Comments on ‘Gene map for depression’ sparks hopes of new generation of treatments 

by Julia Evans on April 30, 2018

Hello,

I have over the years put this sort of research up for question – see below for those historic posts I can find easily.

The texts on this ‘new’ research linking 14 independent gene locations directly to depression.

1) https://www.nature.com/articles/s41588-018-0090-3

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression by Naomi R. WrayStephan Ripke, & others in the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium: Published in Nature Genetics (2018) : doi:10.1038/s41588-018-0090-3 : Received: 28 July 2017 : Accepted: 14 February 2018 : Published online: 26 April 2018

2) https://www.theguardian.com/science/2018/apr/26/gene-map-for-depression-sparks-hopes-of-new-generation-of-treatments

‘Gene map for depression’ sparks hopes of new generation of treatments

A 200-strong team of researchers from across the globe have mapped the genetic variants that increase the risk of depression  by Ian Sample, Science Editor : Guardian : Thursday 26 Apr 2018 16.00 BST

3) https://www.theguardian.com/commentisfree/2018/apr/29/revolution-in-our-understaning-of-depression-will-be-life-transforming

“What are these genes and what do they tell us about the root causes of depression? ”

This revolution in our understanding of depression will be life-transforming by Edward Bullmore : The Guardian : Sunday 29 April 06.00 BST

The discovery of genes that are linked to the crippling condition throws up exciting new possibilities for its successful treatment

Edward Bullmore is head of the department of psychiatry, Cambridge University and author of The Inflamed Mind (Short Books)

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Positions from which I have commented in the past

– Problems which stopped the drug companies’ research

The problems indicated by the evidence in a Financial Times article – Source:  Health: no room for gloom by Clive Cookson and Andrew Jack, 14 June 2010 :

1)  Drugs cannot be proved to work any more reliably than interventions based on giving recognition.

2)  There is no such thing as a standard depression or normal functioning, so trials to prove effectiveness cannot take place.  Evaluation against normal functioning does not work in the field of psychic distress or mental ill-health.

3)  The effect of taking notice of people’s distress, needs to be taken very seriously indeed.

4) Evaluation fails the test….. drugs have weak “endpoints”.  It is not possible to measure success.

…..

Research by the drug companies has stopped – the detail

See the section – ‘Evidence: The probability that paying attention to human subjects is at least as effective as drugs.’in: Challenges to Government’s principles used to define the care of mental ill-health by Julia Evans on 15thJuly 2010 : Available here

….

Summary: Clinical trials are being abandoned by drug companies in the area of mental ill-health as there is no way to absolutely define symptoms of mental ill-health and there is evidence that giving attention to the sufferers works at least as well as drugs.

…..

The problems indicated by the evidence in a Financial Times article (reference at end of section):

1)  Drugs cannot be proved to work any more reliably than interventions based on giving recognition.

2)  There is no such thing as a standard depression or normal functioning, so trials to prove effectiveness cannot take place.  Evaluation against normal functioning does not work in the field of psychic distress or mental ill-health.

3)  The effect of taking notice of people’s distress, needs to be taken very seriously indeed.  It is the same as the Hawthorne effect.  If human beings pay attention within a relationship of trust to another human being, they start to feel better……  Further, psychopractitioners are trained in working within relationships of trust to either stabilise or change.  Why does the government persecute us?

…..

Drugs are a high-risk area for investment within mental health – it is official.  Science does not give new leads. – extract in italics.

 Several of the largest drugmakers have recently decided to curb or cease research in the field, reducing the funding and expertise available to find better treatments………………..   The withdrawal reflects growing financial pressures on the industry to cut spending on high-risk low-profit areas such as mental health, where there are few new scientific leads in the laboratory and many cheap generic drugs are coming on to the market

……

Evaluation fails the test….. drugs have weak “endpoints”.  It is not possible to measure success. from article

In February Andrew Witty, chief executive of GlaxoSmithKline, said his company would stop work on antidepressants, bringing an end to research……. GSK denied that its decision was related to the public criticism, regulatory scrutiny and litigation over suicidal feelings and other alleged side-effects generated by Seroxat in recent years…… Rather, Mr Witty said there were more promising and productive areas of research…, while antidepressants were “among the most expensive, high-risk” drugs to develop, with weak “endpoints” that made it difficult to measure likely success until late in the development process. AstraZeneca took a similar view a few weeks later, winding down its discovery work on depression and other mental disorders as it pared back in-house research spending.

