Review on the role of hippocampus in autism spectrum disorder: Recent insights into neuropathology, genetics, and emerging therapeutic strategies
Poorna Manasa Bhamidimarri, Khalood Mohamed Alhosani, Heng Cai, Haya Al-Ali, Yara Abukhaled, Hasan Tawamie, Sahar Abdelaziz, Mouna Fawaz, Junaid Kashir, Yasmin Sajjad, Lamiya Mohiyiddeen, M.H. Fakih, Hamdan Hamdan
Abstract
The hippocampus, central to learning, memory, and social behavior, is increasingly implicated in the pathophysiology of autism spectrum disorder (ASD). Structural and functional disruptions in this region contribute to core ASD traits through impaired neurogenesis, abnormal dendritic morphology, excitatory/inhibitory imbalance, and altered connectivity with large-scale brain networks. Neuroimaging studies revealed changes in hippocampal volume, subfield-specific anomalies in the CA1 and dentate gyrus, and reduced functional connectivity within these regions. Genetic mutations in Shank3, Syngap1, Fmr1, and Nlgn3 disrupt synaptic plasticity and social memory circuits, while epigenetic alterations and environmental exposures further impair regulatory processes. Neuroinflammation exacerbates ASD pathology through microglial activation and cytokine release. Collectively, current evidence positions hippocampal dysfunction as central to ASD, emphasizing its relevance as both a biomarker and a therapeutic target to improve clinical outcomes.