2022
Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode
Rhee TG, Shim SR, Forester BP, Nierenberg AA, McIntyre RS, Papakostas GI, Krystal JH, Sanacora G, Wilkinson ST. Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode. JAMA Psychiatry 2022, 79: 1162-1172. PMID: 36260324, PMCID: PMC9582972, DOI: 10.1001/jamapsychiatry.2022.3352.Peer-Reviewed Original ResearchMeSH KeywordsDepressive Disorder, MajorElectroconvulsive TherapyHumansKetamineRandomized Controlled Trials as TopicSuicide, AttemptedConceptsStandardized mean differenceMajor depressive episodeSerious adverse eventsElectroconvulsive therapyAdverse eventsDepressive episodeClinical trialsDepression severityEfficacy outcomesSystematic reviewUnique adverse effect profileMeta-analyses (PRISMA) reporting guidelinesSafety of ketamineAdverse effect profileData extractionEuropean clinical trialsDiagnosis of depressionModerate methodological qualityMedical Subject Headings termsPreferred Reporting ItemsCognition/memoryRandom-effects modelSubject Headings termsAcute phaseEffect profileImaging the effect of ketamine on synaptic density (SV2A) in the living brain
Holmes SE, Finnema SJ, Naganawa M, DellaGioia N, Holden D, Fowles K, Davis M, Ropchan J, Emory P, Ye Y, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Imaging the effect of ketamine on synaptic density (SV2A) in the living brain. Molecular Psychiatry 2022, 27: 2273-2281. PMID: 35165397, PMCID: PMC9133063, DOI: 10.1038/s41380-022-01465-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsBrainDepressive Disorder, MajorHumansKetamineMacaca mulattaMembrane GlycoproteinsNerve Tissue ProteinsPositron-Emission TomographyConceptsKetamine's therapeutic effectsMajor depressive disorderTherapeutic effectPositron emission tomographyPosttraumatic stress disorderHealthy controlsSynaptic connectionsSynaptic vesicle protein 2APost-synaptic mechanismsEffects of ketamineDiscovery of ketamineNon-human primatesAntidepressant effectsDepressive disorderSingle administrationSynaptic densityPsychiatric disordersDepression severityKetamineEmission tomographyTerminal densityLiving brainStress disorderRobust reductionDissociative symptomsmTORC1 inhibitor effects on rapid ketamine-induced reductions in suicidal ideation in patients with treatment-resistant depression
Averill LA, Averill CL, Gueorguieva R, Fouda S, Sherif M, Ahn KH, Ranganathan M, D'Souza DC, Southwick SM, Sanacora G, Duman RS, Krystal JH, Abdallah CG. mTORC1 inhibitor effects on rapid ketamine-induced reductions in suicidal ideation in patients with treatment-resistant depression. Journal Of Affective Disorders 2022, 303: 91-97. PMID: 35101523, DOI: 10.1016/j.jad.2022.01.104.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsDepressionDepressive Disorder, MajorHumansKetamineMechanistic Target of Rapamycin Complex 1SirolimusSuicidal IdeationConceptsAntisuicidal effectsAntidepressant effectsSuicidal ideationKetamine-induced reductionTreatment-resistant depressionLimited treatment optionsCross-over trialMajor depressive episodeOral rapamycinPublic health crisisKetamine administrationTreatment optionsDepressive episodeParent studyOverall severityKetamineTwo weeksBeck ScaleRapamycin complex 1Mechanistic targetPatientsSignificant main effectHealth crisisRobust improvementFuture studies
2021
Mental health impact of the COVID-19 pandemic in U.S. military veterans: a population-based, prospective cohort study
