2024
Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder
Asch R, Worhunsky P, Davis M, Holmes S, Cool R, Boster S, Carson R, Blumberg H, Esterlis I. Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder. Journal Of Affective Disorders 2024, 361: 415-424. PMID: 38876317, PMCID: PMC11250898, DOI: 10.1016/j.jad.2024.06.025.Peer-Reviewed Original ResearchMetabotropic glutamate receptor 5Bipolar disorderGlutamate receptor 5Positron emission tomographyFear processingEmotional processingAssociated with greater activationEmotion processing taskAssociated with impulsivityFunctional brain differencesAssociated with functional alterationsParietal brain regionsPathology of BDIncreased cortical activityAssociated with difficultiesDepressive disorderHealthy comparisonReceptor availabilityBrain differencesPre/postcentral gyriAttention difficultiesGreater activationBrain regionsPsychomotor functionTreatment developmentAuthor Correction: Synaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Author Correction: Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 55. PMID: 38472206, PMCID: PMC10933370, DOI: 10.1038/s41531-024-00674-6.Peer-Reviewed Original ResearchSynaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 42. PMID: 38402233, PMCID: PMC10894197, DOI: 10.1038/s41531-024-00655-9.Peer-Reviewed Original ResearchSynaptic density lossPositron emission tomographyBinds to synaptic vesicle glycoprotein 2AAssociated with symptom severityParkinson's diseaseHigh-resolution positron emission tomographySynaptic vesicle glycoprotein 2ADuration of illnessPositron emission tomography scanBrain perfusionIllness durationSymptom severitySeverity of symptomsHC groupSubstantia nigraSynaptic densityLiving brainPD individualsClinical insightsDensity lossPD patientsEmission tomographyBrainSynaptic lossSynapse loss
2019
Lower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
2018
Cerebellar and Prefrontal Cortical Alterations in PTSD: Structural and Functional Evidence
Holmes SE, Scheinost D, DellaGioia N, Davis MT, Matuskey D, Pietrzak RH, Hampson M, Krystal JH, Esterlis I. Cerebellar and Prefrontal Cortical Alterations in PTSD: Structural and Functional Evidence. Chronic Stress 2018, 2: 2470547018786390. PMID: 30035247, PMCID: PMC6054445, DOI: 10.1177/2470547018786390.Peer-Reviewed Original ResearchPosttraumatic stress disorderIntrinsic connectivity distributionMedial prefrontal cortexTensor-based morphometryPTSD groupFunctional connectivityPrefrontal cortexPathophysiology of PTSDGray matter volumeWhole-brain connectivityKey brain regionsMiddle temporal gyrusDorsolateral prefrontal cortexDefault mode networkCentral executive networkFunctional connectivity analysisPFC alterationsCortical alterationsHealthy comparison participantsAltered volumeFunctional alterationsMatter volumeUnmedicated individualsCerebellar involvementBrain regions
2017
Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study
Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS. Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study. Biological Psychiatry 2017, 83: 61-69. PMID: 28939116, DOI: 10.1016/j.biopsych.2017.08.005.Peer-Reviewed Original ResearchConceptsAnterior cingulate cortexMajor depressive episodeMajor depressive disorderPositron emission tomographyTSPO availabilityDepressive episodeControl subjectsDepressive disorderTranslocator proteinPK11195 positron emission tomographySevere major depressive episodeEmission tomographySuicidal thinkingSuicidal thoughtsPrefrontal cortexInvolvement of inflammationPeripheral inflammatory markersPositron emission tomography studyAnti-inflammatory therapyHealthy control subjectsLeast moderate severityMedication-free patientsEmission tomography studiesTSPO-specific radioligandBrains of individualsTrajectories of depressive and anxiety symptoms in older adults: a 6‐year prospective cohort study
