2024
Stress and substance use disorders: risk, relapse, and treatment outcomes
Sinha R. Stress and substance use disorders: risk, relapse, and treatment outcomes. Journal Of Clinical Investigation 2024, 134: e172883. PMID: 39145454, PMCID: PMC11324296, DOI: 10.1172/jci172883.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PsychologicalHumansRecurrenceRisk FactorsStress, PsychologicalSubstance-Related DisordersTreatment OutcomeConceptsSubstance use disordersDrug-related environmentPathophysiology of addictionAdaptive stress responseSUD treatment outcomesAssociated with substance misuseTreatment outcomesStress-related alterationsDrug motivationIncreased cravingNeurobiological disruptionsMaladaptive copingRepeated stressorsTreatment implicationsSubstance misuseStress pathophysiologyStress responseDrug intakeDrug withdrawalRelapse riskDrug misuseIntervention developmentDisordersCravingRelapseNeural Correlates of Stress and Alcohol Cue-Induced Alcohol Craving and of Future Heavy Drinking: Evidence of Sex Differences
Radoman M, Fogelman N, Lacadie C, Seo D, Sinha R. Neural Correlates of Stress and Alcohol Cue-Induced Alcohol Craving and of Future Heavy Drinking: Evidence of Sex Differences. American Journal Of Psychiatry 2024, 181: 412-422. PMID: 38706332, PMCID: PMC11117176, DOI: 10.1176/appi.ajp.20230849.Peer-Reviewed Original ResearchConceptsAlcohol use disorderPercentage of heavy drinking daysNeural correlates of stressCue-induced cravingHeavy drinking daysAlcohol cravingSex differencesCorrelates of stressDrinking daysAlcohol cue-induced cravingCue-induced alcohol cravingBed nucleus of the stria terminalisSubgenual anterior cingulate cortexAssessment of alcohol cravingHeavy drinkingAlcohol cue reactivityAssociated with poor treatment outcomesCue-induced responsesNeutral cue exposureAssociated with hypoactivationTreatment-seeking adultsHeavy drinking outcomesEvidence of sex differencesVoxel-based regression analysisAnterior cingulate cortex
2023
Hypothalamic‐pituitary‐adrenal and autonomic response to psychological stress in abstinent alcohol use disorder individuals with and without depressive symptomatology
Syed S, Sinha R, Milivojevic V, MacDougall A, LaValle H, Angarita G, Fox H. Hypothalamic‐pituitary‐adrenal and autonomic response to psychological stress in abstinent alcohol use disorder individuals with and without depressive symptomatology. Human Psychopharmacology Clinical And Experimental 2023, 38: e2867. PMID: 37165544, DOI: 10.1002/hup.2867.Peer-Reviewed Original ResearchConceptsAlcohol use disorderRelapse riskDepressive symptomatologyDepressive symptomsAutonomic responsesIndividual relapse riskChronic alcohol useDepressive pathophysiologyAdrenocorticotropic hormoneInhibitory systemPlasma measuresUse disordersClinical practicePhasic changesConsecutive daysAlcohol usePsychological stressStroop performanceDisorder individualsDrinking controlsSymptomatologyImagery exposureCounterbalanced orderSymptomsDepression
2022
Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder
Milivojevic V, Charron L, Fogelman N, Hermes G, Sinha R. Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder. Biomolecules 2022, 12: 1593. PMID: 36358943, PMCID: PMC9687893, DOI: 10.3390/biom12111593.Peer-Reviewed Original ResearchMeSH KeywordsAnxietyArousalCocaineCravingFemaleHumansMaleNeurosteroidsPregnenoloneStress, PsychologicalConceptsDiastolic blood pressureCocaine use disorderHeart ratePrecursor pregnenoloneUse disordersCocaine cravingCue-induced cocaine cravingCue-induced anxietyWeeks of treatmentCue-induced cravingAutonomic arousalChronic cocaine usePreg groupBlood pressureDay groupRelapse riskHigher cocainePregnenolone levelsCue-provoked cravingSeparate daysAutonomic responsesCocaine useTreatment-seeking individualsCravingSteroid systems