Hill ML, Nichter B, Na PJ, Norman SB, Morland LA, Krystal JH, Pietrzak RH. Mental health impact of the COVID-19 pandemic in U.S. military veterans: a population-based, prospective cohort study. Psychological Medicine 2021, 53: 945-956. PMID: 34120667, PMCID: PMC8245339, DOI: 10.1017/s0033291721002361.Peer-Reviewed Original ResearchMeSH KeywordsCOVID-19Depressive Disorder, MajorHumansMental HealthMiddle AgedPandemicsProspective StudiesStress Disorders, Post-TraumaticVeteransConceptsPositive screenPsychiatric distressU.S. military veteran populationMiddle-aged veteransProspective cohort studyProspective cohort surveyMajor depressive disorderMilitary veteran populationMental health problemsMental health impactU.S. military veteransCohort studyDepressive disorderNational HealthPsychiatric symptomsVeteran populationCohort surveyHealth problemsU.S. veteransVeterans StudyClinical implicationsCoronavirus diseaseProtective factorsMeaningful preMental health
2020
Transcriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergenceA robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants
Abdallah CG, Ahn KH, Averill LA, Nemati S, Averill CL, Fouda S, Ranganathan M, Morgan PT, D’Souza D, Mathalon DH, Krystal JH, Driesen NR. A robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants. Neuropsychopharmacology 2020, 46: 478-485. PMID: 32967000, PMCID: PMC7852889, DOI: 10.1038/s41386-020-00864-9.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsConnectomeDepressive Disorder, MajorHumansKetamineMagnetic Resonance ImagingReproducibility of ResultsConceptsConnectome fingerprintN-methyl-d-aspartate modulatorsNovel rapid-acting antidepressantsMajor depressive disorder patientsMechanism of antidepressantsWeeks of sertralineRapid-acting antidepressantsMagnetic resonance imaging studyDepressive disorder patientsExecutive networkEffects of ketamineLongitudinal functional magnetic resonance imaging studyResonance imaging studyFunctional magnetic resonance imaging studyBrain functional connectivityCohort AIntravenous infusionSubanesthetic doseClinical trialsNormal salineDisorder patientsConnectomics signaturesBrain circuitryKetamineImaging studiesModulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin
Abdallah CG, Averill LA, Gueorguieva R, Goktas S, Purohit P, Ranganathan M, Sherif M, Ahn KH, D’Souza D, Formica R, Southwick SM, Duman RS, Sanacora G, Krystal JH. Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Neuropsychopharmacology 2020, 45: 990-997. PMID: 32092760, PMCID: PMC7162891, DOI: 10.1038/s41386-020-0644-9.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsDepressive Disorder, MajorHumansKetamineMechanistic Target of Rapamycin Complex 1SirolimusTreatment OutcomeConceptsAntidepressant effectsKetamine administrationRapamycin pretreatmentMontgomery-Åsberg Depression Rating ScaleDouble-blind cross-over designBenefits of ketamineRobust antidepressant effectsKetamine's antidepressant effectsMajor depressive episodeDepression Rating ScaleCross-over designKetamine exertsOral rapamycinRemission rateDepressive episodePlacebo 2Ketamine 0.5Local blockadeDepressed patientsIntravenous administrationTreatment daysDepression relapseDepression severityKetamineRating Scale
2019
Maintenance of antidepressant and antisuicidal effects by D-cycloserine among patients with treatment-resistant depression who responded to low-dose ketamine infusion: a double-blind randomized placebo–control study
Chen MH, Cheng CM, Gueorguieva R, Lin WC, Li CT, Hong CJ, Tu PC, Bai YM, Tsai SJ, Krystal JH, Su TP. Maintenance of antidepressant and antisuicidal effects by D-cycloserine among patients with treatment-resistant depression who responded to low-dose ketamine infusion: a double-blind randomized placebo–control study. Neuropsychopharmacology 2019, 44: 2112-2118. PMID: 31421635, PMCID: PMC6898334, DOI: 10.1038/s41386-019-0480-y.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionAntisuicidal effectsPlacebo groupKetamine infusionDCS groupD-cycloserineDouble-blind randomized placebo-controlled studyN-methyl-D-aspartate (NMDA) glutamate receptorsHamilton Depression Rating Scale scoresLow-dose ketamine infusionRandomized placebo-controlled studyDepression Rating Scale scoresHAMD item 3Single subanesthetic doseInitial clinical responsePlacebo-controlled studyRating Scale scoresClinical responseDose titrationSubanesthetic doseAugmentation treatmentGlutamate receptorsMixed model analysisSuicidal riskScale scoreIn vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation
Davis MT, Hillmer A, Holmes SE, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Angarita G, Carson RE, Krystal JH, Esterlis I. In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 11490-11495. PMID: 31085640, PMCID: PMC6561298, DOI: 10.1073/pnas.1818871116.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkersBrainDepressive Disorder, MajorFemaleHumansMalePositron-Emission TomographyRadiopharmaceuticalsReceptor, Metabotropic Glutamate 5Suicidal IdeationSuicide PreventionConceptsMGluR5 availabilitySuicidal ideationHC individualsPathophysiology of PTSDLimbic brain regionsVolume of distributionHealthy comparison controlsSuicide risk managementPositron emission tomographyReceptor 5Venous input functionsBrain regionsPTSD individualsEmission tomographyMDD individualsVivo evidenceRecent evidencePotential roleMGluR5PTSDComparison controlsDysregulationMDDIdeationIndividualsLower 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 ResearchMeSH KeywordsAdultDepressionDepressive Disorder, MajorFemaleHumansMaleMembrane GlycoproteinsMiddle AgedNerve Tissue ProteinsPositron-Emission TomographyStress Disorders, Post-TraumaticSynapsesConceptsMajor 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 evidenceSymptomsDepressionSeverityDisordersAlterationsAssociation of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder
Yoon G, Petrakis IL, Krystal JH. Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder. JAMA Psychiatry 2019, 76: 337-338. PMID: 30624551, PMCID: PMC6439824, DOI: 10.1001/jamapsychiatry.2018.3990.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol DrinkingAlcoholismCravingDepressive Disorder, MajorDrug Therapy, CombinationFemaleHumansKetamineMaleMiddle AgedNaltrexonePilot Projects
2018
Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression
Zhou H, Cheng Z, Bass N, Krystal JH, Farrer LA, Kranzler HR, Gelernter J. Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. Translational Psychiatry 2018, 8: 208. PMID: 30287806, PMCID: PMC6172277, DOI: 10.1038/s41398-018-0258-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide association study identifiesRisk genesTop risk genesCalcium ion bindingGenomes reference panelFast excitatory synaptic transmissionGenetic risk variantsGenetic basisEnrichment analysisAssociation studiesExome arrayCell adhesionRisk variantsGenesReference panelGenetic riskAMPA-sensitive glutamate receptorsIntronic variantsIon bindingBiological mechanismsConditional analysisGRIA4Excitatory synaptic transmissionSynaptic transmission
2017
Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
Andersen AM, Pietrzak RH, Kranzler HR, Ma L, Zhou H, Liu X, Kramer J, Kuperman S, Edenberg HJ, Nurnberger JI, Rice JP, Tischfield JA, Goate A, Foroud TM, Meyers JL, Porjesz B, Dick DM, Hesselbrock V, Boerwinkle E, Southwick SM, Krystal JH, Weissman MM, Levinson DF, Potash JB, Gelernter J, Han S. Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence. JAMA Psychiatry 2017, 74: 1153-1160. PMID: 28813562, PMCID: PMC5710224, DOI: 10.1001/jamapsychiatry.2017.2269.Peer-Reviewed Original ResearchConceptsMDD polygenic risk scoresMajor depressive disorderPolygenic risk scoresAlcohol dependenceDepressive disorderSignificant public health burdenPublic health burdenAD comorbidityNational HealthHealth burdenMAIN OUTCOMECase-control statusRisk scoreRisk of ADVeterans StudyYale-PennGenetic susceptibilityMDD statusCommon genetic factorsSubstance dependenceMDD casesAD samplesPolygenic riskGenetic factorsHeritable disorderMultimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder
