First time vertical science, from brain to behaviour through cognition at ESCAP 2015

Ian Goodyer reveals unique research on depression & conduct disorder development

Professor Ian M. Goodyer is one of the Cambridge ‘marriage counsellors’ between neuroscience and youth psychiatry who search for better treatment of depressions and conduct disorders. Neurological and psychiatric researchers at Cambridge University and University College London (UCL) undertake unique, vertical science by executing their studies on the emergence of clinical depression in the human life cycle from brain to behaviour through cognition. As a keynote lecturer at ESCAP 2015 in Madrid, Goodyer spoke about this for the first time to elaborate the collaboration between these two scientific worlds, “that tries to reveal and unravel the interplay on both the neuro and the cognitive level in great detail to understand the emergence of common mental illnesses in adolescents and young adults.”

Professor Ian M. Goodyer (Cambridge)This ongoing research project is part of the NeuroScience in Psychiatric Network (NSPN) programme that combines neuroscience with epidemiology to identify emergent psychopathologies. Goodyer’s keynote speech will focus on depression in the developing adolescent brain and he will discuss the importance of this mental illness for the individual patient and for public mental health.

Lack of precision
Right before the start of the NSPN collaboration, in 2011, professor Goodyer criticized the lack of precision in current clinical typologies, the absence of standard methods to detect neural pathophysiology and the failure to take a mechanistic approach in randomized controlled trials. This had contributed, he said, to “lack of progress in revealing the nature characteristics and outcomes of severe emotional and behavioural disorders in the adolescent years.”

Optimistic
Today, while finishing the first phase of the programme, all participants appear to become optimistic about their alternative to the imperfect practice of neuro-psychiatric research in the decade before NSPN. Goodyer says: “Neuroscience in psychiatry programmes is now geared to bringing together understandings of brain developments and then the deviations from it, that occur in individuals with common mental illnesses, of which depression is one.”

In what way the NSPN study is different and more precise?
Ian Goodyer: “Neuroscientists have been developing technical skills and applying them to small samples, often of normal individuals over the last decade also to small groups of patients. They have more success in the adult brain, but people have began to realize that many things that have been found in small samples, may not be a true representation either of the normal brain or of the illness brain itself. Now this is an opportunity for us to have a sufficiently large study through different levels to try and bring new understandings to these relationships.”

Quantitative methods
“We are now engaged in trying to formulate the typologies by using quantitative methods of characterizing behavioural components of the disorders, linking those to underlying neural and cognitive systems. Inside depression and conduct disorders are likely many subtypes. We can not get at those subtypes without better behavioural and neural precision inside developmentally sensitive and longitudinal studies.”
“First of all, we need to map the neural characteristics of the developing teenage brain. We are completing that piece of work, led by Ed Bullmore, by imaging three hundred teenagers and young adults between fourteen and 24 years of age on at least two occasions over a six to twelve months period. So we will have somewhere between six hundred and nine hundred images of the changing brain. This design will allow us to map the trajectory of brain development in normal individuals in this age range. Obviously, without a map of the normal development, we cannot easily interpret the abnormalities that are supposedly seen in a depressed brain and mind.”

Understanding change

“This first part of the NSPN study is called ‘Understanding Change in the Adolescent to Adult Neurodevelopment’. Ray Dolan is leading on the parallel study in the same individuals, completing a cognitive battery to characterize mental processes that are occurring at the same time. We are trying to map the mental processes at a cognitive level using modern computational methods. And the final component of this normative study is developing the behavioural precision of their self-reported characteristics, including mood, worry, anti social behaviour, obsessionality and personality characteristics. The individuals in the imaging study are three hundred, the individuals in the cognitive study are about seven hundred and those two subsamples are drawn from 2,300 volunteers who completed the questionnaires.”

“We call this an accelerated longitudinal design because the individuals are selected across age range and then we follow-up only three hundred in the imaging study and about  one hundred in the cognitive study. We can then estimate the two longitudinal trajectories without having to do a full prospective investigation on everybody. And because the images and the cognitive samples are drawn from the 2,300 volunteers, we can also estimate back to the full sample, the relationship with their self-reported behavioural characteristics that we have reformulated into behavioural subtypes using modern mathematical techniques.”

Vertical science
“For the first time we have vertical science, going from brain to behaviour through cognition. We are able to do this because we have this important partnership with UCL. Between Cambridge and University College London we have all the expertise we need.  For the next clinical phase we are lucky that Cambridge has extremely good facilities to do the research on individuals with depressions and early onset psychoses. We are now beginning this next phase with recruiting patients and former patients using the same methods and study design so that we can map the brains, cognition and behaviours of individuals who have had depression and conduct disorder, against the normal map of brain development and mind development that we will get from the normative study. That will be unique science that has not been done before.”

Was it your brilliant idea to do it this way, or were you lucky to find yourself in the ideal circumstances?
“I go for a bit of both… We got this idea from our research in developmental psychiatry, and we also have the circumstance that Cambridge and UCL are uniquely placed to work together because of our partnership in neuroscience skills and psychiatric skills.”

This could not have been done earlier?
“I think that scientists tend to focus on one particular question in a rather conservative way. And the technical abilities were not fully developed until relatively recently. I do not think that psychiatrists have been all that impressed with the application of neuroscience to the subject. These are two different worlds – and it has only been in recent years that the bridge between both worlds is becoming something that both sides are prepared to walk over.”

