Fatigue is a prevalent yet often underrecognized symptom across neurological and psychiatric disorders, including depression, schizophrenia, multiple sclerosis, Parkinson’s disease, Alzheimer’s Disease and other dementias. While traditionally viewed as a secondary consequence of these conditions, emerging research suggests that fatigue may instead reflect underlying neuroplasticity — the brain’s adaptive capacity in response to disease, injury, or therapeutic interventions. Advances in neuroimaging, electrophysiology, molecular biology, and computational modeling are revealing how synaptic efficiency, connectivity, neurotransmitter dynamics, molecular mechanism and biochemical pathways contribute to fatigue, providing novel insights into disease progression, recovery potential, and treatment response.

Despite its widespread impact, fatigue remains poorly understood and inadequately addressed in clinical practice. Current assessments rely heavily on subjective measures, lacking the ability to capture its neurobiological underpinnings or its potential as a biomarker. This gap hinders the development of targeted interventions that could optimize recovery and functional outcomes. To bridge this divide, research must integrate molecular biology, neuroimaging, electrophysiology, and computational approaches to elucidate the neural mechanisms driving fatigue. Longitudinal studies are also needed to determine how fatigue correlates with molecular and neuroplastic changes over time, particularly in response to treatment. Additionally, the development of standardized, objective fatigue measures is crucial to improving diagnosis and therapeutic monitoring.

By reframing fatigue as an indicator of neuroplasticity and molecular changes, this Research Topic seeks to refine clinical strategies, advance biomarker discovery, and enhance patient outcomes. We aim to foster interdisciplinary collaboration across neuroscience, psychiatry, and neurology to accelerate progress in this field.

We welcome contributions that explore fatigue through molecular and biochemical analyses, neuroimaging (e.g., fMRI, PET, EEG), electrophysiological studies, neuromodulation techniques (e.g., TMS), and computational modeling, as well as investigations into neurotransmitter dynamics and functional connectivity changes. Key themes include:

- Neurobiological Mechanisms of Fatigue: Exploring how fatigue reflects alterations in synaptic plasticity, connectivity, neurotransmitter function, molecular pathways, and energy metabolism.
- Fatigue as a Clinical and Diagnostic Biomarker: Investigating the relationship between fatigue and molecular changes, disease progression, recovery potential, and treatment responsiveness.
- Objective Measurement and Biomarker Development: Developing novel tools and methodologies for quantifying fatigue using biochemical, molecular, neurophysiological, neuroimaging, or computational approaches.
- Intervention Strategies and Therapeutic Implications: Examining how treatments targeting fatigue influence neuroplasticity, functional recovery, and patient outcomes.

Through these investigations, this Research Topic aims to deepen our understanding of fatigue, paving the way for innovative diagnostic and therapeutic approaches in neurological and psychiatric disorders.

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Fatigue and Neuroplasticity in Neurological and Psychiatric Disorders: Mechanistic Insights and Biomarkers Discovery