Blood Test for Depression and Efficacy of CBT?

So the science press brief from Northwestern University was widely reported earlier this week, including in the Daily Mail.

Original press brief here:

The same authors of this paper had published a previous one on adolescents, though this latest was on adults.

What I would like to know is, how established are these RNA markers for depression? How have the experts responded to this news?

And how can behavioural intervention effectiveness - like cognitive behavioural therapy - possibly be tested for in advance by a blood test of RNA?

It would really be an great leap forward to have a blood test to diagnose depression: but depression currently is diagnosed in the main by assessing behaviour and whilst I understood depression to have inflammatory origins and therefore biological ones - it seems to me rather too much to hope for that 9 RNA markers might determine not only a diagnosis, but efficacy for a therapy that is largely personalised.

I had hoped that the excellent NHS News - Behind the headlines - team might have covered this one. I hope they still might.

Daily Mail:

Published paper:


14 Replies

  • "RNA markers for depression" imply that some sort of chemical imbalance is causing depression. This might be so in some cases. However, the symptoms of brain overload, lack of sleep and coping with things that provide too much stress are also causes of depression and these are physical and not chemical.

    It is easy to recognise many depressed people by the way they move. An indication perhaps that the way they are using themselves may be causing the depression rather than some chemical.

    The brain is a physical system which obeys the laws of physics and engineering. A fact ignored time and time again by medical consultants.

  • It is often overlooked by people in the medical profession because the brain works through chemical impulses. Obviously things in the real world affect our mood etc. but this is due to the hormone balances in the brain, not 'the laws of physics and engineering.'

  • Many of the hormone balances in the brain are dependant on the laws of physics and engineering. The response of the brain to hormone balances is dependant on the laws of physics and engineering.

    If you look for chemicals you will find just find chemicals. What drives the input and the presence of chemicals and the way chemicals appear and disappear. The driving force comes under the laws of physics and engineering.

    The driving force that is influenced by the electrical impulses and the speed of electrical impulses and how many electrical impulses are synchronised with other electrical impulses.

    The behaviour of materials is not chemical it is physical. Forces generated by muscles are physical. The response to various parts of the body are under the remit of the laws of physics and engineering. The response feeds to the brain according to the laws of physics and engineering. The way the brain computes follows the laws of physics and engineering.

    We feel mood in the body. There is physical behaviour in muscles which show that we have a particular mood. It is this physical behaviour of muscles that we feel that tells us that we have a particular mood. There are proprioceptor response which sends signals to the spines via nerves which then are then sent to the brain. This then has an influence on what the brain computes. This comes under the laws of physics and engineering.

    Blood flow in constricted or dilated arteries comes under the laws of physics and engineering. How fast a blood vessel can dilate comes under the laws of physics and engineering. The restriction of a blood vessels can lead to part of the body or brain not receiving enough nutrient. The response an increase in blood pressure to force more blood though comes under the laws of physics and engineering.

    I will be grateful if you can pick holes in this.

  • That's a really interesting alternative prospective on depression which may well hold some merit because there's so little understood about it, doctors just treat it as a chemical imbalance but we don't know what causes it.

    One thing I didn't realise (which I picked up from the documentary on depression I posted about earlier) is that as well as being a chemical imbalance (lack of serotonin and other chemical neurons in the brain) there's actually a physical change taking place, in that the distance between the receptor sites that these chemicals travel between, widens or the receptor sites shrink, as there's less chemical activity there.

    Looking at the brain of a chronically depressed person, it's like looking at the brain of an aged person or someone with a disease like alzheimer's. It's no wonder in its chronic form, its so physically debilitating. Even just remembering simple things, like to eat, or wash or shave becomes a problem, and you have no energy in your limbs. It's a very weird feeling, like all the life or energy has been sucked out of you.

    On a different but related note, I saw a news report yesterday which said scientists have been analysing what effect using smartphones has on the brain and found some interesting results. They have found that using a smartphone daily for long periods causes physical changes in the brain. The brain is adaptive to physical activities that require repetitive movements, and people who used smartphones showed increased cognitive function in a certain area of the brain and on certain tasks, and more senstitivity in their finger tips and thumbs and control over them!

