Brain Medicine Early Online Release

Introduction

Ketamine has been demonstrated to have rapid antidepressant effects, although the mechanism of action that underlies its rapid effects has been under debate for the last few years. The drug has been thought to exert its mood effects by blocking the NMDA receptor; however, binding to the receptor is micromolar, and attempts to develop other antidepressants with NMDA antagonism have yielded few effective follow-on compounds. A few years ago, we argued that the antidepressant effects involved mu-opioid agonist effects (1). We based this on several observations:

1) Ketamine's antinociception effects in rodents could be blocked by administration

Perioperative neurocognitive disorder (PND) is one of the most common perioperative complications in the older surgical population. However, its biomarkers and pathogenesis are largely undetermined, impeding further studies in developing new diagnostic strategies and establishing novel interventions for patients at high risk of PND. This review summarizes the risk factors, mechanisms, and current interventional strategies for PND, and aims to advance the development of innovative preventions and targeted treatments.

Yue, Luo, and colleagues discovered that adenosine signalling is the common underlying mechanism of rapid acting antidepressant therapies, unifying the effects of ketamine, ECT and acute intermittent hypoxia. They use genetically encoded sensors, along with extensive mechanistic dissection, to show that all three induce adenosine surges in mood-regulatory circuits via A1 and A2A receptor activation. The mechanism of action of ketamine primarily involves modulation of mitochondrial metabolism as opposed to NMDA receptor antagonism, thereby presenting the possibility for improvements in derivative products with better therapeutic indices. These outcomes offers a rational framework for gauging therapeutic benefit for depression and raise vexing questions about patterns of caffeine consumption in treatment resistant depression, specifically whether the chronic use has a protective effect or whether the acute use impedes treatment response.

Sleep is a fundamental physiological process essential for maintaining both physical and mental health. While significant advances have been made in understanding the central nervous system mechanisms that regulate sleep-wake cycles, emerging evidence reveals the crucial role of peripheral organs, particularly the digestive system, in modulating brain function and behavior through the microbiota-gut-brain axis. This bidirectional communication network between the gut and the central nervous system directly and indirectly impacts sleep regulation. Disruptions in gut microbiota composition are closely linked to sleep disturbances, and alterations in the microbiota-gut-brain axis have been observed in several sleep disorders and illnesses with comorbid sleep disturbances. This review synthesizes current insights into the interplay between gut microbiota and sleep-wake regulation, highlighting potential routes of the microbiota-gut-brain axis in sleep and gut microbiome interactions and their health implications. Modulating gut microbiota may present a promising strategy for developing novel therapeutic approaches to address sleep disorders.

The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons

Karthikeyan Tangavelou,

Virginie Bondu,

Mingqi Li,

Wei Li,

Francesca-Fang Liao, and

Kiran Bhaskar

Understanding the opioid effects of ketamine: Where are we?

Introduction

Perioperative neurocognitive disorders: Risk factors, mechanisms, and interventional strategies

Adenosine as the metabolic common path of rapid antidepressant action: The coffee paradox

Brain-gut-microbiota interactions in sleep disorders

Alex Tsompanidis: Understanding the role of the placenta in human neurodiversity

A Tribute to Dr. Seymour Reichlin – A role model for vibrant longevity

Alexei Verkhratsky: From neuroglial pathophysiology to therapeutic strategies for brain disorders

David Rubinsztein: Autophagy and neurodegeneration

Philip Hyland: Human responses to extreme stress and trauma

Camilo de la Fuente-Sandoval: Glutamate as biomarker of treatment response in early-stage schizophrenia

David R. Rubinow: Triggers and susceptibility–reproductive steroids and the regulation of affective state

Randy J. Nelson: Disruption of circadian rhythms on brain function and health

Danielle Beckman – a neuroscientist driven by a microscopic obsession: Unravel how viruses play a role in brain pathology

Sara Poletti: From the cradle to the grave

Sophia Shi: Decoding the role of sugar molecules in brain aging and neurodegenerative diseases

Francesco Benedetti: Breaking boundaries between modern psychiatry and clinical medicine

Personal recollections of Seymour “Si” Reichlin, MD, PhD: A maven, a mentor, and a mensch

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

Alpha-particle therapy for neuroendocrine tumors: A focused review

Guy A. Rouleau: Genetic foundations of neurological disease – From risk variants to pathogenic mechanisms

Sex hormones and diseases of the nervous system

A debt owed to a wonderful mentor, Seymour Reichlin

Medical therapy of pituitary adenomas

Is depression a neuroendocrine disease?

An overview of the life and career of Seymour Reichlin, MD, PhD

The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons

Understanding the opioid effects of ketamine: Where are we?

Perioperative neurocognitive disorders: Risk factors, mechanisms, and interventional strategies

The clinician-scientist: An endangered species in psychiatry

Adenosine as the metabolic common path of rapid antidepressant action: The coffee paradox

Cover-to-Cover

Cover-to-Cover

Table of Contents

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

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