Holmes SE, Esterlis I, Mazure CM, Lim YY, Ames D, Rainey‐Smith S, Fowler C, Ellis K, Martins RN, Salvado O, Doré V, Villemagne VL, Rowe CC, Laws SM, Masters CL, Pietrzak RH, Maruff P, Imaging B. Trajectories of depressive and anxiety symptoms in older adults: a 6‐year prospective cohort study. International Journal Of Geriatric Psychiatry 2017, 33: 405-413. PMID: 28736899, PMCID: PMC5773367, DOI: 10.1002/gps.4761.Peer-Reviewed Original ResearchMeSH KeywordsAgedAllelesAlzheimer DiseaseAnxiety DisordersApolipoprotein E4AttentionBrain-Derived Neurotrophic FactorCognitionDepressive DisorderDisease ProgressionExecutive FunctionFemaleHumansLogistic ModelsMaleMiddle AgedPositron-Emission TomographyProspective StudiesQuality of LifeRisk FactorsSex FactorsConceptsOlder adultsAnxiety symptomsPredominant trajectoriesRisk factorsLatent growth mixture modelingAlzheimer's diseaseApolipoprotein epsilon 4 alleleSex-specific risk factorsLower attentional functionBinary logistic regression analysisEpsilon 4 alleleElevated depressive symptomsGrowth mixture modelingLogistic regression analysisQuality of lifePositron emission tomographyNormal older adultsSubthreshold depressiveMale sexBaseline predictorsDepressive symptomsVal66Met alleleClinical depressionLower executive functionAnxiety trajectoriesAltered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence
Holmes SE, Girgenti MJ, Davis MT, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Southwick S, Duman RS, Carson RE, Krystal JH, Esterlis I, Friedman M, Kowall N, Brady C, McKee A, Stein T, Huber B, Kaloupek D, Alvarez V, Benedek D, Ursano R, Williamson D, Cruz D, Young K, Duman R, Krystal J, Mash D, Hardegree M, Serlin G. Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 8390-8395. PMID: 28716937, PMCID: PMC5547601, DOI: 10.1073/pnas.1701749114.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMGluR5 availabilityPositron emission tomographyGlutamate systemMetabotropic glutamate receptor 5Treatment of PTSDHuman posttraumatic stress disorderGlutamate receptor 5Mechanism-based treatmentsExpression of FKBP5Promising treatment targetHuman postmortem tissueTargeted pharmacological treatmentStress psychopathologyPharmacological treatmentExpression of proteinsReceptor 5MGluR5Treatment targetsPostmortem tissueEmission tomographyStress disorderPostmortem samplesPromising targetDisorders
2016
In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study
Holmes SE, Hinz R, Drake RJ, Gregory CJ, Conen S, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS. In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study. Molecular Psychiatry 2016, 21: 1672-1679. PMID: 27698434, DOI: 10.1038/mp.2016.180.Peer-Reviewed Original ResearchConceptsMedicated patientsTSPO availabilityMicroglial activationMicroglial activityNegative symptomsAntipsychotic-naive groupBrain microglial activityRegular intramuscular injectionsPositron emission tomography studySubset of patientsAnti-inflammatory statePrimary negative symptomsBrain of adultAntipsychotic-free patientsPathophysiology of schizophreniaPotential modulatory effectsEmission tomography studiesHealthy comparison subjectsTranslocator proteinNegative Syndrome ScaleEmission Tomography ImagingPositron emission tomography (PET) imagingParietal cortical regionsAntipsychotic medicationMedicated schizophreniaβ-Amyloid, APOE and BDNF Genotype, and Depressive and Anxiety Symptoms in Cognitively Normal Older Women and Men
Holmes SE, Esterlis I, Mazure CM, Lim YY, Ames D, Rainey-Smith S, Martins RN, Salvado O, Dore V, Villemagne VL, Rowe CC, Laws SM, Masters CL, Maruff P, Pietrzak RH, Australian Imaging B. β-Amyloid, APOE and BDNF Genotype, and Depressive and Anxiety Symptoms in Cognitively Normal Older Women and Men. American Journal Of Geriatric Psychiatry 2016, 24: 1191-1195. PMID: 27742526, DOI: 10.1016/j.jagp.2016.08.007.Peer-Reviewed Original ResearchConceptsBDNF genotypeNormal older womenAnxiety symptomsOlder adultsΕ4 carriageOlder womenDepressive symptomsΒ-amyloidGreater severityAustralian Imaging BiomarkersNon-ε4 carriersSeverity of depressiveMet allele carriersSeverity of anxietyGreater depressive symptomsNormal older adultsGreater anxiety symptomsLifestyle StudyΕ4 carriersAPOE genotypeAllele carriersAnalysis of covarianceImaging biomarkersSymptomsDepressive