Scheinost D, Holmes SE, DellaGioia N, Schleifer C, Matuskey D, Abdallah CG, Hampson M, Krystal JH, Anticevic A, Esterlis I. Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder. Neuropsychopharmacology 2017, 43: 1119-1127. PMID: 28944772, PMCID: PMC5854800, DOI: 10.1038/npp.2017.229.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAnterior cingulate cortexIntrinsic functional connectivityMedial prefrontal cortexFunctional connectivityLarge-scale brain networksDepressive disorderMDD groupAnatomical covarianceBrain networksUnmedicated major depressive disorderWhole-brain intrinsic functional connectivitySystem-level disorderIntrinsic connectivity distributionRegional brain structureMultiple brain networksAltered connectivityCommon findingHealthy comparison participantsDepressive symptomsAltered volumeUnmedicated individualsLocal circuitryCingulate cortexDepressive symptomatologyMetabotropic Glutamatergic Receptor 5 and Stress Disorders: Knowledge Gained From Receptor Imaging Studies
Esterlis I, Holmes SE, Sharma P, Krystal JH, DeLorenzo C. Metabotropic Glutamatergic Receptor 5 and Stress Disorders: Knowledge Gained From Receptor Imaging Studies. Biological Psychiatry 2017, 84: 95-105. PMID: 29100629, PMCID: PMC5858955, DOI: 10.1016/j.biopsych.2017.08.025.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPositron emission tomography studyEmission tomography studiesMGluR5 modulationAntidepressant responseStress disorderBipolar disorderStress-related psychiatric disordersTomography studyAntagonism of mGluR5Ketamine’s antidepressant responseSignificant side effectsPromising therapeutic targetReceptor imaging studiesPosttraumatic stress disorderMDD heterogeneityManic mood statesAntidepressant efficacyObsessive-compulsive disorderDepressive disorderSubtype 5Neurotransmitter systemsPsychiatric disordersReceptor 5Side effectsDose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression
Su TP, Chen MH, Li CT, Lin WC, Hong CJ, Gueorguieva R, Tu PC, Bai YM, Cheng CM, Krystal JH. Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology 2017, 42: 2482-2492. PMID: 28492279, PMCID: PMC5686503, DOI: 10.1038/npp.2017.94.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsAsian PeopleBlood PressureBrain-Derived Neurotrophic FactorDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantDose-Response Relationship, DrugDouble-Blind MethodFemaleHeart RateHumansKetamineMaleMiddle AgedPolymorphism, GeneticPsychiatric Status Rating ScalesTaiwanTreatment OutcomeConceptsTreatment-resistant depressionHamilton Depression Rating ScaleAntidepressant effectsKetamine effectsBDNF genotypeBrain-derived neurotrophic factor (BDNF) genotypeChinese populationDose-related efficacyPlacebo-controlled trialSignificant dose-related effectsDepression Rating ScaleNeurotrophic factor genotypeDose-related effectsSingle ketamine infusionMost patientsKetamine infusionTaiwanese patientsAdjunctive ketamineResponder analysisBDNF geneS-ketamineKetamine levelsPatientsMet alleleRating ScaleKetamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression
Esterlis I, DellaGioia N, Pietrzak RH, Matuskey D, Nabulsi N, Abdallah CG, Yang J, Pittenger C, Sanacora G, Krystal JH, Parsey RV, Carson RE, DeLorenzo C. Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression. Molecular Psychiatry 2017, 23: 824-832. PMID: 28397841, PMCID: PMC5636649, DOI: 10.1038/mp.2017.58.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMGluR5 availabilityPositron emission tomographyKetamine administrationControl groupAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced reductionMetabotropic glutamatergic receptorsRapid antidepressant effectsGlutamate receptor antagonistsKetamine-induced changesEffects of ketaminePET imaging studiesMechanism of actionGlutamate surgeAntidepressant effectsAntidepressant efficacyAntidepressant responseGlutamatergic receptorsControl subjectsReceptor antagonistHealthy controlsDepressive disorderSustained decreaseReevaluating the Efficacy and Predictability of Antidepressant Treatments: A Symptom Clustering Approach
