Major Depressive Disorder (MDD) is a prevalent psychiatric disorder that has a complex pathophysiology. In this study we evaluate the expression of PARP1 and the downstream alarmin protein high mobility group box 1 (HMGB1) in two brain areas that have demonstrated pathology in MDD. MDD donors were compared to controls. MDD subgroups that died by suicide were also compared to those that did not die by suicide. Immunoblotting to determine PARP1 and HMGB1 protein expression was performed in white and grey matter from the frontal cortex and the hippocampus. In BA10 white and grey matter, PARP1 protein expression was significantly increased when comparing MDD donors to controls. There was no significant change of HMGB1 expression in white or grey matter. In the CA1 region, there was no significant change in PARP1 protein or gene expression. There was also no significant changes of inflammatory cytokine expression in BA10 white matter.