26 Aug 2050, 0800h. A glorious summer day. I’m in my office, awaiting my weekly supervisory hour with PGY-VI John Smith, our senior resident in the Department of Integrative and Applied Neuroscience (formerly the Department of Psychiatry). I"m feeling reasonably good, considering today is my 114th birthday. I attribute my nonretirement to a fundamental enjoyment of my work. My wife attributes it to her healthful cooking and her insistence on my daily dose of Cerebrum Silver (the perfect blend of M1 receptor agonists, M2 receptor antagonists, liposome-encapsulated nerve growth factors, etc., etc., as the advert says—the best available for your hippocampus). John comes in, looking beat.
"Wow, what a night. Major problem. For the past 2 days almost around the clock I’ve been working on a very agitated and depressed, female CL on pod 7A . . . ."
"Oh, sorry; that’s the institutional designator for Covered Life. Universal Blue HMO. I’ve only got 2.2 authorized days left on her hospitalization, so I’m really up against it. Anyway, I’ve tried everything in the book—IV serotonin receptor agonists with and without autoreceptor antagonists, combined neurotransmitter manipulation, transcranial magnetic stimulation with and without reticular activating system targeting, etc. Something different almost every hour. The patient’s a classic Type 4 Mesolimbic Depression according to the Diagnostic and Statistical Manual of Neuroscience Diseases, so she should be almost completely remitted by now, but she’s had only minimal responses. I’m trying to arrange for the stereotaxic neurohospitalist to microinject her amygdalas with antisense oligo to CRH mRNA to suppress noradrenergic output from her loci coerulei, but the OR schedule is full for the next 48 hours. What else should I do?"
"John, tell me about this woman. How old is she, etc.?"
"She looks to be in her 30s, 10% of ideal body weight, CNS nuclei structurally intact by high-field MRI, cerebral magnetic fields normal bilaterally, continuously telemetered EEG spectral amplitudes slightly diminished, DNA SNP nanoarray unremarkable."
"As I said, nonresponsive to . . ."
"John," I interrupt, "Let me tell you a story. A true story." John rolls his eyes and settles back for the long haul. He’s been this route with me before.
"Fifty-two years ago, in 1998, I was supervising a resident much like yourself. For about 3 months he had been attempting to treat as an outpatient a depressed woman, single, in her early 30s, who had obsessional thoughts about suicide. She was working for a telephone company, still living at home with her parents, and not dating. She had had only one boyfriend in her life, and that was for a few months in high school. According to DSM-IV, the diagnostic manual available at that time, the patient had major depression and comorbid obsessive-compulsive disorder. The resident had tried three or four oral antidepressants, both serotonin- and norepinephrine-uptake inhibitors, with a partial, transient response to each, but no lasting improvement. He, too, was up against it. Along with the resident, I interviewed this young woman. She was very shy—an attractive person, plainly dressed and with no makeup. She spoke very softly and looked down at her hands resting in her lap during almost the entire interview. I confirmed her life history and the symptoms the resident had told me about. I asked her if she felt any better since she had started treatment, and she said yes, a little. "Have any of the pills helped?" "I’m not sure." I asked her if she liked her doctor, and quickly glancing up at the resident, she replied, "Yes." After some additional conversation I indicated that I had just one last question: "What is the one thing you’d most like help with right now?" The patient looked up at me, right into my eyes, and replied, "I want to get married."
John looks at me blankly. "And the point is?"
"John, there’s an old French saying: Plus ça change, plus c’est la même chose."
"Neither do I, John," I reply softly. "Neither do I. Let’s go talk with your patient."
Address reprint requests to Dr. Rubin, Center for Neurosciences Research, MCP—Hahnemann University School of Medicine, Allegheny General Hospital, 320 East North Ave., Pittsburgh, PA 15212-4772; firstname.lastname@example.org (e-mail).