2022
A comparison of methods to harmonize cortical thickness measurements across scanners and sites
Sun D, Rakesh G, Haswell CC, Logue M, Baird CL, O'Leary EN, Cotton AS, Xie H, Tamburrino M, Chen T, Dennis EL, Jahanshad N, Salminen LE, Thomopoulos SI, Rashid F, Ching CRK, Koch SBJ, Frijling JL, Nawijn L, van Zuiden M, Zhu X, Suarez-Jimenez B, Sierk A, Walter H, Manthey A, Stevens JS, Fani N, van Rooij SJH, Stein M, Bomyea J, Koerte IK, Choi K, van der Werff SJA, Vermeiren RRJM, Herzog J, Lebois LAM, Baker JT, Olson EA, Straube T, Korgaonkar MS, Andrew E, Zhu Y, Li G, Ipser J, Hudson AR, Peverill M, Sambrook K, Gordon E, Baugh L, Forster G, Simons RM, Simons JS, Magnotta V, Maron-Katz A, du Plessis S, Disner SG, Davenport N, Grupe DW, Nitschke JB, deRoon-Cassini TA, Fitzgerald JM, Krystal JH, Levy I, Olff M, Veltman DJ, Wang L, Neria Y, De Bellis MD, Jovanovic T, Daniels JK, Shenton M, van de Wee NJA, Schmahl C, Kaufman ML, Rosso IM, Sponheim SR, Hofmann DB, Bryant RA, Fercho KA, Stein DJ, Mueller SC, Hosseini B, Phan KL, McLaughlin KA, Davidson RJ, Larson CL, May G, Nelson SM, Abdallah CG, Gomaa H, Etkin A, Seedat S, Harpaz-Rotem I, Liberzon I, van Erp TGM, Quidé Y, Wang X, Thompson PM, Morey RA. A comparison of methods to harmonize cortical thickness measurements across scanners and sites. NeuroImage 2022, 261: 119509. PMID: 35917919, PMCID: PMC9648725, DOI: 10.1016/j.neuroimage.2022.119509.Peer-Reviewed Original ResearchRemodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder: Results From the ENIGMA-PGC Posttraumatic Stress Disorder Consortium
Sun D, Rakesh G, Clarke-Rubright EK, Haswell CC, Logue MW, O'Leary EN, Cotton AS, Xie H, Dennis EL, Jahanshad N, Salminen LE, Thomopoulos SI, Rashid FM, Ching CRK, Koch SBJ, Frijling JL, Nawijn L, van Zuiden M, Zhu X, Suarez-Jimenez B, Sierk A, Walter H, Manthey A, Stevens JS, Fani N, van Rooij SJH, Stein MB, Bomyea J, Koerte I, Choi K, van der Werff SJA, Vermeiren RRJM, Herzog JI, Lebois LAM, Baker JT, Ressler KJ, Olson EA, Straube T, Korgaonkar MS, Andrew E, Zhu Y, Li G, Ipser J, Hudson AR, Peverill M, Sambrook K, Gordon E, Baugh LA, Forster G, Simons RM, Simons JS, Magnotta VA, Maron-Katz A, du Plessis S, Disner SG, Davenport ND, Grupe D, Nitschke JB, deRoon-Cassini TA, Fitzgerald J, Krystal JH, Levy I, Olff M, Veltman DJ, Wang L, Neria Y, De Bellis MD, Jovanovic T, Daniels JK, Shenton ME, van de Wee NJA, Schmahl C, Kaufman ML, Rosso IM, Sponheim SR, Hofmann DB, Bryant RA, Fercho KA, Stein DJ, Mueller SC, Phan KL, McLaughlin KA, Davidson RJ, Larson C, May G, Nelson SM, Abdallah CG, Gomaa H, Etkin A, Seedat S, Harpaz-Rotem I, Liberzon I, Wang X, Thompson PM, Morey RA. Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder: Results From the ENIGMA-PGC Posttraumatic Stress Disorder Consortium. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2022, 7: 935-948. PMID: 35307575, PMCID: PMC9835553, DOI: 10.1016/j.bpsc.2022.02.008.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderCortical thicknessStructural covarianceComorbid depressionControl subjectsLarge effect sizesStress disorderEffect sizeTrauma-exposed control subjectsCase-control differencesCortical surface areaInflammatory processClinical dataResting-state functional connectivity networksPositive pairwise correlationsCortical differencesCortical regionsCortical neuroanatomyStress hormonesFunctional connectivity networksPTSD casesSmall effect sizesGroup differencesStructural networkStructural connectome
