Current Management of Depression in Cancer Patients

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 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