Beyond Neurotransmitters: The Inflammatory Roots of Anxiety

Neuroinflammation refers to the inflammation of the brain and spinal cord, which can lead to anxiety disorders. Studies show that pro-inflammatory cytokines like IL-6, TNF-α, and IL-β disrupt normal brain function and promote anxiety-like behavior. Inflammation can affect brain regions that regulate emotions, such as the amygdala and the prefrontal cortex. This inflammation also disrupts the balance of serotonin and dopamine, which regulate mood. When this balance is disrupted, it can lead to anxiety. B cells are another type of immune cell that contributes to inflammation in various brain diseases, including neuromyelitis optica and multiple sclerosis. However, corticotropin- releasing hormone plays a crucial role in stress-induced neuroinflammation, contributing to anxiety and activating immune cells, triggering mast cell activation, and disrupting blood-brain barrier permeability. Therefore, neuroinflammation can play a significant role in the progression of anxiety. Furthermore, this review uniquely focuses on the molecular convergence points between inflammation and the specific neural circuits of anxiety. This synthesis moves beyond the general associations of neuroinflammation with mood disorders to detail how the key molecular neuroinflammatory pathways-such as JAK-STAT, NF-κB, PI3K/Akt, MAPK/ERK, mTOR, TNF-α, IFN-γ, and JNK-directly affect brain function and, crucially, the specific fear and vigilance circuits implicated in anxiety disorders. Thus, addressing these neuroinflammatory pathways may serve as a viable therapeutic intervention in the treatment and management of anxiety disorders.