randombio.com | science commentary
Monday, November 19, 2018

'Mental illness' is no longer a useful term

Treating PTSD and other disorders will require understanding synaptic plasticity.

A few weeks ago, an ex-Marine in California committed a mass murder using firearms. He was said to have post-traumatic stress disorder. There were also suggestions that “mental illness” is responsible. But what exactly does this mean?

‘Mental illness’ is not a medical or scientific term. Discussions of it are usually accompanied by calls for increased screening and treatment. So, what is actually wanted is for persons suspected of having the illness to be imprisoned and forcibly treated, in effect making the medical establishment an arm of the state. This is a very dangerous thing to suggest.

Artist's impression of mental illness
The fact that there is no objective way of diagnosing mental illness, if such a thing exists, and no generally accepted way of treating it, opens the door for exaggerated claims of effective­ness from advocates of fringe treatments. I've witnessed many of these in my research career—the latest one being a treatment of neurodegenerative diseases using ultrasound, essentially pointing a sound transducer at the patient's head and hoping it cures them—and their record of success is abysmal.

In psychiatry, the track record is even worse. Diagnoses based on personal interviews are not accepted in any other branch of medicine. There is no scientifically valid consensus about how to treat a mentally ill subject, and no sure way to know if he or she is ever “cured.” Indeed, with such a vague definition, almost any behavior could be construed as evidence of illness. Given the power to do so, Democrats and Republicans would probably lock each other away in mental institutions. This might indeed be desirable, and it would certainly restore silence and civility to politics, but it would be tough to justify scientifically or medically.

This is not to say that things like PTSD and schizophrenia don't exist, or that those who try to help such patients are quacks, as some psychiatrists have claimed, but given our current level of understanding of the brain the best we can do is to tranquilize patients and suppress their hallucinations with drugs and hope for the brain to heal itself.

There are neurological and physical disorders, and maladaptive behaviors and harmful learned responses, and though they often interact, there is nothing in between. The stubborn fact remains that “mental illness” is only a metaphor—the term began as a euphemism, and it remains today in an unscientific netherworld.

PTSD and the DSM-5

Recognition of this fact was why the Diagnostic and Statistical Manual (DSM) was written. Its goal was a modest one: to establish a set of rules so that different psychiatrists could have a consistent set of behavioral criteria, making diagnoses by different professionals consistent with each other. It purports to be a medical manual, but very little of the guidance in the DSM is based on scientific evidence.

As everyone who's ever used a firearm knows, there is a world of difference between consistency and accuracy. When I first used a firearm as a nine-year-old kid, being instructed by my father, I achieved a high level of consistency: every shot I fired at the target landed, I was told by my amused dad, somewhere on the same side of the planet as the target.

In terms of accuracy, my shooting was no better than the DSM, which gives PTSD a botanic-sounding number (PTSD's is 309.81), and provides diagnostic criteria. The criteria are purely subjective, which is to say based on phenomena reported by the subject: he or she has “recurrent, involuntary, and intrusive distressing memories of the traumatic event(s)”, “recurrent distressing dreams”, and “marked physiological reactions to internal or external cues that symbolize or resemble” the event.

This definition makes sense, but the subjective criteria create challenges in distinguishing real PTSD from such things as the need for “trigger warnings” among oversensitive college students. Distress reported by a patient, however real, need not correlate with pathological severity, and could even be caused by something entirely unrelated to the symptoms the patient reports.

The consolation is that treating PTSD when it's misdiagnosed does little harm. But even though we no longer permit lobotomization, not all treatments out there are harmless.

So it falls on deaf ears when a commentator writes, as one did a couple weeks ago, that

More aggressive diagnostic and treatment programs and legal mandates for treatment need to be creatively developed and implemented aggressively in our communities. . . . A mentally ill person who attempts or overtly threatens violence should have his civil rights suspended. Immediate psychiatric and psychological evaluation and a treatment plan must occur.

Before such drastic actions could be contemplated, we must have a way of diagnosing it accurately and treating it. One reason we have no cure for Alzheimer's, for instance, is that there is no sure way of measuring it. All we can do is give cognitive tests and PET scans, both of which measure something that may or may not be related to the disease. If something that is clearly neurological and uniformly fatal is so hard to identify, how much harder for something that is not a disease at all, but a natural response to a traumatic environment?

(One of my pet peeves, by the way, is people who say, every time a new diagnostic test is invented, that the test is useless if there's no cure. Without a test to tell us if a treatment is working, finding a cure may never happen.)

But suppose we take an accurate diagnosis for granted. What treatments are there?

Treatments for PTSD

There are two general types of treatment for PTSD: psychological (cognitive behavioral therapy and eye movement desensitization and reprocessing, aka EMDR), which aims to erase the learned response, and biological treatments, which aim to heal the neurons.

