What Happens When You’re Born with 80% Less Dopamine Than Usual?

Deep brain stimulation.

Imagine being born with a genetic abnormality that compels you to swear uncontrollably, to hurt those you love, and to compulsively destroy yourself.

This tragic syndrome predominantly affects males, and most of these boys never live beyond their thirties (most die of renal failure). It’s a rare genetic disease called Lesch-Nyhan.

There are no initial clues when a Lesch-Nyhan child is born. But within the first year, the syndrome begins to manifest symptoms. A deficiency in a critical enzyme results in problems such as mild retardation, spastic behavior, and excessive uric acid levels which cause pink-orange, sand-like urine and gout. By age two, Lesch-Nyhan children begin injuring themselves. The most common self-attacks are chewing off the fingers and lips, though some Lesch-Nyhan children will also attack other body parts, even going so far as to remove their own noses and eyes.

A recent exploration by Richard Preston in the New Yorker (Aug. 13) explains how affected children’s basal ganglias have only one-fifth the dopamine levels of the average human brain. This section of the brain plays a role in motor control, higher-level thinking, and impulse control. Children with Lesch-Nyhan will do the very opposite of what you ask them to do, often earnestly apologizing as they do it. They are hyperkinetic – they push too hard, they stop too late. It’s rather like the reverse of Parkinson’s disease. The oldest living Lesch-Nyhan man in the world, James Elrod, says simply that you do something harmful, completely against your will, and then you feel bad about it. Preston recounts how on a particular visit, the man attacked his head in a vise-grip, and then proceeded to apologize profusely as he assisted in prying his own fingers away. And it’s not that those with the syndrome don’t feel the pain of their own behavior; it’s a terrifying and short existence.

Until the 1970s, Lesch-Nyhan sufferers were often diagnosed with cerebral palsy. But a study of rats, in which dopamine levels were manipulated, yielded similar self-mutilation behavior. That got scientists exploring Lesch-Nyhan brains. Though they look just like any other human brain, the circuitry is different and the dopamine levels are weak.

One researcher ponders the implications for free will: is fingernail-biting or cuticle chewing so different from actual biting of tissue and bone, save for intensity? How much of a role does dopamine and the impulse response play in addiction, gambling, compulsion, obsession, or even creativity? And what can this teach us about depression and personality disorders? Scientists are only beginning to unlock the mysteries. Preston writes, “The genome could be thought of as a kind of piano with twenty-five thousand keys. In some cases, a few keys may be out of tune, which can cause the music to sound wrong. In others, if one key goes dead the music turns into a cacophony, or the whole piano self-destructs.”

Deep-brain stimulation has been helpful for some Lesch-Nyhan sufferers, though this advanced technique is risky and does not cure what Poe termed poetically as the “imp of the perverse”. It merely seems to quell it for a while.

References:

The New Yorker: “An Error in the Code”
NIH: About Lesch-Nyhan

Images after the bounce – not for my sensitive readers.

If you’re interested in the full article, I encourage you to buy the issue.