A 52-year-old man comes to the office due to low energy and poor sleep. The patient reports feeling stressed since his divorce last year. He has difficulty sleeping through the night and awakens around 4:00 AM most mornings, earlier than he would like. At work, the patient has trouble concentrating and is becoming less productive. Although he loves his children, he no longer enjoys visiting them on the weekends and makes excuses to stay home. The patient says that food is tasteless, and his appetite has decreased significantly over the last 2 months. Blood pressure is 135/84 mm Hg and pulse is 78/min. Physical examination is normal. Mental status examination shows a depressed and anxious mood, with mild psychomotor agitation. He has no psychotic features or suicidal ideation. This patient is most likely to have which of the following abnormalities?
This patient meets the criteria for major depressive disorder with his evident depressed mood, anhedonia, decreased appetite, early-morning awakening insomnia, low energy, impaired concentration, and psychomotor agitation. Hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in subclinical increased cortisol levels (ie, without signs/symptoms of Cushing syndrome), has been associated with depression. The neurocytotoxic effects of hypercortisolemia may play an important role in the pathogenesis of depressive symptoms and associated cognitive deficits. These effects may also explain the association of stress and trauma with the increased risk for the development of depression.
Other findings in depressed patients include decreased hippocampal and frontal lobe volumes, as well as changes in sleep architecture, including both decreased REM sleep latency (ie, decreased time from sleep onset until the start of the first REM sleep period) and decreased slow-wave sleep (Choices B and F).
(Choice A) Enlarged lateral cerebral ventricles are more commonly associated with schizophrenia.
(Choice C) Lactate infusion can provoke panic attacks in susceptible patients and has been used in research to identify those with panic disorder.
(Choice E) Hyperprolactinemia is not associated with major depressive disorder. It can be seen with antipsychotic drug use due to dopamine antagonism in the tuberoinfundibular pathway.
Educational objective:
Major depressive disorder is associated with hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased cortisol levels.