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INFORMATION FOR

Amy Arnsten, PhD

Albert E. Kent Professor of Neuroscience and Professor of Psychology; Member, Kavli Institute of Neuroscience at Yale University

Contact Information

Amy Arnsten, PhD

Mailing Address

  • Neuroscience

    PO Box 208001, 333 Cedar Street

    New Haven, CT 06520-8001

    United States

Research Summary

The Arnsten lab studies molecular influences on higher cognitive function, with the aim of developing rational therapies for mental illness and for age-related cognitive disorders such as Alzheimer's Disease. The work focuses on the prefrontal cortex, a highly evolved brain region that creates our "Mental Sketchpad", allowing us abstract reasoning, high order decision-making, working memory, and thoughtful regulation of attention, behavior and emotion (including inhibition of inappropriate thoughts, actions and feelings). The Arnsten lab has discovered powerful chemical signaling pathways that can impair prefrontal function, e.g. when we are stressed, as well as protective pathways that maintain strong cognitive function. (A youtube video on how the brain is affected by stress during COVID19 pandemic can be found here: https://youtu.be/TsQUeNuvIDY). These pathways are altered by normal aging, and can be genetically altered in mental illness. Based on research in the Arnsten lab, two medications have been developed for human use: guanfacine (Intuniv) for the treatment of Attention Deficit Hyperactivity Disorder, and prazosin for the treatment of Post-Traumatic Stress Disorder.

Specialized terms: Molecular influences on higher cognitive function

Extensive Research Description

The Arnsten Lab studies molecular influences on the higher cognitive functions of the prefrontal cortex (PFC), with the overarching goal of developing rational treatments for cognitive disorders and mental illness. The lab uses a multi-disciplinary approach to understand mechanisms influencing working memory at the cellular and behavioral levels. Research has focused on how the arousal pathways rapidly alter PFC network strength through intracellular signaling mechanisms, a process termed Dynamic Network Connectivity. Our data explain how exposure to stress causes the rapid loss of PFC cognitive abilities, and how genetic mutations in molecules that regulate these pathways can lead to symptoms of mental illness. Dysregulation of these pathways with advancing age leads to loss of neuronal firing, cognitive impairments,and increased vulnerability for degeneration. Understanding these mechanisms has led to successful new treatments for patients with PFC dysfunction, including medications for Attention Deficit Hyperactivity Disorder, Post-Traumatic Stress Disorder and a potential treatment for schizophrenia and bipolar disorder.

Coauthors

Research Interests

Aging; Alzheimer Disease; Behavioral Sciences; Psychology, Child; Mental Health; Neurobiology; Neurosciences; Stress Disorders, Post-Traumatic; Prefrontal Cortex; Cognitive Science

