Medical research: If depression were cancer (2014)

The big shift that's taking place is the gradual removal of nosology (disease classification) from its pedestal in psychiatry - naming symptoms as the foundation of all practice and services, which no other area of medicine does anymore - and replacing it with a scientific framework for discovering dysfunctional mechanisms at every level from genetic to neural to behavioural. This was started by Thomas Insell / NIMH (named in the article) and has been followed in the EU.

The framework is called RDoC and you should familiarise yourself with it if you've been influenced by psychiatric literature or practice as to your own mental health.

TLDR General argument: https://www.youtube.com/watch?v=PeZ-U0pj9LI

More in-depth presentation: https://www.youtube.com/watch?v=hU_5i2clSKI

Slightly more technical introduction: https://www.youtube.com/watch?v=OyGt8-ddacA

Google Scholar search: https://scholar.google.co.uk/scholar?hl=en&q=rdoc

RDoC @ NIMH: https://www.nimh.nih.gov/research-priorities/rdoc/index.shtm...

RDoC inspired EU project: http://www.roamer-mh.org/

Interested if anyone here has an inside take on RDoC.

It's becoming increasingly taboo to suggest that depression and other mental disorders are not diseases per se but may arise purely from the use of the mind. This in turns depends to some extent on a person's ideas and not solely (or even at all) on the presence of pathogens, tissue injuries, faulty genes, etc (though there may be medical consequences).

There could be important social reasons for this taboo. Perhaps it helps people suffering from disorders to get more practical help and sympathy (instead of righteous indignation, unemployment and ostracism).

However, without intellectual honesty there's less hope in the long term of finding solutions to these problems.

As someone who suffered from a major depressive episode that nearly cost me my life, I certainly acknowledge it as a serious disease no different than cancer.

But thinking of it purely in those terms implies that the development of depression can be attributed and therefore remedied by addressing chemical irregularities in the brain. I used to believe that. It put me under stress and fear that somehow, randomly, because of some defected biological mechanism, I would fall victim once again to another episode.

It took me years to finally understand that that's an oversimplification of a highly complex illness. The chemical irregularities that characterize depression are influenced more so by emotional stresses and the interaction of an individual within the social environment, than say, genetics (it can increase the probability of development, but it needs to be "activated" by the environment). I think the best way to approach depression would be to identify and understand the condition not in isolation, but contextually as a coping mechanism to the stresses surrounding us.

Just like cancer is caused by environmental pollutants, depression is caused by toxic social environments. You learn to be helpless. Shine light there and research funding goes bye bye.

By the way, chemotherapy can cause depression. It's not the "normal" depression associated with the realization that one has cancer, but a deeper depression with a separate cause. It seems people who undergo chemo lose the ability to create new neurons in the hippocampus. The hippocampus is the only place in the brain where new neurons are born throughout our life. Losing the ability to create these cells is causing depression.

I disagree that "depression is as biological as cancer and heart disease" due to the fact of etiology. While it does spring up out of the blue in many cases, for the most part depression appears to be triggered by complex life circumstances. That is not say that it is not a real disease state with a discrete biological basis. It should just be kept in mind that often the most salient things involved in getting someone depressed and getting them out of depression are not biomedical.

It's possible that this is a mostly rhetorical statement by the NIMH head, but I've been disappointed the attitude I see a lot of researchers take towards depression, like it's solely the result of bad gene expression or bad brain connectivity.

On the question of whether "mental illnesses" are diseases or simply arise from behaviour (as discussed in comments below).

My personal theory is that they are neither. Most mental illnesses are actually social illnesses. That is: we've engineered a society that is hostile to a set of (perfectly healthy) behavioural phenotypes.

It's already known that within different cultures and environments, those with certain "mental illnesses" fare better or worse.

Nobody with cancer "thrives" depending on their cultural environment, but if you're an engineer on the Autistic spectrum, you might. If you're an artist with ADHD, you thrive. Even schizophrenics do well in some cultural environments.

Force someone who was born bipolar, or with attention deficit in a society that demands them to sit in an office (or classroom) for 8-10 hours a day, every day, at the same time, and focus on the same thing, and sure... they will become "disordered". Just as most people would go crazy in the sort of fluid or even chaotic environment that those people would thrive in.

