2024
The genetics of severe depression
Franklin C, Achtyes E, Altinay M, Bailey K, Bhati M, Carr B, Conroy S, Husain M, Khurshid K, Lencz T, McDonald W, Mickey B, Murrough J, Nestor S, Nickl-Jockschat T, Nikayin S, Reeves K, Reti I, Selek S, Sanacora G, Trapp N, Viswanath B, Wright J, Sullivan P, Zandi P, Potash J. The genetics of severe depression. Molecular Psychiatry 2024, 1-10. PMID: 39406997, DOI: 10.1038/s41380-024-02731-1.Peer-Reviewed Original ResearchGenome-wide association studiesSevere depressionGenome-wide significant lociWhole-exome sequencing studiesAssociated with dysphoriaGenome-wide lociGenome-wide interrogationExome sequencing studiesEarly-onset illnessDegree of impairmentDepressive disorderMDD phenotypesSignificant lociAssociation studiesClinical markers of severitySequencing studiesMDDLociRare variantsClinically actionable findingsEstimates of heritabilityDepressionFamily-basedSevere formGeneticsThe Role of Awe and Other Psychological Factors in Ketamine’s Mechanism of Antidepressant Action
Ansari M, Sanacora G. The Role of Awe and Other Psychological Factors in Ketamine’s Mechanism of Antidepressant Action. Biological Psychiatry Global Open Science 2024, 4: 100353. DOI: 10.1016/j.bpsgos.2024.100353.Peer-Reviewed Original ResearchKetamine vs Electroconvulsive Therapy for Treatment-Resistant Depression
Jha M, Wilkinson S, Krishnan K, Collins K, Sanacora G, Murrough J, Goes F, Altinay M, Aloysi A, Asghar-Ali A, Barnett B, Chang L, Costi S, Malone D, Nikayin S, Nissen S, Ostroff R, Reti I, Wolski K, Wang D, Hu B, Mathew S, Anand A. Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression. JAMA Network Open 2024, 7: e2417786. PMID: 38916891, PMCID: PMC11200139, DOI: 10.1001/jamanetworkopen.2024.17786.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionQIDS-SR16 scoresElectroconvulsive therapy groupElectroconvulsive therapyQIDS-SR16Measure of premorbid intelligencePosttraumatic stress disorder diagnosisTrial of electroconvulsive therapyNonpsychotic depressive episodeImpaired memory recallAssociated with differential improvementStress disorder diagnosisIntravenous ketamineEnd-of-treatment visitInfusion of ketamineMADRS scorePremorbid intelligenceResistant depressionDepressive episodeMeasures mixed-effects modelsFalse discovery rate adjustmentDisorder diagnosisMemory recallSevere depressionDifferential improvementDepression - Advanced Treatments for Treatment-Resistant Depression.
Cristancho M, Fava M, Ingelfinger J, Nikayin S, Sanacora G. Depression - Advanced Treatments for Treatment-Resistant Depression. New England Journal Of Medicine 2024, 390: e44. PMID: 38810184, DOI: 10.1056/nejmp2310181.Peer-Reviewed Original ResearchDepression - Treatment Options and Managing Depression in Primary Care.
Anderson E, Crawford C, Fava M, Ingelfinger J, Sanacora G, Scott-Vernaglia S, Teel J. Depression - Treatment Options and Managing Depression in Primary Care. New England Journal Of Medicine 2024, 390: e44. PMID: 38749042, DOI: 10.1056/nejmp2310180.Peer-Reviewed Original ResearchDepression - Understanding, Identifying, and Diagnosing.
