2025
Bridging animal models and humans: neuroimaging as intermediate phenotypes linking genetic or stress factors to anhedonia
Guo H, Xiao Y, Dong S, Yang J, Zhao P, Zhao T, Cai A, Tang L, Liu J, Wang H, Hua R, Liu R, Wei Y, Sun D, Liu Z, Xia M, He Y, Wu Y, Si T, Womer F, Xu F, Tang Y, Wang J, Zhang W, Zhang X, Wang F. Bridging animal models and humans: neuroimaging as intermediate phenotypes linking genetic or stress factors to anhedonia. BMC Medicine 2025, 23: 38. PMID: 39849528, PMCID: PMC11755933, DOI: 10.1186/s12916-025-03850-4.Peer-Reviewed Original ResearchConceptsIntermediate phenotypesCore symptoms of depressionAmplitude of low-frequency fluctuationNeuroimaging patternsSubtypes of depressionCore depressive symptomsExpression of risk genesDiverse clinical populationsSymptoms of depressionRodent modelsAssociated with depressionLow-frequency fluctuationsStress-related changesDepression subtypesCore symptomsCross-species validationPsychiatric disordersNeuropsychiatric disordersDepressive symptomsBehavioral manifestationsStress modelDepression cohortClinical populationsSensorimotor regionsAnhedonia
2024
Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedoniaEffects of anhedonia on health-related quality of life and functional outcomes in major depressive disorder: A systematic review and meta-analysis
Wong S, Le G, Phan L, Rhee T, Ho R, Meshkat S, Teopiz K, Kwan A, Mansur R, Rosenblat J, McIntyre R. Effects of anhedonia on health-related quality of life and functional outcomes in major depressive disorder: A systematic review and meta-analysis. Journal Of Affective Disorders 2024, 356: 684-698. PMID: 38657767, DOI: 10.1016/j.jad.2024.04.086.Peer-Reviewed Original ResearchConceptsMajor depressive disorderSnaith-Hamilton Pleasure ScaleEffect of anhedoniaDepressive disorderAssociated with depressive symptom severityGroup of mood disordersSocial functioning deficitsSymptoms of anhedoniaDepressive symptom severitySelf-report measuresAnticipatory anhedoniaReward valuationConsummatory anhedoniaReward learningPleasure ScaleInvestigated anhedoniaMood disordersSymptom domainsAnhedoniaHealth-related quality of lifeSymptom severityFunctional outcomesHealth-related qualityQuality of lifeFunctional impairment
2023
Not all traumas are created equal: Phenotypic heterogeneity of PTSD symptoms in relation to index traumas in U.S. military veterans
Kachadourian L, Duek O, Tsai J, Harpaz-Rotem I, Pietrzak R. Not all traumas are created equal: Phenotypic heterogeneity of PTSD symptoms in relation to index traumas in U.S. military veterans. Journal Of Affective Disorders 2023, 340: 728-731. PMID: 37572698, PMCID: PMC10754253, DOI: 10.1016/j.jad.2023.08.012.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderU.S. military veteransMilitary veteransIndex traumaPTSD symptomsDysphoric arousal symptomsIllness/injuryGreater overall severityIndex traumatic eventClinical presentationNational HealthDiagnostic criteriaTreatment approachesGreater severityOverall severityVeterans StudyInterpersonal violenceStress disorderTraumaArousal symptomsSymptomsVeteransPhenotypic heterogeneityTraumatic eventsSeverityUsing latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study
Darrow S, Pizzagalli D, Smoski M, Mathew S, Nurnberger J, Lisanby S, Iosifescu D, Murrough J, Yang H, Weiner R, Sanacora G, Keefe R, Song A, Goodman W, Whitton A, Potter W, Krystal A. Using latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study. Journal Of Affective Disorders 2023, 339: 584-592. PMID: 37467805, DOI: 10.1016/j.jad.2023.07.081.Peer-Reviewed Original ResearchConceptsSelf-report measures“Don't [ruminate], be happy”: A cognitive perspective linking depression and anhedonia
