Brain Medicine Volume 1: Issue 5

EDITORIAL

Exercise as metabolic medicine: Movement counters diet-induced behavioral despair via gut-brain signaling 1

Julio Licinio, Ma-Li Wong and Nicholas Fabiano

INNOVATORS & IDEAS: RISING STAR

Hamilton Oh: A journey studying the science of humanity 5

Hamilton Se-Hwee Oh

INNOVATORS & IDEAS: RESEARCH LEADERS

Illana Gozes: From the pivotal discovery of activity-dependent neuroprotective protein (ADNP) through its investigational drug davunetide: brain molecular medicine providing hope for autism, schizophrenia, and Alzheimer's disease 9

Illana Gozes

Ana Cristina Andreazza: Driven by curiosity – transforming mental health through mitochondrial innovation 13

Ana C. Andreazza

Inga D. Neumann: Molecular underpinnings

Dr. Hamilton Se-Hwee Oh is pioneering groundbreaking research at the intersection of neuroscience, immunology, and aging biology at Mount Sinai's prestigious Brain-Body Institute and Ronald M. Loeb Center for Alzheimer's Disease, where he decodes the complex bidirectional communication between the brain and peripheral organs that drives depression, aging, and neurodegeneration. Working under the renowned mentorship of Drs. Scott Russo and Alison Goate, Dr. Oh bridges neuroscience, immunology, and computational biology to decode how psychological stress accelerates organ aging and how peripheral molecular signals rewire neural circuits affecting mood, cognition, and long-term health. His groundbreaking Stanford PhD research in the Wyss-Coray laboratory yielded three first-authored high-impact publications in Nature and Nature Medicine, including revolutionary discoveries that demonstrated human organs age at differential rates with profound implications for disease susceptibility. Additionally, he identified cerebrospinal fluid synaptic biomarkers that predict Alzheimer's dementia onset years before clinical manifestation. By integrating large-scale human proteomics, single-cell transcriptomics, and mechanistic animal models, Dr. Oh pioneers precision medicine approaches targeting root causes of depression, chronic pain, and age-related neurodegenerative diseases. His innovative research examines how immune cells and metabolic organs amplify or dampen mood symptoms, utilizing cutting-edge metabolomic and proteomic profiling to identify peripheral proteins and metabolites that track depressive behavior. Currently investigating the molecular fingerprints of interventions such as exercise and ketamine, Dr. Oh's multidisciplinary approach positions him at the forefront of developing next-generation therapies. His work exemplifies how young scientists can leverage big data and systems biology to transform our understanding of brain-body interactions, offering hope for millions suffering from neuropsychiatric and neurodegenerative disorders worldwide.

Professor Illana Gozes, Ph.D., is a faculty member at Tel Aviv University. Formerly holding the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, she now directs the Dr. Diana and Zelma Elton Laboratory for Molecular Neuroendocrinology. A world-renowned neurochemist, Professor Gozes currently serves as the President of the European Society for Neurochemistry and Vice President of Drug Development at ExoNavis Therapeutics Ltd. Her groundbreaking research began in the late 1970s and early 1980s when she discovered multiple tubulin forms within a single neuron. She demonstrated that these forms evolve with brain development, play a crucial role in synapse formation, and can be identified using monoclonal tubulin antibodies. At the forefront of molecular neuroscience in the 1980s, Professor Gozes became the first to clone the gene encoding vasoactive intestinal peptide (VIP), a key regulatory neuropeptide in the brain. Her research revealed increased VIP expression during synapse formation. In her quest to identify proteins activated by VIP and facilitate neuro-glial interaction, the Gozes laboratory discovered and cloned a novel protein: activity-dependent neuroprotective protein (ADNP). Subsequent research established ADNP's essential role in brain formation and function. Through a series of highly cited articles, Professor Gozes demonstrated that ADNP regulates thousands of essential genes during brain development in a sex-dependent manner and associates with an intricate array of vital proteins. She uncovered ADNP's key role in autophagy and schizophrenia, revealed a fundamental shared mechanism in autism involving critical binding of ADNP with SHANK3 and actin, and showed ADNP's regulation of microtubule dynamics and Tau interaction, which protects against tauopathy. Furthermore, she discovered somatic mutations in ADNP and related genes in Alzheimer's disease, paralleling tauopathy. Her pioneering work on ADNP-deficient mouse models predicted the ADNP syndrome, an autistic/intellectual disability syndrome driven by de novo mutations in ADNP and presenting with tauopathy. Professor Gozes took a reductionist approach to discover an active site in ADNP, leading to the development of the investigational drug davunetide (NAP). This compound has shown promise in protecting against ADNP deficiency/mutations in animal models and in clinical trials. It has been tested in women suffering from progressive supranuclear palsy (PSP), a pure tauopathy, and in individuals with prodromal Alzheimer's disease, demonstrating effects in a sex-dependent manner. Further promise was shown in schizophrenia patients, suggesting improvement in real-world problem solving and task performance. We are honored that Professor Gozes has agreed to share her life's journey with our readers in this Genomic Press Interview.

