38% of Europeans affected by mental disease

Arguably, one of the most profound findings of 2011 was an epidemiological report on the mental health status of the European Union. Hans-Ulrich Wittchen and his international team of mental health experts have unraveled striking data on just how extensively disorders of the brain impact European society, and if the trend has been changing over the last three decades.   

With an initial goal to systematically assess the prevalence and burden of neurological and mental disorders in the European Union, experts from each disease category met and combined their data, only to find that it was difficult to segregate prevalence between mental and neurological disorders, due to significant overlap. However, it was possible to assess the burden of mental and neurological disease separately, when expressed as disability adjusted life years. Previous knowledge on this subject has been sparse - the World Health Organization reported an estimated 13% of global health burden to be from mental disorders. The World Mental Health Survey quotes that one in three adults suffers from a mental disorder.

Mental and Neurological Disorders Come to the Forefront: Significant Health Burden on Society

Wittchen and colleagues set out to sample all of the EU countries as well as Norway, Iceland, and Switzerland. The team combined retrospective studies, consistent reanalyses of existing epidemiological datasets and supplementary survey data from national experts to gather the best possible comprehensive dataset. 19 epidemiological panels were dispatched and at least one international expert was recruited per diagnostic group. Data was collected as far back as 1980, when the first diagnostic criteria were published on an international level (Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Statistical Classification of Diseases and Related Health Problems (ICD)).
The results were startling: 38% of all Europeans are affected by disorders of the brain. Combined, mental and neurological diseases comprise Europe's largest disease burden, in terms of disability adjusted life years. The highest proportion of this burden was due to anxiety disorder, unipolar depression and insomnia.
Previously, Wittchen and colleagues had published a similar report in 2005, where the numbers were significantly more conservative, citing that 27% of the EU population are affected by mental disorder. However, this study produced a much more restrictive estimate due to age restrictions of the sample (only adults and not kids nor elderly were included), and a much more limited set of criteria for mental disorders. This time around, the team decided to get an unrestricted estimate regardless of age range or disease type.

Wittchen et al., Eur. Neuropsychopharmacol, 2011
Wittchen and Jacobi, Eur. Neuropsychopharmacol, 2005
World Health Organization, The Global Burden of Disease, 2004 Update (WHO, 2008)


By Gina Eom, Alumna MedNeuro 

this article originally appeared in CNS Volume 5, Issue 1, Mental Health Disorders

The DESIRE Project for Epilepsy: Is Collaboration in Science More Efficient Than Competition?

700 million people will have a seizure in their life - that means 1 out 10 human beings. Epilepsy, which can only be diagnosed after a minimum of two seizures (more than 24h apart) is the third most common neurological condition in the European Union following Alzheimer’s disease and stroke.

Despite these facts, the disease is still widely misunderstood and often stigmatizing.  On September 15th 2011, a new piece of legislation entitled the EU Written Declaration on Epilepsy was approved by the European Parliament after being signed by a strong majority of 459 members (out of 751) [1]. The Declaration initiated a change in the funding strategies of the EU: new funds were allocated, and several research projects were created. Today, the EU is handing out 173 million euros that fund a dozen or so European research projects [2]. Among them: the DESIRE project [3].

Epilepsy : a Misunderstood Disease
This enticing acronym stands for “Development and Epilepsy - Strategies for Innovative Research to Improve Diagnosis, Prevention and Treatment in Children with Difficult-to-Treat Epilepsy”. Now that I’m re-reading this I do not think it’s an acronym- if you take the initials of all important words, then remove half of them, you’ll get „DESIRE“. Anyway, the important words here are “children”, and “hard to treat epilepsy”. Epilepsy can hijack the life of people of all ages and it can have many causes [4]. DESIRE focuses on abnormal early (intrauterine) development of the cerebral cortex and its association with epilepsy [4,5]. During neurodevelopment, precursor cells formed in the periventricular region migrate to their correct location where synapses are made and later edited to produce a mature brain. Any interruption of these processes can create cortical abnormalities [5-7]. Most of these malformations have genetic underpinnings, however, environmental factors such as lack of oxygen or intrauterine infection also play a role [4]. These types of epilepsy are difficult to treat because the underlying pathology varies substantially and patients often have severe comorbidities. 

'DESIRE'  FUNDS MORE THAN 250 RESEARCHERS FROM 11 COUNTRIES

The DESIRE project funds the research activities of more than 250 researchers from 25 universities in 11 countries [3]. Since the Charité is one of the partners and DESIRE funds my PhD, I have attended the last four yearly meetings of the project. The last one was in Valetta (Malta) mid-october. I know what you’re wondering and yes, the weather in Malta is beautiful this time of the year. More seriously, it has been fascinating to see the projects evolve over the years. Researchers don't necessarily need a big European project to collaborate and exchange information, but I have personally never seen cooperation between researchers on this scale before.

DESIRE Leads to Scientific Collaboration
Let me explain. One of the eight work packages within the DESIRE project aims to “Identify genetic causes and pathomechanisms of epileptogenic brain malformations”. The first step is to pin down germinal or somatic mutations in patients with a specific type of malformation. Once you have identified a new interesting mutation in a patient you need at least one more patient to be able to claim a possible causality. Since these malformations are extremely rare this can be nearly impossible. In 2014, during the first meeting that I attended, 20-30 researchers and group leaders sat around a table and started exchanging genetic mutations. The amount of information exchanged in one afternoon was overwhelming. In the following years, databanks were created, pools of interesting genes were selected, and samples were sent across Europe to be systematically tested. Today, 150 patients with malformations of the cortical development and 450 with encephalopathies have been included in the project. This led to the identification or confirmation of several mutations (notably in the PIK3/mTOR pathway and in different types of voltage gated sodium channels) [8-10]. In the meantime, samples were analysed in Erlangen (DE) and a pattern of methylation in a specific type of malformation was identified. Epigenetics were previously known to have a role in epilepsy [11] but this was a breakthrough.

Once a mutation is identified, it needs to be tested. Using in-utero electroporation, these mutated gene sequences were introduced into mice, rat, or ferret embryos to create better models for cortical malformations (the latter is a good model for cortical development because it is convoluted like higher mammals [12]). In many cases, the models showed malformations comparable to those observed in patients, and the pathomechanisms could be studied [7], [13].
Every meeting is extremely dense, each member presents the advancement of their project within their work package, even negative results, often before they are published. There is a sense of community; even competitive teams exchange tips and comment on each other’s data. DESIRE ends in September 2018 and it will certainly meet most of the objectives set in 2013. One of the concluding remarks in Malta by Prof Jeffrey L. Noebels member of the Scientific Advisory Committee was that the most impressive work had been done by collaborations between teams within DESIRE. Let us hope this spirit of collaboration will continue on after the end of DESIRE.

by Aliénor Ragot, PhD student AG Holtkamp
This article originally appeared December 2017 in CNS Volume 10, Issue 04, Sleep 

[1] http://bit.ly/2zfet2n/ 
[2] http://bit.ly/2yAAqaU
[3] http://bit.ly/2Am5jBq
[4] http://bit.ly/1wgpTup
[5] Romero DM, Semin Cell Dev Biol, 2017
[6] Fernandez V, EMBO J, 2016
[7] Khalaf-Nazzal R, Hum Mol Genet,2017
[8] Alcantara D, Brain, 2017
[9] Parrini E, Hum Mutation, 2017
[10] Møller RS, Neurol Genet, 2016
[11] Kobow K, Neurosci Lett,2017
[12] Neal J, J Anat, 2007 
[13] Martinez-Martinez MA, Nat Commun, 2016