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OBJECTIVE: Depression and neurocognitive function (NCF), particularly executive functioning (EF), have been associated with overall survival (OS) in patients with glioblastoma (GBM). However, the combined effect of depression and impaired EF has not been reported. METHODS: Patients with GBM (n = 102) completed neuropsychological assessment postoperatively (mean = 23.5 days post surgery) including the Beck Depression Inventory-Second Edition (BDI-II) and the Trail Making Test Part B (TMTB). Median splits were used to determine cut-points indicating the presence of elevated depressive symptoms on the BDI-II (BDI-II > 8) and executive impairment on TMTB (demographically-adjusted z-score < -1.7). Patients were stratified into 4 groups: no depression/no EF impairment (-Dep/-Imp; n = 23), depression/no EF impairment (+Dep/-Imp; n = 28), no depression/EF impairment (-Dep/ + Imp; n = 28), and depression/EF impairment (+Dep/ + Imp; n = 23). The Kaplan-Meier method, log-rank test, and cox regression were used to examine differences in survival between groups. RESULTS: Relative to -Dep/-Imp patients (median OS = 22.8 months), median OS in all other patient groups patients was shorter (+Dep/-Imp OS= 16.6, HR 1.71, CI = 0.91 to 3.22; -Dep/ + Imp OS = 14.8, HR 2.13, CI = 1.14 to 3.99; +Dep/ + Imp OS = 10.8 months, HR 4.15, CI = 2.12 to 8.10). The groups did not differ in terms of distribution of RPA class, extent of resection, initial therapy, salvage therapy with bevacizumab, tumor location, history of depression, and psychotropic medication use. While groups differed in percent of patients with KPS = 70-80 and age > 50, neither KPS nor age modified the independent effect of BDI-II and TMTB on OS in cox regression models. CONCLUSION: The presence of depressive symptoms and impaired EF are independently associated with shorter survival in patients with GBM. This retrospective analysis was unable to determine if these factors were independent of tumor molecular markers. Routine neuropsychological assessment of mood and cognition can help refine prognosis and facilitate initiation of psychological and cognitive interventions, which are likely to improve patient quality of life and may extend survival time.