2021
This is Your Brain in Meltdown
Arnsten A, Mazure CM, Sinha R. This is Your Brain in Meltdown. Scientific American 2021, 306: 48-53. PMID: 22486116, PMCID: PMC4774859, DOI: 10.1038/scientificamerican0412-48.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal GlandsBrainFemaleHumansHydrocortisoneMaleNeurotransmitter AgentsPrefrontal CortexPyramidal CellsSex FactorsStress, Psychological
2018
Central and Peripheral Biomarkers of Stress Response for Addiction Risk and Relapse Vulnerability
Milivojevic V, Sinha R. Central and Peripheral Biomarkers of Stress Response for Addiction Risk and Relapse Vulnerability. Trends In Molecular Medicine 2018, 24: 173-186. PMID: 29396148, PMCID: PMC6511993, DOI: 10.1016/j.molmed.2017.12.010.Peer-Reviewed Original ResearchMeSH KeywordsBehavior, AddictiveBiomarkersCentral Nervous SystemHumansPeripheral Nervous SystemRecurrenceRisk FactorsStress, PsychologicalSubstance-Related DisordersConceptsSubstance use disordersTreatment of SUDsDevelopment of SUDHigh relapse rateFunctional brain alterationsCentral stress responseAdrenal axis markersStress response measuresRelapse ratePeripheral biomarkersClinical symptomatologyBrain alterationsUse disordersCandidate biomarkersAutonomic responsesRelapse vulnerabilityPutative biomarkersAddiction riskStress responseBiomarkersTreatmentResponsePathophysiologySymptomatologyPrevention
2016
Neural stress reactivity relates to smoking outcomes and differentiates between mindfulness and cognitive-behavioral treatments
Kober H, Brewer JA, Height KL, Sinha R. Neural stress reactivity relates to smoking outcomes and differentiates between mindfulness and cognitive-behavioral treatments. NeuroImage 2016, 151: 4-13. PMID: 27693614, PMCID: PMC5373945, DOI: 10.1016/j.neuroimage.2016.09.042.Peer-Reviewed Original ResearchConceptsCognitive-behavioral treatmentFunctional magnetic resonance imagingStress reactivityMindfulness-based treatmentsAmerican Lung Association's FreedomUnderstanding of stressPsychological mechanismsMindfulness trainingNegative affectConjunction analysisMid insulaCBT groupStress provocationSmoking outcomesBrain regionsCessation treatmentEfficacy of MTCurrent studyEntire sampleDrug useSmoking cessationImportant implicationsMagnetic resonance imagingMindfulnessInsulaDynamic neural activity during stress signals resilient coping
Sinha R, Lacadie CM, Constable RT, Seo D. Dynamic neural activity during stress signals resilient coping. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8837-8842. PMID: 27432990, PMCID: PMC4978278, DOI: 10.1073/pnas.1600965113.Peer-Reviewed Original ResearchConceptsDorsal anterior cingulate cortexVentrolateral prefrontal cortexResilient copingNeural activationPrefrontal cortexFunctional magnetic resonance imaging studyDorsolateral prefrontal cortex regionsNeutral visual stimuliVentromedial prefrontal cortexHealthy stress responseDynamic neural activityPrefrontal cortex regionsAnterior cingulate cortexFrequency of argumentsMagnetic resonance imaging studyResonance imaging studyVmPFC activationEmotional eatingNeural processesStress processingVisual stimuliViolent stimuliBinge alcohol intakeBrain networksRight insula
2013
Cumulative Adversity Sensitizes Neural Response to Acute Stress: Association with Health Symptoms
Seo D, Tsou KA, Ansell EB, Potenza MN, Sinha R. Cumulative Adversity Sensitizes Neural Response to Acute Stress: Association with Health Symptoms. Neuropsychopharmacology 2013, 39: 670-680. PMID: 24051900, PMCID: PMC3895244, DOI: 10.1038/npp.2013.250.Peer-Reviewed Original ResearchConceptsMedial orbitofrontal cortexAdverse health symptomsStress-induced activityHealth symptomsOrbitofrontal cortexCumulative adversityAcute stressMagnetic resonance imaging resultsAdverse health outcomesNeural responsesCornell Medical IndexFunctional magnetic resonance imaging resultsHigh-Ca groupRight hippocampusRight amygdalaHealthy individualsCA groupHealth outcomesMedical IndexLateral prefrontal cortexSignificant associationSymptomsHealth consequencesPrefrontal cortexTemporal regionsThe Effects of Stress on Physical Activity and Exercise
