Prefrontal interneuron genes underlie neurobiological processes shared between psychiatric disorders

Previous reports on brain co-expression networks, mostly applied to tissue homogenates, have utilized cluster-based strategies for assigning genes to a unique co-expression cluster. This feature is incompatible with the diversity of cell populations and cellular components involved. Single-cell RNA-sequencing provides a finer-grained resolution than bulk tissue when interrogating brain cell types, dynamic states, and functional processes. We uncovered co-expression patterns across different brain cell types by applying tensor decomposition to single-nucleus transcriptomes from the prefrontal cortex of male patients with depression who died by suicide. We identified a gene set differentially co-expressed in inhibitory neurons between patients and controls and enriched for genes associated with major depression and schizophrenia.