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The OCD Amsterdam- Bergen-Worldwide Express

Since 2000 we have a strong brain imaging research line on obsessive-compulsive disorder (OCD) in Amsterdam. Initiated by the department of Psychiatry, but always in strong collaboration with the department of Anatomy and Neurosciences, the brain imaging expertise on OCD at VUmc is an excellent basis for a leading position in the international OCD field.

Text by Odile van den Heuvel

In 2014, we strengthened our international collaborations by starting two great challenging projects: one in Bergen (Norway) and one global initiative with 26 sites from all over the world. Odile van den Heuvel, psychiatrist/associate professor and team leader section Neuropsychiatry (co-leader Ysbrand van der Werf) at the department of Anatomy & Neurosciences, tell us about the OCD achievements of 2014 and the plans for 2015.

The basis at section Neuropsychiatry

Since 2008, Stella de Wit and Froukje de Vries, residents in Psychiatry (GGZ inGeest) and PhD students at the section Neuropsychiatry, worked on various MRI studies in OCD (funded by NWO ZonMW VENI, Hersenstichting NL, NARSAD young investigators’ award to Odile van den Heuvel). They found that the neural correlates of both working memory and response inhibition are good endophenotypes for OCD: both the OCD patients and their unaffected siblings show compensatory task-related hyperactivation of frontal cortices and altered fronto-limbic connectivity (de Wit et al. American Journal of Psychiatry 2012; de Vries, et al. Biol Psychiatry, in press; van Velzen et al., under review). Stella also studied the neural response to symptom provocation, the ability to regulate the provoked emotions and the effects of transcranial magnetic stimulation (TMS) on emotion regulation (de Wit et al., under review). The results stimulate to future studies on the added value of rTMS to enhance the effects of cognitive behaviour therapy (CBT) in treatment-resistant patients.

Imaging the direct effect of concentrated exposure in vivo

CBT, mainly the so-called ‘exposure-in vivo with response prevention’ (i.e. exposure to situations that trigger obsessions with complete restriction to perform compulsive behaviors in response to it), is the ‘golden standard’ treatment for OCD. Unfortunately, CBT therapists are scarce (leading to long waiting lists) and a normal weekly 45-60 minutes session CBT is often too short and infrequent for OCD patients to experience a reduction in anxiety and a change in behaviour, leading to drop-out and non-response. That is exactly why professor Gerd Kvale and Bjarne Hansen (leading the OCD team, Haukeland University Hospital, Bergen, Norway) developed an concentrated CBT. The first experiences are great: good response, little relapse (20%) after follow-up, and very efficient treatments (cure within 1 week!). But, the remaining questions are: what is changing in the neural network function after 1 week of concentrated CBT and is it possible to reduce the relapse rate even further by using D-cycloserine, a partial NMDA agonist. With the combination of their great expertise in concentrated CBT and our expertise in brain imaging, we now have the ideal team to answers these questions. In the 2nd week of January 2015 Odile van den Heuvel (now visiting professor at Haukeland University Hospital) and Stella de Wit will travel to Bergen to help with the pilot scan sessions.

Enhancing NeuroImaging and Genetics by Mega-Analysis (ENIGMA): the strength of data sharing

In 2010, the OCD Brain Imaging Consortium (OBIC) was founded, including scientists from Spain, UK, Brazil, Japan, Korea and the Netherlands, aiming to perform mega-analyses on pooled structural MRI scans of OCD patients and healthy controls. After 3 years of hard work, this resulted in the first great OBIC publication (de Wit, van den Heuvel; American Journal of Psychiatry 2014;171:340-9). We found, that some differences in brain volume become only apparent at later age: for instance the volume of the striatum shows a group by age interaction, indicating that in OCD patients there is a preservation of striatal volume during maturation/aging, in contrast to the normal age-related volume decrease in controls. This suggest altered neuroplasticity as a result of chronic compulsive behaviors in these patients. This hypotheses stimulated some next steps: extension of the study to the full age range of patients, including pediatric samples and elderly, and to combine MRI correlates and genetic characteristics. The idea arose just at the moment that a worldwide initiative started, ENIGMA: Enhancing NeuroImaging and Genetics by Mega-Analyses, lead by Professor Paul Thompson (University of South California, USA). The overall goal is to unite the brain imaging and genomics communities to solve biomedical problems that no one group could answer alone. Professor Dan Stein (Cape Town University, South Africa) and Odile van den Heuvel, proposed to assemble an ENIGMA-OCD working group within ENIGMA, based on the former OBIC members. In less than one year time, 26 OCD expert groups from all over the world joined the ENIGMA-OCD working group. Very recently, Paul Thompson was awarded a NIH U54 grant, making ENIGMA one of the NIH Centers of Excellence funded under the BD2k (Big Data to Knowledge) program. For the ENIGMA-OCD working group (lead by van den Heuvel & Stein), this award enables the appointment of a new member in the team: Premika Boedhoe, who will start as a PhD student in January 2015.