, Fujita M, Rajeevan N, Seibyl J, Krystal J, van Dyck C, Charney D, Innis R. [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia. Psychiatry Research 1999, 91: 163-173. PMID: 10641580, DOI: 10.1016/s0925-4927(99)00027-x.Peer-Reviewed Original ResearchConceptsDuration of illnessHealthy control subjectsControl subjectsGamma-aminobutyric acidLeft precentral gyrusSuperior occipital gyrusPANSS scoresPrecentral gyrusOccipital gyrusSignificant differencesTotal brain uptakeNon-smoking patientsGray matter atrophyConstant infusion paradigmPathophysiology of schizophreniaCortical brain regionsSingle photon emissionTypical antipsychoticsAtypical antipsychoticsCigarette smokingInhibitory neurotransmissionBrain uptakeInfusion paradigmMatter atrophyPostmortem studies