Rutherford A, McDougle S, Joormann J. “Don't [ruminate], be happy”: A cognitive perspective linking depression and anhedonia. Clinical Psychology Review 2023, 101: 102255. PMID: 36871425, DOI: 10.1016/j.cpr.2023.102255.Peer-Reviewed Original ResearchConceptsPositive affectNegative affectSustained negative affectCognitive constructsCognitive theoryCognitive perspectiveLack of pleasureCognitive deficitsSpecific thoughtsIntervention effortsDifferent theoretical lensesAffectRuminationAnhedoniaDeficitsExtant literatureMemoryDepressionHallmark featureComputational modelingTheoretical lensesEnvironmental cuesLess focusDebilitating disorderCues
2022
Evaluating Anhedonia as a risk factor in suicidality: A meta-analysis
Gillissie E, Le G, Rhee T, Cao B, Rosenblat J, Mansur R, Ho R, McIntyre R. Evaluating Anhedonia as a risk factor in suicidality: A meta-analysis. Journal Of Psychiatric Research 2022, 158: 209-215. PMID: 36603315, DOI: 10.1016/j.jpsychires.2022.12.024.Peer-Reviewed Original Research
2020
Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats
Nunes EJ, Rupprecht LE, Foster DJ, Lindsley CW, Conn PJ, Addy NA. Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats. Neuropharmacology 2020, 171: 108089. PMID: 32268153, PMCID: PMC7313677, DOI: 10.1016/j.neuropharm.2020.108089.Peer-Reviewed Original ResearchConceptsSucrose preference testVentral tegmental areaMuscarinic M5 receptorsCholinergic toneM5 receptorsBehavioral effectsFemale ratsDepressive-like behavioral effectsIntra-VTA infusionAnxiogenic-like effectsAcetylcholinesterase inhibitor physostigmineAnxiety-related behaviorVTA administrationCholinergic modulationCholinergic receptorsMuscarinic receptorsInhibitor physostigmineSwim testTegmental areaMale ratsMood disordersVTA infusionsFST behaviorRatsPhysostigmineCumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity
Barthas F, Hu MY, Siniscalchi MJ, Ali F, Mineur YS, Picciotto MR, Kwan AC. Cumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity. Biological Psychiatry 2020, 88: 541-553. PMID: 32276717, PMCID: PMC7434704, DOI: 10.1016/j.biopsych.2020.02.008.Peer-Reviewed Original ResearchConceptsPrefrontal cortical activityCortical activityIndividual layer 2/3 pyramidal neuronsLayer 2/3 pyramidal neuronsStress exposureDepressive-like phenotypeTwo-photon calcium imagingSocial stressChronic social stressIndividual prefrontal neuronsMedial prefrontal cortexPyramidal neuronsMotor subregionsNeural dysfunctionResilient miceCalcium imagingPrefrontal neuronsAbnormal levelsPrefrontal cortexSocial defeatDistinct neural responsesStress-induced lossGoal-directed actionsEnsemble activityDefeat sessions
2018
Latent typologies of DSM-5 PTSD symptoms in U.S. military veterans
Byrne SP, Harpaz-Rotem I, Tsai J, Southwick SM, Pietrzak RH. Latent typologies of DSM-5 PTSD symptoms in U.S. military veterans. Psychiatry Research 2018, 273: 266-273. PMID: 30658212, DOI: 10.1016/j.psychres.2018.12.094.Peer-Reviewed Original ResearchConceptsHigh symptom classPosttraumatic stress disorderSymptom classUse disordersLifetime historyDSM-5 PTSD symptomsPTSD symptomsLatent class analysisDrug use disordersNicotine use disorderDSM-5 posttraumatic stress disorderDSM-5 criteriaU.S. military veteransMajor depressiveCognitive impairmentU.S. veteransSymptomsPersonalized approachHigher symptomsStress disorderGeneralized anxietyMilitary veteransThree-class solutionDisordersVeteransExploratory Graph Analysis of the Multidimensional Schizotypy Scale
