The Role of Natural Extracts in Depression: Modulating Neurotransmitters for Antidepressant Effects

Abstract

Objective: This study explores the neurobiological underpinnings of Major depressive disorder (MDD), focusing on neuroimaging, neurotransmitter dysregulation, and emerging therapeutic approaches, to identify potential avenues for innovative treatment development. Methods: A review of recent neuroimaging studies, postmortem analyses, and neurotransmitter research was conducted to synthesize findings on structural and functional brain changes in MDD. The monoamine, glutamate, and GABAergic theories of depression were evaluated alongside emerging evidence for plant-derived therapeutics. Results: Neuroimaging reveals structural brain changes in MDD, including reduced brain volumes, enlarged lateral ventricles, and white matter microstructural deficits suggestive of myelin sheath loss. Postmortem studies report altered neuronal and glial density, as well as synaptic gene expression. Dysregulation of neurotransmitters—Gamma-amino butyric acid (GABA), glutamate, serotonin, dopamine, and norepinephrine—impairs synaptic communication, contributing to mood disturbances. While the monoamine theory attributes depressive symptoms to neurotransmitter deficiencies, recent findings highlight the roles of glutamate dysregulation and GABAergic deficits. Notably, plant extracts demonstrate antidepressant potential by modulating neurotransmitter levels and influencing the GABAergic system. Conclusion: Advances in understanding the pathophysiology of MDD underscore the need to target specific neurotransmitter systems. Emerging evidence supports the development of innovative treatments, including plant-based interventions, to address the limitations of current therapies and improve patient outcomes.