What kind of clinical implications will this study have, do you think?
“I would like to think that the first result will be that neuroimaging will become an important tool for clinical decision making. So patients with depression, early onset psychoses and behavioural problems will be able to have scans of their brains and tests of their mental functions that will actually contribute to clinical decisions of their treatments and their management. Many subjects have this, but we do not. Then at least clinical scientists will be able to move the subject along at the patient level and ask exactly how these kinds of techniques – knowing what we will hopefully know by then – will assist them in choosing psychological and pharmacological treatments. And being able to observe the course of the disorder by repeated scanning over the duration of therapy.”

Not ambitious enough
“That is perhaps very ambitious, but I think that one of the patterns in psychiatry – and perhaps a little bit in neuroscience too – has been that we are not ambitious enough. We have not been able to persuade funding bodies and indeed governments of our ambition. And that has made it awkward for governments to get behind and support mental illness in general.”
“My personal motivation in this was how our colleagues in cancer medicine over forty years completely changed the perception, the government approaches and the funding approaches to their subject. They were highly successful and it has benefitted patients enormously all over Europe and in many places in the world. We need to take this lesson seriously and get more ambitious.”

And speak the language that governments will understand?
“Correct. And I do not think that academics are particularly strong at that.”

The urgency
So what is the urgency, put into words that governments will understand?
“Depression is the second most lethal disorder behind lung cancer for men in the UK and probably worldwide. It is around the fourth biggest lethal illness for women. So if mortality is important, government strategies regarding depression must change.”
Peter Fonagy, from UCL, and I have become very much aware of the importance of talking to the public face of government about mental health. Peter is particularly strong at it. Voicing the urgency of proper research is a priority matter and I hope that over the next few years this will become as important in the minds of clinical academics in mental health as any other aspect of mental health.”
“I am delighted to hear that Norman Sartorius is still so active and that he strongly advocates to educate young psychiatrist in communication, presentation and other policy skills. I fully agree with Norman on that.”

Speaking for the people
“There is another strategy that we need to copy. In the past couple of decades, cancer charities have started to work together. They now become a very important influence on the government in the UK and worldwide. In the UK they developed an umbrella organization called ‘Cancer UK’ and I think that has been the biggest brand influence on government policy, even more so than academics because they are perceived as speaking with one voice for the people.”

Marketing
“Marketing is another naivity in psychiatry. This is partially because small challenges become spokesmen only for themselves – we urgently need to think bigger, get together and be stronger.”
“Organizations like ESCAP were set up initially to create a common ground for a small group of professionals. Today they need to recognize that they may be small, but they can pack a big punch at the policy and marketing level – there is definitely a need for expert help from those who know about these things. Sometimes marketing professionals are prepared to help charities to get started for very little money.”

Professional and careful
“I think that ESCAP should be speaking to the large organizations on an international level such as the United Nations, Unesco, WHO and of course to European bodies like the European Medicines Agency and to organizations who have an investment and a role in the care and the welfare of young people in Europe. I think it is possible to get all this activated and the medium term plan would be that organizations like ESCAP need an arm that is dedicated to this kind of work. This is a bit like lobbying the European Parliament – ESCAP could work with a team of professionals and become an umbrella name for the ones who would lobby on behalf of young people’s mental health research and clinical care. These things should not be done by one country alone, but from the common interest. I have experienced, when I was secretary-general of IACAPAP, that if you do not prepare country representatives for dialogue, you risk factions and disengagements from individuals who suddenly feel that they are put into positions that they had not been able to consider. So this work always needs to be done with very thorough preparation.”

For the common good
What could be the reason for this lack of cooperation on an international level, even between the international organisations themselves?
“Because they have been far too driven by unscientific theory and personal beliefs and perceptions of what works, rather than seeing the bigger prize. This is exactly what ‘cancer’ saw: there will be a much bigger prize if everyone cooperated. Like they did, we should say: ‘Come on, we have to stop this. The organizations are small, they are driven by small values and big, often unproven, ideas and we need to come together for the common good.’ The motivation to do this should be driven by the need to get investment rather than create a new theory. And investment can only come by persuasion at the government and national and international levels. When people are speaking about themselves or their views, that is far less impressive than when they go collectively to speak about the needs of children and young people.”
“The two great hooks – to speak in a marketing phrase – that I have noticed as being successful is that doing something well will cost any nation and Europe  as a whole less money in the long term. Furthermore doing something well will create a positive environment towards those governments by their own people – that is a potential electoral effect. These are things that governments will like to hear. If you do not create that understanding and if you do not appreciate what it is that politicians and civil servants are looking for, then you are blinkered: people will be polite… and then they will turn away.”

Bigger approach
“Child psychiatry has only really begun to generate theory and clinical facts in the last thirty years with incredible work of pioneers like Michael Rutter who have put us in the position we are in now. This next era has to be more detailed and more multidisciplinary than in the past, and we need a much bigger approach. In our age with this vast amount of knowledge and technologies, it is impossible to work with a small team within one faculty like Michael Rutter did."
“To be able to handle this and still have some time left for our own work, we need partnerships. With charities, local authorities, marketing and communication professionals and  working with international organizations in order not to be alone. We need to build these networks to try and get this perceptual change, to get the subject as valid to others and particularly to those who have to make policy decisions.” 

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Read the abstract and view the original slide presentation: "Depression in children and adolescents: a developmental perspective" (Madrid, 2015).

Read more about the NSPN Study.

Read more about Ian Goodyer.