54th Annual Meeting of the American College of Neuropsychopharmacology Final Program December 6-10, 2015 Diplomat Resort and Spa Hollywood, Florida President: Raquel E. Gur, M.D., Ph.D. Program Committee Chair: Bita Moghaddam, Ph.D. Program Committee Co-Chair: Carlos A. Zarate, M.D. ACNP AMERICAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 54th ANNUAL MEETING GENERAL PROGRAM HOLLYWOOD, FLORIDA DIPLOMAT RESORT & SPA DECEMBER 6-10, 2015 Disclosures for 2015 speakers (mini-panel, panel, study group, and plenary) and poster presenters may be found online at: www.acnp.org (click the Annual Meeting tab). ACNP Annual Meeting Book 2015 rev13.indd 1 11/10/15 9:58 AM ii ACNP 54th Annual Meeting • Final Program 2nd Floor Convention Center Meeting rooms for panel, mini-panel, plenary, and study group sessions are on the 2nd floor of the Convention Center (map above). An 8th concurrent session will be in Great Hall 5-6 on the 3rd floor. Poster sessions and group lunches are also on the 3rd floor (map below). 3rd Floor Convention Center GRAND BALLROOM EAST GRAND BALLROOM WEST ATLANTIC BALLROOM 3 ATLANTIC BALLROOM 2 ATLANTIC BALLROOM 1 REGENCY BALLROOM 3 REGENCY BALLROOM 2 DIPLOMAT BALLROOM 3 1 ELEVATORS WALKWAY TO RESORT ESCALATORREGISTRATION TERRACE 2 5 4 REGENCY BALLROOM 1 FREIGHT ELEVATOR SERVICE ELEVATORS M W S E R V IC E C O R R ID O R S E R V IC E C O R R ID O R THE WESTIN DIPLOMAT CONVENTION CENTER S N WE ESCALATOR ELEVATORS SERVICE ELEVATORS GREAT HALL 2 GREAT HALL 1 GREAT HALL 6 GREAT HALL 5 GREAT HALL 4 GREAT HALL 3 FREIGHT ELEVATOR WM M W TERRACE REGISTRATION THE WESTIN DIPLOMAT CONVENTION CENTER S N WE ACNP Annual Meeting Book 2015 rev13.indd 2 11/10/15 9:58 AM iii ACNP 54th Annual Meeting • Final Program Resort, Second Floor Conference rooms for committee and board meetings are located on the 2nd and 3rd floor of the hotel. Most small meetings have been scheduled on the hotel side. Resort, Third Floor NORTH TOWER 204 205 208 207 EXECUTIVE OFFICES M W 209 206 203 202 201 SOUTH TOWER 220 219 217 216 W M WALKWAY TO CONVENTION CENTER 213 215 212 214 218 ELEVATORSSKYWALK ESCALATORS TERRACETERRACE TERRACE SERVICE ELEVATORS ELEVATORS SERVICE ELEVATORS BUSINESS CENTER THE WESTIN DIPLOMAT CONVENTION CENTER E W SN NORTH TOWER SOUTH TOWER 305 308 307 EXECUTIVE OFFICES M W 309 306 303 302 301 123223 320 319 317 316 W M 313 315 312 311 310 314 318 ELEVATORSELEVATORS SERVICE ELEVATORS SKYWALK ROTALACSEROTALACSE TERRACETERRACE TERRACE SERVICE ELEVATORS THE WESTIN DIPLOMAT CONVENTION CENTER E W SN ACNP Annual Meeting Book 2015 rev13.indd 3 11/10/15 9:58 AM iv ACNP 54th Annual Meeting • Final Program Program at a Glance Saturday, December 5, 2015 8:00 AM - 3:00 PM Room 319-320 ACNP Council Meeting 8:00 AM - 5:00 PM Diplomat Ballroom 5 ACNP Membership Committee Meeting 9:00 AM - 5:00 PM Atlantic Ballroom 1 NIAAA State-of-the-Science on Treating the Comorbidity of Alcohol Use Disorders and PTSD 9:00 AM - 5:30 PM Room 321 CINP Executive Council Meeting 10:00 AM - 7:00 PM Grand Ballroom Foyer Registration 3:00 PM - 5:00 PM Room 217 Neuropsychopharmacology & Neuropsycho- pharmacology Reviews Editors Meeting 4:00 PM - 5:30 PM Room 202 ACNP Ethics Committee Meeting 5:00 PM - 6:30 PM Room 217 ACNP Publications Committee Meeting 6:30 PM - 8:30 PM Great Hall 2 ACNP Travel Award Poster Reception (by invitation) Sunday, December 6, 2015 7:00 AM - 7:00 PM Grand Ballroom Foyer Registration 7:00 AM - 8:30 AM Room 201 ACNP Public Information Committee Meeting 7:30 AM - 9:30 AM Grand Ballroom Foyer Morning Break 8:30 AM - 11:30 AM Regency Ballroom 1-2 Neuropsychopharmacology Reviews Plenary: Stress and Development: Molecular, Neurobiological, and Genetic Approaches to Understanding Pathology 11:30 AM - 1:00 PM Lunch on own 11:30 AM - 1:00 PM Room 212/213 ACNP Past President’s Luncheon 11:30 AM - 1:00 PM Diplomat Ballroom 5 ACNP Program Committee Meeting 11:30 AM - 1:00 PM Room 316 NIMH U19 Program Project–Duke–UNC–Pfizer 11:30 AM - 1:00 PM Diplomat Ballroom 4 ACNP Liaison Committee Meeting 11:30 AM - 1:00 PM Diplomat Ballroom 2 Neuropsychopharmacology Editorial Board Meeting 1:00 PM - 2:30 PM Regency Ballroom 1-2 Q & A Forum with NIH Institutes 2:30 PM - 4:30 PM Grand Ballroom Foyer Afternoon Coffee Break 2:30 PM – 5:30 PM Regency Ballroom 1-2 Hot Topics 6:00 PM - 7:00 PM Room 220 ACNP Associate Member Reception (by invitation) 7:00 PM - 9:00 PM Infinity Pool Deck Opening Reception Monday, December 7, 2015 6:45 AM - 8:00 AM Room 212-213 CDI Booster Session 7:00 AM - 6:00 PM Grand Ballroom Foyer Registration Monday, December 7, 2015 7:00 AM - 8:00 AM Room 216 ACNP Under-represented Minority Task Force Meeting 7:00 AM - 8:00 AM Diplomat Ballroom 5 ACNP Travel Awardee and Past Travel Awardee Breakfast 7:30 AM - 9:30 AM Grand Ballroom Foyer Morning Break 8:00 AM - 11:30 AM Grand Ballroom President’s Plenary 10:30 AM - 4:30 PM Great Hall 1-4 Poster Viewing 11:30 AM - 1:30 PM Regency Ballroom 2 Data Blitz 11:30 AM - 1:30 PM Great Hall 1-4 Lunch 1:30 PM - 3:00 PM Grand Ballroom Distinguished Lecture 2:30 PM - 4:30 PM Grand Ballroom Foyer Afternoon Coffee Break Panel Sessions 3:00 PM - 5:30 PM Diplomat Ballroom 1-2 The Molecular Pathology and Dynamics of Spine Loss in Schizophrenia 3:00 PM - 5:30 PM Regency Ballroom 3 A Multi-Modality Imaging Approach For The Identification of Brain Biomarkers of Clinical Outcomes in Human Addiction 3:00 PM - 5:30 PM Regency Ballroom 2 Functional Neurogenomics in Schizophrenia: Recent Accomplishments and Future Perspectives 3:00 PM - 5:30 PM Atlantic Ballroom 1 Opportunities and Challenges for Buprenorphine in Treating Depression 3:00 PM - 5:30 PM Atlantic Ballroom 2 Going With Your Gut: Appetitive Hormones and the Regulation of Substance Use 3:00 PM - 5:30 PM Atlantic Ballroom 3 Extinction: New Directions from Basic Science to Clinical Interventions 3:00 PM - 5:30 PM Regency Ballroom 1 As Good as It Gets? New Insights From Genetic and Circuitry-Based Models of OCD and Tourette Syndrome Study Group Session 3:00 PM - 5:30 PM Great Hall 5-6 Reproducibility and Robustness of Experimental Data in the Neurosciences - Opportunities for Improvements 5:30 PM - 7:30 PM Great Hall 1-4 Poster Session I with Reception 7:30 PM - 8:30 PM Room 220 ACNP Under-represented Minority Task Force Reception (by invitation) Tuesday, December 8, 2015 7:00 AM - 6:00 PM Grand Ballroom Foyer Registration 7:00 AM - 8:30 AM Diplomat Ballroom 4 ACNP Education & Training Committee Meeting 7:00 AM - 8:30 AM Room 201 ACNP Membership Advisory Task Force Meeting 7:00 AM - 8:30 AM Room 303 American Journal of Psychiatry Editorial Board Meeting Tuesday, December 8, 2015 7:00 AM - 8:30 AM Room 322 CME Institute Executive Directors Meeting 7:00 AM - 8:30 AM Room 312-313 Under-represented Minority Breakfast 7:30 AM - 8:30 AM Room 212-213 ACNP & NIH Leadership Meeting 7:30 AM - 9:30 AM Grand Ballroom Foyer Morning Break Mini Panel Sessions 8:30 AM - 9:45 AM Regency Ballroom 1 Sharing is Caring: An Overview of the Data Sharing Landscape 9:45 AM - 11:00 AM Regency Ballroom 1 Brain-Wide ‘Glymphatic’ Pathway: Visualization and Function Panel Sessions 8:30 AM - 11:00 AM Regency Ballroom 3 Behavioral Implications of Adult Neurogenesis and Its Potential as Treatment Target 8:30 AM - 11:00 AM Regency Ballroom 2 The Role of Epigenetic Mechanisms in the Transition into Alcohol Addiction 8:30 AM - 11:00 AM Atlantic Ballroom 1 From Animals to Humans: The Role of Neuroinflammation in Psychosis and Psychosis Risk 8:30 AM - 11:00 AM Atlantic Ballroom 2 Genetic Approaches to Delay Discounting: Human and Non-Human Animal Approaches 8:30 AM - 11:00 AM Atlantic Ballroom 3 The Road to Recovery: Delineating the Neural Circuits of Compulsive Drug Use Study Group Sessions 8:30 AM - 11:00 AM Diplomat Ballroom 1-2 The Future of Sex Difference Research in Neuropsychopharmacology 8:30 AM - 11:00 AM Great Hall 5-6 rt-fMRI Neurofeedback: Are We There Yet? 10:30 AM - 4:30 PM Great Hall 1-4 Poster Viewing 11:00 AM - 1:00 PM Grand Ballroom Women’s Luncheon 11:00 AM - 12:30 PM Great Hall 1-4 Lunch 12:30 PM - 1:30 PM Room 209 PMG Board Meeting 1:30 PM - 3:00 PM Regency Ballroom 1 Career Development Session 2:30 PM - 4:30 PM Grand Ballroom Foyer Afternoon Coffee Break Mini Panel Sessions 3:00 PM - 4:15 PM Regency Ballroom 1 Social (Cognitive) Functioning in Schizophrenia: Course, Mechanisms, and Treatment 4:15 PM - 5:30 PM Regency Ballroom 1 Neuropsychiatric Disorders in Isolated Populations Panel Sessions 3:00 PM - 5:30 PM Diplomat Ballroom 1-2 Signals From the 4th Dimension: How the Extracellular Matrix Regulates Synaptic Plasticity and Neuropsychiatric Disease 3:00 PM - 5:30 PM Regency Ballroom 3 Neuroimaging, Addiction and Big Data: Opportunities and Challenges ACNP Annual Meeting Book 2015 rev13.indd 4 11/10/15 9:58 AM v ACNP 54th Annual Meeting • Final Program Program at a Glance Tuesday, December 8, 2015 3:00 PM - 5:30 PM Regency Ballroom 2 Schizophrenia as a “Dysplasticity” Disorder 3:00 PM - 5:30 PM Atlantic Ballroom 1 Inflammation-Induced Modulation of Motivation: Impact on Neurotransmitters and Neurocircuits 3:00 PM - 5:30 PM Atlantic Ballroom 2 Molecular Mechanisms Underlying Psychopathology and Treatments in OCD 3:00 PM - 5:30 PM Atlantic Ballroom 3 Research Paradigms and Non-Pharmacological Interventions Aimed to Prevent the Onset and Progression of Bipolar Disorder in Children Study Group Session 3:00 PM - 5:30PM Great Hall 5-6 Training Aspects of International Research Collaborations: Experiences from Multinational Initiatives in Biological Psychiatry Between the USA, Europe, Asia, and Africa 5:30 PM - 7:30 PM Great Hall 1-4 Poster Session II with Reception 6:00 PM - 11:00 PM Room 319-320 ACNP Council Meeting – Committee Chair Reports 6:00 PM - 11:00 PM Room 318 ACNP Committee Chairs Waiting Room Wednesday, December 9, 2015 6:45 AM - 8:30 AM Room 201 ASCP Board of Directors Meeting 6:45 AM - 8:00 AM Room 212-213 CDI Booster Session 7:00 AM - 8:30 AM Diplomat Ballroom 4 SOBP Program Committee Meeting 7:00 AM - 8:00 AM Room 216 MD & MD/PhD Travel Awardee Roundtable (by invitation) 7:30 AM - 5:30 PM Grand Ballroom Foyer Registration 7:30 AM - 9:30 AM Grand Ballroom Foyer Morning Break Mini Panel Sessions 8:30 AM - 9:45 AM Regency Ballroom 1 Prenatal Maternal Environment, Immune Mechanisms, and Neurodevelopment Relevant to Psychiatric Disorders and Preventive Mechanisms 9:45 AM - 11:00 AM Regency Ballroom 1 Harnessing Sex-Differences as Biological Clues in Neurodevelopmental Psychiatry Panel Sessions 8:30 AM - 11:00 AM Diplomat Ballroom 1-2 Complimentary and Integrative Treatment for Mood and Anxiety Disorders 8:30 AM - 11:00 AM Regency Ballroom 3 Synaptic Addiction: New Insights Into the Cellular Mechanisms of Drug Action and Substance Use Disorders 8:30 AM - 11:00 AM Regency Ballroom 2 Normalizing Cognitive Impairments in Schizophrenia: New Leads From Novel Glutamatergic Manipulations 8:30 AM - 11:00 AM Atlantic Ballroom 1 The Research Domain Criteria (RDoC) Initiative: New Data Across Psychiatric Conditions and Age Groups 8:30 AM - 11:00 AM Atlantic Ballroom 2 Caffeine Interactions with Dopamine in Adolescence: An Unappreciated Risk for Obesity and Addiction? Wednesday, December 9, 2015 8:30 AM - 11:00 AM Atlantic Ballroom 3 Mining a Genomic Hotspot for Psychosis: Mechanistic Insights from 22q11.2 Microdeletions Study Group Session 8:30 AM - 11:00 AM Great Hall 5-6 The Sunshine Act: Implications for Neuropsychiatric Researchers and Neuropsychiatric Research - An ACNP Liaison Committee-Sponsored Study Group 10:30 AM - 4:30 PM Great Hall 1-4 Poster Viewing 11:15 AM - 12:30 PM Regency Ballroom 2 Business