Autophagy in Schizophrenia: A Continuum From Developmental Vulnerability to Progressive Neuronal Stress? A Scoping Review

作者：Andreas S. Lappas, Μαρία Ιωάννου, Myrto Samara, Nikos G Christodoulou · 发表于：Schizophrenia Bulletin · 年份：2025 · DOI：10.1093/schbul/sbaf130 · 被引用次数：3 · 研究领域：Autophagy in Disease and Therapy、Tryptophan and brain disorders、Schizophrenia research and treatment

BACKGROUND AND HYPOTHESIS: Autophagy, the cell's primary degradation and recycling system, is essential for neuronal homeostasis. A structured synthesis of studies directly investigating autophagy in schizophrenia (SCZ) is lacking. This scoping review aimed to map the available evidence directly assessing autophagy processes in SCZ. STUDY DESIGN: We systematically searched Medline (via Ovid), Embase, and PsycINFO from inception to February 2025. Twenty-four eligible studies-encompassing clinical cohorts, postmortem brain tissue, animal and cellular SCZ-relevant models-were thematically analyzed. STUDY RESULTS: Findings indicated impaired autophagy in SCZ, implicating it in 3 main processes: (1) disrupted neurodevelopment/synaptic pruning, (2) lysosomal dysfunction/proteostasis, (3) compromised mitochondrial turnover/metabolic homeostasis. Antipsychotic treatment showed variable effects, with some agents partially restoring autophagic markers, whereas others heightened dysfunction. Transcriptomic studies identified autophagy-related gene signatures with potential diagnostic relevance. Synthesizing these findings, impaired autophagy emerged as a possible mechanistic link between early neurodevelopmental vulnerability and progressive cellular stress, which may underlie disease progression in some cases. CONCLUSIONS: Autophagy dysfunction may contribute to both early neurodevelopmental and later progressive cellular changes in SCZ. However, much of the current evidence derives fr...