Somatostatin Expression Is Associated with Mitochondrial-Related Gene Expression in a Brain Region-Specific Manner:...

Somatostatin (SST) is a critical neuropeptide whose deficiency is implicated in schizophrenia, major depressive disorder, and Alzheimer's disease. Mitochondrial dysfunction is a convergent pathological mechanism in these conditions. However, whether SST expression is associated with mitochondrial-related gene expression in the human brain remains unexplored.

We analyzed the GSE53987 dataset (n = 205 postmortem human brain samples across three regions: hippocampus, pre-frontal cortex, and associative striatum; four diagnostic groups: schizophrenia, bipolar disorder, major depressive disorder, and controls). SST expression was modeled as a continuous variable in linear regression models simultaneously adjusting for brain region, diagnosis, age, and sex. Analyses were performed both across all samples and within each brain region separately. Findings were examined for replication in GSE5281 (n = 161 non-demented control brain samples from six regions profiled by laser-capture microdissection).

After covariate adjustment, SST expression was significantly associated with BCL2 (adj.P = 6.49 × 10⁻⁴), MFN2 (adj.P = 1.76 × 10⁻³), and SOD2 (adj.P = 2.68 × 10⁻³). Brain region-stratified analyses revealed distinct patterns: hippocampus showed associations with SOD2, BCL2, and MFN2; pre-frontal cortex with BCL2, TFAM, ATP5A1, and PPARGC1A; associative striatum showed no significant associations. Analysis of GSE5281 showed similar region-specific SST-mitochondrial gene association patterns, with Superior Frontal Gyrus showing the strongest concordance (8/11 genes significant).

SST expression is associated with specific mitochondrial-related genes in a brain region-dependent manner. These hypothesis-generating findings warrant future experimental investigation of the SST-mitochondria relationship in neural tissue.