NAC – The Amino Acid That Turns Psychiatry on Its Head

November 1, 2018

One of the most intriguing things to me in psychiatry is the push-pull between specific diagnoses and common factors. Are all psychiatric disorders basically the same or are they radically different from one another?

The way diagnoses are made in the DSM-5 (Diagnostic and Statistical Manual, 5th edition) generally gives the impression that each disorder differs from the others in precise ways: a major depression is diagnosed by a person having 5 or more of 9 symptoms for two weeks or more; symptoms, whereas panic disorder, which requires 4 or more out of a dozen other symptoms.

So, if you only have 4 depression symptoms, you can’t be diagnosed as having major depression. And if you only have 3 panic disorder symptoms, you don’t have that diagnosis. Fair enough: You have to draw the line somewhere. But is your 4-symptom depression or 3-symptom panic really different than that of the person who has the full number of required symptoms?

Complicating matters is this: Many people “meet criteria” for having many DSM-5 psychiatric diagnoses at once. You can have panic disorder and major depression — along with social anxiety disorder and specific phobias. Then the question arises: Do you have two, three, or four different problems? Couldn’t your several diagnoses all result from a single problem in your brain, a set of circuits or brain centers with abnormally increased or decreased activity that cause either a few or a lot of symptoms?

This may seem like an almost theological dispute, similar to the question of the number of angels dancing on the head of a pin.

But in the real world it’s not at all trivial. Should you ignore one of the diagnoses—say, panic disorder—and only treat the depression, you’re likely to have a worse outcome than if both conditions are addressed. Yet, similar treatments often work for both conditions. Both SSRI medications and cognitive behavioral therapy (CBT) help depression and panic disorder, though the treatments may need to be customized for each disorder.

On the other hand, some treatments help one condition and not the other. Bupropion is a powerful antidepressant, but not very effective for panic disorder. Whereas lorazepam, a benzodiazepine, helps panic disorder but may be counterproductive in depression. On the third hand, so to speak, if you could identify common circuit problems that underlie a wide range of psychiatric disorders, maybe you could find a single treatment that could help a wide variety of problems. On the fourth hand(!), there’s the possibility that people with one diagnosis—say, major depression—may have any number of different circuit abnormalities, just as your fever of 103 may result from a wide range of bacterial or viral infections, or a host of other causes.

Lumpers vs. splitters

Psychiatry is thus like many other fields: with contending bands of lumpers and splitters. Extreme lumpers contend that there is only one dimension of psychopathology (Caspi). Extreme splitters point out that PTSD from combat differs from PTSD from violent assault, which differs from PTSD from sexual assault, and that each benefits from different treatment approaches.

What does neuroscience have to say? Over the last decade or so, thanks to an initiative sponsored by Thomas Insel, MD, PhD, the former Director of the National Institute of Mental Health, researchers have hopscotched over this controversy by focusing on brain circuits. The Research Domain Criteria (RDoC) initiative of 2008 focused research on identifying brain circuits that may go awry in many different disorders, common abnormalities that may underlie many different conditions.

Overall, the research on brain circuits generally gives support to lumpers: It’s generally the same circuits that go awry in nearly all psychiatric disorders, though perhaps with different emphasis for different disorders.

Which gets me to N-acetylcysteine.

N-acetylcysteine, or NAC, is an over-the-counter compound that can be purchased at your local health food store. As with dozens if not hundreds of other compounds, NAC has its devotees and detractors, its enthusiasts and skeptics.

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Related: NAC – The Benefits of L-Cysteine