The investigation of the impact of Bipolar Manic Depression (BMD) on the progression of diseases in patients with glioblastoma

Bipolar manic depression (BMD) affects ۰.۸–۱.۲% of the global population and is associated with a lifelong burden of mood instability, pro‑inflammatory immune profiles, and dysregulated stress‑hormone axes. Glioblastoma (GBM) remains the most lethal primary brain tumour, with a median survival of ۱۲–۱۵ months despite maximal therapy. Emerging clinical observations and preclinical models suggest that a pre‑existing or tumour‑induced BMD may accelerate GBM progression. This review synthesises evidence from clinical, epidemiological, genetic, and mechanistic studies to examine whether BMD acts as a disease accelerator in GBM. We analyse three intersecting pathways: (i) neuroendocrine – chronic HPA‑axis overactivity and glucocorticoid resistance, which impair anti‑tumour immunity; (ii) immuno‑inflammatory – elevated IL‑۶, TNF‑α, and CCL۳ suppression that fosters an immunosuppressive microenvironment; and (iii) genetic – shared susceptibility loci (e.g., PDE۴B, ANKRD۵۵) that simultaneously increase bipolar risk and predict worse glioma survival. Behavioural factors, including treatment non‑adherence and delayed diagnosis, further compound the clinical picture. The review also critically examines the dual role of mood stabilisers and antidepressants, which may exert conflicting direct anti‑tumour effects (e.g., lithium enhances temozolomide cytotoxicity in vitro and in animal models) while risking adverse drug–drug interactions and mood destabilisation. We conclude that bipolar manic depression is a plausible, multi‑factorial accelerator of glioblastoma progression. Future prospective cohort studies and integrated psycho‑oncology trials are urgently needed to establish causality and to develop personalised monitoring and treatment strategies for this exceptionally vulnerable patient population.Bipolar manic depression (BMD) affects ۰.۸–۱.۲% of the global population and is associated with a lifelong burden of mood instability, pro‑inflammatory immune profiles, and dysregulated stress‑hormone axes. Glioblastoma (GBM) remains the most lethal primary brain tumour, with a median survival of ۱۲–۱۵ months despite maximal therapy. Emerging clinical observations and preclinical models suggest that a pre‑existing or tumour‑induced BMD may accelerate GBM progression. This review synthesises evidence from clinical, epidemiological, genetic, and mechanistic studies to examine whether BMD acts as a disease accelerator in GBM. We analyse three intersecting pathways: (i) neuroendocrine – chronic HPA‑axis overactivity and glucocorticoid resistance, which impair anti‑tumour immunity; (ii) immuno‑inflammatory – elevated IL‑۶, TNF‑α, and CCL۳ suppression that fosters an immunosuppressive microenvironment; and (iii) genetic – shared susceptibility loci (e.g., PDE۴B, ANKRD۵۵) that simultaneously increase bipolar risk and predict worse glioma survival. Behavioural factors, including treatment non‑adherence and delayed diagnosis, further compound the clinical picture. The review also critically examines the dual role of mood stabilisers and antidepressants, which may exert conflicting direct anti‑tumour effects (e.g., lithium enhances temozolomide cytotoxicity in vitro and in animal models) while risking adverse drug–drug interactions and mood destabilisation. We conclude that bipolar manic depression is a plausible, multi‑factorial accelerator of glioblastoma progression. Future prospective cohort studies and integrated psycho‑oncology trials are urgently needed to establish causality and to develop personalised monitoring and treatment strategies for this exceptionally vulnerable patient population.

کلیدواژه ها:

Bipolar disorder ، Glioblastoma ، Disease progression ، Neuro inflammation ، HPA axis ، Cancer survival ، Psychiatric comorbidity ، Drug repurposing