2020
PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imaging
2018
BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise
Pitts BL, Whealin JM, Harpaz-Rotem I, Duman RS, Krystal JH, Southwick SM, Pietrzak RH. BDNF Val66Met polymorphism and posttraumatic stress symptoms in U.S. military veterans: Protective effect of physical exercise. Psychoneuroendocrinology 2018, 100: 198-202. PMID: 30388593, DOI: 10.1016/j.psyneuen.2018.10.011.Peer-Reviewed Original ResearchMeSH KeywordsAgedAmino Acid SubstitutionBrain-Derived Neurotrophic FactorCase-Control StudiesExerciseFemaleHumansMaleMethionineMiddle AgedMilitary PersonnelPolymorphism, Single NucleotideProtective FactorsResilience, PsychologicalSeverity of Illness IndexStress Disorders, Post-TraumaticUnited StatesValineVeteransConceptsMet allele carriersBDNF Val66Met polymorphismAllele carriersVal66Met polymorphismPhysical exerciseGreater severityPTSD symptomsU.S. military veteransTrauma burdenBrain-derived neurotrophic factor (BDNF) Val66Met polymorphismPast-month PTSD symptomsNeurotrophic factor Val66Met polymorphismMilitary veteransLifetime trauma burdenHigh trauma burdenVal/ValAdrenal (HPA) axis reactivityPosttraumatic stress disorder (PTSD) symptomsBDNF releaseCurrent PTSD symptomsProtective effectRe-experiencing symptomsAxis reactivityPosttraumatic stress symptomsSymptoms
2017
Multimodal 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 symptomatologyKetamine-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 decrease
2016
Association of Drinking Problems and Duration of Alcohol Use to Inhibitory Control in Nondependent Young Adult Social Drinkers
Hu S, Zhang S, Chao HH, Krystal JH, Li CS. Association of Drinking Problems and Duration of Alcohol Use to Inhibitory Control in Nondependent Young Adult Social Drinkers. Alcohol Clinical And Experimental Research 2016, 40: 319-328. PMID: 26833431, PMCID: PMC4742397, DOI: 10.1111/acer.12964.Peer-Reviewed Original ResearchConceptsAlcohol Use Disorders Identification TestYears of drinkingStop-signal reaction timeAlcohol useAge-related changesAlcohol misuseInhibitory controlAUDIT scoresDrinking problemsNondependent drinkersProlonged stop signal reaction timeChronic alcohol useAnterior cingulate cortexPresupplementary motor areaDisorders Identification TestRight inferior frontal gyrusResponse inhibitionSuperior temporal gyrusYoung adult social drinkersFunctional magnetic resonanceAdult social drinkersSignal reaction timeCerebral responsesInferior frontal gyrusHigher AUDIT
2014
Altered global brain signal in schizophrenia
Yang GJ, Murray JD, Repovs G, Cole MW, Savic A, Glasser MF, Pittenger C, Krystal JH, Wang XJ, Pearlson GD, Glahn DC, Anticevic A. Altered global brain signal in schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 7438-7443. PMID: 24799682, PMCID: PMC4034208, DOI: 10.1073/pnas.1405289111.Peer-Reviewed Original ResearchConceptsGlobal brain signalBrain dysfunctionHealthy subjectsBipolar patientsCortical powerBipolar disorderNeuropsychiatric conditionsFunctional MRIPatient samplesBrain connectivitySchizophreniaComplex neurobiologyDiagnostic specificityPatientsBrain signalsAlterationsDysfunctionSymptomsFindingsBaselineBrainMRIVentral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia
Anticevic A, Savic A, Repovs G, Yang G, McKay DR, Sprooten E, Knowles EE, Krystal JH, Pearlson GD, Glahn DC. Ventral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia. Schizophrenia Bulletin 2014, 41: 133-143. PMID: 24782562, PMCID: PMC4266289, DOI: 10.1093/schbul/sbu051.Peer-Reviewed Original ResearchConceptsVentral anterior cingulate cortexBipolar illnessPsychosis historyWhole-brain connectivityBipolar patientsConnectivity alterationsBrain connectivityCo-occurring psychosisChronic schizophrenia patientsHealthy comparison subjectsBipolar disorder patientsPsychotic bipolar disorder patientsBipolar disorder groupAnterior cingulate cortexFunctional connectivity studiesPsychotic bipolar disorderLifetime psychosisChronic schizophreniaPsychotic symptomsDisorder patientsPatientsComparison subjectsSchizophrenia patientsBipolar disorderCingulate cortex
2013
Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus
Pietrzak RH, Gallezot JD, Ding YS, Henry S, Potenza MN, Southwick SM, Krystal JH, Carson RE, Neumeister A. Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus. JAMA Psychiatry 2013, 70: 1199-1205. PMID: 24048210, PMCID: PMC4026855, DOI: 10.1001/jamapsychiatry.2013.399.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderNorepinephrine transporter availabilityLocus coeruleusPTSD groupTransporter availabilityHC groupVeterans Affairs Medical CenterStress disorderPTSD symptomsClinician-Administered PTSD ScalePositron emission tomography studyEmission tomography studiesPositron emission tomographyAnxious arousal symptomsNoradrenergic dysfunctionMedical CenterStudy groupMAIN OUTCOMEPTSD symptom clustersPTSD ScaleHealthy adultsCoeruleusBrain regionsChronic stressEmission tomographyRare SERINC2 variants are specific for alcohol dependence in individuals of European descent
Zuo L, Wang KS, Zhang XY, Li CS, Zhang F, Wang X, Chen W, Gao G, Zhang H, Krystal JH, Luo X. Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent. Pharmacogenetics And Genomics 2013, 23: 395-402. PMID: 23778322, PMCID: PMC4287355, DOI: 10.1097/fpc.0b013e328362f9f2.Peer-Reviewed Original ResearchDeep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence
Xie P, Kranzler HR, Krystal JH, Farrer LA, Zhao H, Gelernter J. Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence. Addiction Biology 2013, 19: 955-964. PMID: 23855403, PMCID: PMC3815683, DOI: 10.1111/adb.12072.Peer-Reviewed Original ResearchConceptsOpioid dependenceSubstance dependenceRare variantsN-methyl-D-aspartate (NMDA) glutamate receptorsCo-occurring alcohol dependenceHealthy control subjectsControl subjectsNMDA systemOpioid abuseGlutamate receptorsSchizophrenia risk genesSD riskAlcohol dependenceSignificant associationCocaine dependenceAdditional subjectsOD riskRisk genesDISC1African AmericansFirst demonstrationCommon variantsRiskSubjectsMinor allele frequencyCharacterizing Thalamo-Cortical Disturbances in Schizophrenia and Bipolar Illness