    I think we need to change how we see the brain, it's got this "plasticity" about it and seems to be a constantly changing organ that adapts to our environment, bodies, habits, lifestyle and stimulus. How these changes occur is still something we don't fully understand.

    How many have experienced this common experience of forgetting a regularly used simple phone number or password, one you normally could remember easily? Once you get it wrong, it's like the brain loses its pathway to where that info is stored and you can't remember it.. you try more combinations and each is wrong. Then finally, after forgetting about it for a while, it comes back to you clear as day like a neural link is restablished firmly, and you think..ahhh of course, that's it, how on earth did I forget!

  • Had the seasonal flu badly this year so the brain was not functioning well enough to reply earlier.

    There is no way of looking at the brain of a chronically depressed person. There are fMRI scan techniques, but I have not seen any reports of these done on a chronically depressed person yet. fMRI scans have a a spatial resolution in the region of 1 to 6 millimetres and a temporal resolution of 1 to 2 seconds.

    There is a branch of mathematics called fuzzy logic. This is based on how the neurons actually behave in the brain when determining the results to logical inputs. This is now a well developed branch of mathematics , unfortunately not studied by the psychiatrists who determine treatments for those who are mentally unwell and have the legal status to do investigations.

    Everything we do is dependant on timing synchronisations between one part of the brain and another. When everything is going well we do not notice how dependant we are on things being synchronised in the right order and at the right time. If the timing synchronisation goes awry we notice it. For example: I unwrapped the cling-film wrapped sandwiches. I put the sandwiches in the bin and the cling-film went into the fridge. Esther Rantzen, when she did this, had the intention of putting the sandwiches in the fridge and the cling-film in the bin. She had not changed the intention. The timing synchronisation of the various muscular movements on automatic were not accurately synchronised to carry out the intended task so another task occurred instead.

    I am familiar with the forgetting of the telephone number situation. There is a branch of mathematics and computing which deals with interrogating databases. In a computer program you compare name with telephone number via a table of names and telephone numbers. The brain to save time has a link of commonly recalled items. If we miss access the link we have to access all the other links first. Timing synchronisation can cause an assumption to be made that name is not in the list of commonly recalled items. Again this is a timing synchronisation problem.

    As you say, our brains are not static there are constantly changing. This requires the ability to constantly learn for ourselves how we actually work. The brain is constantly having to determine if the body is functioning as expected. This takes up a lot of processing power.

    Nutrient is supplied by blood vessels and waste products are removed by blood vessels. At the same time the brain must not over heat.

    Thus there are feedback mechanisms involved which affect how parts of the brain function in response to parts of the brain doing something. Most doctors or consultants never studied feedback mechanisms and do not know what they are. So a lot of useful body responses to stimuli are totally ignored with the result is that the wrong conclusions get drawn.

  • Hi Johnsmith. I am new here, and it is only coincidence that it is two of your posts that have captured my attention. You said you would be grateful if someone could pick holes in your above post. Well I’m no neurophysiologist, but here goes:

    “Many of the hormone balances in the brain are dependant on the laws of physics and engineering. The response of the brain to hormone balances is dependant on the laws of physics and engineering.”

    Actually ALL of the hormones balances in the brain are dependent on the laws of physics. All hormones are chemical, and all chemistry is dependent on physics.

    “The behaviour of materials is not chemical it is physical. Forces generated by muscles are physical. The response to various parts of the body are under the remit of the laws of physics and engineering.”

    I’m not sure what this means. It seems to suggest that some physiological processes can be physical but not chemical. Actually, all physiology is chemical (i.e. bodies are comprised of systems, which are comprised of organs, which are comprised of tissues, which are comprised of chemicals, which are comprised of particles – more or less). I am altering your neurochemistry through the mere act of arranging these words up on your screen. Your cognitive processing of this syntax is a product of complex biophysics. There is chemistry, and therefore physics, at every level of human activity.

    You also insinuate in your previous post that some depressions might be chemical imbalances, but that others are physical. Again, I’m not sure what this means. If you want my view, I would say that all mental states are products of complex biophysics, but it does not therefore follow that any depression is necessarily a ‘chemical imbalance’. As far as I am aware, there is no compelling evidence for a ‘biochemical imbalance’ theory of depression; and good reason to doubt the efficacy of antidepressants as a simplistic remedy in correcting these illusive ‘imbalances’.

