Anxiety and Depression
Program Committee
Brenda Penninx (program leader)
Eco de Geus (program leader)
Zoltan Bochdanovits
Dorret Boomsma
Peter Heutink
Odile van den Heuvel
Adriaan Lammertsma
Christel Middeldorp
Guus Smit
Jan Smit
Oliver Stiedl
Dick Veltman
Matthijs Verhage
Rationale
Depression and anxiety disorders have a high lifetime prevalence (16% and 10%, respectively) and are associated with substantial morbidity and mortality. According to the World Health Organization depression will be the second most important medical disorder worldwide by the year 2020. Anxiety and depression are considered to be complex brain traits that result from the interplay of multiple genetic and environmental determinants. Part of these genetic and environmental risk factors are likely to overlap; comorbidity is high and both disorders share a number of symptoms in common and can be successfully treated with similar (serotonergic) antidepressants. Within VU/VUmc there is a strong track record in neuroscience research on anxiety and depression in three areas: genetics, endophenotypes, and synapse function. The core aim of this program is to strengthen the research in these areas by building lasting cross-links between them.
Background
Cross-linking genetics and synapse function builds on previous collaborative efforts of the investigators involved. Using the prominent participation of VU/VUmc researchers in large international GWA consortia that detect new genes for anxiety and depression, a pipeline was being build to annotate promising replicated region in humans by cellular screens and animal studies, up to the generation of animal models expressing phenotypes based on newly identified gene defects. The Neuroscience Campus Amsterdam is committed to deliver this pipeline and its annotated genes to the Centre for Medical Systems Biology which intimately connects the Anxiety and Depression research program to the Netherlands Genomics Initiative (NGI), a designated priority area of the Dutch government.
Brain imaging
Full understanding of the genetic (and gene-environmental interactive) pathways to mental disorders needs to show how genetic variation can influence the structure and functional responsiveness of the prefrontal and limbic brain structures involved in emotion regulation. To do so we will exploit the wide range of brain imaging facilities available at the VUmc to examine brain correlates of anxiety and depression: structural and functional MRI, MEG, PET, TMS as well as the more classic facilities like EEG (for a complete overview see the Brain Imaging program). SPECT facilities are available through collaboration with the Amsterdam Medical Center.
Executive Summary
The overall aim of the anxiety and depression program is to identify genomic regions and gene variants that mediate vulnerability to these affective disorders; to understand this vulnerability at the synaptic and brain systems level; to determine their interaction with age, sex and environmental challenges; and to use this understanding to explain the observed patterns of brain activity of behaving humans. Ongoing research has already linked clinical outcomes to neuroanatomy of postmortem tissue, autonomic nervous system and Hypothalamus-Pituitary-Axis function, serum markers such as vitamin D, inflammation, and (f)MRI traits, as well as receptor characteristics obtained from GABA-ergic (flumazenil), dopaminergic (raclopride), and serotonergic PET ligands. By cross-linking these, and other novel endophenotypes to newly detected genetic variants for anxiety and depression the program will uncover part of the actual pathways from ‘molecule to mind’ for these afflictions.
Future Perspectives
Translational targets are improved diagnostics and prognostics, and stronger evidence-based and personalized therapeutic intervention. The program will provide new insights into pathophysiology of depression and suggest previously unsuspected etiologic pathways for these diseases. This will translate into better care for patients by
- improving early detection of individuals at risk, which is a critical concern for clinicians
- identifying new therapeutic targets
- developing targeted interventions based on genetically defined risk.