Christensen A, Gross G, Golino H, Silvia P, Kwapil T. Exploratory Graph Analysis of the Multidimensional Schizotypy Scale. Schizophrenia Research 2018, 206: 43-51. PMID: 30573405, DOI: 10.1016/j.schres.2018.12.018.Peer-Reviewed Original ResearchConceptsMultidimensional Schizotypy ScaleConfirmatory factor analysisSchizotypy scalesExploratory graph analysisNegative schizotypy dimensionsFour-factor modelThree-factor modelPositive schizotypyNegative schizotypySchizotypy dimensionsSchizotypy factorsQuestionnaire measuresDisorganized dimensionBrief versionSchizotypyDifferential associationsFactor analysisFuture researchIndependent samplesModel fitTheoretical dimensionsDimensional structureContrasting contributions of anhedonia to obsessive-compulsive, hoarding, and post-traumatic stress disorders
Pushkarskaya H, Sobowale K, Henick D, Tolin DF, Anticevic A, Pearlson GD, Levy I, Harpaz-Rotem I, Pittenger C. Contrasting contributions of anhedonia to obsessive-compulsive, hoarding, and post-traumatic stress disorders. Journal Of Psychiatric Research 2018, 109: 202-213. PMID: 30572276, PMCID: PMC8549853, DOI: 10.1016/j.jpsychires.2018.11.029.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderObsessive-compulsive disorderValue-based choiceGambling TaskStress disorderSelf-reported risk takingBehavior-based measuresRisk perceptionAspects of anhedoniaRole of anhedoniaEffect of anhedoniaRisk-taking propensitySymptoms of depressionTransdiagnostic constructCompulsive disorderBehavioral outcomesGeneral depressionIndex of difficultyAnhedoniaRisk takingUnique contributionIndividual risk aversionPsychotic disordersPerceptionTaskAccounting for the uncounted: Physical and affective distress in individuals dropping out of oral naltrexone treatment for opioid use disorder
Carroll KM, Nich C, Frankforter TL, Yip SW, Kiluk BD, DeVito EE, Sofuoglu M. Accounting for the uncounted: Physical and affective distress in individuals dropping out of oral naltrexone treatment for opioid use disorder. Drug And Alcohol Dependence 2018, 192: 264-270. PMID: 30300800, PMCID: PMC6203294, DOI: 10.1016/j.drugalcdep.2018.08.019.Peer-Reviewed Original ResearchConceptsOpioid use disorderOral naltrexoneUse disordersAffective symptomsVoucher-based contingency managementDysphoric symptomsAffective distressOral naltrexone treatmentMultiple baseline characteristicsBaseline characteristicsNaltrexone treatmentHigh riskNaltrexoneSomatic symptomsSymptomsContingency managementTreatmentHigh rateDistressSubstantial evidenceTrialsTheoretical benefitsDisordersAffective discomfortParticipantsAnhedonia in depression and schizophrenia: A transdiagnostic challenge
Lambert C, Da Silva S, Ceniti AK, Rizvi SJ, Foussias G, Kennedy SH. Anhedonia in depression and schizophrenia: A transdiagnostic challenge. CNS Neuroscience & Therapeutics 2018, 24: 615-623. PMID: 29687627, PMCID: PMC6489811, DOI: 10.1111/cns.12854.Peer-Reviewed Original ResearchPresentation and Neurobiology of Anhedonia in Mood Disorders: Commonalities and Distinctions
Rizvi S, Lambert C, Kennedy S. Presentation and Neurobiology of Anhedonia in Mood Disorders: Commonalities and Distinctions. Current Psychiatry Reports 2018, 20: 13. PMID: 29520717, DOI: 10.1007/s11920-018-0877-z.Peer-Reviewed Original ResearchConceptsReward processing deficitsMood disordersBipolar patientsProcessing deficitsPresence of residual symptomsNeurobiology of anhedoniaBehavioral activation systemSymptoms of anhedoniaAnhedonia severityTreating anhedoniaReward processingRemitted patientsBipolar disorderReward behaviorTrait factorsBehavioral presentationAnhedoniaReward systemResidual symptomsMoodRecent FindingsEvidenceDisordersRewardAt-riskDeficits
2017
Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers
Pappas A, Bey A, Wang X, Rossi M, Kim Y, Yan H, Porkka F, Duffney L, Phillips S, Cao X, Ding J, Rodriguiz R, Yin H, Weinberg R, Ji R, Wetsel W, Jiang Y. Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers. JCI Insight 2017, 2: e92052. PMID: 29046483, PMCID: PMC5846902, DOI: 10.1172/jci.insight.92052.Peer-Reviewed Original ResearchAmphetamineAnhedoniaAnimalsAntimanic AgentsBehavior, AnimalBipolar DisorderCentral Nervous System StimulantsChronobiology DisordersCognitive DysfunctionFemaleHippocampusLithium CompoundsMaleMiceMice, KnockoutMotor ActivityN-MethylaspartateNerve Tissue ProteinsPhenotypeProsencephalonReceptors, AMPAReceptors, N-Methyl-D-AspartateSocial Behavior DisordersSynapsesAssessment of nicotine withdrawal-induced changes in sucrose preference in mice