    Hope that’s of some interest.

  • Thanks for your reply. I am grateful for you pointing out that you are not sure what the phrase:

    “The behaviour of materials is not chemical it is physical. Forces generated by muscles are physical. The response to various parts of the body are under the remit of the laws of physics and engineering.”


    I suspect I may need to try and improve my wording. I like your term complex biophysics. I am going to read up on the meaning of the word to see if it fits what I want to say.

    "You also insinuate in your previous post that some depressions might be chemical imbalances, but that others are physical. Again, I’m not sure what this means."

    Again it shows the sort of problems I have. I know what I mean, but cannot necessarily use the right words to get across what it is I mean. Your phrasing I certainly agree with.

    To give an example: I have found from experience that if I do not get enough sleep I suffer increased pain. My ability to control my muscles has decreased (muscles are applying pressure to sensitive areas). The increased pain can lead to me feeling very depressed.

    Is the depression from a chemical imbalance or is the depression from the fact that my brain has not had enough required sleep.

    Is the depression from a chemical imbalance or is the depression from a pain overload?

    The pain overload is physical. The loss of ability to control my muscles is from a tired brain. Again physical.

    The brain is designed not to overheat or not to suffer starvation when parts of it are working to capacity. Nutrient is supplied by blood vessals and so an overworking brain in one area may remove so much nutrient that the brain in the areas following may not have enough nutrient to function well and so must be shut down. The shutting down may be depression.

    This is the interplay of my thinking.

    I would be grateful for any suggestions on wording.

  • Thanks for this Johnsmith, I enjoyed reading this post.

    I am no expert here, and probably don’t understand your point well enough to help you explain it better.

    I wonder if you are trying to separate what some psychiatrically-minded professionals might call ‘endogenous’ and ‘reactive’ depression. The former tends to support the idea of the traditional and indiscriminate ‘biochemical imbalance’, whereas the latter describes a mood state induced by life events (not excluding faulty biochemistry , but reachable by psychotherapy). I personally prefer to view all depressions as a complex interplay of biopsychosocial factors, for which individuals need to discover their own unique vulnerabilities and protective factors. For you, it sounds like a regular sleep pattern and good physical health is important. If your physical health becomes compromised, you start to feel low and depressed. I expect social factors such as a valued social role and key relationships are crucial too. For others – due to unique life experiences, psychological/personality, social and/or physiological factors – it might take much more, or much less, to impact on their mood in this way. I personally don’t rate the scientific validity of the ‘biochemical balance’ theory in the first place, or the state of the antidepressant evidence-base, so tend be critical of simplistic definitions and widespread drug-treatment of depression – whilst accepting that some people feel it worked for them.

    Not sure if that helps?

  • Depressions may be a complex interplay of biopsychosocial factors, but there are other things at play which may have a greater influence and never have been looked at.

    The things that have never been looked at is the physics of the brain as an engineering system.

    Here I am thinking of nutrient provision by the blood supply and the prevention of the brain from over heating. There is the communication required between one part of the brain and another to keep every thing synchronised. Another factor is the inputs from the muscular spinal reflex system which may or may not cause information overload. Sleep plays a large factor also.

    Posture is something I know a little bit about. From life experience and mindfulness study I have learnt that unhealthy posture and breathing habits can drive all sorts of mental health problems.

    For example in depression there is a tendency to raise the collar bone and bend the chest. There is tendency to recognise that someone is depressed from there posture and the way they do things. Change the way someone's posture manifests and the depth of the depression changes. The question I have does all the extra energy being put into the bad posture create an overload which requires that the brain shuts done in some parts. The shutting down also leaves to bereavement for lose of function and you are in a nasty cycle. This description is a bit airy fairy and may not be robust but it comes out of my many years of Alexander Technique knowledge and experience. Not sure how this can be robustly tested in a trial. Any ideas.

  • Thanks for this Johnsmith.

