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When "Mental" Illness Isn't

Neuroskeptic iconNeuroskepticBy NeuroskepticDecember 22, 2012 10:08 PM


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There's a theory that 'psychiatric diseases' like depression and schizophrenia aren't diseases because they're not diagnosed on the basis of any kind of biological abnormality, but purely on symptoms - unlike 'real' diseases like cancer and AIDS. Now, in my view there's quite a bit of truth in that - but there's also a serious flaw in the argument. Sometimes, disorders diagnosed on the basis of psychiatric symptoms do turn out to have had a clear biological cause. So the original diagnosis of a psychiatric disease was correct: there was indeed a disease. This is happening more and more often now because of biomedical advances. A group of German neurologists and psychiatrists recently wrote about a case of a man diagnosed with bipolar disorder:


In February 2009, a 28-year-old presented to our clinic with a first episode of depression. He reported depressed mood, anhedonia, decreased drive, reduced alertness and concentration. The symptoms responded well to quetiapine 100 mg. Fourteen months later, a first manic episode with logorrhea [excessive speech], aggressive and disinhibited behavior occurred... it completely remitted after treatment with quetiapine 1000 mg. A diagnosis of bipolar I disorder was made. Two months later, the patient presented with another depressive episode... Despite treatment with quetiapine, aripiprazole, lithium, valproate and escitalopram, the patient did not improve...

So far, seems like a fairly typical case of bipolar. However, it turned out that...

Neurological examination was remarkable for extrapyramidal symptoms with left-sided rigor and bradykinesia [slowed movements]. On initial and concurrent magnetic resonance imaging (MRI), numerous subcortical lesions in the frontal lobes were detected... Screening for autoimmune antibodies detected NMDAR antibodies.

It turned out the patient had autoimmune encephalitis: his body was generating antibodies that blocked the brain's key NMDA receptors; the drug ketamine blocks it too. Treatment with immunosuppressant drugs was started and he recovered fairly quickly. For a first-hand account of the disease, in which it was also diagnosed as a psychiatric disorder initially, see the recent book Brain On Fire. Now, let's imagine that this had happened in 1960. What would the guy's story have been then? He'd have been seen by a psychiatrist and diagnosed with bipolar, just as he was today. Depending on how severe the depression was, and whether or not he had any more episodes, he might well have ended up in a psychiatric hospital. But he probably wouldn't have been diagnosed with a neurological disorder. He'd have tested negative for all the neurological diseases known at the time. No-one tested for NMDA antibodies back then, because NMDA receptors weren't even discovered until 1981. It's true that his neurological exam showed a movement disorder (left-sided rigor and bradykinesia), but this might well have been written off as a side effect of the high dose antipsychotics he was taking, which cause similar movement disorders. 50 years ago this guy, and many others like him, could well have ended up committed to an asylum. 100 years ago, I think it would have been almost certain he'd have been deemed 'insane' and locked up at some point. If so, some of the people in psychiatric hospitals 50 or 100 years ago will have had this disease - or others. And if we didn't know about anti-NMDA encephalitis until recently, who's to say what we'll discover next?


Choe CU, Karamatskos E, Schattling B, Leypoldt F, Liuzzi G, Gerloff C, Friese MA, and Mulert C (2012). A clinical and neurobiological case of IgM NMDA receptor antibody associated encephalitis mimicking bipolar disorder. Psychiatry research PMID: 23246244

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