Meeting (ACNP members only) 12:30 PM - 2:00 PM Great Hall 1-4 Lunch 12:30 PM - 2:00 PM Grand Ballroom Travel Award Luncheon (by invitation) 1:00 PM - 2:00 PM Diplomat Ballroom 5 Corporate Liaison Luncheon (by invitation) 2:30 PM - 4:30 PM Grand Ballroom Foyer Afternoon Coffee Break Panel Sessions 3:00 PM - 5:30 PM Diplomat Ballroom 1-2 Sex Hormones, the Medial Prefrontal Cortex and Their Role on Eating Disorder Behavior in Basic Science and Human Brain Imaging Studies 3:00 PM - 5:30 PM Regency Ballroom 3 A Fresh Perspective on Neuregulin in Schizophrenia 3:00 PM - 5:30 PM Regency Ballroom 2 Real-Life Proxies of Social Context in Affective Problems Across the Lifespan: Evidence From Human and Rodent Studies 3:00 PM - 5:30 PM Atlantic Ballroom 1 Advances From 3 Hallmark Genetic Consortia on Endophenotypes in Schizophrenia to Four Collaborations Operating at the Exciting Frontiers of Genomic Science 3:00 PM - 5:30 PM Atlantic Ballroom 2 The Role of Neuroinflammation in Depression: PET Imaging and Clinical Implications 3:00 PM - 5:30 PM Atlantic Ballroom 3 Fear Generalization: Neurobiological and Behavioral Mechanisms Across the Pre-Clinical and Clinical Spectrum 3:00 PM - 5:30 PM Regency Ballroom 1 Probing the Perinatal Expression of Risk for Mental Disorder: Basic Molecular, Neurobiological, Neuroimaging and Clinical Intervention Studies in Pregnancy and Fetal Development Study Group Session 3:00 PM - 5:30 PM Great Hall 5-6 Neurocircuit-Based Interventions in Addictions: When and How? 5:30 PM - 7:30 PM Great Hall 1-4 Poster Session III with Reception 7:30 PM - 8:30 PM Diplomat Ballroom 4 Women Mentees and Mentors Reception Thursday, December 10, 2015 7:00 AM - 8:00 AM Room 212 ACNP, ECNP, CINP, and AsCNP Leadership Meeting 7:00 AM - 9:00 AM Grand Ballroom Foyer Morning Break 7:30 AM - 3:00 PM Grand Ballroom Foyer Registration Thursday, December 10, 2015 Panel Sessions 8:00 AM - 10:30 AM Diplomat Ballroom 1-2 The Role of Impulsivity vs. Impulse Control on the Developmental Trajectories of SUD - New Insights from Neuroimaging Research 8:00 AM - 10:30 AM Regency Ballroom 3 Ontogeny of Autism: Identification of Very Early Signs of Autism Spectrum Disorder in Humans and Mice 8:00 AM - 10:30 AM Regency Ballroom 2 Using Neural Connectivity Biomarkers in Major Depressive Disorder (MDD) to Identify Subtypes and Predict Treatment Response 8:00 AM - 10:30 AM Atlantic Ballroom 1 Combining Imaging Modalities in Understanding and Treating Stress-Related Disorders 8:00 AM - 10:30 AM Atlantic Ballroom 2 Genomes and Cells: New Models for Target Discovery and Validation 8:00 AM - 10:30 AM Atlantic Ballroom 3 Studies of Stress Identify Novel Signal Transduction and Epigenetic Antidepressant Targets 8:00 AM - 10:30 AM Regency Ballroom 1 Orphan GPCRs and Psychiatric Disorders Study Group Session 8:00 AM - 10:30 AM Great Hall 5-6 Addictions Neuroclinical Assessment: The Search Continues 9:00 AM - 12:00 PM Room 319-320 ACNP Council Meeting 10:30 AM - 12:00 PM Grand Ballroom Foyer Brunch Mini Panel Sessions 12:00 PM - 1:15 PM Regency Ballroom 1 Revisiting the Mu Opiate Receptor for the Treatment of Depression 1:15 PM - 2:30 PM Regency Ballroom 1 DBS and the Identification of Circuits Mediating Depression Panel Sessions 12:00 PM - 2:30 PM Diplomat Ballroom 1-2 The Re-Emergence of Serotonergic Hallucinogens as Tools for Neuropsychopharmacology 12:00 PM - 2:30 PM Regency Ballroom 3 Beta Arrestin Signaling: An Avenue to Novel Psychopharmacology 12:00 PM - 2:30 PM Regency Ballroom 2 Novel Molecular Targets in Cocaine Addiction 12:00 PM - 2:30 PM Atlantic Ballroom 1 Visualizing Neurocircuit Dynamics in Rodent Models of Addiction and Anxiety 12:00 PM - 2:30 PM Atlantic Ballroom 2 Translational Neural Network Approaches for Identifying Individualized Targets for Neurostimulation in Mood Disorders and OCD 12:00 PM - 2:30 PM Atlantic Ballroom 3 New Twists on Transmembrane Transporter Function in Psychiatric and Neurodegenerative Disorders Study Group Session 12:00 PM - 2:30 PM Regency Ballroom 1 Methodological Challenges in Human Pharmacogenetic Studies in Alcohol and Drug Abuse – What has Early Experience Taught us, Where to Next? ACNP Annual Meeting Book 2015 rev13.indd 5 11/10/15 9:58 AM ACNP Annual Meeting Book 2015 rev13.indd 6 11/10/15 9:58 AM vii ACNP 54th Annual Meeting • Final Program Tuesday, December 8th Morning Mini-Panel Sessions • Sharing is Caring: An Overview of the Data Sharing Landscape . . . . .107 • Brain-Wide ‘Glymphatic’ Pathway: Visualization and Function . . . . .108 Morning Panel Sessions • Behavioral Implications of Adult Neurogenesis and Its Potential as Treatment Target . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109 • The Role of Epigenetic Mechanisms in the Transition Into Alcohol Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110 • From Animals to Humans: The Role of Neuroinflammation in Psychosis and Psychosis Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111 • Genetic Approaches to Delay Discounting: Human and Non-Human Animal Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .112 • The Road to Recovery: Delineating the Neural Circuits of Compulsive Drug Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .113 Morning Study Group Session • The Future of Sex Difference Research in Neuropsychopharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .114 • rt-fMRI Neurofeedback: Are We There Yet? . . . . . . . . . . . . . . . . . . . .115 Women’s Luncheon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .116 Career Development Session . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117 Afternoon Mini-Panel Sessions • Social (Cognitive) Functioning in Schizophrenia: Course, Mechanisms, and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . .118 • Neuropsychiatric Disorders in Isolated Populations . . . . . . . . . . . . . . .119 Afternoon Panel Sessions • Signals From the 4th Dimension: How the Extracellular Matrix Regulates Synaptic Plasticity and Neuropsychiatric Disease . . . . . . . .120 • Neuroimaging, Addiction and Big Data: Opportunities and Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .121 • Schizophrenia as a “Dysplasticity” Disorder . . . . . . . . . . . . . . . . . . . .122 • Inflammation-Induced Modulation of Motivation: Impact on Neurotransmitters and Neurocircuits . . . . . . . . . . . . . . . . . . . . . . . . . .123 ACNP Annual Meeting Book 2015 rev13.indd 7 11/10/15 9:58 AM viii ACNP 54th Annual Meeting • Final Program Tuesday, December 8th (continued) Afternoon Panel Sessions • Molecular Mechanisms Underlying Psychopathology and Treatments in OCD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .124 • Research Paradigms and Non-Pharmacological Interventions Aimed to Prevent the Onset and Progression of Bipolar Disorder in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125 Afternoon Study Group Sessions • Training Aspects of International Research Collaborations: Experiences from Multinational Initiatives in Biological Psychiatry Between the USA, Europe, Asia, and Africa . . . . . . . . . . .126 Wednesday, December 9th Morning Mini-Panel Sessions • Prenatal Maternal Environment, Immune Mechanisms, and Neurodevelopment Relevant to Psychiatric Disorders and Preventive Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .129 • Harnessing Sex-Differences as Biological Clues in Neurodevelopmental Psychiatry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .130 Morning Panel Sessions • Complimentary and Integrative Treatment for Mood and Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .131 • Synaptic Addiction: New Insights Into the Cellular Mechanisms of Drug Action and Substance Use Disorders . . . . . . . . .132 • Normalizing Cognitive Impairments in Schizophrenia: New Leads From Novel Glutamatergic Manipulations . . . . . . . . . . . .133 • The Research Domain Criteria (RDoC) Initiative: New Data Across Psychiatric Conditions and Age Groups . . . . . . . . .134 • Caffeine Interactions with Dopamine in Adolescence: An Unappreciated Risk for Obesity and Addiction? . . . . . . . . . . . . . . .135 • Mining a Genomic Hotspot for Psychosis: Mechanistic Insights from 22q11 .2 Microdeletions . . . . . . . . . . . . . . . . . . . . . . . . .136 Morning Study Group Session • The Sunshine Act: Implications for Neuropsychiatric Researchers and Neuropsychiatric Research - An ACNP Liaison Committee-Sponsored Study Group . . . . . . . . . . . .137 ACNP Annual Meeting Book 2015 rev13.indd 8 11/10/15 9:58 AM ix ACNP 54th Annual Meeting • Final Program Wednesday, December 9th (continued) Afternoon Panel Sessions • Sex Hormones, the Medial Prefrontal Cortex and Their Role on Eating Disorder Behavior in Basic Science and Human Brain Imaging Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .138 • A Fresh Perspective on Neuregulin in Schizophrenia . . . . . . . . . . . . . .139 • Real-Life Proxies of Social Context in Affective Problems Across the Lifespan: Evidence From Human and Rodent Studies . . . .140 • Advances From Three Hallmark Genetic Consortia on Endophenotypes in Schizophrenia to Four Collaborations Operating at the Exciting Frontiers of Genomic Science . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .141 • The Role of Neuroinflammation in Depression: PET Imaging and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . .142 • Fear Generalization: Neurobiological and Behavioral Mechanisms Across the Pre-Clinical and Clinical Spectrum . . . . . . . . . . . . . . . . . .143 • Probing the Perinatal Expression of Risk for Mental Disorder: Basic Molecular, Neurobiological, Neuroimaging and Clinical Intervention Studies in Pregnancy and Fetal Development . . . . . . . . .144 Afternoon Study Group Sessions • Neurocircuit-Based Interventions in Addictions: When and How? . . .145 Thursday, December 10th Morning Panel Sessions • The Role of Impulsivity vs . Impulse Control on the Developmental Trajectories of SUD - New Insights from Neuroimaging Research . . .147 • Ontogeny of Autism: Identification of Very Early Signs of Autism Spectrum Disorder in Humans and Mice . . . . . . . . . . . . . . .148 • Using Neural Connectivity Biomarkers in Major Depressive Disorder (MDD) to Identify Subtypes and Predict Treatment Response . . . . . .149 • Combining Imaging Modalities in Understanding and Treating Stress-Related Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .150 • Genomes and Cells: New Models for Target Discovery and Validation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .151 • Studies of Stress Identify Novel Signal Transduction and Epigenetic Antidepressant Targets . . . . . . . . . . . . . . . . . . . . . . . . . . . .152 • Orphan GPCRs and Psychiatric Disorders . . . . . . . . . . . . . . . . . . . . . .153 ACNP Annual Meeting Book 2015 rev13.indd 9 11/10/15 9:58 AM x ACNP 54th Annual Meeting • Final Program Thursday, December 10th (continued) Morning Study Group Session • Addictions Neuroclinical Assessment: The Search Continues . . . . . . .154 Afternoon Mini-Panel Sessions • Revisiting the Mu Opiate Receptor for the Treatment of Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .155 • DBS and the Identification of Circuits Mediating Depression . . . . . . .156 Afternoon Panel Sessions • The Re-Emergence of Serotonergic Hallucinogens as Tools for Neuropsychopharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157 • Beta Arrestin Signaling: An Avenue to Novel Psychopharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .158 • Novel Molecular Targets in Cocaine Addiction . . . . . . . . . . . . . . . . . .159 • Visualizing Neurocircuit Dynamics in Rodent Models