Epigenetic and Transcriptomic Pathways Underlying Animal Models of Cognitive and Psychiatric Disorders: A Scoping...

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Neuropsychiatric disorders arise from complex genetic, environmental, and molecular brain interactions.
• Animal models offer controlled systems to study these mechanisms.
• Transcriptomic and epigenomic technologies have advanced understanding of disease pathways.

Purpose of the Study:

• To systematically map and synthesize epigenetic and transcriptomic findings in animal models of autism spectrum disorder (ASD), schizophrenia, depression, and Rett syndrome.
• To characterize evidence breadth, identify molecular pathway convergence/divergence, and highlight translational gaps.
• To explore therapeutic implications based on animal model data.

Main Methods:

• Scoping review guided by PRISMA-ScR methodology.
• Inclusion of studies using chromatin accessibility, DNA methylation, RNA sequencing (single-cell and bulk), and histone modification profiling.
• Quality appraisal of 63 primary experimental studies using a modified CAMARADES checklist.

Main Results:

• Multi-omics analyses highlight cell-type and context-dependent epigenetic changes beyond general stress responses.
• Isoform-specific histone modifications and HDAC/MeCP2 binding to synaptic plasticity genes were observed.
• Single-cell RNA sequencing consistently showed transcriptional alterations in parvalbumin-positive (PV+) interneurons.

Conclusions:

• Convergent epigenetic disruptions in neural circuits related to synaptic structure and inhibitory function may underlie neuropsychiatric phenotypes in animal models.
• Emphasizes the significance of circuit- and cell-type-specific epigenetics.
• Identifies potential therapeutic targets and avenues for neuropsychiatric disorders.