Anderson E, Crawford C, Fava M, Ingelfinger J, Nikayin S, Sanacora G, Scott-Vernaglia S, Teel J. Depression - Understanding, Identifying, and Diagnosing. New England Journal Of Medicine 2024, 390: e41. PMID: 38692291, DOI: 10.1056/nejmp2310179.Peer-Reviewed Original Research497. Prefrontal Cortex Astroglia Modulate Anhedonia-Like Behavior
Codeluppi S, Xu M, Bansal Y, Lepack A, Duric V, Chow M, Muir J, Bagot R, Licznerski P, Wilber S, Sanacora G, Sibille E, Duman R, Pittenger C, Banasr M. 497. Prefrontal Cortex Astroglia Modulate Anhedonia-Like Behavior. Biological Psychiatry 2024, 95: s302. DOI: 10.1016/j.biopsych.2024.02.996.Peer-Reviewed Original ResearchThe Rapidly Shifting Ketamine Landscape in the US
Wilkinson S, Palamar J, Sanacora G. The Rapidly Shifting Ketamine Landscape in the US. JAMA Psychiatry 2024, 81: 221-222. PMID: 38170542, DOI: 10.1001/jamapsychiatry.2023.4945.Peer-Reviewed Original Research
2023
Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments
Krystal J, Kaye A, Jefferson S, Girgenti M, Wilkinson S, Sanacora G, Esterlis I. Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2305772120. PMID: 38011560, PMCID: PMC10710048, DOI: 10.1073/pnas.2305772120.Peer-Reviewed Original ResearchPsychedelic renaissance: Revitalized potential therapies for psychiatric disorders
Rhee T, Davoudian P, Sanacora G, Wilkinson S. Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders. Drug Discovery Today 2023, 28: 103818. PMID: 37925136, DOI: 10.1016/j.drudis.2023.103818.Peer-Reviewed Original ResearchPsychiatric disordersLysergic acid diethylamideClinical trialsUS Clinical Trials RegistryClinical Trials RegistryPotential therapeutic effectsTrials RegistryTherapeutic effectPotential therapyTherapeutic agentsN-dimethyltryptamineAcid diethylamideLargest causePsychedelic compoundsDisordersPsychotherapeutic approachesSafety concernsTrialsPotential interactive effectsCutting-edge reviewPsychedelic substancesRegistryTherapyCognitive behavioral therapy following esketamine for major depression and suicidal ideation for relapse prevention: The CBT-ENDURE randomized clinical trial study protocol
Kitay B, Murphy E, Macaluso M, Corlett P, Hershenberg R, Joormann J, Martinez-Kaigi V, Nikayin S, Rhee T, Sanacora G, Shelton R, Thase M, Wilkinson S. Cognitive behavioral therapy following esketamine for major depression and suicidal ideation for relapse prevention: The CBT-ENDURE randomized clinical trial study protocol. Psychiatry Research 2023, 330: 115585. PMID: 37935086, DOI: 10.1016/j.psychres.2023.115585.Peer-Reviewed Original ResearchConceptsCognitive behavioral therapyMajor depressionSuicidal ideationRelapse preventionBehavioral therapyStudy protocolHigh riskClinical trial study protocolLong-term treatment approachKey secondary outcomesTrial study protocolHigh relapse rateHigh-risk populationSignificant suicidal ideationHospital dischargeSecondary outcomesPrimary outcomeRelapse rateFeasibility trialEsketamineTreatment approachesPatientsSuicide attemptsTherapySupplemental indicationsPlacebo’s role in the rapid antidepressant effect
Sanacora G, Colloca L. Placebo’s role in the rapid antidepressant effect. Nature Mental Health 2023, 1: 820-821. DOI: 10.1038/s44220-023-00141-w.Peer-Reviewed Original ResearchRandomized placebo-controlled studyPlacebo-controlled studyRapid antidepressant effectsRapid antidepressant responseRapid antidepressant actionsStudy arm assignmentAntidepressant actionAntidepressant effectsAntidepressant responseSurgical anesthesiaTreatment assignmentHigh ratePlaceboAnesthesiaKetamineTreatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions
McIntyre R, Alsuwaidan M, Baune B, Berk M, Demyttenaere K, Goldberg J, Gorwood P, Ho R, Kasper S, Kennedy S, Ly-Uson J, Mansur R, McAllister-Williams R, Murrough J, Nemeroff C, Nierenberg A, Rosenblat J, Sanacora G, Schatzberg A, Shelton R, Stahl S, Trivedi M, Vieta E, Vinberg M, Williams N, Young A, Maj M. Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry 2023, 22: 394-412. PMID: 37713549, PMCID: PMC10503923, DOI: 10.1002/wps.21120.Peer-Reviewed Original ResearchTreatment-resistant depressionTranscranial magnetic stimulationEuropean Medicines AgencyIntravenous ketamineManagement of TRDRepetitive transcranial magnetic stimulationOlanzapine-fluoxetine combinationSecond-generation antipsychoticsSignificant symptomatic reliefManual-based psychotherapiesSerious public health implicationsTheta-burst transcranial magnetic stimulationQuality of carePublic health implicationsIntranasal esketaminePartial respondersAdjunctive treatmentElectroconvulsive therapySymptomatic reliefConventional antidepressantsMedication switchingAntidepressant trialsRisk factorsInvestigational interventionMagnetic stimulationPrefrontal cortex astroglia modulate anhedonia-like behavior