Stults-Kolehmainen MA, Sinha R. The Effects of Stress on Physical Activity and Exercise. Sports Medicine 2013, 44: 81-121. PMID: 24030837, PMCID: PMC3894304, DOI: 10.1007/s40279-013-0090-5.Peer-Reviewed Original ResearchConceptsInfluence of stressWork-family conflictFace of stressLifetime cumulative adversityStress-related reductionLevel of stressStages of changeHuman participantsIndicators of PAPerceived stressEffects of stressCumulative adversityLife eventsRole strainJob strainExercise adoptionTheoretical orientationOlder adultsPsychological stressSubjective measuresPreliminary evidencePhysical activityStudies of exercisePA relationshipHigh-quality prospective researchStress as a Common Risk Factor for Obesity and Addiction
Sinha R, Jastreboff AM. Stress as a Common Risk Factor for Obesity and Addiction. Biological Psychiatry 2013, 73: 827-835. PMID: 23541000, PMCID: PMC3658316, DOI: 10.1016/j.biopsych.2013.01.032.BooksMeSH KeywordsBehavior, AddictiveBrainCuesFeeding BehaviorHumansHyperphagiaMotivationObesityRisk FactorsStress, PsychologicalConceptsNeurobiology of stressHP foodsIncentive salienceFood motivationIntegrative heuristic modelFood-related motivationDevelopment of addictionBiology of stressNeural mechanismsNeurobiological mechanismsAddiction relapsePalatable foodAddictive drugsAllostatic loadMotivationRisk factorsSalienceHigh levelsNeurobiologyHeuristic modelEnergy homeostasisWeight gainAddictionFuture directionsDopaminergic activity
2012
Cumulative Adversity and Smaller Gray Matter Volume in Medial Prefrontal, Anterior Cingulate, and Insula Regions
Ansell EB, Rando K, Tuit K, Guarnaccia J, Sinha R. Cumulative Adversity and Smaller Gray Matter Volume in Medial Prefrontal, Anterior Cingulate, and Insula Regions. Biological Psychiatry 2012, 72: 57-64. PMID: 22218286, PMCID: PMC3391585, DOI: 10.1016/j.biopsych.2011.11.022.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexGray matter volumeCumulative adversityPrefrontal cortexLife eventsSmaller gray matter volumeAnterior cingulateMatter volumeCingulate regionsRecent stressful life eventsCommunity participantsHealthy community participantsCumulative life eventsStressful life eventsStress-related psychopathologyAdverse life eventsAnterior cingulate regionsChronic stress effectsInsula regionsLife traumaKey prefrontalMedial prefrontalCommunity sampleOrbitofrontal cortexRight insula
2011
Effects of Adrenal Sensitivity, Stress- and Cue-Induced Craving, and Anxiety on Subsequent Alcohol Relapse and Treatment Outcomes
Sinha R, Fox HC, Hong KI, Hansen J, Tuit K, Kreek MJ. Effects of Adrenal Sensitivity, Stress- and Cue-Induced Craving, and Anxiety on Subsequent Alcohol Relapse and Treatment Outcomes. JAMA Psychiatry 2011, 68: 942-952. PMID: 21536969, PMCID: PMC3668981, DOI: 10.1001/archgenpsychiatry.2011.49.Peer-Reviewed Original ResearchConceptsAlcohol-dependent patientsAlcohol relapseCue-induced alcohol cravingTreatment outcomesAdrenal sensitivityAlcohol cravingCommunity mental health centerCue-induced anxietyEarly alcohol recoveryHPA axis dysregulationHPA axis functionHPA axis responseMental health centersCue-induced alcoholAlcohol cuesStress-induced alcoholHospital-based research unitAlcohol-dependent individualsCue-Induced CravingCorticotropin levelsAxis dysregulationAxis functionAdrenal axisRelapse riskHealthy controls
2008
Chronic Stress, Drug Use, and Vulnerability to Addiction
