Brain Medicine Volume 1: Issue 4

EDITORIAL

Cardiac rhythms as windows into brain stimulation response: Promise and pitfalls in precision psychiatry 1

Julio Licinio and Helen S. Mayberg

INNOVATORS & IDEAS: RISING STAR

Andrea Ballesio: Mechanisms of sleep-mood interactions 4

Andrea Ballesio

INNOVATORS & IDEAS: RESEARCH LEADERS

Hermona Soreq: Revolutionizing neuroscience by elucidating the roles of poly(A) tails, mRNA stability, and acetylcholine in brain-body communication throughout the lifespan 7

Hermona Soreq

Károly Mirnics: Many medications and chemicals might not be as safe for the developing brain as we think they are; this will greatly depend on your genotype, habits, and environmental factors

Dr. Andrea Ballesio is a tenure-track researcher (RTT) in Clinical Psychology at the Faculty of Medicine and Psychology, Sapienza University of Rome. He works in the Clinical Psychology & Psychophysiology Lab of the Department of Psychology, where he investigates the causes and consequences of poor sleep and insomnia and the clinical efficacy of psychotherapeutic interventions for sleep disorders. Dr. Ballesio's research aims to shed light on the psychophysiological and psychoneuroimmunological mechanisms linking insomnia and mood disturbances, particularly depression. To serve this aim, he mostly employs longitudinal and experimental models in humans. He is a member of the European Sleep Research Society (ESRS), the European Insomnia Network (EIN), the European Academy of Cognitive Behaviour Therapy for Insomnia, the European Psychoneuroimmunology Network, and the International Society of Psychoneuroendocrinology (ISPNE). He received the 2023 ISPNE Early Career Scholar Award. Dr. Ballesio is also a licensed psychotherapist, working in the clinical centre of the Department of Psychology, Sapienza University of Rome. We are delighted that Dr. Ballesio shares his insights from the Genomic Press Interview with our community.

Hermona Soreq, PhD, holds the Endowed Slesinger Professorship of Molecular Neuroscience at the Hebrew University of Jerusalem. She is an internationally recognized molecular neuroscientist known for her research into the cholinergic system and the small RNA regulators driving the parasympathetic system in men and women under daily and acute stress responses and neurodegenerative diseases like Alzheimer's and Parkinson's diseases (AD, PD). Her studies have long been focused on the roles of acetylcholine in the mammalian nervous system. In the 1980s, Professor Soreq and coworkers cloned the human cholinesterase genes, identified several disease-related mutations and single nucleotide polymorphisms (SNPs) that may impair their functions, and described the unusual features these mutations conferred on carriers under acute stress, exposure to anticholinesterase poisons and diverse disease conditions, including but not limited to myasthenia gravis, ischemic stroke, schizophrenia, bipolar disorder, AD and PD as well as daily stress responses. Soreq further identified microRNA-132 as a principal controller of the cholinergic pathway and studied its impact as well as of other cholinergic-targeted microRNAs as regulators of parasympathetic brain and body functions and neuroinflammation. More recently, she has shifted her interest to the re-discovered transfer RNA fragments (tRFs), and showed that their rapidly declined control over cholinergic transcripts may lead to the fast cognitive deterioration of women living with AD; that they are prominently altered in PD patients’ biofluids and that their levels are sex-relatedly modified in the blood of newborn babies, dependent on pre-delivery stress. Her multi-leveled interests in the stress and sex-related cholinergic aspects of AD, PD, adult, and pre-delivery trauma further reflect the impact on acute stress responses as the kernel of the neuroscience research in the current Israeli landscape and has further enabled her a wide-angle view of diverse cholinergic-regulated states and diseases. We are delighted that Professor Soreq answered the Genomic Press Interview, generously sharing her life's trajectory with our readers.

