Cortical transcriptomic dysregulation in Autism spectrum disorder: A conceptual synthesis.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition in which human post-mortem cortical transcriptomic studies have identified recurrent but context-sensitive molecular abnormalities. This narrative review synthesises RNA sequencing (RNA-seq) evidence from ASD cortex and organises recurrent findings into three interacting cortical domains: synaptic/neuronal programmes, immune-glial programmes, and RNA-regulatory processes. Across bulk cortical datasets, the most reproducible signals include relative downregulation of neuronal and synaptic expression programmes together with upregulation of glial-associated and neuroimmune signatures, whereas transcript-level analyses further implicate alternative splicing, microexon dysregulation, differential transcript usage, and isoform-level perturbation. Single-nucleus and related cell-resolved approaches localise these abnormalities to defined neuronal and glial populations, while long-read strategies strengthen inference on transcript structure and isoform complexity. Within this framework, mitochondrial-related findings are best interpreted as a linked bioenergetic component rather than an equally established standalone transcriptomic domain. The review also summarise the principal interpretive constraints of cortical ASD transcriptomics, including region specificity, developmental stage, cohort heterogeneity, cell-type composition, post-mortem tissue quality, and cross-platform comparability.