Prince Hamlet’s Depression and its Neuroanatomical Correlate

“How weary, stale, flat and unprofitable seem to me all the uses of this world!” Shakespeare’s arguably depressed and suicidal Prince Hamlet uttered those words to himself almost five centuries ago. But what if he had confessed them in his doctor’s office today, how would his mood disorder be approached?

Well, in my dream the Prince’s family physician would issue a covered referral to a psychiatrist who would begin by pulling out her “Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)” and asking if he has suffered at least three symptoms from a list that includes, but is not limited to diminished appetite, disturbed sleep, pessimistic thoughts, loss of weight, feelings of worthlessness and decreased sex drive. To which the Prince might answer as he did half a millennium ago, “I have of late, but wherefore I know not, lost all my mirth, forgone all custom of exercises; and indeed it goes so heavily with my disposition…” But our thorough psychiatrist wouldn’t stop there. In addition to this inclusion criteria, she would focus on exclusion criteria, ensuring no evidence of schizophrenia, recent traumatic events or anything else that might explain his mood. Notwithstanding the recent death of Hamlet’s father, she decides to press on.

Because she is trained as a brain scientist, she would order and interpret the results of his functional magnetic resonance imaging (fMRI) studies, and based on decade old studies such as W.C. Drevets et al, she would watch for evidence of decreased activity in a specific area of his prefrontal cortex. Lastly, based on the publications of the psychiatrist and Nobel Laureate Eric R. Kandel that she had come across in her medical school Psychiatric Genetics course, she would genotype the Prince looking for an anomalous locus on the long arm of his chromosome number 18. Assuming a remarkable result on all of these tests, the psychiatrist would reassure the insurance company that while no one of the tests is diagnostic of depression, together they support the supposition that Mr. Hamlet’s disorder is based in part on a verifiable, physical anomaly and therefore treatment should be covered by his insurance policy.

That’s how it goes in my dream. But perhaps the Prince said it best, “A dream itself is but a shadow.”