Károly Mirnics is Director and Hattie B. Munroe Professor of Psychiatry, Biochemistry & Molecular Biology, Pharmacology & Experimental Neuroscience, Munroe-Meyer Institute for Genetics and Rehabilitation at the University of Nebraska Medical Center (UNMC). Dr. Mirnics earned his medical degree from the University of Novi Sad School of Medicine (in the former war-torn country of Yugoslavia that does not exist anymore) and his Ph.D. from Semmelweis University in Budapest, Hungary. He completed his postdoctoral fellowship at the University of Pittsburgh, where he established his laboratory in 2000. In 2006, his laboratory moved to the Department of Psychiatry at Vanderbilt University in Nashville, TN. In 2010, Dr. Mirnics was named James G. Blakemore Professor of Psychiatry and served as the departmental vice chair for research and the associate Director of the Vanderbilt Kennedy Center for Human Development. In 2016, he joined UNMC, becoming the Director of the Munroe-Meyer Institute for Genetics and Rehabilitation (MMI). With over 1,000 employees and trainees and roots tracing back to 1919, MMI is among the world's most extensive clinical, research, education, and outreach institutes for intellectual and developmental disabilities (IDD). Funded by the National Institutes of Health (NIH), Dr. Mirnics's innovative research uses a variety of genetic, molecular, cell biology, and behavioral tools across multiple disease models; he has authored over 150 scientific publications, which have been cited more than 17,000 times. As a passionate advocate for diversity, access, and inclusion of individuals with intellectual and developmental disabilities, he currently serves on the board of directors of Special Olympic International (SOI). He chairs the SOI Global Medical Advisory Committee that develops strategies to address the health challenges of more than six million athletes across over 200 countries. He led UNMC's effort to build a highly advanced, award-winning, 20,000 m² multidisciplinary building that serves individuals with intellectual and developmental disabilities across the lifespan. We are delighted that Dr. Mirnics shares his personal and professional paths with our readers.

Introduction

The Tachykinin 2 pathway has been shown to modulate fear memory consolidation in healthy animals and humans. Here, we studied the Tac2 pathway antagonist Osanetant administered shortly after immobilization stress on fear memory consolidation in female mice. Osanetant reduced freezing during fear expression, indicating diminished fear memory consolidation. These findings support the potential preventive therapeutic role of Osanetant in a posttraumatic stress disorder-like model.

Fear is a survival mechanism triggered by certain threats that result in instant defensive responses, allowing one to preserve their well-being. Fear memory refers to the association between a neutral and an aversive stimulus (unconditioned

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Table of Contents

Cardiac rhythms as windows into brain stimulation response: Promise and pitfalls in precision psychiatry

The challenge of depression

Study design and core questions

Andrea Ballesio: Mechanisms of sleep-mood interactions

Hermona Soreq: Revolutionizing neuroscience by elucidating the roles of poly(A) tails, mRNA stability, and acetylcholine in brain-body communication throughout the lifespan

Károly Mirnics: Many medications and chemicals might not be as safe for the developing brain as we think they are; this will greatly depend on your genotype, habits, and environmental factors

Raül Andero Galí: Bridging animal and human studies to understand stress and memory

Tatia Lee: Neuropsychology and human neuroscience research insights inform the theoretical and translational framework for fostering brain and psychological health

Etienne Sibille: Investigating the cellular and molecular bases of depression and aging for innovative therapeutics

Helen Lavretsky: Translational neuroscience of integrative medicine

Carlos A. Zarate, Jr.: Using clinical translational neuroscience to develop the next generation of antidepressant treatments that act more rapidly and effectively

Raz Yirmiya: The inflammatory underpinning of depression

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

Dynamic memory enqrams: Unveiling the celular mechanisms of memory encoding, consolidation, generalizaton, and updating in the brain

Heart rate modulation and clinical improvement in major depression: A randomized clinical trial with accelerated intermittent theta burst stimulation

NK3R antagonism reduces fear expression in a PTSD-like model of female mice

Introduction

Table of Contents

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Table of Contents

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

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Table of Contents

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