of Addiction and Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .160 • Translational Neural Network Approaches for Identifying Individualized Targets for Neurostimulation in Mood Disorders and OCD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .161 • New Twists on Transmembrane Transporter Function in Psychiatric and Neurodegenerative Disorders . . . . . . . . . . . . . . . . . . .162 Afternoon Study Group Sessions • Methodological Challenges in Human Pharmacogenetic Studies in Alcohol and Drug Abuse – What has Early Experience Taught us, Where to Next? . . . . . . . . . . . . . . . . . . . . . . . . .163 Poster Sessions Poster Session I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165 Poster Session II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .205 Poster Session III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .245 Disclosures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .283 Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .293 ACNP Annual Meeting Book 2015 rev13.indd 10 11/10/15 9:58 AM 1 ACNP 54th Annual Meeting • Final Program Acknowledgments The American College of Neuropsychopharmacology appreciates the support of our supporting corporations: Alkermes, Inc . Astellas Pharma Boehringer Ingelheim Eli Lilly USA, LLC Euthymics/Neurovance Forest Laboratories, Inc . Forum Pharmaceuticals H . Lundbeck A/S, Denmark Hoffmann-LaRoche, Inc . Intra-Cellular Therapies, Inc . Janssen Pharmaceuticals, Inc . Otsuka America Pharmaceutical, Inc . Otsuka Pharmaceutical Development and Commercialization, Inc . Sunovion Pharmaceuticals, Inc . Takeda Pharmaceuticals Vanderbilt University School of Medicine Department of Psychiatry and the American College of Neuropsychopharmacology express appreciation to the following companies for their support of this educational activity by providing an unrestricted educational grant: Alkermes, Inc . Eli Lilly USA, LLC Janssen Pharmaceuticals, Inc . ACNP Annual Meeting Book 2015 rev13.indd 1 11/10/15 9:58 AM 2 ACNP 54th Annual Meeting • Final Program Council Officers and Council President Raquel E . Gur President-Elect Alan Frazer President-Elect Designate Anissa Abi-Dargham Secretary David Rubinow Secretary-Elect Joseph Coyle Treasurer David J . Kupfer Council Barry Everitt Suzanne N . Haber Peter W . Kalivas David A . Lewis Robert C . Malenka James Meador-Woodruff Marina Wolf Council-Elect Antonello Bonci Rita Valentino Program Committee 2015 Program and Scientific Communications Committee Chair Bita Moghaddam Co-Chair Carlos A . Zarate Council Liaison Alan Frazer Members: Caleb Adler Olusola Ajilore Susan Andersen Anne Andrews Gary Aston-Jones Carlos Bolanos-Guzman John Bruno Cheryl Corcoran Michael Davidson Melissa DelBello Pamela DeRosse Ariel Deutch Stephen Deutsch Darin Dougherty Stephanie Dulawa Cindy Ehlers Mary-Anne Enoch Rita Goldstein David Grandy Robert Greene Ming-Hu Han Robert Innis Katherine Karlsgodt Amanda Law Francis Lee Anil Malhotra Stephen Marder Keri Martinowich Barbara Mason Daniel Mathalon Colleen McClung Mary Phillips Paul Phillips Uma Rao Scott Russo Thomas Schulze Jeremy Veenstra- VanderWeele Karoly Mirnics ACNP Annual Meeting Book 2015 rev13.indd 2 11/10/15 9:58 AM 3 ACNP 54th Annual Meeting • Final Program General Information Dates and Location Dates Sunday, December 6, 2015 - Thursday, December 10, 2015 Location Diplomat Resort & Spa, Hollywood, Florida Program Book All scientific registrants will receive a Program Book as part of their registration material . The Program Book is also available on the ACNP website, www .acnp .org . Itinerary Planner All scientific registrants will be able to access the itinerary planner for the 54th ACNP Annual Meeting at: https://acnp .societyconference .com/conf/ ACNP Executive Office ACNP Executive Office 5034A Thoroughbred Lane Brentwood, Tennessee 37027 USA Phone: 615-324-2360 Fax: 615-523-1715 E-mail: acnp@acnp .org ACNP Annual Meeting Book 2015 rev13.indd 3 11/10/15 9:58 AM 4 ACNP 54th Annual Meeting • Final Program Continuing Medical Education The 2015 ACNP Annual Meeting has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education through the joint providership of Vanderbilt University School of Medicine and the ACNP . Vanderbilt University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians . Vanderbilt University School of Medicine designates this live activity for a maximum of 33 .50 AMA PRA Category 1 Credit(s)TM . Physicians should claim only the credit commensurate with the extent of their participation in the activity . There will be a $40.00 charge for scientific registrants to obtain CME credits. CME instructions will be available at the meeting registration desk and on the ACNP website (www .acnp .org) . It is the policy of Vanderbilt University School of Medicine to require disclosure of financial relationships from individuals in a position to control the content of a CME activity; to identify and resolve conflicts of interest related to those relationships; and to make disclosure information available to the audience prior to the CME activity . Presenters are required to disclose discussions of unlabeled/unapproved uses of drugs or devices during their presentations . Program Overview/Statement of Need The Annual Meeting of the American College of Neuropsychopharmacology is designed to meet the educational needs of ACNP members and invited non-member colleagues . Current data suggests that in any given year more than 20% of the U .S . adult population suffers from a diagnosable mental disorder . Four of the ten leading causes of disability in the U .S . are psychiatric disorders, including schizophrenia, depression, bipolar disorder, and obsessive-compulsive disorder . ACNP members have been among the leaders in identifying underlying mechanisms for these disorders and developing new treatment strategies . The desired results for the meeting are that ACNP members and their invited guests learn of the latest developments in preclinical and clinical research being performed by their colleagues and world experts in order to 1) enhance understanding of the neurobiological bases of current best practice approaches, 2) enhance understanding of neurobiological and clinical science underpinnings in development of novel therapeutic strategies, particularly for treatment-resistant forms of illness, and 3) lead to improvements in study designs for proposed clinical and basic studies . ACNP Annual Meeting Book 2015 rev13.indd 4 11/10/15 9:58 AM 5 ACNP 54th Annual Meeting • Final Program Continuing Medical Education (continued) Target Audience The target audience includes members of the American College of Neuropsychopharm- acology and invited experts . The audience includes physicians, psychologists, and basic neuroscientists from across the United States as well as Europe and Asia . The physicians include a number of specialties, with psychiatrists representing the majority of attendees, and neurologists next most common . Psychologists include clinical psychologists and neuropsychologists . Learning Objectives: After participating in this CME activity, participants should be able to: • Describe and discuss how the results of recent or ongoing basic science and/or clinical studies of psychiatric disorders in your area of interest or a related area impact your current or potential future research projects . • Describe and discuss how you will change or modify a current approach or strategy in your current or potential future research projects based on what you learned from the results of recent or ongoing basic science and/or clinical studies of psychiatric disorders in your area of interest or a related area . • Describe and discuss how recent progress in identifying genetic variations that are risk factors for the development of psychiatric disorders affect your current or potential future research projects . Americans with Disabilities Act It is the policy of Vanderbilt University School of Medicine not to discriminate against any person on the basis of disabilities . If you feel you need services or auxiliary aids mentioned in this act in order to fully participate in this continuing education activity, please call the Executive Office at 615-324-2360 or send an email to acnp@acnp .org Meeting Evaluation All meeting attendees are urged to complete an evaluation of the meeting . Attendees who are requesting CME credit for the meeting are required to complete the evaluation . This form is available online only . You may complete the evaluation in the ACNP Computer Center located in Diplomat Ballroom 1 & 2 foyer or on-line at www .acnp .org (click the Annual Meeting tab) . All evaluations must be completed by January 12, 2016 . ACNP Annual Meeting Book 2015 rev13.indd 5 11/10/15 9:58 AM 6 ACNP 54th Annual Meeting • Final Program Code of Behavior ACNP does not accept inappropriate or suggestive acts or comments that demean another person by reason of his or her gender, gender identity or expression, race, religion, ethnicity, age or disability . Any reports of such behavior will be investigated and acted upon as indicated by the specific findings of the investigation . Future ACNP Annual Meetings Dates Hotel Location December 4-8, 2016 Diplomat Resort & Spa Hollywood, Florida December 3-7, 2017 JW Marriott Desert Springs Resort Palm Springs, California December 9-13, 2018 Diplomat Resort & Spa Hollywood, Florida December 8-12, 2019 Diplomat Resort & Spa Hollywood, Florida In Memoriam Albert Sjoerdsma February 27, 2014 John David Leander November 14, 2014 B . Kenneth Koe October 7, 2015 Joel Elkes October 30, 2015 Lori Altshuler November 5, 2015 ACNP Annual Meeting Book 2015 rev13.indd 6 11/10/15 9:58 AM 7 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Neuropsychopharmacology Reviews Plenary “Stress and Development: Molecular, Neurobiological, and Genetic Approaches to Understanding Pathology” Co-Chairs: Kerry Ressler and Jordan Smoller 8:30 AM Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex Bruce McEwen 8:55 AM Local Circuits and Neural Pathways Linking Adult Hippocampal Neurogenesis With Fear Generalization Amar Sahay 9:20 AM Sex-Specific Transmission of Maternal Stress: Placenta and Neurodevelopment Tracy Bale 9:45 AM Gene-Environment-Epigenetic Regulation of FKBP5: Implications for Translational Research Elisabeth Binder 10:10 AM Neuro-Development of Emotion Regulation and the Role of Caregiving Nim Tottenham 10:35 AM Discussion Kerry Ressler and Jordan Smoller ACNP Annual Meeting Book 2015 rev13.indd 7 11/10/15 9:58 AM 8 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex Bruce McEwen The Rockefeller University The hippocampus provided the gateway into much of what we have learned about stress and brain structural and functional plasticity, and this initial focus has expanded to other interconnected brain regions, such as the amygdala and prefrontal cortex . Starting with the discovery of adrenal steroid, and later, estrogen receptors in the hippocampal formation, and subsequent discovery of dendritic and spine synapse remodeling and neurogenesis in the dentate gyrus, mechanistic studies have revealed both genomic and rapid non-genomic actions of circulating steroid hormones in the brain . Many of these actions occur epigenetically and result in ever-changing patterns of gene expression, in which there are important sex differences that need further exploration . Moreover, glucocorticoid and estrogen actions occur synergistically with an increasing number of cellular mediators that help determine the qualitative nature of the response . The hippocampus has also been