Dr. Ana Cristina Andreazza is a Professor of Pharmacology Toxicology and Psychiatry at the University of Toronto, holding the Thomas C. Zachos Chair in Mitochondrial Research and a Tier II Canada Research Chair in Molecular Pharmacology of Mood Disorders. As the visionary Founder and Scientific Director of the Mitochondrial Innovation Initiative (Mito2i), she leads pioneering research on the role of mitochondrial dysfunction in neurological and psychiatric diseases, organ transplants, and novel therapeutic strategies. Her groundbreaking work has revolutionized our understanding of the relationship between mitochondrial function and mental health disorders, particularly bipolar disorder. Dr. Andreazza's career was inspired by early curiosity, family influence, and a commitment to reduce the stigma surrounding metabolic and psychiatric conditions. Her innovative work bridges multiple disciplines, aiming to discover biomarkers that could enable personalized treatments in mental health. A recipient of numerous prestigious awards, including membership in the Royal Society of Canada College of New Scholars, Dr. Andreazza has published over 200 peer-reviewed papers and is internationally recognized for her contributions to metabolic psychiatry. In this Genomic Press Interview, she shares insights into her remarkable journey from studying wine chemistry in Brazil to becoming a leading force in mitochondrial research while discussing her perspectives on collaborative science and innovation. Driven by a passion for teaching and collaborative science, Dr. Andreazza continues to foster innovation and mentorship in the mitochondrial research community.

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Table of Contents

Exercise as metabolic medicine: Movement counters diet-induced behavioral despair via gut-brain signaling

Introduction

Hamilton Oh: A journey studying the science of humanity

Illana Gozes: From the pivotal discovery of activity-dependent neuroprotective protein (ADNP) through its investigational drug davunetide: brain molecular medicine providing hope for autism, schizophrenia, and Alzheimer's disease

Ana Cristina Andreazza: Driven by curiosity – transforming mental health through mitochondrial innovation

Inga D. Neumann: Molecular underpinnings of the brain oxytocin system and its involvement in socio-emotional behaviour: More than a love story

Michael C. Oldham: Clarifying the cellular and molecular architecture of the human brain in health and disease through gene coexpression analysis

John M. Oldham: Personality styles and personality disorders, a dimensional framework

Siegfried Kasper: The importance of back-translation of clinical findings to basic science

Neuromodulation techniques in obsessive-compulsive disorder: Current state of the art

Rethinking the impact and management of electroconvulsive therapy session number in depression

Exercise mitigates the effects of a cafeteria diet on antidepressant-like behavior associated with plasma and microbial metabolites in adult male rats

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Stress, chromatin, and long noncoding RNA: A new frontier in psychiatric biology

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Neural mechanisms of cognitive generalization across species: From hippocampus to cortex

Romina Mizrahi: The crucial role of positron emission tomography (PET) in precision medicine in psychiatry