Translational research into mental disorders

Four Dutch research groups can start work within the ERA-Net NEURON

22 January 2019

Mental disorders are an important cause of illnesses, death and reduced quality of life among citizens in Europe. Biomedical and health research provide important knowledge that can increase our understanding of mental disorders and help to improve the diagnosis, treatment and rehabilitation procedures for these. ERA-Net NEURON is a European network that focuses on disease-related neurosciences. The focus of this call is to facilitate translational research into mental health and mental disorders, such as mood disorders, anxiety disorders, psychotic disorders, autism spectrum disorders and addiction problems.

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With this call, NEURON wants to especially encourage multidisciplinary approaches and translational research proposals that combine fundamental and clinical research. Ultimately, the research must contribute to the development of new strategies for prevention, diagnosis, therapy and rehabilitation. Nineteen research councils from sixteen countries launched a joint call for transnational research proposals about “Mental Disorders”. The total budget is about 12.3 million euros. Dutch researchers are involved in four of the fourteen projects funded. With this, they have realised an extra investment of more than 3.8 million euros. Two research projects have a Dutch project leader.

This is the third time the Netherlands has participated in the research programme of the NEURON network. The participation of the Dutch projects within this call and their funding are being realised by NWO, the Netherlands Brain Foundation, Netherlands Organisation for Health Research and Development (ZonMw) and the Stichting tot Steun VCVGZ.

More detailed information can be found in the news release of ERA-NET Neuron.

Proposals awarded funding

The four proposals awarded funding in which Dutch partners are involved are listed below in alphabetical order, together with a brief description of the research project. The projects have a duration of three years.

DECODE! - Decrypting Cadherin-13 function in cortico-cerebellar circuitry underlying neurodevelopmental disorders!
Dutch partner: Dr Nael Nadif Kasri, Radboudumc Nijmegen (coordinator), in collaboration with Germany, Canada and France

Autism Spectrum Disorders (ASD) are a heterogeneous group of neurological disorders that are characterised by deficits in social behaviour and communication, together with limited, repetitive patterns of behaviour, interests or activities. Recent progress in human genetics has led to the identification of hundreds of genes that are associated with autistic-like behaviour. Recently, rare genetic variations in the protein cadherin-13 (CDH13) were linked to ASD. CDH13 mainly plays a role at the location where neurons communicate with each other: in the synapse. The aim of the project DECODE! is to use mouse models and models with human material to investigate which specific changes in the function of the brain are caused by a CDH13 deficiency. With this approach, we want to obtain insight into which symptoms might be linked to the loss of function of this protein. Ultimately, this will help us to design a targeted treatment for specific ASD symptoms.

MiGBAN - Microbiome Gut-Brain interaction in Anorexia Nervosa
Dutch partner: Prof. Roger Adan, University Medical Center Utrecht, in collaboration with Germany (coordinator), Austria and France

Anorexia nervosa (AN) is a severe chronic disorder. Several studies have shown that the composition of the microbiome (the bacteria that live in the gut) has as an important influence on the development of psychiatric disorders and weight regulation disorders. The fasting associated with AN induces severe disruptions of the microbiome. The aim of this study is to investigate the microbiome associated with AN and to find new treatment possibilities. The microbiome of AN patients with a short disease duration will be compared with the microbiome of chronic AN patients. It is hypothesised that changes in the microbiome of the chronically ill patients will be more severe. Furthermore, polyunsaturated fatty acids and probiotics (living bacteria that are favourable for the mental health) will be administered to patients with the aim of improving the composition of the microbiome. The results in people will be compared with parallel research in rodents to gain a better understanding of the underlying mechanisms.

OPCphrenia - Oligodendrocyte precursor cell dysfunction linked to schizophrenia: from mechanisms towards new therapeutic strategies
Dutch partner: Prof. Steven A. Kushner, Erasmus MC Rotterdam, in collaboration with France (coordinator) and Canada

Schizophrenia is a heritable neurological disorder. The primary symptoms are hallucinations, delusions, and reduced cognition, attention and social function. Previous studies have revealed that fast-spiking inhibitory interneurons, a type of brain cell, play a role in schizophrenia. The brain cells of schizophrenia patients have a less good myelin layer (insulating fatty layer), as a result of which they are probably less effective in coordinating brain activity. Myelin is produced by oligodendrocytes. FSI interneurons also play a highly stimulating role in the development of oligodendrocytes. This supports the suspicion that the dysfunction of FSI interneurons plays a causative role in schizophrenia. The aim of this research is to describe the substances that these interneurons secrete to communicate with oligodendrocytes. A possible therapeutic strategy that will be investigated consists of balancing the quantities of these substances to prevent the dysfunctioning of the oligodendrocytes.

UNMET - UNveiling the MEchanism(s) underlying the switch to mania during antidepressant treatment: The role of glutamate
Dutch partner: Dr Judith Homberg, Radboudumc Nijmegen (coordinator), in collaboration with Slovakia, Germany, Belgium and Italy

Bipolar disorder (BD) is a severe psychiatric disorder that is characterised by the alternation between different moods, such as mania, hypomania and depression. The treatment of BD is difficult due to the opposing nature of the symptoms. Consequently, there is a considerable need for new treatments aimed at the underlying disease mechanisms. A clinical characteristic of BD is the tip from a depressive to a manic state during the treatment with antidepressants. The aim of this research is to use both animal models and people to study the neurobiological mechanisms that underlie this tipping. It is hypothesised that the neurotransmitters serotonin and dopamine cause an increase of the neurotransmitter glutamate in a brain circuit involved with mood. It will also be investigated whether the tipping to mania can be prevented by using existing medication targeted at the glutamate level as a supplement to the treatment with standard antidepressants. This is also potentially relevant for the treatment of BD in the broader context.

More information

Melanie Neijts, m.neijts@nwo.nl, tel: +31 70 349 4033

Source: NWO