2024
Characterizing the Most Vulnerable Prefrontal Cortical Neurons in Schizophrenia
Arnsten A, Datta D. Characterizing the Most Vulnerable Prefrontal Cortical Neurons in Schizophrenia. American Journal Of Psychiatry 2024, 181: 861-864. PMID: 39350618, DOI: 10.1176/appi.ajp.20240731.Peer-Reviewed Original Research
2022
The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion
Arnsten A, Joyce M, Roberts A. The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion. Neuroscience & Biobehavioral Reviews 2022, 145: 105000. PMID: 36529312, PMCID: PMC9898199, DOI: 10.1016/j.neubiorev.2022.105000.Peer-Reviewed Original ResearchConceptsCortical pathwaysStress exposureDendritic spine lossChronic stress exposureAnti-depressant treatmentDeep brain stimulationPrefrontal cortical areasExcessive dopamineNeuromodulatory treatmentSSRI medicationNorepinephrine releaseSpine lossSubgenual cingulateCortical areasBrain stimulationChronic stressBA25MedicationsDorsolateral PFCTreatmentExposurePsychic painPainKetamineSymptoms
2015
Stress weakens prefrontal networks: molecular insults to higher cognition
Arnsten AF. Stress weakens prefrontal networks: molecular insults to higher cognition. Nature Neuroscience 2015, 18: 1376-1385. PMID: 26404712, PMCID: PMC4816215, DOI: 10.1038/nn.4087.Peer-Reviewed Original ResearchDopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders
Arnsten AF, Wang M, Paspalas CD. Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders. Pharmacological Reviews 2015, 67: 681-696. PMID: 26106146, PMCID: PMC4485014, DOI: 10.1124/pr.115.010512.Peer-Reviewed Original ResearchConceptsCell firingPyramidal cell dendritesD2 receptor familyFrontal eye fieldPrimate prefrontal cortexGABA interneuronsCortical dopamineDopamine actionGlutamate releaseEndogenous dopamineDA cellsCell dendritesD1R agonistDendritic spinesCognitive disordersOrbital PFCEye fieldPositive symptomsLikely projectResponse cellsCognitive deficitsPrefrontal cortexStimulation speedFeedback neuronsD1R
2014
A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation
McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten A, Picciotto MR, Weinberger AH, Ashare R, Sinha R. A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation. Journal Of Psychopharmacology 2014, 29: 300-311. PMID: 25516371, PMCID: PMC4376109, DOI: 10.1177/0269881114562091.Peer-Reviewed Original ResearchConceptsPlacebo-treated subjectsFunctional magnetic resonance imagingCentral noradrenergic pathwaysPrefrontal cognitive dysfunctionSystolic blood pressureClinical outcome dataAd libitum smokingNovel translational approachStress-induced reinstatementMagnetic resonance imagingNicotine-deprived smokersBlood pressureNoradrenergic pathwaysAgonist guanfacineCognitive dysfunctionTreatment periodTobacco cravingQuit attemptsOutcome dataSmokingComplete abstinenceCortisol levelsTranslational investigationsCigarette useGuanfacineGuanfacine extended release for the treatment of attention-deficit/hyperactivity disorder in children and adolescents
Connor DF, Arnsten A, Pearson GS, Greco GF. Guanfacine extended release for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. Expert Opinion On Pharmacotherapy 2014, 15: 1601-1610. PMID: 24992513, DOI: 10.1517/14656566.2014.930437.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderHyperactivity disorderSymptoms of ADHDEvidence-based treatmentsTraumatic stressBehavioral dysregulationADHD studiesSmall effect sizesPrefrontal cortexAdolescents 6Behavioral conditionsAdolescentsEffect sizeGXRPsycINFO databasesGuanfacinePsychostimulantsShire PharmaceuticalsOpen trialChildrenPotential promiseSecond-line treatmentDisordersAntihypertensive agentsAdrenoreceptor agonist
2012
Neuromodulation of Thought: Flexibilities and Vulnerabilities in Prefrontal Cortical Network Synapses
Arnsten AF, Wang MJ, Paspalas CD. Neuromodulation of Thought: Flexibilities and Vulnerabilities in Prefrontal Cortical Network Synapses. Neuron 2012, 76: 223-239. PMID: 23040817, PMCID: PMC3488343, DOI: 10.1016/j.neuron.2012.08.038.Peer-Reviewed Original ResearchGuanfacine for the treatment of cognitive disorders: a century of discoveries at Yale.
