Nuclear factor-κB as a key inflammatory mediator in psychiatric diseases: A narrative review

Table 1 Clinical and preclinical evidence of nuclear factor-κB dysregulation across psychiatric disorders

Disorder	Human findings	Preclinical models	Proposed core mechanisms
MDD	Tissue/cell type: PBMCs, post-mortem PFC and hippocampus. NF-κB metric: ↑ Nuclear translocation, ↑ p65 activation. Direction: Positive correlation with IL-6, TNF-α levels[20-22]	AUDA (sEH inhibitor), adiponectin, exercise[23-25,27]	NF-κB-driven neuroinflammation, microglial activation, cytokine release
Schizophrenia	Tissue/cell type: Peripheral leukocytes, post-mortem brain. NF-κB metric: ↑ TLR4/TNFR2, ↑ RelB; ↓ IKKβ/NIK mRNA. Direction: Complex dysregulation with kinase downregulation[33,35]	MK-801-induced model, ALA supplementation[16]	Microglial NF-κB/NLRP3 activation, immune-transcriptional dysregulation
PTSD	Tissue/cell type: Monocytes, PBMCs. NF-κB metric: ↑ NF-κB target gene expression. Direction: Associated with ↑ IL-1β, IL-6, TNF-α[44,45]	Fear conditioning models, NF-κB inhibition in BLA[40-42]	NF-κB-dependent fear memory reconsolidation, microglial priming
BD	Tissue/cell type: PBMCs. NF-κB metric: ↑ NF-κB-associated lncRNA CHAST (particularly in females)[48]. Direction: Gender-specific dysregulation patterns[5,49]	In vitro models of oxidative stress	NF-κB activity fluctuates with manic/depressive episodes; interacts with oxidative stress and mitochondrial dysfunction
ASD	Tissue/cell type: Peripheral blood. NF-κB metric: ↑ Multiple NF-κB-associated lncRNAs (ANRIL, NKILA, CHAST)[52]. Direction: Upregulation correlated with immune activation	IUGR rat model, AHR–NF-κB signaling[16,53]	Microglial synaptic pruning, NF-κB/IL-6 axis in social behavior deficits

TNF-α: Tumor necrosis factor-alpha; MDD: Major depressive disorder; PTSD: Post-traumatic stress disorder; BD: Bipolar disorder; ASD: Autism spectrum disorder; PBMCs: Peripheral blood mononuclear cells; PFC: Prefrontal cortex; AUDA: 12-[[(tricyclo[3.3.1.13:7]dec-1-ylamino)carbonyl]amino]-dodecanoic acid; ALA: Α-linolenic acid; BLA: Basolateral amygdala; IUGR: Intrauterine growth restriction; lncRNA: Long non-coding RNA; IL-6: Interleukin-6; NLRP3: NOD-, LRR- and pyrin domain-containing protein 3; NF-κB: Nuclear factor-κB.