One of the strangest new ideas is photobiomodulation, a form of light therapy advocated by Michael R. Hamblin at Mass General[1]. The idea is to shine a red or near-infrared LED (15 mW/cm2) or laser (700 mW/cm2) at the patient's forehead. Hamblin hypothesizes that light inactivates nitric oxide, a powerful oxidizing molecule, in the patient's brain, and helps the mitochondria produce more energy in the form of ATP. It's also claimed that it increases blood flow, presumably by heating. The problem, of course, is that the skull is nearly opaque at these wavelengths: at 810 nanometers, only between 0.45% and 4.2% of the light gets through, far too little to have much effect, so there is a certain amount of skepticism about this technique.

Hamblin also claims that infrared light can treat traumatic brain injury (TBI). The patient wears goggles to prevent eye exposure. TBI is the biggest cause of epilepsy in people between ages 15 and 24, and phototherapy slightly increases the risk of seizures[2]. This does suggest that it might be doing something, but whether it has anything to do with nitric oxide or mitochondria, and whether it can really treat TBI and PTSD as claimed, is, at this point, mostly speculation.

As Flandreau and Toth point out[3], since diagnosis of PTSD relies on a patient interview and the DSM's description is a “moving target,” even creating a good animal model of PTSD is a challenge. So, cognitive therapy and desensitization have the upper hand at the moment.

Is PTSD a form of TBI?

It turns out that PTSD and TBI have many things in common. Some of this may be that getting a concussion is psychologically as well as physically traumatic. But some researchers now suspect that there's a pathophysiological overlap as well[4]. Blast and impact forces to the brain can cause chronic neuroinflammation. Animal studies show that chronic stress, such as that produced by repeated social defeat, also causes neuroinflammation.

Would something as simple as taking an aspirin, a non-steroidal anti-inflammatory drug, treat PTSD? We'd be lucky if it were that simple. Other parts of the neuroendocrine system, such as glucocorticoid receptors and hormones such as GH, ACTH, and TSH, are likely also involved. But another theory says it all comes down to neurotransmitters in the brain.

The theory is that regulation of catecholamine neurotransmitters, such as noradrenaline, is messed up in PTSD. In support of this, clinical trials of prazosin, an α1-adrenergic antagonist often used as an antihypertensive, showed some promise when given at high doses (16 mg/day). However, the fact that such high doses were needed is a red flag to pharmacologists that the effect could be nonspecific, so the results are unclear.

Neurologic treatments

One place to look is the brain's fear center, called the amygdala, and the hippocampus, which is involved in spatial memory. MRI studies show that these two brain structures are smaller in maltreated children and adults with PTSD, which suggests that these regions lose cells under conditions of extreme psychological stress[6].

Another treatment is vagus nerve stimulation coupled with extinction training, where the subject is exposed to conditioned PTSD cues while the vagus nerve, which reduces heart rate and sends many signals back to the brain, is stimulated[7]. This increases the extinction of PTSD-like symptoms in animals. The idea is that PTSD is a conditioned response, and vagus nerve stimulation feeds back to the parts of the brain called the basolateral amygdala, infralimbic medial prefrontal cortex, and noradrenergic locus coeruleus, relying on neural plasticity to decouple the memory from the emotional response.[8]

What else can be done for PTSD? It will be a long time before we fully understand the brain, but it looks like PTSD is a lot like phantom limb syndrome, where synapses in the brain have gotten miswired. This happens because of synaptic plasticity; if so, synaptic plasticity must be used to re-wire those connections.

So far, though, these treatments are experimental. It is far too early to think about forcing treatment on PTSD sufferers. Anyway, if an effective treatment is found—one that's backed up by a real, statistically valid double-blind clinical trial rather than over-optimistic press releases—they will come. They are, after all, not crazy.

1. Hamblin MR (2016). Shining light on the head: Photobiomodulation for brain disorders. BBA Clinical 6, 113–124. (Open access article)

2. Newman TB, Wu YW, Kuzniewicz MW, Grimes BA, McCulloch CE (2018). Childhood seizures after phototherapy. Pediatrics 142, e20180648. https://www.ncbi.nlm.nih.gov/pubmed/30249623

3. Flandreau El, Toth M (2018). Animal models of PTSD: a critical review. Curr Top. Behav. Neurosci 38, 47–68. https://www.ncbi.nlm.nih.gov/pubmed/28070873

4. Hendrickson RC, Schindler AG, Pagulayan KF (2018). Untangling PTSD and TBI: challenges and strategies in clinical care and research. Neurotrauma 18, 106

5. Koola MM, Varghese SP, Fawcett JA (2014). High-dose prazosin for the treatment of post-traumatic stress disorder. Therap. Adv. Psychopharm 4, 43–47. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896131/

6. Smith ME (2005). Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: a meta-analysis of structural MRI studies. Hippocampus 15, 798–807.

7. Noble LJ, Souza RR, McIntyre CK (2018). Vagus nerve stimulation as a tool for enhancing extinction in exposure-based therapies. Psychopharmacology (Berl.) Aug. 8. DOI: 10.1007/s00213-018-4994-5

8. Hays SA (2016). Enhancing rehabilitative therapies with vagus nerve stimulation. Neurotherapeutics 13, 382–394.

nov 19 2018, 7:23 am. edited 9:05 am. last edited nov 27, 2018, 7:48 am

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