* * *

A Thought Experiment:

Imagine you were born into a world where the predominant behavioural phenotype is bipolar or ADHD: there are no set work hours, only goal posts. Teams work in frenzies of 24 - 36 sleepless hours, followed by a day or two off. Maybe one week there's no work, but then for a month it's crunch time. Some days you work nights, some days you work early in the morning. Everyone wears many hats, otherwise they'd become bored; and you're expected to do the same.

To everyone, this is just the way things are. To you... your stress levels are through the roof, you can't focus in such an environment, yet everyone is wondering what's this guy's problem? Why does he have such a hard time working in a fluid environment? Why does he need special treatment and be given evenly-distributed work at predictable hours?

Clearly there's some sort of disorder going on here. So you read some pamphlets and you see a Doctor... maybe there is something wrong with you, you think. It's so natural for everyone else, yet you can barely function in society. Luckily for you, there is "help": the standard treatment for Rigid Thought Pattern Disorder is a 50mc dose of LSD every three days. Sure, it makes you not quite feel like yourself, but look at how much you've been improving since you started treatment! You no longer sleep regular hours like you used to, you're no longer displaying Rigid Thought Patterns. Just give the treatment some time and you'll get used to the side effects.

* * *

I have no science to back this up of course. Just something I think about sometimes at 3 in the morning while I'm having a particularly productive night...

(Yes it's likely that this would be a rather inefficient world in many ways, so it makes sense for the predominant behavioural phenotype to be more predictable and stable. The point being, in both cases the non-neurotypical individual can have a positive impact if they're not regarded as deficient, but if instead we see these differences in behaviour the same way we see differences in height, strength, or any other physical attribute.)

> The problem stems — yet again — from the disorder's fuzzy definition: grouping everyone with a diagnosis of major depressive disorder into one genetic study is like looking for the genetic risk factors for fever, explains Flint. “You would have lumped together autoimmune disease, infection, cancer and a whole set of different conditions.”

This is quite the problem, yes.

But ultimately the perceived intractability and the root cause of the difficulty of investigating this phenomenon is the subjective nature of the reports of the symptoms. Clearly _something_ is up, we can see that from macro-behavioural patterns and cases of attempted suicide -- but these diagnostics are crude.

What is needed are robust bullet-proof objective diagnostics[1][2]. It's great that we've progressed beyond "humours" and "hysterics" and "demons" but compared to other areas of modern medical research we are practically in the stone ages as the article points out.

For instance: we could have genetic, bio-chemical, neuro-chemical, and/or neuro-wiring diagnostics. Any others? Until there is a comprehensive set of biological markers scientists are of course going to be reluctant to research this. It's unfortunate but I can't say I blame them.

And what if the majority of major depressive disorders turn out to be down to wiring? And what about the perfectly natural reactive depression one gets when someone close to you dies or when a relationship breaks up and you lose your partner and/or your kids. Are we now saying that we oughtn't feel this way? And what if the way we've structured society plays a large role in our individual well-being and wellness, what then? What if it turns out to be part of the human condition, as is perhaps the case with existential depression[3]?

Absolutely the best book I've read on depression and suicide is Night Falls Fast[4] by Kay Redfield Jamision, a Johns Hopkins psychiatry professor. It's a few years old now but I don't think that the topics and themes in it will ever date even though the science in it might. It is filled with compassion, it strives for precision. I cannot recommend this book highly enough.

Welcome your thoughts on the matter.

[1] https://www.ncbi.nlm.nih.gov/pubmed/19396703

[2] http://www.newsweek.com/first-blood-test-depression-holds-pr...

[3] http://www.davidsongifted.org/db/Articles_id_10554.aspx

[4] https://www.nytimes.com/books/first/j/jamison-night.html

> genetic studies have come up empty-handed

Perhaps we should focus more on data with a hereditary component (?) This would eliminate depressions that are really sadness caused by life events.

Also, I wonder if clustering techniques have been tried to the fullest in separating genetic data.