Witte Hoogendijk: the biomarkers of psychiatry
As a professor of biological psychiatry, Witte Hoogendijk searches for physiological and genetic markers of mental disorders. In addition to the story the patient tells, he also tries to find clues in their genes, blood and brains.
‘We want to improve our care for psychiatric patients. In order to do so, we try to find reliable markers that can provide information about, for example, the subtype of the disorder and the way the patient might respond to the medicine we prescribe. My fields of interest are anxiety disorders and depression. For these fields, we search for such biomarkers that characterise patient subgroups, or endophenotypes, using for example differences in gene expression that can be measured in the blood. But we also use imaging techniques to define structural and functional abnormalities in the brain of affected people compared to healthy controls.’
Witte Hoogendijk combined his specialisation in psychiatry with a PhD project on functional changes in the depressed brain. Ever since, he has integrated patient care with neuroscientific research projects. His group collaborates with many other research teams, both within the VU and in other universities within and outside the Netherlands.
Psychiatry arguably is one of the research areas that will be hugely influenced by the technical developments of recent years, for example in high-throughput genetic and biochemical screening and functional imaging of the nervous system. Genome-wide association studies and genome wide gene expression studies helped Hoogendijk and his colleagues to identify a subset of genes that can distinguish people with an enhanced risk of depression from the general population.
‘The studies where we determine gene transcription differences are very promising’, Hoogendijk explains. ‘Measuring the amount of messenger RNA in blood samples of patients is almost as close as we can get to the phenotype. We can directly see the effects of a disorder, for example depression, on the transcription activity, and try to relate that to the clinical phenotype. Another very interesting line of research is the combination of neuroimaging with genetic variation. We try to relate the genetic background of patients to functional differences in their brain activity.’
It will take some time before techniques like genetic profiling will become standard clinical practice in the field of psychiatry, Hoogendijk adds. ‘For over five thousand years, people have been thinking about psychiatric problems. We have seen many theories gain popularity, and then disappear into oblivion again. Biology on the other hand has been steadily moving forward, small steps at a time. Psychiatry is now applying that knowledge. If we can find biomarkers for mental disorders that are reliable and efficient, they will find the way to the clinic. But it might as well turn out that psychiatric disease is too heterogeneous to capture in the rigid framework of biological science. In that case intermediate phenotypes, such as functional neuroimaging or transcriptomic data are needed. The next ten years will tell.’