Chekroud AM, Gueorguieva R, Krumholz HM, Trivedi MH, Krystal JH, McCarthy G. Reevaluating the Efficacy and Predictability of Antidepressant Treatments: A Symptom Clustering Approach. JAMA Psychiatry 2017, 74: 370-378. PMID: 28241180, PMCID: PMC5863470, DOI: 10.1001/jamapsychiatry.2017.0025.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAffectAgedAntidepressive AgentsBupropionCitalopramCluster AnalysisDepressive Disorder, MajorDose-Response Relationship, DrugDrug Therapy, CombinationDuloxetine HydrochlorideFemaleHumansMaleMianserinMiddle AgedMirtazapineRandomized Controlled Trials as TopicSleepSyndromeTreatment OutcomeVenlafaxine HydrochlorideYoung AdultConceptsCore emotional symptomsDepressive severitySymptom clustersHamilton Depression Rating ScaleDepression Outcomes trialDifferent antidepressant medicationsHAM-D scaleHigh-dose duloxetinePhase 3 trialEmotional symptomsPatient-reported dataDepression Rating ScaleSequenced Treatment AlternativesGroup of symptomsCluster of symptomsDepressive symptom checklistMixed-effects regression analysisDepressive Symptomatology ScaleAntidepressant therapyAntidepressant treatmentAntidepressant medicationOutcome trialsCombining MedicationsAtypical symptomsAdditional placeboTrajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis
Gueorguieva R, Chekroud AM, Krystal JH. Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis. The Lancet Psychiatry 2017, 4: 230-237. PMID: 28189575, PMCID: PMC5340978, DOI: 10.1016/s2215-0366(17)30038-x.Peer-Reviewed Original ResearchConceptsActive medicationActive treatmentClinical trialsDepression severityHamilton Depression Rating Scale scoresDepression Rating Scale scoresClinical Global Impression scoresIndividual patient-level dataDouble-blind treatmentPlacebo-controlled trialPatterns of relapseGlobal Impression scoresIndividual patient dataPrevention of relapseTrajectory class membershipTreatment of depressionMajor depressive disorderRating Scale scoresPatient-level dataPost-traumatic stress disorderTreatment discontinuationAntidepressant treatmentClinical responseAlcohol Research CenterAntidepressant medication
2016
Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder
Murrough JW, Abdallah CG, Anticevic A, Collins KA, Geha P, Averill LA, Schwartz J, DeWilde KE, Averill C, Jia-Wei Yang G, Wong E, Tang CY, Krystal JH, Iosifescu DV, Charney DS. Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder. Human Brain Mapping 2016, 37: 3214-3223. PMID: 27144347, PMCID: PMC4980239, DOI: 10.1002/hbm.23235.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrain MappingDepressive Disorder, MajorFemaleHumansImage Interpretation, Computer-AssistedMagnetic Resonance ImagingMaleMiddle AgedNeural PathwaysPrefrontal CortexConceptsGlobal brain connectivityMedial prefrontal cortexPrefrontal cortexRight subgenual anterior cingulate cortexVentromedial prefrontal cortexCingulate cortexMontgomery-Åsberg Depression Rating ScaleSymptom severityBrain connectivitySubgenual anterior cingulate cortexDepression Rating ScaleMedication-free patientsMajor depressive disorderKey pathological featureDepressive symptom severitySubgenual cingulate cortexHum Brain MappAnterior cingulate cortexHigher symptom severityFunctional connectivity analysisFunctional magnetic resonancePathological featuresHealthy groupAltered connectivityDepressive disorder