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AbnormallyReducedDorsomedialPrefrontalCorticalActivityandEffectiveConnectivityWithAmygdalainResponsetoNegativeEmotionalFacesinPostpartumDepressionEydieL.Moses-Kolko,M.D.,SusanB.Perlman,Ph.D.,KatherineL.Wisner,M.D.,M.S.,JeffreyJames,B.S.,A.TovaSaul,B.A.,andMaryL.Phillips,M.D.DepartmentofPsychiatry,WesternPsychiatricInstituteandClinic,UniversityofPittsburghMedicalCenter,Pittsburgh;theDepartmentsofObstetricsandGynecologyandReproductiveSciencesandRadiology,UniversityofPittsburghMedicalCenter,Pittsburgh;theDepartmentsofEpidemiologyandWomen’sStudies,UniversityofPittsburgh;andtheDepartmentofPsychologicalMedicine,CardiffUniversitySchoolofMedicine,Cardiff,UnitedKingdomAbstractObjective—Postpartummajordepressionisasignificantpublichealthproblemthatstrikes15%ofnewmothersandconfersadverseconsequencesformothers,children,andfamilies.Theneuralmechanismsinvolvedinpostpartumdepressionremainunknown,butbrainprocessingofaffectivestimuliappearstobeinvolvedinotheraffectivedisorders.Theauthorsexaminedactivityinresponsetonegativeemotionalfacesinthedorsomedialprefrontalcortexandamygdala,keyemotionregulatoryneuralregionsofimportancetobothmotheringanddepression.Method—Postpartumhealthymothers(N=16)andunmedicateddepressedmothers(N=14)underwentfunctionalmagneticresonanceimagingblood-oxygen-level-dependentacquisitionduringablock-designedfaceversusshapematchingtask.Atwo-wayanalysisofvariancewasperformedexaminingmaineffectsofconditionandgroupandgroup-by-conditioninteractiononactivityinbilateraldorsomedialprefrontalcorticalandamygdalaregionsofinterest.Results—Depressedmothersrelativetohealthymothershadsignificantlyreducedleftdorsomedialprefrontalcorticalface-relatedactivity.Indepressedmothers,therewasalsoasignificantnegativecorrelationbetweenleftamygdalaactivityandpostpartumdepressionseverityandasignificantpositivecorrelationbetweenrightamygdalaactivityandabsenceofinfant-relatedhostility.Therewasreliabletop-downconnectivityfromtheleftdorsomedialprefrontalcortextotheleftamygdalainhealthy,butnotdepressed,mothers.Conclusions—Significantlydiminisheddorsomedialprefrontalcortexactivityanddorsomedialprefrontalcortical-amygdalaeffectiveconnectivityinresponsetonegativeemotionalfacesmayrepresentanimportantneuralmechanism,oreffect,ofpostpartumdepression.Reducedamygdalaactivityinresponsetonegativeemotionalfacesisassociatedwithgreaterpostpartumdepressionseverityandmoreimpairedmaternalattachmentprocessesinpostpartumdepressedmothers.Thebirthofachildisagreatlyanticipatedanddesiredlifeevent,butitisparadoxicallyaccompaniedbymaternaldepressionin15%ofnewmothers(1).Postpartumdepressionisnotonlydisablingandpotentiallylife-threatening,butitalsointerfereswithmother-infantCopyright€2010AmericanPsychiatricAssociation.Allrightsreserved.AddresscorrespondenceandreprintrequeststoDr.Moses-Kolko,WesternPsychiatricInstituteandClinic,UniversityofPittsburghMedicalCenter,3811O’HaraSt.,Pittsburgh,PA15213;MosesEL@upmc.edu..PreviouslypresentedasaposterattheAnnualMeetingoftheSocietyforBiologicalPsychiatry,Vancouver,BritishColumbia,May14–16,2009.NIHPublicAccessAuthorManuscriptAmJPsychiatry.Authormanuscript;availableinPMC2012March5.Publishedinfinaleditedformas:AmJPsychiatry.2010November;167(11):1373–1380.doi:10.1176/appi.ajp.2010.09081235.NIH-PAAuthorManuscriptNIH-PAAuthorManuscriptNIH-PAAuthorManuscriptrelationalprocesses,withconsequentadverseeffectsonthesocioemotionalandcognitivedevelopmentofoffspring(2).Despitewiderrecognitionofitstragicoutcomes,stigma,lackofeducationaboutthedisorderanditstreatment,andpoordiscriminationofthedisorderfromnormalmaternaladjustmentcontinuetobesignificanttreatmentbarriers(3).Forwomenwhodoseektreatment,outcomesaredisappointing.Ofdepressedmotherswhoreceived8weeksofpharmacologictreatment(4)or12weeksofinterpersonalpsychotherapy(5),only30%–50%successfullyachievedremission,whichissimilartoremissionratesfordepressioninthegeneralpopulation(6).Greatermechanisticunderstandingofpostpartumdepressionisneeded.Hypothalamic-pituitary-adrenalaxisdysregulation(7-9)andhypoestrogenemiaappeartobeimportantpathophysiologicalprocessesinpostpartumdepression(10).Incontrast,thereislittleunderstandingoftheneuralmechanismsofemotionprocessinginthedisorder.Innonpostpartumadultdepression,neuroimagingstudieshavehighlightedtheroleofdysfunctionwithinkeysocialcognitionandemotionregulatoryregions,includingthedorsomedialprefrontalcortex,togetherwithamygdalaandstriatalemotionprocessingregions,inresponsetoself-andother-relevantemotionalstimuli(11,12).Innormativemotherhood,severalinvestigatorshavereportedmedialprefrontalcortexandsubcorticallimbicactivityinresponsetoinfantvideos(13)andinfantcries(14-16).Furthermore,healthymothersdisplayedgreateractivitywithinthebilateralamygdalaandmedialprefrontalcortexinresponsetofacesoftheirownchildversuslessfamiliarinfants(17,18).Suchpatternssuggestthatmaternalamygdalaactivityinresponsetosalientemotionalcuesaswellasengagementofsocialcognitionregionsinvolvedinempathyandself-otherrelationalprocesses(19)maycompriseaneuralcircuitrythatsupportsattunementtoinf