……. 

AND mental disorders in human subjects are difficult to identify. Extract from article

At the heart of the problem is the difficulty in first identifying appropriate patients to take part in clinical trials and then proving that they do better on the new drug candidate than on placebo (dummy pills). “That is the number one reason why we as an industry are moving away from an area that has an incredible burden of disease,” says Frank Yocca, AstraZeneca’s head of discovery for central nervous system drugs. Clinical trials are particularly hard to organise for antidepressants because, for a start, medical definitions of depression and its severity are not as clear-cut as for most other diseases. In addition, reliable “bio markers”, objective measurements of disease progress such as brain scans or blood tests, are unavailable.

….. 

Everyone, whether on drug or placebo, seems to get better.  AND surprise, surprise, interaction with another human being supports the cure or is essential to the cure.

Then there is the large – and mysteriously growing – placebo effect, which makes it hard to demonstrate statistically that patients taking the active drug are doing better than those on dummy pills. Psychiatrists have long recognised that patients with depression and other mood disorders are susceptible to the suggestion that they will get better. But it is not clear why placebo power should have increased, as analysis of clinical trials over the past 30 years shows it has.

“It would be like invoking magic to suggest that people are becoming more suggestible,” says John Geddes, professor of psychiatry at Oxford University. “The change is more likely to be an artefact of the way patients are recruited to clinical trials.”

Everyone, whether on drug or placebo, seems to get better – “which is catastrophic if you are trying to discover how effective the drug is”, says Prof Geddes, who chaired the depression and anxiety part of the UK Medical Research Council’s recent mental health research review. “Everyone in the field knows that this happens.” So researchers are discussing ways to reduce the problem – for example, dropping placebo-controlled trials and comparing new drugs with the best existing treatments.

……..

Conclusion

There is no evidence that one solution: currently drugs or cbt works better than one human being giving another human being some attention especially if the practitioner is trained and receives regular supervision in working within a relationship of trust.

Source:  Health: no room for gloom by Clive Cookson and Andrew Jack  Financial Times  14 June 2010

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So what are the problems with this research into depression genes? 

On the basis of a quick think, I would investigate 3 areas:

The model of how human beings operate in use by the researcher’s and the relationship between the subject & its body.

Whether there is a control group of a similar number of human beings, who have never had feelings of depression and therefore do not have the 4 genes thought to be causal. This group could also test the effect of being told that the researchers are interested in ‘depression’.

The relationship to who is funding this research. A word, researchers have to prove the research has social benefits before they get funding to play with expensive techniques or machinery.

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Some comments from the 3 articles quoted above

– From Ian Sample, Guardian, 26thApril 2018:

“If you have a lower genetic burden of depression, perhaps you are more resistant to the stresses we all experience in life,” said study senior author Cathryn Lewis, professor of statistical genetics, King’s College London,

Note: this is a professor of statistical genetics. Wikipedia’s definition : Statistical genetics is a scientific field concerned with the development of statistical methods for drawing inferences from genetic data. The term is most commonly used in the context of human genetics.

So Dr Lewis does not have to bother about ‘what is a human being?’, she correlates a with b. What happens between a and b, is none of her business.  She also assumes that the definitions of a and b, are stable and repeatable. So when I am depressed, my body behaves in the same way yours does, and the causes of our depressions are the same. What has made me depressed, is irrelevant, as it is the 44 genes acting in concert which produce depression.

– Guardian 29thApril 2018 : by Edward Bullmore

His opening argument: ‘Depression runs in families, we know. But it is only very recently, and after considerable controversy and frustration, that we are beginning to know how and why. The major scientific discoveries reported last week by the Psychiatric Genomics Consortium in Nature Genetics are a hard-won breakthrough in our understanding of this very common and potentially disabling disorder.