Codeluppi S, Xu M, Bansal Y, Lepack A, Duric V, Chow M, Muir J, Bagot R, Licznerski P, Wilber S, Sanacora G, Sibille E, Duman R, Pittenger C, Banasr M. Prefrontal cortex astroglia modulate anhedonia-like behavior. Molecular Psychiatry 2023, 28: 4632-4641. PMID: 37696873, PMCID: PMC10914619, DOI: 10.1038/s41380-023-02246-1.Peer-Reviewed Original ResearchGlial fibrillary acidic proteinAnhedonia-like behaviorPrefrontal cortexCell depletionDiphtheria toxin administrationDepressive-like behaviorChronic stress modelTreatment of depressionDiphtheria toxin receptorFibrillary acidic proteinDevelopment of anhedoniaCortical astrogliaToxin administrationDesigner receptorsCell activityAcidic proteinViral expressionToxin receptorDesigner drugsExperimental depletionAstrogliaDeficitsReceptorsDepressionCritical roleSingle-Dose Psilocybin Treatment for Major Depressive Disorder
Raison C, Sanacora G, Woolley J, Heinzerling K, Dunlop B, Brown R, Kakar R, Hassman M, Trivedi R, Robison R, Gukasyan N, Nayak S, Hu X, O’Donnell K, Kelmendi B, Sloshower J, Penn A, Bradley E, Kelly D, Mletzko T, Nicholas C, Hutson P, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis M, Nelson-Douthit C, Wilson S, Brown C, Linton W, Johnson M, Ross S, Griffiths R. Single-Dose Psilocybin Treatment for Major Depressive Disorder. JAMA 2023, 330: 843-853. PMID: 37651119, PMCID: PMC10472268, DOI: 10.1001/jama.2023.14530.Peer-Reviewed Original ResearchConceptsMajor depressive disorderSheehan Disability Scale scoresAdverse eventsDisability scale scorePsilocybin treatmentDay 43Scale scoreSecondary outcomesSingle doseDepressive disorderExclusion criteriaPsychological supportMontgomery-Asberg Depression Rating Scale scoreSerious treatment-emergent adverse eventsDay 8Key secondary outcome measuresTreatment-emergent adverse eventsDepression Rating Scale scoresActive substance use disorderFifth Edition diagnosisIdentical-appearing capsulesOverall adverse eventsPhase 2 trialSerious adverse eventsSevere adverse eventsThe Intricate Interaction Between Expectations and Therapeutic Outcomes of Psychedelic Agents
Colloca L, Nikayin S, Sanacora G. The Intricate Interaction Between Expectations and Therapeutic Outcomes of Psychedelic Agents. JAMA Psychiatry 2023, 80: 867-868. PMID: 37405764, PMCID: PMC10868530, DOI: 10.1001/jamapsychiatry.2023.1412.Peer-Reviewed Original ResearchUsing 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 measuresKetamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression
Anand A, Mathew S, Sanacora G, Murrough J, Goes F, Altinay M, Aloysi A, Asghar-Ali A, Barnett B, Chang L, Collins K, Costi S, Iqbal S, Jha M, Krishnan K, Malone D, Nikayin S, Nissen S, Ostroff R, Reti I, Wilkinson S, Wolski K, Hu B. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. New England Journal Of Medicine 2023, 388: 2315-2325. PMID: 37224232, DOI: 10.1056/nejmoa2302399.Peer-Reviewed Original ResearchConceptsTreatment-resistant major depressionPatient-reported qualityElectroconvulsive therapyMajor depressionECT groupKetamine groupTreatment phaseMusculoskeletal adverse effectsSubanesthetic intravenous ketamineWeeks of treatmentInitial treatment phaseIntravenous ketamineSecondary outcomesPrimary outcomeNoninferiority marginTrial groupECT clinicsNoninferiority trialPatientsComparative effectivenessKetamineClinical sitesAdverse effectsDepressionThree timesLong-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study
Zaki N, Chen L, Lane R, Doherty T, Drevets W, Morrison R, Sanacora G, Wilkinson S, Popova V, Fu D. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study. Neuropsychopharmacology 2023, 48: 1225-1233. PMID: 37173512, PMCID: PMC10267177, DOI: 10.1038/s41386-023-01577-5.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionEsketamine treatmentMontgomery-Åsberg Depression Rating Scale (MADRS) total scoreCommon treatment-emergent adverse eventsLong-term extension studyTreatment-emergent adverse eventsEsketamine nasal sprayMean cumulative durationLong-term tolerabilityNew safety signalsHealth-related qualityMaintenance of responseLong-term treatmentMajor depressive disorderLong-term safetyPhase 3Scale total scoreMaintenance phaseOral antidepressantsData cutoffAdverse eventsMaintenance treatmentSustained efficacyEligible participantsDepression ratingsCandidate biomarkers in psychiatric disorders: state of the field
Abi-Dargham A, Moeller S, Ali F, DeLorenzo C, Domschke K, Horga G, Jutla A, Kotov R, Paulus M, Rubio J, Sanacora G, Veenstra-VanderWeele J, Krystal J. Candidate biomarkers in psychiatric disorders: state of the field. World Psychiatry 2023, 22: 236-262. PMID: 37159365, PMCID: PMC10168176, DOI: 10.1002/wps.21078.Peer-Reviewed Original ResearchError-related negativityAutism spectrum disorderAnxiety disordersSpectrum disorderFunctional magnetic resonance imaging (fMRI) measuresEvent-related brain potentialsPost-traumatic stress disorderSocial anxiety disorderTreatment responseCandidate biomarkersGeneralized anxiety disorderResting-state functional magnetic resonance imaging (rsfMRI) measuresDefinitive testingBrain potentialsNeuroscience literatureElectrophysiological indicesStress disorderMagnetic resonance imaging (MRI) measuresNaturalistic settingConnectomic measuresNumerous candidate biomarkersPresence of illnessMobile health toolsIndividual levelBiomarker validation process