Public Health Interests

Aging; Mental Health; Child/Adolescent Health

Research Image

Selected Publications

  • Clinical experience with the a2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19"Fesharaki-Zadeh A, Lowe N, Arnsten A. Clinical experience with the a2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19" Neuroimmunology Reports 2023, 3: 100154. DOI: 10.1016/j.nerep.2022.100154.
  • P477. Anatomical Evaluation of Calcium-Related Schizophrenia Risk Genes in Rhesus Macaque Dorsolateral Prefrontal CortexDatta D, Mentone S, Morozov Y, Arnsten A. P477. Anatomical Evaluation of Calcium-Related Schizophrenia Risk Genes in Rhesus Macaque Dorsolateral Prefrontal Cortex Biological Psychiatry 2022, 91: s281-s282. DOI: 10.1016/j.biopsych.2022.02.713.
  • Cerebrospinal fluid and brain PET measures of synaptic density glycoprotein 2A: Biomarkers of synaptic density in Alzheimer’s diseaseMecca A, Ashton N, Ashton N, Chen M, O'Dell R, Naganawa M, Toyonaga T, Zhao W, Nabulsi N, Brinkmalm A, Brinkmalm A, Kvartsberg H, Kvartsberg H, Schöll M, Schöll M, Arnsten A, Huang Y, Blennow K, Blennow K, Zetterberg H, Zetterberg H, Carson R, van Dyck C, Nilsson J, Nilsson J. Cerebrospinal fluid and brain PET measures of synaptic density glycoprotein 2A: Biomarkers of synaptic density in Alzheimer’s disease Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.054831.
  • Synaptic Loss is Associated With Cognitive Impairment in Early Alzheimer’s Disease: A PET Imaging Study With [11C]UCB-JO'Dell R, Mecca A, Sharp E, Banks E, Banks E, Bartlett H, Bartlett H, Chen M, Naganawa M, Toyonaga T, Harris J, Harris J, Ni G, Ni G, Zhao W, Nabulsi N, Wyk B, Wyk B, Huang Y, Carson R, Arnsten A, van Dyck C. Synaptic Loss is Associated With Cognitive Impairment in Early Alzheimer’s Disease: A PET Imaging Study With [11C]UCB-J Biological Psychiatry 2021, 89: s107-s108. DOI: 10.1016/j.biopsych.2021.02.276.
  • Association of Aß deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [11C]UCB-JO'Dell R, Mecca A, Chen M, Naganawa M, Toyonaga T, Lu Y, Lu Y, Godek T, Godek T, Harris J, Harris J, Bartlett H, Bartlett H, Banks E, Banks E, Kominek V, Kominek V, Zhao W, Nabulsi N, Ropchan J, Ye Y, Wyk B, Wyk B, Huang Y, Arnsten A, Carson R, van Dyck C. Association of Aß deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [11C]UCB-J American Journal Of Geriatric Psychiatry 2021, 29: s37-s40. DOI: 10.1016/j.jagp.2021.01.034.
  • Principal component analysis of synaptic density measured with [11C]UCB-J PET in Alzheimer's diseaseO'Dell R, Higgins-Chen A, Gupta D, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Lu Y, Banks E, Banks E, Bartlett H, Bartlett H, Harris J, Harris J, Zhao W, Nabulsi N, Wyk B, Wyk B, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in Alzheimer's disease American Journal Of Geriatric Psychiatry 2021, 29: s47-s48. DOI: 10.1016/j.jagp.2021.01.041.
  • Association between cerebral amyloid accumulation and synaptic density in Alzheimer’s disease: A multitracer PET studyO'Dell R, Mecca A, Chen M, Godek T, Godek T, Harris J, Harris J, Bartlett H, Bartlett H, Banks E, Banks E, Kominek V, Zhao W, Naganawa M, Toyonaga T, Lu Y, Lu Y, Nabulsi N, Ropchan J, Ye Y, Wyk B, Wyk B, Varma P, Arnsten A, Huang Y, Carson R, van Dyck C. Association between cerebral amyloid accumulation and synaptic density in Alzheimer’s disease: A multitracer PET study Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.043631.