Alkhlaif Y, Bagdas D, Jackson A, Park AJ, Damaj IM. Assessment of nicotine withdrawal-induced changes in sucrose preference in mice. Pharmacology Biochemistry And Behavior 2017, 161: 47-52. PMID: 28919072, PMCID: PMC6408212, DOI: 10.1016/j.pbb.2017.08.013.Peer-Reviewed Original ResearchConceptsSucrose preference testNicotine withdrawalSpontaneous nicotine withdrawalLight-dark box testDark box testPositive affective stimuliSucrose preferenceAffective signsSmoking relapse ratesΑ6 KO miceSubcutaneous osmotic minipumpsWithdrawal-induced changesUnderlying neurobiological factorsPreference testRelapse rateOsmotic minipumpsKO miceTobacco useNicotine dependenceKnockout miceAnimal modelsNicotinic subunitsDay 15MiceDifferent dosesPosttraumatic Stress Disorder Symptom Clusters and Acquired Capability for Suicide: A Reexamination Using DSM‐5 Criteria
Spitzer EG, Zuromski KL, Davis MT, Witte TK, Weathers F. Posttraumatic Stress Disorder Symptom Clusters and Acquired Capability for Suicide: A Reexamination Using DSM‐5 Criteria. Suicide And Life-Threatening Behavior 2017, 48: 105-115. PMID: 28261858, DOI: 10.1111/sltb.12341.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorder (PTSD) symptom clustersPTSD symptom clustersSymptom clustersSpecific PTSD symptom clustersSix-factor Anhedonia modelTrauma-exposed undergraduatesInterpersonal-psychological theoryDSM-5 criteriaAcquired CapabilitySuppressor variableCommonality analysisAnhedonia modelBivariate correlationsSuicideComplex relationshipAnhedoniaFacetsUndergraduatesRelationshipStructure coefficientsFindingsTheoryEffects of paclitaxel on the development of neuropathy and affective behaviors in the mouse
Toma W, Kyte S, Bagdas D, Alkhlaif Y, Alsharari S, Lichtman A, Chen Z, Del Fabbro E, Bigbee J, Gewirtz D, Damaj M. Effects of paclitaxel on the development of neuropathy and affective behaviors in the mouse. Neuropharmacology 2017, 117: 305-315. PMID: 28237807, PMCID: PMC5489229, DOI: 10.1016/j.neuropharm.2017.02.020.Peer-Reviewed Original ResearchConceptsCancer chemotherapeutic drugsCancer patientsPreclinical modelsSide effectsAffective symptomsMajor dose-limiting side effectDose-limiting side effectChemotherapeutic drugsLight/dark box testNerve fiber dysfunctionPaclitaxel-treated miceProgression-free survivalSucrose preference testDepression-like behaviorOvarian cancer patientsSevere side effectsAnxiety-like behaviorPotential therapeutic interventionsEffect of paclitaxelAnhedonia-like stateDark box testCold allodyniaNeuropathic painNegative affective symptomsNociceptive effects
2016
Regulating task-monitoring systems in response to variable reward contingencies and outcomes in cocaine addicts
Morie KP, De Sanctis P, Garavan H, Foxe JJ. Regulating task-monitoring systems in response to variable reward contingencies and outcomes in cocaine addicts. Psychopharmacology 2016, 233: 1105-1118. PMID: 26861797, DOI: 10.1007/s00213-015-4191-8.Peer-Reviewed Original ResearchConceptsReward processingTask successConsummatory reward processingEvent-related potentialsSpeeded response taskValue of rewardsMeasures of anhedoniaCocaine usersNeural measuresReward contingenciesPredictive cuesReward motivationReward receiptReward outcomesTask contingenciesResponse taskActive cocaine abusersReward probabilityHedonic toneAnticipatory responsesVulnerability markerReward scheduleMonitoring deficienciesAnhedoniaReward
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