Sinha R. Chronic Stress, Drug Use, and Vulnerability to Addiction. Annals Of The New York Academy Of Sciences 2008, 1141: 105-130. PMID: 18991954, PMCID: PMC2732004, DOI: 10.1196/annals.1441.030.Peer-Reviewed Original ResearchMeSH KeywordsArousalChronic DiseaseCorticotropin-Releasing HormoneDisease SusceptibilityEmotionsFemaleHumansHypothalamo-Hypophyseal SystemIllicit DrugsLimbic SystemMaleNeurotransmitter AgentsPituitary-Adrenal SystemRewardSelf MedicationStress, PhysiologicalStress, PsychologicalSubstance Withdrawal SyndromeSubstance-Related DisordersSympathetic Nervous SystemConceptsCompulsive drug seekingStress-related riskDevelopment of addictionChronic drug useEarly life stressMotivational systemsIndividual-level variablesRelapse susceptibilityRelapse vulnerabilityDrug seekingAutonomic arousalDrug useLife stressDrug-experienced animalsSpecific stressorsChild maltreatmentSubstance useMesolimbic dopamineStress exposureStress regulationAddictionChronic stressCentral noradrenergic systemNoradrenergic systemButyric acid pathway
2007
Inhibitory control and emotional stress regulation: Neuroimaging evidence for frontal–limbic dysfunction in psycho-stimulant addiction
Li CS, Sinha R. Inhibitory control and emotional stress regulation: Neuroimaging evidence for frontal–limbic dysfunction in psycho-stimulant addiction. Neuroscience & Biobehavioral Reviews 2007, 32: 581-597. PMID: 18164058, PMCID: PMC2263143, DOI: 10.1016/j.neubiorev.2007.10.003.Peer-Reviewed Original ResearchConceptsInhibitory controlPrefrontal activityDrug seekingHabitual drug seekingCognitive inhibitory controlCompulsive drug seekingVentromedial prefrontal regionsFrontal-limbic dysfunctionStress-related cravingAnterior cingulate cortexStress regulationPsychological processesNeural underpinningsSalient stimuliStress processingPrefrontal regionsComponent processesStriatal responsesDrug use behaviorsCingulate cortexNeural systemsPsychostimulant dependenceUse behaviorsNeural pathwaysAddiction
2006
Stress-Induced Cocaine Craving and Hypothalamic-Pituitary-Adrenal Responses Are Predictive of Cocaine Relapse Outcomes
Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ. Stress-Induced Cocaine Craving and Hypothalamic-Pituitary-Adrenal Responses Are Predictive of Cocaine Relapse Outcomes. JAMA Psychiatry 2006, 63: 324-331. PMID: 16520439, DOI: 10.1001/archpsyc.63.3.324.Peer-Reviewed Original ResearchMeSH KeywordsAdrenocorticotropic HormoneAdultBehavior, AddictiveCocaine-Related DisordersCuesFemaleFollow-Up StudiesHospitalizationHumansHydrocortisoneHypothalamo-Hypophyseal SystemMaleMiddle AgedPituitary-Adrenal SystemProspective StudiesSecondary PreventionStress, PsychologicalSubstance Abuse Treatment CentersTreatment OutcomeConceptsAdrenal axis responseCocaine cravingRelapse outcomesAxis responseCocaine relapseAdrenal responseInpatient treatmentCocaine relapse outcomesCue-induced cocaine cravingStress-induced drug cravingCocaine useCocaine dependenceCox proportional hazards regressionCommunity mental health centerProportional hazards regressionMental health centersProspective study designDrug cue exposureStress-related increasesTreatment-seeking cocaine dependent individualsHazards regressionHypothalamic-PituitaryHealth centersCocaine-dependent individualsRelapse
2001
How does stress increase risk of drug abuse and relapse?
Sinha R. How does stress increase risk of drug abuse and relapse? Psychopharmacology 2001, 158: 343-359. PMID: 11797055, DOI: 10.1007/s002130100917.Peer-Reviewed Original ResearchConceptsDrug abuseSubstance abuseMost major theoriesHuman laboratory studiesField of addictionDrug seekingDrug useTreatment developmentMajor theoriesAbuse altersStress exposureVulnerable individualsHuman researchAbuseAddictsEmpirical evidencePreclinical evidenceClinical observationsRelapseAnimal studiesPreclinical researchSeekingGreater understandingAddictionResearch