In their paper, Schwartz and colleagues review the risk factors for depression and suicide in patients with cancer and argue convincingly that screening for depression can be simply and quickly performed. They also delineate the efficacy and potential adverse effects of psychotherapeutic or psychopharmacologic treatments for these patients. Buttressing the identification and treatment of depression in the cancer patient are vital, ongoing scientific developments that flow from an increased understanding of interactions among the brain, endocrine system, and immune system. This rapidly evolving body of neurobiological knowledge has catalyzed fundamental changes in how we conceptualize depression in cancer patients and has important ramifications regarding the treatment and prevention of depressive syndromes in this setting.
HPA Axis Hyperactivity
Indeed, recent advances in biological psychiatry have included discoveries of neurochemical, neuroendocrine, and neuroanatomic alterations in patients with major depression. Such findings include hypothalamic-pituitary-adrenal axis hyperactivity, alterations of the hypothalamic-pituitary-thyroid axis, diminished serotonergic neurotransmission, structural and functional brain abnormalities, impaired sleep architecture, and activation of the immune system.[1]
Although few of these biological alterations have been systematically investigated in medically ill patients, certain effects have been observed in cancer patients with comorbid depression—notably hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis,[2-4] as manifested by nonsuppression of plasma cortisol concentrations following dexamethasone(Drug information on dexamethasone) administration, and increased immune activity, as manifested by elevated levels of proinflammatory cytokines [4].
HPA axis hyperactivity in patients with cancer and comorbid depression is likely due, at least in part, to central nervous system (CNS) hypersecretion of corticotropin-releasing factor (CRF). The preeminent CNS stress hormone, CRF is located in neurons both inside and outside the hypothalamus. Within the hypothalamus, CRF-containing neurons that project from the paraventricular nucleus to the median eminence[5] control the secretion of adrenocorticotropic hormone (ACTH) and beta-endorphin from the anterior pituitary[6]; ACTH, in turn, stimulates cortisol secretion from the adrenal cortex. In addition to its neuroendocrine role in extrahypothalamic circuits throughout the nervous system, CRF also coordinates behavioral, autonomic, and immune responses to stress.
Whether HPA axis hyperactivity (and other neurochemical/neuroendocrine perturbations) influences immune function, cancer progression, and survival is currently a matter of intense scrutiny and debate. Spiegel and colleagues have recently documented that women with metastatic breast cancer who exhibit a reduced diurnal variability in cortisol secretion have not only diminished natural killer cell function, but also increased mortality over a 6-year follow-up period.[7]
Proinflammatory Cytokines