If your parents have been depressed, the chances that you have been or will be depressed are significantly increased. The background risk of depression in the general population is about one in four – each of us has a 25% chance of becoming depressed at some point in our lives. And if your parents have been depressed, your risk jumps by a factor of three.

However, controversy has long swirled around the question of nature or nurture.’

Prof Bullmore’s conclusion : This is telling us that we shouldn’t be thinking about a black-and-white distinction between us and them, between depressed patients and healthy people: it is much more likely that our complex genetic inheritance puts all of us on a continuous spectrum of risk.

My conclusion : The experimenters have proved that we are all at risk, whether we have risky genes or not.  They have no idea whether low risk genes will produce as much depression as high risk ones.

OR

From Psychiatric Genomics Consortium in Nature Genetics  : 2017 : All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

I do not understand how this result refines anything as it implies a continuous risk of depression for us all. The researchers have had much fun and spent a lot of money achieving this result. They have not answered what causes depression nor what is the relation between symptoms of depression and our bodies – may be because the relation is unique to each of us.

– From Psychiatric Genomics Consortium’s text in Nature Genetics  : 2017, the abstract for Genome-wide association analyses identify 44 risk variants and refines the genetic architecture of major depression

Quote : We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology.

So the cause of the higher risk factor could be social, or educational, and our bodies put us at risk. So what is the relation between our body and psychic symptoms of depression? Why does body mass differ? Just because there is a correlation does not mean there is a direct, one on one relation.

– From Ian Sample’s 26thApril 2018, Guardian article :

Jonathan Flint, who studies the genetics of depression at the University of California in Los Angeles said: “Our current treatments for depression are relatively ineffective – roughly speaking, only about half of patients improve – so we really need better therapies.”

So a geneticist asserts that a perfectly adjusted, non-depressed subject is a possible result after treatment in 100% of the cases. All human subjects can be treated and made better. Well – this is the medical model. But is it possible when dealing with depression, anxiety and so on?

– Conclusion of Edward Bullmore : 28thApril 2018, Guardian article :

In short, I believe that a deeper understanding of the genetics of depression will lead us beyond the question we started from: is it nature or nurture, gene or environment? The answer will turn out to be both.

So they have found nothing about what causes depression, mostly because how the thinking, speaking being is related to his or her’s very own body, has not been constructed.

Conclusion

Sigmund Freud, who in his early years as a doctor examined the nervous system in animals, presents a way in which this probably works in The Project for a Scientific Psychology: 23rd & 25th September & 5th October 1895: Sigmund Freud : Information  here. It is a shame the 200 researchers did not read it, before embarking on such an expensive research project based in the absolute certainty that the medical model of a reciprocal relationship between symptoms and their physical manifestation or in this case, psychic symptoms of depression and the 44 independent and significant loci of genomes or genes or something. That there is one cause of depression common to all human beings, across cultures, or even in groups of those defined as obese or those categorised as of lower educational attainment, is not questioned. The researchers have no model what happens in the gap between the 44 independent and significant loci of genes and the subject’s depression. The drug companies gave it up as insolvable – but these researchers need funding to continue expensively relating a to b whilst paying no attention to what happens in the gap.

 

  Julia Evans

Practicing Lacanian Psychoanalyst, Earl’s Court, London

 

Further texts:

Do the ‘evidence-based’ results of brain scanning debunk Freud both scientifically and in the clinic? by Julia Evans on September 5, 2012  or here

Research which aims to understand and prevent adverse effects of psychological therapies – yes, really by Julia Evans on March 8, 2012 or here

Simplification is necessary in research. But it has limitations in providing a grand theory of everything.   by Julia Evans on March 3, 2012 or here

The Government as Sadeian experimenter by Julia Evans on August 17, 2011 or here

Challenges to Government’s principles used to define the care of mental ill-health by Julia Evans on 15thJuly 2010 : Available here

Research and punish – Ethics today : 18th April 2012 : Éric Laurent or here