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
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 abnormalitiesAttenuation 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
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
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
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
2001
CURRENT 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 ResearchConceptsPathophysiology of schizophreniaMajor psychiatric disordersPsychiatric disordersPathophysiologyCurrent perspectivesPsychiatric researchDisordersCurrent eraSource of hopePatientsSchizophrenia
1999
Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists
Krystal J, Belger A, D'Souza D, Anand A, Charney D, Aghajanian G, Moghaddam B. Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists. Neuropsychopharmacology 1999, 21: s143-s157. DOI: 10.1016/s0893-133x(99)00102-5.Peer-Reviewed Original ResearchHealthy human subjectsNMDA antagonist effectsNMDA antagonistsClinical studiesMetabotropic glutamate receptor agonistN-methyl-D-aspartate (NMDA) subtypeD2 receptor blockadeGlutamate receptor agonistsD2 receptor stimulationDopamine 2 receptorNovel pharmacologic strategiesEffects of ketaminePathophysiology of schizophreniaCourse of schizophreniaNovel pharmacotherapeutic strategiesHuman subjectsHyperglutamatergic stateSerotonin 2AGlutamate neuronsGlutamate releaseCerebral cortexPharmacologic strategiesCurrent antipsychoticsPharmacotherapeutic strategiesSubanesthetic dosesComparison 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 studiesNo 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 alterations