Neuroimmunology, endocrinology, and neuroscience research have significantly advanced our understanding of the intricate connections between neural processes, immune responses, and metabolic regulation. Emerging evidence highlights how dysregulation within these systems—particularly through chronic inflammation, oxidative stress, and disruptions of the gut-liver-brain axis and circadian/diurnal rhythms—can profoundly influence both psychiatric and physical health outcomes. Furthermore, substance use and misuse (e.g., alcohol, opioids, stimulants) are increasingly recognized as key modifiers of neuroimmune and metabolic function, capable of exacerbating inflammation, disrupting metabolic homeostasis, and altering neuroimmune communications. Chronic substance use can further potentiate oxidative stress and circadian rhythm disturbances, thereby contributing to a feed-forward cycle of neuroimmune and metabolic dysregulation.

Recently, chronic inflammation and metabolic disturbances have been increasingly recognized as common underlying factors in psychiatric disorders such as depression, anxiety, schizophrenia, and various metabolic conditions including obesity and type-2 diabetes. Substance use disorders frequently co-occur with these conditions and may share or amplify these underlying biological mechanisms. Despite this knowledge, gaps persist concerning exactly how these interactions operate mechanistically, the directionality of their associations, and their potential clinical applicability.

This Research Topic aims to deepen our knowledge regarding the complex and bidirectional interactions between brain mechanisms, immune functioning, metabolic processes, and psychophysiological health—including the role of substance use and misuse. Additionally, the Topic seeks contributions probing into the role of gut microbiota, circadian rhythm disruptions, and substance-related neuroimmune and metabolic changes in these integrated mechanisms, posing questions on the potential therapeutic implications of modulating these intricate systems.

We welcome articles addressing, but not limited to, the following themes:

- Influence of chronic inflammation on psychiatric disorders such as anxiety, depression, and schizophrenia
- Mechanistic roles of oxidative stress in psychiatric and metabolic pathophysiology
- The role of substance use (e.g., alcohol, opioids, stimulants) as modifiers of neuroimmune and metabolic function
- Bidirectional associations between metabolic disorders (e.g., diabetes, obesity) and mental health outcomes
- Roles of the gut-brain axis in behavioral and neurological conditions
- Impacts and mechanisms of sleep and circadian disruptions in neuroimmune and metabolic dysregulation

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Neuroimmune and metabolic pathways influencing psychiatric and physical well-being