Cell-type-specific DNA methylation patterns associated with suicide are enriched in excitatory neurons

The study analyzed DNA methylation in brain tissue from 199 individuals who died by suicide and 190 non-psychiatric control subjects. Bulk tissue analysis revealed no significant methylation differences; however, cell-type-specific analysis identified 605 differentially methylated cytosines in excitatory neurons, 10 in inhibitory neurons, and 28 in oligodendrocyte precursor cells. Most differences occurred in males and were predominantly found in excitatory neurons. These changes were associated with synaptic processes and small GTPase signaling. The study found no significant differences in epigenetic aging. The findings suggest that suicide-associated DNA methylation patterns are primarily neuron-specific and may remain undetectable in bulk tissue analysis.