  • In vivo measurement of widespread synaptic loss and associated tau accumulation in early Alzheimer’s diseaseMecca A, O'Dell R, Chen M, Naganawa M, Toyonaga T, Godek T, Godek T, Harris J, Harris J, Bartlett H, Bartlett H, Zhao W, Gallezot J, Nabulsi N, Ropchan J, Ye Y, Wyk B, Wyk B, Arnsten A, Huang Y, Carson R, van Dyck C. In vivo measurement of widespread synaptic loss and associated tau accumulation in early Alzheimer’s disease Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.037791.
  • Biochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortexLeslie S, Datta D, Wang M, van Dyck C, Arnsten A, Nairn A. Biochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.042017.
  • ASSOCIATION BETWEEN CEREBRAL AMYLOID ACCUMULATION AND SYNAPTIC DENSITY IN ALZHEIMER'S DISEASE: A MULTITRACER PET STUDYO'Dell R, Mecca A, Chen M, Godek T, Godek T, Harris J, Harris J, Bartlett H, Bartlett H, Zhao W, Naganawa M, Toyonaga T, Lu Y, Lu Y, Nabulsi N, Wyk B, Wyk B, Varma P, Arnsten A, Huang Y, Carson R, van Dyck C. ASSOCIATION BETWEEN CEREBRAL AMYLOID ACCUMULATION AND SYNAPTIC DENSITY IN ALZHEIMER'S DISEASE: A MULTITRACER PET STUDY American Journal Of Geriatric Psychiatry 2020, 28: s123-s124. DOI: 10.1016/j.jagp.2020.01.153.
  • IC‐P‐140: ASSOCIATION BETWEEN MGLUR5 AND SYNAPTIC DENSITY: A MULTI‐TRACER STUDY IN HEALTHY AGING AND ALZHEIMER'S DISEASEMecca A, Chen M, Godek T, Godek T, Harris J, Harris J, Bartlett H, Bartlett H, Toyonaga T, Naganawa M, Salardini A, Salardini A, Arnsten A, Nabulsi N, Lim K, Lim K, Najafzadeh S, Ropchan J, Huang Y, Carson R, Strittmatter S, Dyck C, Dyck C. IC‐P‐140: ASSOCIATION BETWEEN MGLUR5 AND SYNAPTIC DENSITY: A MULTI‐TRACER STUDY IN HEALTHY AGING AND ALZHEIMER'S DISEASE Alzheimer's & Dementia 2019, 15: p115-p115. DOI: 10.1016/j.jalz.2019.06.4254.
  • P2‐349: ASSOCIATION BETWEEN MGLUR5 AND SYNAPTIC DENSITY: A MULTI‐TRACER STUDY OF HEALTHY AGING AND ALZHEIMER'S DISEASEMecca A, Chen M, Godek T, Godek T, Harris J, Harris J, Bartlett H, Bartlett H, Toyonaga T, Naganawa M, Salardini A, Salardini A, Arnsten A, Nabulsi N, Lim K, Lim K, Najafzadeh S, Ropchan J, Huang Y, Carson R, Strittmatter S, Dyck C, Dyck C. P2‐349: ASSOCIATION BETWEEN MGLUR5 AND SYNAPTIC DENSITY: A MULTI‐TRACER STUDY OF HEALTHY AGING AND ALZHEIMER'S DISEASE Alzheimer's & Dementia 2019, 15: p729-p729. DOI: 10.1016/j.jalz.2019.06.2756.
  • P2‐365: PET IMAGING OF SYNAPTIC DENSITY (SYNAPTIC VESICLE GLYCOPROTEIN 2A, SV2A) IN ALZHEIMER'S DISEASE: INITIAL EXPERIENCEChen M, Mecca A, Naganawa M, Finnema S, Finnema S, Toyonaga T, Gallezot J, McDonald J, McDonald J, Michalak H, Michalak H, Nabulsi N, Huang Y, Arnsten A, Carson R, Dyck C, Dyck C. P2‐365: PET IMAGING OF SYNAPTIC DENSITY (SYNAPTIC VESICLE GLYCOPROTEIN 2A, SV2A) IN ALZHEIMER'S DISEASE: INITIAL EXPERIENCE Alzheimer's & Dementia 2018, 14: p832-p832. DOI: 10.1016/j.jalz.2018.06.1056.
  • IC‐P‐183: PET IMAGING OF SYNAPTIC DENSITY (SYNAPTIC VESICLE GLYCOPROTEIN 2A, SV2A) IN ALZHEIMER'S DISEASE: INITIAL EXPERIENCEMecca A, Chen M, Naganawa M, Finnema S, Finnema S, Toyonaga T, Lin S, Lin S, Gallezot J, McDonald J, McDonald J, Michalak H, Michalak H, Nabulsi N, Huang Y, Arnsten A, Carson R, Dyck C, Dyck C. IC‐P‐183: PET IMAGING OF SYNAPTIC DENSITY (SYNAPTIC VESICLE GLYCOPROTEIN 2A, SV2A) IN ALZHEIMER'S DISEASE: INITIAL EXPERIENCE Alzheimer's & Dementia 2018, 14: p152-p153. DOI: 10.1016/j.jalz.2018.06.2250.