Arnsten AF, Jin LE. Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale. The Yale Journal Of Biology And Medicine 2012, 85: 45-58. PMID: 22461743, PMCID: PMC3313539.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderPrefrontal cortexCognitive disordersHigher-order cognitive abilitiesDeficit hyperactivity disorderPFC cognitive functionCognitive abilitiesHyperactivity disorderCognitive functionMemory functionPFC functionAgonist guanfacineBrain regionsGuanfacineRecent researchNeurobiologyYale Medical SchoolCentury of discoveryDisordersTherapeutic targetTourette syndromePostsynaptic spinesEmotionsMemorySyndrome
2010
The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder
Arnsten A. The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Review Of Neurotherapeutics 2010, 10: 1595-1605. PMID: 20925474, PMCID: PMC3143019, DOI: 10.1586/ern.10.133.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderPrefrontal cortexHyperactivity disorderPFC functionPFC gray matterPFC pyramidal cellsPyramidal cell networksDorsolateral prefrontal cortexPFC connectionsReceptors inhibitsPyramidal cellsAdrenergic agonistsDendritic spinesVentromedial prefrontal cortexGray matterRelated disordersBrain regionsNeuropsychiatric disordersPotassium channelsDisordersPatientsRecent dataPhysiological connectionTreatmentExecutive functioningDynamic Network Connectivity: A new form of neuroplasticity
Arnsten AF, Paspalas CD, Gamo NJ, Yang Y, Wang M. Dynamic Network Connectivity: A new form of neuroplasticity. Trends In Cognitive Sciences 2010, 14: 365-375. PMID: 20554470, PMCID: PMC2914830, DOI: 10.1016/j.tics.2010.05.003.Peer-Reviewed Original Research
2009
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten AF. Stress signalling pathways that impair prefrontal cortex structure and function. Nature Reviews Neuroscience 2009, 10: 410-422. PMID: 19455173, PMCID: PMC2907136, DOI: 10.1038/nrn2648.Peer-Reviewed Original ResearchConceptsPrefrontal functionMemory abilityUncontrollable stressPrefrontal cortex structurePrefrontal pyramidal cellsControl of behaviorCognitive abilitiesEmotional operationsPrefrontal networkImpair performanceMental illnessPrefrontal dysfunctionPrefrontal cortexPrefrontal gray matterPrefrontal neuronsMemory functionStress impairsPersistent firingNeurochemical environmentStress exposureNeurochemical eventsCortex structureHigh levelsEmotionsChronic stress
2000
Genetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function
ARNSTEN A, Lombroso P. Genetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function. Journal Of The American Academy Of Child & Adolescent Psychiatry 2000, 39: 1201-1203. PMID: 10986819, DOI: 10.1097/00004583-200009000-00022.Peer-Reviewed Original ResearchThrough the Looking Glass: Differential Noradenergic Modulation of Prefrontal Cortical Function
Arnsten A. Through the Looking Glass: Differential Noradenergic Modulation of Prefrontal Cortical Function. Neural Plasticity 2000, 7: 133-146. PMID: 10709220, PMCID: PMC2565372, DOI: 10.1155/np.2000.133.Peer-Reviewed Original ResearchStress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine α-1 receptor mechanisms
Arnsten A. Stress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine α-1 receptor mechanisms. Progress In Brain Research 2000, 126: 183-192. PMID: 11105647, DOI: 10.1016/s0079-6123(00)26014-7.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAmygdalaAnimalsAttentionCalcium SignalingCyclic AMPCyclic AMP-Dependent Protein KinasesDopamineHaplorhiniHelplessness, LearnedHumansMemory DisordersModels, NeurologicalModels, PsychologicalNerve Tissue ProteinsNoiseNorepinephrinePhosphatidylinositol Diacylglycerol-LyasePrefrontal CortexRatsReceptors, Adrenergic, alpha-1Receptors, Dopamine D1Second Messenger SystemsStress, PhysiologicalType C PhospholipasesConceptsMemory functionSensory cortexLong-term memory consolidationLong-term memoryPrefrontal cortical functionAssociative memory functionStress-induced deficitsAttentional regulationFocus of attentionAversive eventsMemory consolidationSalient signalsCortical functionProminent stimulusNorepinephrine αHigh levelsAmygdalaCortexCatecholamine releaseAttentionMemoryStimuliDeficitsΒ-receptor stimulationD1 receptors