a gateway to understanding lasting epigenetic effects of early-life experiences . These findings in animal models have resulted in translation to the human brain and have helped change thinking about the nature of brain malfunction in psychiatric disorders and during aging, as well as the mechanisms of the effects of early-life adversity on the brain and the body . Bruce S . McEwen obtained his Ph .D . in Cell Biology in 1964 from The Rockefeller University . He is a member of the US National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences . He served as President of the Society for Neuroscience in 1997-98 . As a neuroscientist and neuroendocrinologist, McEwen studies environmentally-regulated, variable gene expression in brain, mediated by circulating steroid hormones and endogenous neurotransmitters in relation to brain sexual differentiation and the actions of sex and stress hormones on the adult brain, in particular related to structural and functional plasticity via epigenetic mechanisms . His laboratory discovered adrenal steroid receptors in the hippocampus in 1968 . His laboratory combines molecular, ACNP Annual Meeting Book 2015 rev13.indd 8 11/10/15 9:58 AM 9 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex Bruce McEwen (continued) anatomical, pharmacological, physiological and behavioral methodologies and relates their findings to human clinical information . His current research focuses on stress effects on amygdala and prefrontal cortex, as well as hippocampus, and his laboratory also investigates sex hormone effects and sex differences in these brain regions involved in cognitive function and mood regulation . He served on the MacArthur Foundation Research Network on Socioeconomic Status and Health, in which he has helped to reformulate concepts and measurements related to stress and stress hormones in the context of human societies, which led to the concept of “allostatic load and overload” that describes the wear and tear on the body and brain from chronic stress and related life style behaviors that lead to dysregulation of physiological stress pathways that are normally protective . He is also a member of the National Council on the Developing Child which focuses on biological embedding of early life experiences and promoting healthy brain development . He is the co-author of a book with science writer, Elizabeth Lasley, for a lay audience called “The End of Stress as We Know It”, published in 2002, and “The Hostage Brain” with science writer, the late Harold M . Schmeck, Jr ., published in 1994, both of which are now available as eBooks . ACNP Annual Meeting Book 2015 rev13.indd 9 11/10/15 9:58 AM 10 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Local Circuits and Neural Pathways Linking Adult Hippocampal Neurogenesis with Fear Generalization Amar Sahay Massachusetts General Hospital and Harvard Medical School The generation of adaptive fear responses to ambiguous threats in the environment is critically dependent on how contextual information is encoded and relayed across multiple circuits . Inefficient encoding of ambiguous threats results in inappropriate retrieval of aversive memories and activation of fear circuits to produce heightened avoidance behavior, overgeneralization of fear, hyper vigilance and arousal, symptoms that characterize anxiety disorders such as post-traumatic stress disorder . Recent studies by us and others have found that adult-born neurons in the hippocampus play a critical role in discrimination of ambiguous threats and modulating generalization of fear . One neural mechanism by which this may be accomplished is pattern separation, a process by which interference between similar memories is minimized . However, despite these advances, fundamental questions remain unaddressed . First, what are the local circuit mechanisms by which adult-born hippocampal neurons contribute to pattern separation and memory precision? Second, what are the neural pathways linking encoding operations performed by the dentate gyrus-CA3 circuit with circuits subserving stress and fear responses? I will discuss ongoing studies that have begun to illuminate these questions . Dr . Amar Sahay is Assistant Professor of Psychiatry at Harvard Medical School and Director of the laboratory of Adult Hippocampal Neurogenesis, Cognition and Mood Regulation in the Center for Regenerative Medicine at Massachusetts General Hospital . He is principal faculty of the Harvard Stem Cell Institute of Harvard University and an Associate member of the BROAD Institute of Harvard and MIT . Dr . Sahay earned his doctorate from the Johns Hopkins University School of Medicine and carried out postdoctoral research at Columbia University . The mission of Dr . Sahay’s laboratory is to generate fundamental insights into the roles of adult hippocampal neurogenesis in encoding, memory processing and modulation of mood . By integrating cellular-, circuit-, systems- and behavioral ACNP Annual Meeting Book 2015 rev13.indd 10 11/10/15 9:58 AM 11 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Local Circuits and Neural Pathways Linking Adult Hippocampal Neurogenesis with Fear Generalization Amar Sahay (continued) interrogation of adult hippocampal neurogenesis, his research program aspires to optimize hippocampal functions in PTSD and during aging (http://www .sahaylab . com) . Dr . Sahay is the recipient of numerous awards including NIH K99 Pathway to Independence award, NIMH-BRAINS award, NARSAD Young Investigator awards and career development awards from the Society for Neuroscience and the American College of Neuropsychopharmacology . His research program is supported by Whitehall Foundation, Harvard Stem Cell Institute, Inscopix Decode Award, Ellison Medical Foundation and the National Institute of Mental Health . ACNP Annual Meeting Book 2015 rev13.indd 11 11/10/15 9:58 AM 12 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Sex-Specific Transmission of Maternal Stress: Placenta and Neurodevelopment Tracy Bale University of Pennsylvania Adversity experienced during gestation is a risk factor in neurodevelopmental disorder susceptibility . Specifically, maternal stress during pregnancy predisposes offspring to sex-biased disorders including schizophrenia, attention deficit/ hyperactivity disorder, and autism spectrum disorders . Animal models have demonstrated disease-relevant endophenotypes in prenatally stressed offspring . We have previously identified a sensitive period of early pregnancy where maternal stress produces male-specific programming effects on offspring stress pathway development and neuroendocrine regulation . Mechanistically, the placenta plays a critical role in transmitting the potentially deleterious and sex- specific effects of maternal stress to the developing brain . In our mouse model of early prenatal stress, we have found robust and male-specific changes in placental gene expression patterns and biochemical measures across gestation . We have subsequently utilized mouse genetics to demonstrate the importance of placental function in neurodevelopmental programming, including trophoblastic-specific targeting of genes identified in whole genome screening in our mouse model that recapitulate disease-relevant endophenotypes . Such studies support a critical importance of the placenta in transmission of maternal experiences and exposures during pregnancy on the fetal brain . Tracy L . Bale is Professor of Neuroscience in the Department of Psychiatry in the Perelman School of Medicine and the Biomedical Sciences Department in the School of Veterinary Medicine . She completed her Ph .D . in pharmacology and neurobiology at the University of Washington, and her postdoctoral fellowship at the Salk Institute . Her research focuses on understanding the role of stress dysregulation in neurodevelopmental and neuropsychiatric diseases, and the sex differences that underlie disease vulnerability using mice as the model organism . She is the Director of the Neuroscience Center and the Co-director of the Penn Center for the Study of Sex and Gender in Behavioral Health, funded by a NIMH ACNP Annual Meeting Book 2015 rev13.indd 12 11/10/15 9:58 AM 13 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Sex-Specific Transmission of Maternal Stress: Placenta and Neurodevelopment Tracy Bale (continued) and ORWH SCOR P50 grant . She serves on many internal and external advisory committees, panels, and boards and is currently a Reviewing Editor at the Journal of Neuroscience and serves as Chair of the NNRS study section . She has been the recipient of several awards for her research in this area including the career development award for early career achievement and promise by the Society for Neuroscience, the Richard E . Weitzman Memorial award as exceptionally promising young investigator award by the Endocrine Society, and Medtronic Award from the Society for Women’s Health Research for outstanding research that has led to the improvement of women’s health . ACNP Annual Meeting Book 2015 rev13.indd 13 11/10/15 9:58 AM 14 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Gene-Environment-Epigenetic Regulation of FKBP5: Implications for Translational Research Elisabeth Binder Emory University School of Medicine Stress responses and related outcomes vary markedly across individuals . Elucidating the molecular underpinnings of this variability is of great relevance for developing individualized prevention strategies and treatments for stress- related disorders . An important modulator of stress responses is the FK506 binding protein 51 (FKBP5/FKBP51) . FKBP5 acts as a co-chaperone that modulates glucocorticoid receptor activity in response to stressors but also a multitude of other cellular processes in both the brain and periphery . Notably, the FKBP5 gene is regulated via complex interactions among environmental stressors, FKBP5 genetic variants, and epigenetic modifications of glucocorticoid-responsive genomic sites . These interactions can result in FKBP5 disinhibition that has been shown to contribute to a number of aberrant phenotypes in both rodents and humans . Consequently, FKBP5 blockade may hold promise as treatment intervention for stress-related disorders, and recently developed selective FKBP5 blockers show encouraging results in vitro and in rodent models . While risk for stress-related disorders is conferred by multiple environmental and genetic factors, the findings related to FKBP5 illustrate how a deeper understanding of the molecular and systemic mechanisms underlying specific gene-environment interactions may provide insights into the pathogenesis of stress-related disorders . Elisabeth Binder has studied Medicine at the University of Vienna, Austria and Neuroscience at Emory University in Atlanta, GA, USA . Following a postdoctoral training at the Max-Planck Institute of Psychiatry in Munich, Germany, she returned to Emory University as an Assistant Professor in the Departments of Psychiatry and Behavioral Sciences and Human Genetics . In 2007, she was appointed as research group leader at the Max-Planck Institute of Psychiatry within the Minerva Program of the Max-Planck Society . ACNP Annual Meeting Book 2015 rev13.indd 14 11/10/15 9:58 AM 15 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Gene-Environment-Epigenetic Regulation of FKBP5: Implications for Translational Research Elisabeth Binder (continued) Since August 2013, Elisabeth Binder is the director of the Department of Translational Research in Psychiatry at the Max-Planck Institute of Psychiatry . She also holds an appointment