Although clinical and preclinical studies have shown elevated levels of HMGB1 in the blood and cerebrospinal fluid of patients with Parkinson's disease, stroke, traumatic brain injury, epilepsy, autism, depression, multiple sclerosis, and amyotrophic lateral sclerosis, it is unclear to what extent HMGB1 contributes to the disease phenotype. Here, HMGB1 is linked to depressive disorder.