    I am afraid my anatomy and physiology, and especially my neuroanatomy and neurophysiology is pretty basic. I therefore have no way of knowing whether there is any mileage in your ideas, or if they are as flawed as trying to explain depression through humoralism.

    I wish you luck.

  • Do you think there might be a correlation between diet/sleep and the hormonal imbalance in the brain being disturbed because the conditions are not right to make the hormones (a deficit in nutritional materials needed or the sleep cycle being crucial, being too short)?

    Or do you think it should be thought of as a more a process that goes wrong locally in the brain itself, more along the lines of a physical disease in which perhaps the genetic makeup of a cell goes wrong and it replicates.. I have a rare condition in my knee (P.V.N.S) it shows you can have a cancer-like disorder with cells genes going faulty and the cells replicating locally in a mutated manner.

    Another explanation is behaviour and the mind itself causing the brain to reduce serotonin production? As a person withdraws from activities, its like a muscle that weakens because it's not being used?

    I think possibly a combination of the first and last explanation, based on the images I've seen of the brain and how the receptor sites physically change (the gap widens and they shrink). But the physical change could be an after-effect to the chemical imbalance or deficit, a normal? adaptive response to a chemical change.

  • When my sleep gets disturbed my ability to remember events decreases and my ability to control how my muscles behave decreases. This has the effect of slowing everything down. With everything slowing down I get less done.

    The slowing down interferes with timing synchronisations and mistakes can occur because the activity was not carried out in a specific order.

    “Cracked” ISBN: 9781848315563 a book written by James Davies Senior Lecturer Social Anthropology and Psychotherapy at The University of Roehampton (London UK) details some of the misleading and dishonest research results that have been presented in Professional Journals and conferences.

    “Bad Pharma” ISBN 978-0-00-735074-2 a book written by Ben Goldacre in 2012 details how drug companies mislead doctors and harm patients.

    In the 6th September 2014 New Scientist there was an article which referred to Diederik Stapel who in 2011 admitted to inventing the data in dozens of psychology research papers.. The New Scientist referred to 24 of Stapel's papers which are known to be fraudulent. The New Scientist in previous editions has referred to Fraudulent results in Scientific papers by other Authors.

    Chemicals such as serotonin production are useful for pharma companies. You can attempt to measure what is present and then produce a compound which will increase or decrease serotonin production. This is a overkill approach which does not look at what physical process is causing the problem in the first place. You then quote: you have this problem. This is caused by this and here is the solution. The patient has only quoted symptoms. The symptoms are assumed to be caused by the events examined in a trial. No checking has been done at all.

    Different causes can produce the same symptoms. Different causes require different treatments.

  • I watched a very interesting documentary about depression the other day, which really opened my eyes to this disease and gave me a whole different prospective on it. I was diagnosed with depression last year after being diagnosed with another life-long physical illness. At the time, I had no idea I was depressed and feared I had cancer or something horribly wrong. I visited the NHS Direct website, checked all my symptoms and realised all the symptoms I was experiencing matched clinical depression, went to see my GP and got a diagnosis.

    I think depression is one of the most misunderstood diseases and yet one of the most common (it's said nearly every adult will experience it during their lifetime to some degree). It's also very costly to the economy as it's an illness that takes months and often years to recover fully from. For some unlucky people with severe depression that is hard to treat, it can mean the end of a career or can prevent you achieving all you should in life. I had depression during the middle of my university studies and also while running a business which suffered greatly so I can sympathise with anyone who has it, especially those who have to support a family and hold down a job.

    Clinical depression, in its worse chronic form can be so bad that it's comparable to any major physical disability. A person literally can't move out of bed, won't dress, eat or wash themselves. And the worse thing is, people think you're just lazy or tell you to pull yourself together and snap out of it. Yet you don't have the physical energy and feel exhausted. Your mind just doesn't seem to function, you're constantly feeling mentally drained and can't focus on simple tasks or think clearly. And you're probably experiencing unexplained pain and aches, a general feeling of malaise.