as an Associate Professor in the Dept . of Psychiatry and Behavioral Sciences at Emory University School of Medicine . Her main research interests are the identification of molecular moderators of the response to environmental factors, with a focus on early trauma and gene x environment interactions . She studies how such factors influence trajectories to psychiatric disease or well-being to ultimately use this information for novel prevention and treatment strategies . ACNP Annual Meeting Book 2015 rev13.indd 15 11/10/15 9:58 AM 16 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Neuro-Development of Emotion Regulation and the Role of Caregiving Nim Tottenham Columbia University Early experiences critically shape the structure and function of the brain . Perturbations in typical/species-expected early experiences are known to have profound neural effects, especially in regions important for emotion regulation . Parental care is one species-expected stimulus that plays a fundamental role in the development of emotion neurocircuitry . Phasic variations in parental presence during sensitive periods of development affect the state of emotional networks on a moment-to-moment basis . Also, it appears that increasing independence from caregivers cues the termination of the sensitive period for environmental input into emotion network development . This talk will discuss how early parental care, the central nervous system, and behaviour come together to form a ‘neuro- environmental loop’, contributing to the formation of stable emotion regulation circuits . To achieve this end, I focus on the interaction of parental care and the developing amygdala-medial prefrontal cortex (mPFC) network – which lies at the core of human emotional functioning . I will discuss how individual or group variations in parental-independence, across chronic and brief timescales, might contribute to neural and emotional phenotypes that have implications for long- term mental health . Nim Tottenham, Ph .D . is an associate professor of Psychology at Columbia University . Her research uses magnetic resonance imaging and behavioral methods to examine the development of the human amygdala and its neural connections and associated emotional development, including emotional reactivity and management with the aim of identifying sensitive periods for human amygdala- cortical development . She examines limbic-cortical development in both typical groups of children and adolescents and those who have experienced early life adversity (parental deprivation) . She is a recipient of the American Psychological Association’s Distinguished Scientific Award for Early Career Contribution to Psychology, the National Institute of Mental Health Biobehavioral Research ACNP Annual Meeting Book 2015 rev13.indd 16 11/10/15 9:58 AM 17 ACNP 54th Annual Meeting • Final Program PL 8:30 AM - 11:30 AM Neuropsychopharmacology Reviews Plenary Regency 1-2 Neuro-Development of Emotion Regulation and the Role of Caregiving Nim Tottenham (continued) Awards for Innovative New Scientists (BRAINS) Award, and the Developmental Science Early Career Researcher Prize . She received her bachelor’s degree in Psychology from Barnard College of Columbia University and her doctoral degree from the University of Minnesota . She received postdoctoral training from the Sackler Institute for Developmental Psychobiology at Weill Cornell Medical College . More information on her research and laboratory can be found at: http://tottenhamlab .psych .columbia .edu/ . ACNP Annual Meeting Book 2015 rev13.indd 17 11/10/15 9:58 AM 18 ACNP 54th Annual Meeting • Final Program PL 1:00 PM - 2:30 PM Institute Director’s Session Regency 1-2 Q & A Forum with NIH Institutes Directors Chair: Raquel Gur Panelists: Neil Buckholtz NIA George Koob NIAAA Bruce Cuthbert NIMH Richard Nakamura NIH Nora Volkow NIDA ACNP Annual Meeting Book 2015 rev13.indd 18 11/10/15 9:58 AM 19 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Hot Topics Co-Chairs: Bita Moghaddam and Carlos Zarate 2:30 PM Deconstructing Ventral Hippocampal Control of Anxiety-Related Behavior and Learned Fear Jessica Jimenez 2:45 PM Deficits in Working Memory Performance in Schizophrenia are Associated With the Absence of an Inverted-U Relationship Between Dorsolateral Prefrontal Cortex Activation and Working Memory Load Jared Van Snellenberg 3:00 PM A Single Dose of SSRI Alters the Neural Circuit Underlying the Management of Attentional Resources to Emotional Distraction Within 3 Hours Julia Sacher 3:15 PM Arithmetic and Local Circuitry Underlying Dopamine Prediction Errors Neir Eshel 3:30 PM Metabotropic Glutamate Receptor 5 Binding in Individuals With Schizophrenia Gregor Hasler 3:45 PM A Novel Genetic Method of Measuring the Receptor-Specific Component of PET Radioligand Binding in Human Brain Without Pharmacological Blockade Robert Innis ACNP Annual Meeting Book 2015 rev13.indd 19 11/10/15 9:58 AM 20 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Hot Topics Co-Chairs: Bita Moghaddam and Carlos Zarate 4:00 PM Affective Neurodynamics Predict Depression Treatment Response Aaron Heller 4:15 PM Impact of Chronic Ethanol Self-Administration on Kappa Opioid Receptor Regulation of Dopamine Signaling in Nonhuman Primates Cody Siciliano 4:30 PM Dopamine-Dependent Working-Memory Performance is Mediated by Dynamic Connectivity Between Brain Networks Guillermo Horga 4:45 PM Reduced Amplitude Low-Frequency BOLD Signal Oscillations in Early Illness Schizophrenia Patients and Individuals at Clinical High Risk for Psychosis Susanna Fryer 5:00 PM Selective Estrogen Modulation Increases Dorsolateral Prefrontal Cortex Activity During Emotional Inhibition in Schizophrenia Thomas Weickert 5:15 PM GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine Pascal Bonaventure ACNP Annual Meeting Book 2015 rev13.indd 20 11/10/15 9:58 AM 21 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Deconstructing Ventral Hippocampal Control of Anxiety- Related Behavior and Learned Fear Tuesday, Poster #16 Jessica Jimenez*, Alexander Goldberg, Gokhan Ordek, Stephanie Pena, Katy Su, Rene Hen, Mazen Kheirbek Columbia University Background: Understanding the distributed neural circuits that mediate normal, adaptive anxiety-related behavior may provide insight into how they may be disrupted in anxiety disorders . The ventral hippocampus (vHPC) has become appreciated for its role in anxiety-related behaviors, serving as a circuit hub that connects cognitive association regions with limbic structures that directly regulate mood . Although some studies have observed vHPC activity changes during anxiety-related behaviors, it is still not understood if this activity is specific to innately aversive tasks, if vHPC can directly modulate anxiety behavior, and through which downstream limbic structures these effects on behavior are mediated . Methods: We have used cell-type specific calcium imaging in vivo in freely behaving mice using miniaturized microscopes to visualize vHPC activity during anxiety-related behaviors . We expressed GCaMP6f in vHPC, and a gradient index lens was implanted above vCA1 . We imaged the activity patterns of the same population of vCA1 neurons across multiple behavioral dimensions, including innately anxiogenic tasks (Open Field Test (OFT), Elevated Plus Maze (EPM), and Elevated Zero Maze (EZM)), innately rewarding tasks (novel object exploration and sucrose pellet consumption), and learned fear tasks (contextual fear conditioning (CFC)) . For optogenetic manipulations, we virally expressed Arch or ChR2 opsins in vHPC and implanted a fiber optic either directly in vHPC or at vHPC terminal fields in the Basomedial Amygdala (BMA) or Lateral Hypothalamus (LHA) . Results: In our imaging experiments, we found that vHPC neurons increase their activity in innately anxiogenic environments, including the center of the Open Field test and the open arms of the Elevated Plus Maze (EPM) and Zero Maze, ACNP Annual Meeting Book 2015 rev13.indd 21 11/10/15 9:58 AM 22 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Deconstructing Ventral Hippocampal Control of Anxiety- Related Behavior and Learned Fear Tuesday, Poster #16 (continued) Jessica Jimenez* but not to exploration of a novel object . Alternatively, in CFC, re-exposure to a previously conditioned environment decreases activity within vHPC, suggesting a differential processing of learned versus innately fearful environments . To understand how these activity changes are generated within the local vHPC circuit, we imaged calcium activity in local inhibitory interneurons (VGAT+ neurons) and found a reduction in inhibitory interneuron activity in innately anxiogenic environments, such as the open arms of the EPM . This points to a local circuit mechanism by which the vHPC is engaged during exploration of anxiogenic environments . To understand how the vHPC may modulate anxiety-related behavior, we employed optogenetic techniques within vHPC and at downstream terminal fields in two subcortical nuclei implicated in anxiety, fear, and behavioral responses to stress, the BMA and LHA . Our results indicate that direct vHPC silencing disrupts the formation of a contextual fear memory . Further, modulation of vHPC-LHA terminals impacts innate anxiety and aversion, but not contextual fear conditioning, while vHPC-BMA terminal modulation impacts contextual fear memory but not innate anxiety behavior . Ongoing studies are aimed at understanding the interplay between behavioral state and activity within vHPC, utilizing pharmacological and behavioral manipulations to modulate anxiety levels of mice during exploration of the EZM while recording local population dynamics . Conclusions: Our findings demonstrate a unique population-level activity signature for anxiogenic environments within vHPC . Further, the varying activity changes between innate and learned fear behaviors suggest diverse circuit mechanisms for processing exploration of an innately anxiogenic environment and previously conditioned fearful environments . Our results also reveal a potential circuit mechanism for increased population activity during innate anxiety behaviors, possibly through disinhibition of the local vCA1 circuit . The specificity of vHPC-LHA and vHPC-BMA terminal modulation effects on innate ACNP Annual Meeting Book 2015 rev13.indd 22 11/10/15 9:58 AM 23 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Deconstructing Ventral Hippocampal Control of Anxiety- Related Behavior and Learned Fear Tuesday, Poster #16 (continued) Jessica Jimenez* and learned fear behavior suggests a projection specific segregation in vHPC function, possibly mediated through projection-specific cell populations within the vHPC . This study provides a functional map of the cell-types and long-range circuits that underlie the vHPC contribution to innate and learned anxiety-related behavior . ACNP Annual Meeting Book 2015 rev13.indd 23 11/10/15 9:58 AM 24 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Deficits in Working Memory Performance in Schizophrenia are Associated With the Absence of an Inverted-U Relationship Between Dorsolateral Prefrontal Cortex Activation and Working Memory Load Wednesday, Poster #180 Jared Van Snellenberg*, Ragy Girgis, Guillermo Horga, Elsmarieke van de Giessen, Mark Slifstein, Najate Ojeil, Holly Moore, Edward Smith, Daphna Shohamy, Jeffrey Lieberman, Anissa Abi-Dargham Columbia University Medical Center Background: Patients with schizophrenia exhibit strong deficits on working memory (WM) tasks, but after over two decades of research the neurophysiological