中枢脑源性神经营养因子信号失调的致抑郁症机制OA

Depression is a highly prevalent psychiatric disorder characterized by core symptoms of persistent anhedonia and depressed mood for a minimum of two weeks,which severely compromises global physical and psychologi-cal health.Accumulating clinical observations and preclinical animal studies have unraveled its sophisticated pathogenic mechanisms and established multiple etiological frameworks.The canonical monoamine deficiency theory has greatly pro-moted the development and clinical application of first-line monoamine-targeted antidepressants.Nevertheless,these con-ventional agents possess a slow therapeutic action,typically requiring over two weeks of continuous medication,and exhib-it inadequate efficacy in patients with treatment-resistant depression(TRD).In comparison,novel rapid-acting ketamine-derived antidepressants represented by esketamine confer robust therapeutic efficacy against TRD.Nonetheless,owing to its potential psychotomimetic side effects and abuse liability,esketamine is only FDA-approved for patients with TRD and major depressive disorder accompanied by severe suicidal ideation.Fully elucidating the intricate pathogenic mechanisms underlying depression is therefore essential for developing next-generation antidepressants with rapid efficacy and minimal adverse effects.Emerging evidence indicates that dysregulated central brain-derived neurotrophic factor(BDNF)signal-ing is critically implicated in the pathogenesis of depression and mediates the therapeutic effects of multiple antidepres-sants.This review aims to elaborate on this topic and dissect its reciprocal crosstalk with other mainstream pathogenic mechanisms,including monoamine deficiency,glutamatergic excitotoxicity,oxidative stress,and neuroinflammation.Collectively,this work offers mechanistic insights and translational implications for developing novel BDNF-targeted anti-depressant strategies.