1999
Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder
Southwick S, Bremner J, Rasmusson A, Morgan C, Arnsten A, Charney D. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biological Psychiatry 1999, 46: 1192-1204. PMID: 10560025, DOI: 10.1016/s0006-3223(99)00219-x.Peer-Reviewed Original ResearchConceptsRole of norepinephrineClinical studiesNorepinephrine's roleTrauma-related alterationsRe-experiencing symptomsFear-provoking stimuliTreatment of PTSDPosttraumatic stress disorderChronic uncontrollable stressPharmacologic treatmentClinical findingsNeuronal reactivityIntrusive memoriesAdrenergic blockersEnhanced encodingSelective attentionPreclinical studiesReceptor sensitivityAversive eventsNorepinephrineTraumatic stressNovel stimuliStress disorderMAO inhibitorsUncontrollable stressDevelopment of the Cerebral Cortex: XIV. Stress Impairs Prefrontal Cortical Function
Lombroso P, ARNSTEN A. Development of the Cerebral Cortex: XIV. Stress Impairs Prefrontal Cortical Function. Journal Of The American Academy Of Child & Adolescent Psychiatry 1999, 38: 220-222. PMID: 9951224, DOI: 10.1097/00004583-199902000-00024.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1998
The biology of being frazzled.
Arnsten A. The biology of being frazzled. Science 1998, 280: 1711-2. PMID: 9660710, DOI: 10.1126/science.280.5370.1711.Peer-Reviewed Original Research
1997
The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer’s disease
van Dyck C, Lin C, Robinson R, Cellar J, Smith E, Nelson J, Arnsten A, Hoffer P. The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer’s disease. Psychopharmacology 1997, 132: 217-226. PMID: 9292621, DOI: 10.1007/s002130050339.Peer-Reviewed Original ResearchConceptsRegional cerebral blood flowParietal regional cerebral blood flowCerebral blood flowAlzheimer's diseaseAD patientsBlood flowDouble-blind trialWeeks of treatmentAD drug therapyProbable Alzheimer's diseaseParietal association cortexSingle photon emissionPlacebo TIDRCBF abnormalitiesCholinergic drugsDrug therapyHealthy controlsRCBF ratiosPharmacological interventionsHealthy subjectsAssociation cortexPatientsLinopirdineBrain regionsNeuropsychological functionCatecholamine regulation of the prefrontal cortex
Arnsten A. Catecholamine regulation of the prefrontal cortex. Journal Of Psychopharmacology 1997, 11: 151-162. PMID: 9208378, DOI: 10.1177/026988119701100208.Peer-Reviewed Original ResearchConceptsPrefrontal cortexAdrenergic receptorsAlpha-1 adrenergic receptorsPFC functionPFC cognitive functionAlpha 2A-adrenergic receptorD1 receptor stimulationTreatment of disordersCatecholamine regulationCatecholamine releaseDA stimulationCatecholamine stimulationD2 familyProminent symptomReceptor stimulationModulatory influencePFC dysfunctionCognitive functionSubcortical structuresReview evidenceDetrimental actionsCatecholamines dopamineReceptorsStimulationNorepinephrinePathogenesis of Tourette's Syndrome
Leckman J, Peterson B, Anderson G, Arnsten A, Pauls D, Cohen D. Pathogenesis of Tourette's Syndrome. Journal Of Child Psychology And Psychiatry 1997, 38: 119-142. PMID: 9232461, DOI: 10.1111/j.1469-7610.1997.tb01508.x.Peer-Reviewed Original Research