Cytokine dysregulation and hippocampal neurogenesis: A shared mechanism underlying cognitive impairments across neuropsychiatric and neurodegenerative disorders.

Neuropsychiatric and neurodegenerative disorders, such as major depressive disorder, bipolar disorder, schizophrenia, Alzheimer's disease, and Parkinson's disease, all show a neuroimmune signature with dysregulated inflammatory cytokine profile and cognitive impairment. Although these deficits are clinically relevant, the immunological mechanisms that cause cognitive dysfunction across these conditions remain poorly defined. Recent studies demonstrate that inflammatory cytokines actively modulate adult hippocampal neurogenesis, a process critical for learning, memory, and affective regulation. Here, we synthesise clinical evidence to characterise the disorder-specific inflammatory profile of each of these five disorders, representing each profile with three frequently dysregulated cytokines rather than a single cytokine signature shared across conditions. We also integrate preclinical data where cytokines induce behavioural, cognitive, and hippocampal-related deficits in animal and cellular models. Hence, this review develops a mechanistic framework that links brain-immune communication directly to cognitive impairment through hippocampal neurogenesis, thereby suggesting neuroimmune targets for therapeutic intervention.