Anticevic A, Cole MW, Repovs G, Murray JD, Brumbaugh MS, Winkler AM, Savic A, Krystal JH, Pearlson GD, Glahn DC. Characterizing Thalamo-Cortical Disturbances in Schizophrenia and Bipolar Illness. Cerebral Cortex 2013, 24: 3116-3130. PMID: 23825317, PMCID: PMC4224238, DOI: 10.1093/cercor/bht165.Peer-Reviewed Original ResearchConceptsThalamo-cortical systemThalamic connectivityBipolar illnessResting-state functional magnetic resonance imagingSensory-motor cortexSevere mental illnessFunctional magnetic resonance imagingMagnetic resonance imagingThalamic dysconnectivityThalamic seedsClinical presentationNeuropsychiatric syndromeBrain dysconnectivityThalamic nucleiBipolar patientsSchizophrenia patientsSensory gatingMental illnessResonance imagingDysconnectivityCerebellar regionsDiagnostic membershipPrefrontal cortexSchizophreniaIllnessKetamine Effects on Memory Reconsolidation Favor a Learning Model of Delusions
Corlett PR, Cambridge V, Gardner JM, Piggot JS, Turner DC, Everitt JC, Arana FS, Morgan HL, Milton AL, Lee JL, Aitken MR, Dickinson A, Everitt BJ, Absalom AR, Adapa R, Subramanian N, Taylor JR, Krystal JH, Fletcher PC. Ketamine Effects on Memory Reconsolidation Favor a Learning Model of Delusions. PLOS ONE 2013, 8: e65088. PMID: 23776445, PMCID: PMC3680467, DOI: 10.1371/journal.pone.0065088.Peer-Reviewed Original ResearchConceptsMemory strengthMemory reconsolidationIndividual brain responsesError-dependent learningPsychotogenic effectsSubsequent memoryFear memoryBizarre beliefsBrain responsesDelusional beliefsPrediction errorImpact of ketamineIndividual vulnerabilityBrain signalsSubject studyReconsolidationIndependent samplesLearning procedureMemoryKetamine effectsDelusionsBeliefsPlacebo administrationPsychosisNMDA receptor antagonistNeural Correlates of Impulsivity in Healthy Males and Females with Family Histories of Alcoholism
DeVito EE, Meda SA, Jiantonio R, Potenza MN, Krystal JH, Pearlson GD. Neural Correlates of Impulsivity in Healthy Males and Females with Family Histories of Alcoholism. Neuropsychopharmacology 2013, 38: 1854-1863. PMID: 23584260, PMCID: PMC3746701, DOI: 10.1038/npp.2013.92.Peer-Reviewed Original ResearchConceptsAlcohol use measuresNeural correlatesFHP individualsImpulse controlHigher self-reported impulsivityGreater BOLD signalFHN groupSelf-reported impulsivityAlcohol useInferior frontal gyrusLeft anterior insulaUse measuresImpulsivity factorsAnterior insulaFrontal gyrusGreater activationImpulsivityAddictive disordersNeural systemsScanner measuresSuccessful inhibitionBOLD signalSex differencesBehavioral traitsAddictionIncreased brain uptake and oxidation of acetate in heavy drinkers
Jiang L, Gulanski BI, De Feyter HM, Weinzimer SA, Pittman B, Guidone E, Koretski J, Harman S, Petrakis IL, Krystal JH, Mason GF. Increased brain uptake and oxidation of acetate in heavy drinkers. Journal Of Clinical Investigation 2013, 123: 1605-1614. PMID: 23478412, PMCID: PMC3613911, DOI: 10.1172/jci65153.Peer-Reviewed Original ResearchConceptsHeavy drinkersBrain uptakeN-acetylaspartateLight drinkersChronic heavy drinkingNew therapeutic approachesGreater brain uptakeAlcohol detoxificationConsequences of drinkingTherapeutic approachesMagnetic resonance spectroscopyMore brainHeavy drinkingDrinkersBrainWeeksBloodDrinksGlutamateDrinkingResonance spectroscopyEffects of memantine on event-related potential, oscillations, and complexity in individuals with and without family histories of alcoholism.