  • P3‐088: THE AGING RHESUS MONKEY IS AN APPROPRIATE NEW ANIMAL MODEL FOR STUDYING THE ETIOLOGY AND TREATMENT OF TAU PATHOLOGY IN ASSOCIATION CORTEXArnsten A, Carlyle B, Leslie S, Preuss T, Crimins J, Datta D, Anita H, Dyck C, Rosene D, Nairn A, Paspalas C. P3‐088: THE AGING RHESUS MONKEY IS AN APPROPRIATE NEW ANIMAL MODEL FOR STUDYING THE ETIOLOGY AND TREATMENT OF TAU PATHOLOGY IN ASSOCIATION CORTEX Alzheimer's & Dementia 2018, 14: p1099-p1099. DOI: 10.1016/j.jalz.2018.06.1444.
  • 399 Ketamine and Guanfacine Effects on Activation and Connectivity during Working Memory: A Functional Magnetic Resonance Imaging InvestigationDriesen N, McCarthy G, Arnsten A, Morgan P, He G, Bloch M, Krystal J. 399 Ketamine and Guanfacine Effects on Activation and Connectivity during Working Memory: A Functional Magnetic Resonance Imaging Investigation Biological Psychiatry 2017, 81: s163. DOI: 10.1016/j.biopsych.2017.02.416.
  • Catecholamine mechanisms in the prefrontal cortex: proven strategies for enhancing higher cognitive functionBerridge C, Arnsten A. Catecholamine mechanisms in the prefrontal cortex: proven strategies for enhancing higher cognitive function Current Opinion In Behavioral Sciences 2015, 4: 33-40. DOI: 10.1016/j.cobeha.2015.01.002.
  • Catecholamine influences on prefrontal cortex circuits and functionArnsten A, Berridge C. Catecholamine influences on prefrontal cortex circuits and function 2014, 161-173. DOI: 10.1017/cbo9781139035491.015.
  • Fleeting ThoughtsArnsten A. Fleeting Thoughts 2013, 49-54. DOI: 10.1093/med/9780199837755.003.0005.
  • Attention deficit hyperactivity disorderBerridge C, Devilbiss D, Spencer R, Schmeichel B, Arnsten A. Attention deficit hyperactivity disorder 2012, 303-320. DOI: 10.1017/cbo9780511980053.018.
  • Pharmacologic approaches to cognitive rehabilitationMcAllister T, Arnsten A. Pharmacologic approaches to cognitive rehabilitation 2008, 298-320. DOI: 10.1017/cbo9781316529898.022.
  • Estrogen enhances stress-induced prefrontal cortex dysfunction: relevance to Major Depressive Disorder in womenShansky R, Arnsten A. Estrogen enhances stress-induced prefrontal cortex dysfunction: relevance to Major Depressive Disorder in women Dialogues In Clinical Neuroscience 2006, 8: 478-481. PMCID: PMC3181833.
  • Noradrenergic Enhancement of Prefrontal Cortical Cognitive FunctionArnsten A. Noradrenergic Enhancement of Prefrontal Cortical Cognitive Function CNS Neuroscience & Therapeutics 2006, 6: 11-12. DOI: 10.1111/j.1527-3458.2000.tb00164.x.
  • Chapter 11 Molecular Pharmacology and the Treatment of Tourette's Syndrome and Attention Deficit-Hyperactivity DisorderArnsten A. Chapter 11 Molecular Pharmacology and the Treatment of Tourette's Syndrome and Attention Deficit-Hyperactivity Disorder 2005, 183-iv. DOI: 10.1016/b978-012738903-5/50012-6.
  • Patricia Goldman-Rakic A RemembranceArnsten A. Patricia Goldman-Rakic A Remembrance Neuron 2003, 40: 465-470. DOI: 10.1016/s0896-6273(03)00685-8.
  • Neurochemical Modulation of Prefrontal Cortical Function in Humans and AnimalsArnsten A, Robbins T. Neurochemical Modulation of Prefrontal Cortical Function in Humans and Animals 2002, 51-84. DOI: 10.1093/acprof:oso/9780195134971.003.0004.