underpinnings of these deficits remain unknown . In spite of early findings supporting the concept of ‘hypofrontality’, alterations in the activation of dorsolateral prefrontal cortex (DLPFC), or other prefrontal regions, have not been reliably observed during WM task performance . However, recent work in healthy individuals has demonstrated an inverted-U relationship between DLPFC activation and WM load during a task with eight WM loads, the self- ordered WM task (SOT), suggesting that simple comparisons of the magnitude of activation between patients and healthy individuals will fail to capture a critical feature of how the brain instantiates WM . The present study employed the SOT in unmedicated and medicated patients with schizophrenia in order to examine whether an alteration in this pattern of activation is related to WM deficits in these patients . Methods: Participants included 21 unmedicated patients with schizophrenia, 30 medicated patients with schizophrenia, and 45 healthy control participants . All three groups were matched on age, gender, and parental socio-economic status . Participants performed the SOT during functional Magnetic Resonance Imaging on a Philips 1 .5 Tesla Intera scanner at the Columbia MRI Center at Columbia University Medical Center (TR = 2 s, whole-brain coverage with 3 mm isotropic voxels) . In each trial of the SOT participants are presented with eight line drawings of 3D objects in an array . On each step of the trial the object positions are ACNP Annual Meeting Book 2015 rev13.indd 24 11/10/15 9:58 AM 25 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Deficits in Working Memory Performance in Schizophrenia are Associated With the Absence of an Inverted-U Relationship Between Dorsolateral Prefrontal Cortex Activation and Working Memory Load Wednesday, Poster #180 (continued) Jared Van Snellenberg* pseudo-randomly rearranged, and participants must select any object that they have not previously selected, thereby producing a gradual increase in WM load over the eight steps of each trial . Data were analyzed in a series of robust regression (or robust t-test) models using alphasim to correct for multiple comparisons (P < 0 .05 in all cases); first restricted to a bilateral DLPFC region-of-interest (ROI), then in whole-brain analyses . Two outcome measures were evaluated in these models: 1) overall activation in response to the SOT (average activation across all eight WM loads), in keeping with standard analyses in the literature, and 2) the fit at each voxel in each subject (i .e . a first-level analysis) to an inverted-U shape identified in an independent sample of healthy individuals (Study 1 from Van Snellenberg et al ., 2015) . Performance on the SOT was analyzed using a maximum likelihood estimate of WM capacity described elsewhere (Van Snellenberg et al ., 2014) . Results: Both patient groups showed a significant reduction in WM capacity relative to controls (all P < 0 .0005) . Within the DLPFC ROI, unmedicated patients showed greater activation of right DLPFC relative to controls, but this was not related to WM capacity . Medicated patients showed a poorer inverted-U fit in left DLPFC compared to controls, a finding that was observed in an overlapping but slightly posterior region of left DLPFC in unmedicated patients in the whole- brain analysis (it did not appear in the ROI analysis because many of the cluster’s voxels were posterior to the ROI) . A follow-up analysis combing both patient groups showed a significant reduction in the inverted-U fit in this region in patients as compared to healthy controls . Morever, both healthy controls and patients with schizophrenia exhibited a positive relationship between inverted-U fit in left DLPFC and WM capacity . Thus, at least some of the deficit in WM capacity in patients with schizophrenia can be explained by the lack of an inverted-U response to WM load in this region . Moreover, whole-brain analyses demonstrated that ACNP Annual Meeting Book 2015 rev13.indd 25 11/10/15 9:58 AM 26 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Deficits in Working Memory Performance in Schizophrenia are Associated With the Absence of an Inverted-U Relationship Between Dorsolateral Prefrontal Cortex Activation and Working Memory Load Wednesday, Poster #180 (continued) Jared Van Snellenberg* both patient groups showed excess activation of two default-mode network (DMN) regions, the medial prefrontal cortex (mPFC) and posterior cingulate . Moreover, all three groups exhibited a negative relationship between activation of mPFC and WM capacity . Given that this region was suppressed by the task in all three groups, inadequate suppression of mPFC during WM performance may also account for some of the deficit in WM performance in patients . Conclusions: These findings demonstrate two mechanisms that are associated with WM deficits in patients with schizophrenia: 1) the absence of an inverted-U relationship between WM load and activation of the left DLPFC, and 2) a failure to fully suppress activation in the medial PFC during WM performance . Notably, overall levels of activation in left DLPFC were normal in patients, and while patients exhibited abnormally elevated activation in right DLPFC, this increase was not observed to have any impact on WM capacity across individuals . These findings point to two little-studied pathophysiological mechanisms that may play a significant role in WM impairments in patients with schizophrenia, and which do not appear to be impacted by treatment with antipsychotic medications . ACNP Annual Meeting Book 2015 rev13.indd 26 11/10/15 9:58 AM 27 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 A Single Dose of SSRI Alters the Neural Circuit Underlying the Management of Attentional Resources to Emotional Distraction Within 3 Hours Wednesday, Poster #116 Claudia Barth, Hadas Okon-Singer, Lina Schaare, Lydia Hellrung, Jöran Lepsien, Inga Burmann, Arno Villringer, Julia Sacher* Max Planck Institute Background: Accumulating evidence supports Selective Serotonin Reuptake Inhibitor (SSRI) drug-action to reduce the attentional bias to negative information, which has been proposed to underlie depressive symptomatology (Browning, Holmes, & Harmer, 2010) . This change in emotional processing is mediated by a prefrontal-limbic neural system that SSRIs modulate on a time-scale that is much shorter than the 10-14 days typically viewed as required for an adequate antidepressant response (Harmer & Cowen, 2013) . However, existing work in this field is limited by the paucity of paradigms that can reflect on the ability to manage attention resources in the face of emotional distraction . An emotional modification of a perceptual load task (emo-PLT) has recently been applied to investigate neural changes in emotional processing induced by a dietary supplement (Terburg et al ., 2013) . This paradigm allows for variation of cognitive difficulty in the midst of emotional distraction . Although the management of processing emotional information during varying cognitive challenges is a skill often substantially impaired in depression, little is known about the response in the underlying neural network to the most commonly prescribed antidepressants . To address this, we study the acute neuropharmacological impact of a single dose of escitalopram on the neural circuit underlying the management of attentional resources to emotional distraction . Methods: To investigate this, 21 healthy subjects performed an emotional modification of a perceptual load task (Okon-Singer et al ., 2014) during fMRI scanning following a single oral dose of escitalopram (20 mg) or placebo in a randomized, cross-over design . fMRI data was acquired on a 3-Tesla MR scanner at tmax for escitalopram and analyzed in SPM8 using standardized preprocessing . ACNP Annual Meeting Book 2015 rev13.indd 27 11/10/15 9:58 AM 28 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 A Single Dose of SSRI Alters the Neural Circuit Underlying the Management of Attentional Resources to Emotional Distraction Within 3 Hours Wednesday, Poster #116 (continued) Julia Sacher* We applied a flexible factorial design with emotion (negative/neutral) and load (low/high) as within-subjects factors for the SSRI and the placebo conditions . We conducted a whole-brain voxel-wise general linear model (GLM) analysis on the first level and tested the resulting contrast maps for effects of load, emotion and their interactions (whole-brain family wise error (FWE) corrected p<0 .05, and extend-threshold 10 voxels) to validate the task . To identify the functional localization of the task-specific cortico-limbic regions implicated in navigating attention to varying cognitive load during negative emotional distraction, we performed a paired t-test comparing load (whole-brain FWE corrected p<0 .05, and extend-threshold 10 voxels) only during negative distraction for the respective single-subject contrasts for the placebo condition . We then performed a secondary region-of-interest (ROI) analysis in these regions to assess the extent of acute SSRI-specific neural signal change in the emotion-cognition circuit . Results: A 2 x 2 x 2 repeated-measures ANOVA with drug, load, and emotion as within-subject factors revealed main effects of load (F (1,20)=304, p<0 .00001) and emotion (F (1,20)=8,197, p<0 .01) for reaction times, and a main effect for load (F(1,20) =,5,567 p = 0 .029) for accuracy . In the placebo condition, these behavioral effects were paralleled by positive main effects of load (high – low) in frontal, visual and cerebellar regions (whole brain, FWE-corrected p<0 .05) . The contrast of negative minus neutral pictures showed that during distraction by negative emotion, there was significant BOLD activation in brain regions known to be involved in the management and processing of emotional information, namely the insula, temporal cortex, amygdala/hippocampus and orbitofrontal cortex (OFC) (whole brain, FWE-corrected p<0 .05) . A single oral dose of escitalopram, however, substantially attenuated the BOLD responses in these brain regions: ROI analyses revealed a 146±24 (mean±SD) percent signal change in amygdala, insula and OFC (p<0 .0000001, Bonferroni corrected) . ACNP Annual Meeting Book 2015 rev13.indd 28 11/10/15 9:58 AM 29 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 A Single Dose of SSRI Alters the Neural Circuit Underlying the Management of Attentional Resources to Emotional Distraction Within 3 Hours Wednesday, Poster #116 (continued) Julia Sacher* Conclusions: We demonstrate feasibility to apply a paradigm that detects the management of attentional resources for a cognitively challenging task in the midst of emotional distraction in a single-SSRI-dose psychopharmacological fMRI-design . Our data are consistent with the emerging theory that changes in the neural circuit underlying emotion-processing following SSRI-intake are detectable on an acute time-scale as we find changes as early as 3 hours post- administration . Furthermore, we provide strong evidence that a single dose of escitalopram can significantly reduce the BOLD response in the neural circuit underlying the behavioral interference of irrelevant emotional distractors contrasting different levels of cognitive load . These results emphasize that the management of attentional resources to negative stimuli during varying stages of cognitive challenge could represent a key mechanism of action during SSRI treatment . Our findings have important implications for the early evaluation of antidepressant efficacy in clinical populations and individuals