Narayanan B, Stevens MC, Jiantonio RE, Krystal JH, Pearlson GD. Effects of memantine on event-related potential, oscillations, and complexity in individuals with and without family histories of alcoholism. Journal Of Studies On Alcohol And Drugs 2013, 74: 245-57. PMID: 23384372, PMCID: PMC3568163, DOI: 10.15288/jsad.2013.74.245.Peer-Reviewed Original ResearchConceptsNMDA receptor functionFHN subjectsFamily historyReceptor functionFHP individualsAlpha activityN-methyl-D-aspartate receptor functionNMDA receptor antagonist memantineEffects of memantineAuditory oddball discrimination taskPositive family historyFamily history-negative subjectsEvent-related potentialsAlcoholism family historyCortical information processingOddball discrimination taskFHN individualsMemantine administrationAcute effectsDrug interactionsP3b amplitudeFHP subjectsMemantineSeparate occasionsTheta activityNKAIN1–SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent
Zuo L, Wang K, Zhang XY, Krystal JH, Li CS, Zhang F, Zhang H, Luo X. NKAIN1–SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent. Drug And Alcohol Dependence 2013, 129: 254-264. PMID: 23455491, PMCID: PMC3628730, DOI: 10.1016/j.drugalcdep.2013.02.006.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesExpression quantitative loci (eQTL) analysisGene regionMetabolic pathwaysQuantitative loci analysisSNP-expression associationsCis-acting regulatory effectsDiscovery sampleSNP-disease associationsNumerous genesReplication sampleLocus analysisAssociation studiesAssociation analysisRisk SNPsTranscript expressionSNPsRegulatory effectsGenesPathwayEuropean descentExpression
2012
Genome‐Wide Significant Association Signals in IPO11‐HTR1A Region Specific for Alcohol and Nicotine Codependence
Zuo L, Zhang X, Wang F, Li C, Lu L, Ye L, Zhang H, Krystal JH, Deng H, Luo X. Genome‐Wide Significant Association Signals in IPO11‐HTR1A Region Specific for Alcohol and Nicotine Codependence. Alcohol Clinical And Experimental Research 2012, 37: 730-739. PMID: 23216389, PMCID: PMC3610804, DOI: 10.1111/acer.12032.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBeta KaryopherinsBlack or African AmericanCase-Control StudiesChromosomes, Human, Pair 5FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociReceptor, Serotonin, 5-HT1ATobacco Use DisorderWhite PeopleConceptsGenome-wide significance levelSingle nucleotide polymorphismsReplication cohortDiscovery cohortAlcohol dependenceExpression quantitative loci (eQTL) analysisPeripheral blood mononuclear cell samplesNeuropsychiatric disordersWide significant association signalsMononuclear cell samplesGenome-wide association studiesQuantitative loci analysisGene-disease association analysisCis-eQTL analysisTop single nucleotide polymorphismsCis-acting regulatory effectsSignificant association signalsBrain tissue samplesAmerican controlsEuropean American controlsRisk single nucleotide polymorphismsAfrican-American controlsSevere subtypeGenomic regionsAfrican American casesGlobal Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History
Anticevic A, Brumbaugh MS, Winkler AM, Lombardo LE, Barrett J, Corlett PR, Kober H, Gruber J, Repovs G, Cole MW, Krystal JH, Pearlson GD, Glahn DC. Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History. Biological Psychiatry 2012, 73: 565-573. PMID: 22980587, PMCID: PMC3549314, DOI: 10.1016/j.biopsych.2012.07.031.Peer-Reviewed Original ResearchConceptsPsychosis historyRisk factorsBipolar patientsSymptom severityResting-state functional magnetic resonanceAmygdala-mPFC connectivityFronto-limbic dysfunctionSevere clinical courseBipolar I patientsEmotion regulation regionsPsychotic symptom severityFunctional magnetic resonanceClinical courseI patientsLimbic structuresBipolar illnessConnectivity deficitsAmygdala findingsConnectivity abnormalitiesPathophysiological modelBipolar IPatientsBipolar disorderDysconnectivityAbnormal inhibition