Two VIDI awards for excellent proposals

On May 30, it was announced that Odile van den Heuvel (VUmc) and Matthijs Brouwer (AMC) each were awarded with a VIDI grant to execute their projects in coming years. Hence Amsterdam Neuroscience acquired 2 out of the 14 VIDI grants awared by ZON MW this year. We congratulate them on this achievements.

Odile A. van den Heuvel, psychiatrist and professor of Neuropsychiatry at the Department of Psychiatry and the Department of Anatomy & Neurosciences (VUmc) will use the VIDI grant of €800,000 for an ambitious lifespan project on obsessive-compulsive disorder (OCD) focusing on the interaction between brain, behaviour and environment.

Obsessive-compulsive disorder (OCD) is a neurodevelopmental disorder characterized by repetitive anxiety-provoking thoughts and ritualistic behaviours. Symptoms often start at childhood and vary across different stages of development and disease. The course of disease is mostly chronic. The hypotheses underlying this research proposal are: 1) that symptoms emanate from the inability to efficiently control emotions and behaviours, due to altered maturation of the prefrontal cortex early in life; 2) that chronic symptoms, by the power of repetition, cause neuroplastic changes in brain function and structure during the course of the disease; and 3) that the plasticity of the brain circuits is a powerful entry to innovate treatment.

The proposal is based on the vision that the field of neurodevelopmental disorders, such as OCD, warrant a lifespan approach to disentangle neural mechanisms involved in cause and consequence of the disorder.

The proposal includes 3 interrelated projects. 1) To uncover vulnerability (and resilience) to disease and the effects of pre/peri/neonatal environmental factors on brain maturation, project A (in collaboration with the Generation R Study in Rotterdam) will focus on neurodevelopment in normal school-aged children. 2) To establish age and disease stage-specific markers of disease, in project B variation in subcortical volume across the lifespan (age 10 to 55) will be related to fluctuations in the concentration of glutamate, the most important player in brain plasticity. 3) To improve cognitive control and the response to behavioural therapy in chronic OCD patients, project C invests in the development of non-invasive rTMS-induced neuromodulation of the brain circuits, by comparing the mechanisms of action of two stimulation protocols.

Age- and disease stage-specific brain markers of disease will lead to innovative prevention and treatment alternatives targeting more specifically the mechanisms of disease in the individual patient.

Matthijs Brouwer, neurologist and senior investigator at the Department of Neurology (AMC) will use the VIDI grant of €800,000 on research aimed at revealing the causes of brain inflammation.

With currently available diagnostic tests, it's difficult for doctors to quickly identify the correct diagnosis in patients suspected of an infection of the brain. In this project he will evaluate new diagnostic tests to identify the cause of disease and speed up time to treatment in a large group of patients.

Encephalitis is a severe inflammation of the brain that can be caused by viruses, bacteria and other microorganisms, or autoimmune disease. The incidence of encephalitis is 5 per 100.000 population per year, the associated case-fatality rate is high (10-20%), and half of surviving patients have neurological or cognitive deficits. The epidemiology is changing due to emerging pathogens, such as tick-born encephalitis.

The current diagnostic methods for encephalitis are insufficient. In a recent prospective pilot study he found that a cause-specific diagnosis was made in only 50% of encephalitis patients. We need better diagnostic methods to improve treatment and prognosis of patients with encephalitis.

The aim of his Vidi project is to improve the cause-specific diagnosis of encephalitis.

In a prospective multicentre surveillance study he will include 4000 suspected encephalitis patients through my existing research network on neurological infectious diseases. He will initiate a pathogen discovery programme using ground-breaking sequencing techniques aimed at identifying new causes of encephalitis. Furthermore, he will go beyond the state-of-the art by using cerebrospinal fluid (CSF) mRNA biosignature analysis to differentiate benign from life-threatening causes of encephalitis. To this end he will set up a surveillance programme collecting clinical data, blood and CSF samples. In addition to the pathogen discovery programme and mRNA biosignatures, he will analyse the diagnostic accuracy of biomarkers, multiplex PCRs and anti-neuronal antibodies.

Matthijs Brouwer: “With my Vidi project I reach for an increase in the proportion of patients with a cause-specific diagnosis from 50% to 70%. Pathogen discovery sequencing will enable us to redefine encephalitis and lead to an array of new research possibilities.”