at risk . ACNP Annual Meeting Book 2015 rev13.indd 29 11/10/15 9:58 AM 30 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Arithmetic and Local Circuitry Underlying Dopamine Prediction Errors Wednesday, Poster #262 Neir Eshel*, Michael Bukwich, Vinod Rao, Vivian Hemmelder, Ju Tian, Naoshige Uchida Harvard Medical School Background: Dopamine neurons signal prediction error, or the difference between actual and predicted reward . Prediction errors are thought to be crucial for both adaptive learning and the development of addiction . However, despite two decades of investigation, little is known about how prediction errors are calculated in the brain . Methods: To determine how dopamine neurons calculate prediction error, we combined optogenetic manipulations with extracellular recordings in the ventral tegmental area (VTA) while mice engaged in classical conditioning . Our techniques allowed us to tag recorded neurons as either dopaminergic or GABAergic, and selectively stimulate or inhibit these neurons while recording from other neurons in the circuit . We performed 4 experiments, with a total of 33 mice and 632 VTA neurons . Results: We demonstrate that dopamine neurons perform subtraction, a computation that is ideal for reinforcement learning but rarely observed in the brain . Furthermore, selectively exciting and inhibiting neighboring GABA neurons in the VTA reveals that these neurons are a source of subtraction: they inhibit dopamine neurons when reward is expected, casually contributing to prediction error calculations . In particular, we found that stimulating VTA GABA neurons subtracts from dopamine reward responses (P < 0 .001, t-test), as if reward is more expected, and that inhibiting VTA GABA neurons increases dopamine reward responses (P < 0 .001, t-test), as if reward is less expected . Finally, bilaterally stimulating VTA GABA neurons dramatically reduces anticipatory licking to conditioned odours (P < 0 .001, mixed effects linear model), consistent with an important role for these neurons in reinforcement learning . VTA GABA neurons, therefore, help put the “prediction” in “prediction error .” ACNP Annual Meeting Book 2015 rev13.indd 30 11/10/15 9:58 AM 31 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Arithmetic and Local Circuitry Underlying Dopamine Prediction Errors Wednesday, Poster #262 (continued) Neir Eshel* Conclusions: Together, our results uncover the arithmetic and local circuitry underlying dopamine prediction errors . This provides a framework for understanding how alterations in the circuitry--in particular, inhibition of VTA GABA neurons--can stimulate a vicious cycle leading to substance addiction . ACNP Annual Meeting Book 2015 rev13.indd 31 11/10/15 9:58 AM 32 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Metabotropic Glutamate Receptor 5 Binding in Individuals With Schizophrenia Wednesday, Poster # 156 Funda Akkus, Valerie Treyer, Simon Ametamey, Cyrill Burger, Anass Johayem, Alfred Buck, Gregor Hasler* University of Bern Background: The implication of N-methyl-D-aspartate (NMDA) receptors in schizophrenia has received increasing interest over the last years . NMDA receptor function is modified by metabotropic glutamate receptors subtype 5 (mGluR5) suggesting that mGluR5 can also be involved in the pathogenesis of schizophrenia . This notion is corroborated by genetic studies showing that allele frequency distribution of an intragenic microsatellite of the mGluR5 gene, GRM5, is associated with schizophrenia . Here, we report the results of a study investigating mGluR5 in schizophrenia in vivo via positron emission tomography (PET) with the mGluR5-specific radiotracer 3-(6-methyl-pyridin-2-ylethynyl)- cyclohex-2-enone-O-11C-methyl-oxime ([11C]ABP688) . Methods: [11C]ABP688 PET was carried out in 15 individuals with schizophrenia (6 female) and 15 healthy controls (6 female) . Psychopathology in cases and controls was assessed by the SCID-I, PANSS, BAI, BDI, and the Bern Psychopathology Scale (BPS) . In subjects with schizophrenia, antipsychotic medication was transformed into chloropromazine equivalents . Exclusion criteria comprised current psychiatric (for subjects with schizophrenia additional current psychiatric disorders), medical, or neurological disorders, history of substance dependence, pregnancy, and breastfeeding . We applied a bolus/infusion protocol, previously evaluated for PET with [11C] ABP688, which allows reliable measurement of the relative distribution volume (DVR) and reduces potential bias due to arterial blood sampling needed for absolute quantification . With this protocol equilibrium between the tracer in tissue and blood is achieved 40 min after the start of radioligand infusion . A total of 600–800 MBq of [11C]ABP688 in a 50-mL volume was administered using an infusion pump . Individual dynamic uptake curves were checked for suitability . ACNP Annual Meeting Book 2015 rev13.indd 32 11/10/15 9:58 AM 33 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Metabotropic Glutamate Receptor 5 Binding in Individuals With Schizophrenia Wednesday, Poster # 156 (continued) Gregor Hasler* PET data was analyzed with PMOD (Version 3 .4, www .pmod .com, PMOD Technologies, Zurich, Switzerland) . Results: Groups were age-matched (t28 = 0 .172, p > 0 .86): subjects with schizophrenia were 38 .2 ± 10 .7 years old (mean ± standard deviation), healthy controls were 37 .5 ± 10 .6 years old . Individuals with schizophrenia reported an average illness duration of 15 .6 ± 11 .6 years with an illness onset at 22 .6 ± 7 years . They were under stable medication with atypical neuroleptics (risperidone, paliperidone, quetiapine, or clozapine) except for one subject who was treated with fluanxol . Individuals with schizophrenia scored higher than healthy controls in both BDI (t28 = 5 .365, p < 0 .001) and BAI (t28 = 2 .648, p < 0 .05) . No significant difference in mGluR5 DVR between subjects with schizophrenia and healthy controls was found in a repeated measures analysis of variance with 12 brain regions as a within-subjects factor and diagnostic group as a between- subjects factor (F(28,1) = 0 .11; p > 0 .9) . Furthermore, no significant difference in mGluR5 DVR between patients and controls was found when accounting for sex, age, BDI scores, and BAI scores as covariates (F(24,1) = 0 .082; p > 0 .7) . Adding smoking status as a second between-subjects factor in the statistical model we found a highly significant difference between smokers and non-smokers (F(22,1) = 185 .632; p < 0 .0001) but no significant interaction between smoking and diagnosis (F(22,1) = 0 .320; p > 0 .5) . We found a small potential effect of antipsychotic medication on mGluR5 DVR levels in only one region, the medial orbitofrontal cortex (mOFC), and only for non-smokers: higher chlorpromazine equivalent was associated with increased mGluR5 DVR in the mOFC of non-smokers (rho = 0 .9, p < 0 .02) . Focusing on the same region we identified an interaction between diagnostic group and gender (F(22,1) = 8 .706; p < 0 .01), as well a non-significant trend for a triple interaction group-by-gender-by-smoking (F(22,1) = 3 .884; p < 0 .1) . Schizophrenia was associated with higher mGluR5 DVR in female non-smokers, but with lower mGluR5 DVR in male non-smokers . ACNP Annual Meeting Book 2015 rev13.indd 33 11/10/15 9:58 AM 34 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Metabotropic Glutamate Receptor 5 Binding in Individuals With Schizophrenia Wednesday, Poster # 156 (continued) Gregor Hasler* Within the schizophrenia group no significant correlations were found between clinical and demographic variables and mGluR5 DVR (PANSS sum score p ≥ 0.26; PANSS negative subscale p ≥ 0.49; PANSS positive subscale p ≥0.21; PANSS general psychopathology subscale p ≥ 0.09; BPS language subscale p ≥ 0.07; BPS affection subscale p ≥ 0.6; BPS motor subscale p ≥ 0.45; BDI p ≥ 0.24; BAI p ≥ 0.15; onset of illness p ≥ 0.13; duration of illness p ≥ 0.05). Conclusions: We did not find differences in mGluR5 binding between individuals with schizophrenia and controls . Because antipsychotic drugs such as clozapine appeared to affect mGluR5, our findings may be clinically relevant . They also provide further insights into the high comorbidity between schizophrenia and tobacco addiction, e .g ., smoking may counteract the potential upregulation of mGluR5 by antipsychotic drugs . ACNP Annual Meeting Book 2015 rev13.indd 34 11/10/15 9:58 AM 35 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 A Novel Genetic Method of Measuring the Receptor-Specific Component of PET Radioligand Binding in Human Brain Without Pharmacological Blockade Monday, Poster Board #123 Paolo Zanotti-Fregonara, Mattia Veronese, Rong Xu, Sami Zoghbi, Jeih-San Liow, Masahiro Fujita, Victor Pike, Robert Innis* NIMH Background: One of the most important performance characteristics of a positron emission tomographic (PET) radioligand is its ‘signal-to-noise’ ratio – i .e ., the amount of radioligand specifically bound to its target receptor compared to that which adsorbs nonspecifically to proteins and lipids in brain . The typical way to measure this ratio is to displace the specifically bound radioligand with pharmacological doses of similarly binding drug and then measure the residual (or nondisplaceable) uptake . Here, we describe a genomic method that can measure the specific and nondisplaceable components of radioligand uptake based on the relative regional density of the mRNA transcript of the target receptor but does not require pharmacological blockade . Methods: This genetic method was tested using brain imaging results from 12 healthy volunteers injected with tracer doses of 18F-FIMX, a radioligand we recently developed to quantify metabotropic glutamate receptor 1 (mGluR1) (Xu et al ., J Med Chem, 56, 2013) . Regional values of total brain uptake (VT) were quantified with the ‘gold standard’ compartmental method that includes serial concentrations of the parent radioligand (separated from radiometabolites) in arterial plasma . The relative density of mGluR1 gene transcripts in brain regions were obtained from the Allen Brain Atlas (Hawrylycz et al ., Nature, 489:391, 2012) . A modification of the Lassen plot was used to correlate some measure of specific binding —in this case, the relative density of mGluR1 gene transcript— with VT and then estimate the amount of nondisplaceable uptake (VND) by extrapolating the value of VT when the specific binding equals zero (Cunningham et al ., J Cereb Blood Flow Metab, 30:46, 2010) . ACNP Annual Meeting Book 2015 rev13.indd 35 11/10/15 9:58 AM 36 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 A Novel Genetic Method of Measuring the Receptor-Specific Component of PET Radioligand Binding in Human Brain Without Pharmacological Blockade Monday, Poster Board #123 (continued) Paolo Zanotti-Fregonara, Mattia Veronese, Rong Xu, Sami Zoghbi, Jeih-San Liow, Masahiro Fujita, Victor Pike, Robert Innis* Results: Because gene transcript and expressed protein are not always linearly related, we first performed a linear regression for multiple brain regions of the mGluR1 gene transcript (y-axis) and VT (x-axis) . The two variables were strongly correlated (Pearson’s r = 0 .965; p<0 .0001) . The x-intercept of this plot equalled VND (0 .5 mL • cm-3), as it was the residual value of VT when specific binding was extrapolated to be zero . Because VND is usually the same for all brain regions and even between species, we performed a standard receptor-blocking study (using pharmacological doses of a related drug) in monkey and found a