    More interesting too, due to the nature of depression, you might feel ok in yourself. Quite upbeat mentally some days, and not suicidal or down, but you will experience mood swings and may feel a sense of hopelessness the next day. You may not associate your health condition and symptoms as being depression. Yet you know something is not right. You might think you're losing your mind, or have some other physical illness. Your thinking then becomes rather gloomy and it's a negative cycle you can't seem to break out of, probably you're not sleeping well either. Lack of sleep and not eating regularly begins to take its toll on you physically. You may compensate with comfort eating, caffeine or even stimulating drugs. Often drug-abuse and addictions have an underlying depression cause as people try to self-medicate to feel normal or just find the energy to get things done.

    I would recommend people watch this documentary for a better understanding of depression, both from a patients prospective, and also a scientific one (it shows you how it affects and changes physiology of the brain and why SSRI anti-depressant drugs are an effective treatment in repairing and reversing the damage - despite the negative reputation they have gained). If anyone has a partner or relative with depression, this documentary is worth watching to understand better how you can help them and what they're experiencing.

    Depression is nothing to be ashamed of, it's a serious illness, but there's the 'mental illness' stigma attached to it which makes people reluctant to talk about it or admit they have it even. After watching this documentary, you can see how the illness is not really a 'mental illness' it's got a real physical basis, there's a chemical and physical change taking place in the brain which makes it difficult for the brain to work, and it's a often a genetically linked disease and a degenerative disease - it gets worse over time if left untreated.

    You shouldn't be afraid to go to your doctor, going sooner rather than later is best. I started an SSRI drug called called Escitalopram and the change and recovery I made after 2 months was astonishing. My mother had depression some years before mine and she too took Ecitalopram and recovered quickly too and came off it in a few months. We have spoken to other people it's worked for too, so it seems to be a good medication with minimal side-effects. A little tip I'd like to share with anyone starting an SSRI drug (my doctor agrees with this)...the first 4 weeks are when you experience the worse side effects as your brain has to adjust to the effect of the drug. Some who are sensitive may find to very difficult to tolerate these side effects around others, and may stop treatment. An alternative, is to 'taper up' the dose (the reverse of how doctors usually take you off these drugs!). Start on a very low dose (5mg) and stay at that dose until the side effects go away (which will be very mild) and then increase the dose to 10mg. Then to 20mg if needed. And so on. The process before the drug begins to work may take a bit longer (6-8 weeks instead of 4) but if you need to manage day to day without bad side effects, this approach is a good way that worked well for me. (Check with your doctor though before you adjust the dosage if you're told to start on a higher dose).

    I found taking the anti-depressant at night about 1-2 hours before bed is best, it helps you sleep and the side effects will be less the next day.

    Anyway, here's the link to the depression documentary..

    It's Episode 2 - Deeply Depressed. Those with an Android tablet can watch it there freely by downloading the Viewster app.

  • Depression diagnosis is not always obvious and is not just behavioural. You can have very real physical symptoms too, eg aches and pains, loss of memory, insomnia, lack of appetite..for a doctor or the patient, it may not be immediately obvious you're depressed, as you may feel ok in your mood.

    There's a long checklist of symptoms (many physical) on the NHS Direct website and if you can tick several of those, there's a good chance you're experiencing some form of depression (it does have and take different forms), or perhaps its best to think of it as a spectrum disorder..with chronic clinical depression at the extreme end, and mild depressive episodes at the other which you're able to shake off...but then you can have bi-polar disorder, which also has a depression component to it. Manic depressive persons too that have a tendency to become aggressive, violent or mistrusting of people. Then there's the seasonal affective disorder or (SAD) as it's called, a type of depression linked to winter and possibly linked to a lack of sunlight. A lot of people seem to get that in the winter, and when they move to a warm sunny climate they suddenly feel their spirits are lifted and feel energised. Some respond to sun-lamps even. It's very strange, it's almost like a photosynthesis plant response!

    Whatever form of depression you have, there's a lot to be said for positive thinking and keeping mentally stimulated and busy. It can help a lot. I think you have to think of the brain like a muscle. It needs use and exercise, like muscles as it seizes up. Even a person who has surgery has to exercise their muscles to aid recovery, so it is with depression I think. The stimulation and recovery can take different forms, maybe arts, or reading/writing, playing mentally challenging games, or learning a new hobby like programming.

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