Neuroinflammation—A Crucial Factor in the Pathophysiology of Depression—A Comprehensive Review
Andreea Sălcudean, Cristina-Raluca Bodo, Ramona Amina Popovici, Maria Melania Lica, Mariana Păcurar, Ramona-Elena Crăciun, Andrada-Ioana Crișan, V.R. Enatescu, Ileana Marinescu, Dora-Mihaela Cîmpian, Andreea Georgiana Nan, Andreea-Bianca Sasu, Ramona-Camelia Anculia, Elena Gabriela Strete
Abstract
Depression is a multifactorial psychiatric condition with complex pathophysiology, increasingly linked to neuroinflammatory processes. The present review explores the role of neuroinflammation in depression, focusing on glial cell activation, cytokine signaling, blood-brain barrier dysfunction, and disruptions in neurotransmitter systems. The article highlights how inflammatory mediators influence brain regions implicated in mood regulation, such as the hippocampus, amygdala, and prefrontal cortex. The review further discusses the involvement of the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, and the kynurenine pathway, providing mechanistic insights into how chronic inflammation may underlie emotional and cognitive symptoms of depression. The bidirectional relationship between inflammation and depressive symptoms is emphasized, along with the role of peripheral immune responses and systemic stress. By integrating molecular, cellular, and neuroendocrine perspectives, this review supports the growing field of immunopsychiatry and lays the foundation for novel diagnostic biomarkers and anti-inflammatory treatment approaches in depression. Further research in this field holds promise for developing more effective and personalized interventions for individuals suffering from depression.