similar VND value (0 .6 mL • cm-3) after correcting for differences in plasma protein binding of the radioligand . Conclusions: Regional PET values of mGluR1 binding were strongly correlated with mGluR1 transcript density; thus, the VND of the radioligand could be estimated without pharmacological blockade, which is often impossible or even dangerous to do in human subjects . Furthermore, because VND for this and most PET radioligands is uniform throughout the brain, the specific binding—and thus the “signal-to-noise” ratio—of this radioligand can be determined for all brain regions . In addition to introducing a novel method to determine the receptor- specific component of radioligand binding, this study also shows how a publicly available database (i .e ., the Allen Brain Atlas) can be used to determine if a gene transcript is linearly related to the expressed protein across brain regions for any previously published PET radioligand . One common assumption of postmortem studies of mRNA densities is that they reflect the density of the expressed protein . This method can now test that assumption for targets that have been imaged with PET . We are now studying several other targets measured with PET and are finding, as might be expected, that gene transcript is sometimes, but not always, correlated with the density of expressed protein . ACNP Annual Meeting Book 2015 rev13.indd 36 11/10/15 9:58 AM 37 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Affective Neurodynamics Predict Depression Treatment Response Monday, Poster #78 Aaron Heller*, Tom Johnstone, Michael Peterson, Greg Kolden, Ned Kalin, Richard Davidson University of Miami Background: Depression is a debilitating illness that causes suffering world- wide . There are many empirically supported treatments, but few biomarkers predict whether an individual will improve . Developing biological tests to predict treatment response across treatment approaches could facilitate improved outcomes . In parallel, abnormalities in affective processing are core to depression . The majority of neuroimaging work has examined the magnitude of neural responses to emotion in depression, yet other affective neurodynamics may help to characterize the illness and predict treatment response . Methods: Thirty-nine unmedicated patients with major depressive disorder were scanned using event-related fMRI in an emotional regulation paradigm . Patients then received an eight-week trial of interpersonal psychotherapy (IPT), venlafaxine or fluoxetine . Hamilton Rating Scale of Depression (HAM-D) was collected pretreatment and at eight-weeks to assess symptom severity . To examine whether affective neurodynamics predicted treatment response, we examined the time-to-peak of fMRI BOLD activity in response to affective stimuli (IAPS slides) . Results: Across all three-treatment types, a more rapid neural response in the medial Prefrontal Cortex (mPFC) to both positive and negative emotional stimuli predicted better treatment response (a greater drop in HAM-D) . Furthermore, a more rapid neural response in the amygdala to negative, but not positive stimuli predicted a poorer outcome across treatments . Effects were significant when controlling for pretreatment treatment HAM-D score so cannot be attributable to initial severity . These effects were also significant when examining more traditional neural markers such as the amplitude of fMRI BOLD activity indicating that time-to-peak may be a unique neural biomarker predicting treatment response . ACNP Annual Meeting Book 2015 rev13.indd 37 11/10/15 9:58 AM 38 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Affective Neurodynamics Predict Depression Treatment Response Monday, Poster #78 (continued) Aaron Heller* Conclusions: Across three separate treatments for depression (both psychotherapy and pharmacotherapy), we found that a specific affective neurodynamic predicted treatment response over an eight-week trial . These findings extend research that has solely examined the magnitude of neural responding, in that rapid responses in structures important for emotional regulation, such as the mPFC predicted better treatment outcome . Conversely, rapid time-to-peak of subcortical areas, such as the amygdala appeared to be maladaptive . Taken together, these data suggest that regardless of treatment type, rapid engagement of regulatory circuits facilitate treatment response while rapid engagement of subcortical emotional processing areas may be disadvantageous . ACNP Annual Meeting Book 2015 rev13.indd 38 11/10/15 9:58 AM 39 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Impact of Chronic Ethanol Self-Administration on Kappa Opioid Receptor Regulation of Dopamine Signaling in Nonhuman Primates Monday, Poster #256 Cody Siciliano*, Erin Calipari, Steven Fordahl, James Melchior, Jordan Yorgason, Yolanda Mateo, Christa Helms, David Lovinger, Kathleen Grant, Sara Jones Wake Forest School of Medicine Background: Although alcoholism is one of the most prevalent disorders in the United States, with over 18 million individuals meeting the criteria for an alcohol use disorder, the neurobiological bases of this condition remain obscure . Recently, it has been demonstrated that kappa-opioid receptor (KOR) signaling in the striatum plays a critical role in the increased reinforcing efficacy of ethanol following ethanol vapor exposure in rodent models . However, changes in KOR signaling following voluntary ethanol drinking remain to be elucidated . Additionally, because numerous KOR agonists/antagonists are available clinically, understanding how KOR sensitivity relates to drinking behaviors, especially in nonhuman primate models of drinking, may open a novel avenue for therapeutic interventions . Here we examined the effects of chronic voluntary ethanol self- administration in macaques on dopamine neurotransmission and the ability of KORs to regulate dopamine release in the nucleus accumbens core . Methods: Three cohorts of nonhuman primates were given free access to 4% ethanol (w/v) for 22 hr/day . These cohorts were composed of either male cynomolgus, female rhesus or male rhesus macaques, and were given access to ethanol for 6, 12, or 18 months, respectively . Ex vivo fast-scan cyclic voltammetry was then conducted in brain slices containing the nucleus accumbens core to determine ethanol-induced alterations in dopamine terminal function including dopamine release and uptake kinetics as well as the ability of U50,488 (KOR agonist) to inhibit dopamine release . Results: Chronic ethanol drinking increased dopamine uptake rates, which could have implications for reductions in basal dopamine tone in vivo following ethanol drinking . Further, across sex, strain and exposure length ethanol consumption augmented the ability of KORs to inhibit dopamine release, demonstrating that ACNP Annual Meeting Book 2015 rev13.indd 39 11/10/15 9:58 AM 40 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Impact of Chronic Ethanol Self-Administration on Kappa Opioid Receptor Regulation of Dopamine Signaling in Nonhuman Primates Monday, Poster #256 (continued) ethanol-induced increases in KOR sensitivity are widespread and independent of other factors . Finally, in male subjects KOR sensitivity was positively correlated with lifetime ethanol intake, suggesting that changes in KOR regulation of dopamine release may be a determinant of aberrant ethanol drinking behaviors . Conclusions: Although it has been proposed that nonhuman primate models of ethanol abuse represent the most promising avenue for elucidating the neurobiology of alcoholism and for identifying molecular targets for pharmacotherapeutic compounds, investigations have been largely limited to behavioral, endocrine or brain imaging analyses due to practical constraints . Here we show, for the first time, that voluntary ethanol self-administration has a unique effect on KOR sensitivity and regulation of dopamine release directly at the dopamine terminal that was positively correlated with drinking behavior . In conjunction with human and rodent work, these data suggest that ethanol-induced dysregulation of the dynorphin/KOR system may drive the motivation to administer ethanol, and thus drive the development of addiction . The dynorphin/KOR system plays a large role in regulating affective states in humans, and KOR agonists produce conditioned place aversion in rodents . Thus, it is possible that supersensitivity of this system may produce negative affective states, leading to increased consumption and motivation to administer ethanol in an attempt to ameliorate these effects with ethanol . Further supporting this hypothesis, dopamine uptake rates were also increased, which could promote a state of low dopamine tone, which has also been associated with anhedonia . Additionally, the relationship between KOR sensitivity and drinking provides a potential mechanism for the comorbidity of early life stress and alcoholism, as stress has been linked to increases in dynorphin/KOR system activity in both animal and human investigations . Together, these data provide novel insight into ethanol-induced dysregulation of dopamine neurotransmission and suggest that dopaminergic dysfunction may be mediating the increase in voluntary drinking during the early stages of ethanol abuse/dependence . Importantly, KOR antagonists may provide a novel avenue to reduce drinking behaviors in alcoholics . ACNP Annual Meeting Book 2015 rev13.indd 40 11/10/15 9:58 AM 41 ACNP 54th Annual Meeting • Final Program PL 2:30 PM - 5:30 PM Hot Topics Regency 1-2 Dopamine-Dependent Working-Memory Performance is Mediated by Dynamic Connectivity Between Brain Networks Wednesday, Poster #171 Clifford Cassidy, Jared Van Snellenberg, Caridad Benavides, Mark Slifstein, Zhishun Wang, Holly Moore, Anissa Abi-Dargham, Guillermo Horga* Columbia University/NYSPI Background: Research in the last decade has uncovered an intrinsic organization of the brain into functional networks that operate partly in parallel during rest and are thought to interact during complex cognitive processes such as working memory, an interaction that may afford maintenance and manipulation of perceptual information towards goal-directed actions . Understanding how brain networks interact during cognition to facilitate flexible adaptations to changing demands could provide new insights into the basis of interindividual differences in working-memory performance and clarify the perplexing nature of the deficit in working memory in schizophrenia . Dopamine is critical for working memory processing in the cortex and elsewhere although it is not clear how dopamine influences internetwork connectivity and whether such an action could mediate its effects on working memory performance . Methods: We addressed these questions in healthy volunteers (HV) with fMRI (using an n-back working-memory task) and PET imaging using the radiotracer [11C]FLB457 before and after amphetamine administration to measure the change in binding potential (ΔBPND) of the radiotracer as an index of dopamine release capacity in cortical and subcortical extrastriatal regions including thalamus, midbrain, and hippocampus . MRI measures were available for 39 HV, 15 of whom also had PET measures and for 15 unmedicated individuals with schizophrenia . Brain networks were defined by group spatial independent component analysis using GIFT software . Networks with working-memory-load-dependent activity were selected for analysis of functional connectivity including left and right fronto-parietal networks (lFPN, rFPN), cingulo-opercular netwo