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‘A biological marker for people at risk for suicide. That would be wonderful’

Interview with Dick Swaab

Dick SwaabThe latest translations of his book are displayed on the table in front of him: English (We are our Brains), Russian, Chinese, Taiwanese…
Brain researcher Dick Swaab has broad interests, but two subjects top his list: depression and Alzheimer. ‘These are the biggest problems society currently faces’. People who are depressed have a supersensitive stress-axis. This makes them overreact to negative events. Moreover, a number of depressed people are at risk for suicide. The question is, which of them? Examination of the brain tissue of people who committed suicide has taught us that the glutamate system in their prefrontal cortex (PFC) shows heightened activity. ‘I now understand why a low dosage of ketamine, which was used formally as an anesthetic, has such beneficial effects in depressive patients who think about suicide,’ says Swaab, who would like to convince psychiatrists of this. ‘Because ketamine inhibits glutamate action.’

Swaab will investigate whether the changes in the PFC also occur in cerebrospinal fluid and in blood. “If this were to lead us to find a marker for people who run the risk of suicide, then that would be wonderful. Literature on this topic has so far not been clear. Fellow researchers using postmortem brain material ignore the fact that suicide takes place on the basis of a psychiatric problem: depression, schizophrenia, borderline. We don’t.” In order to see whether the findings are specific to suicide in depression, he would also like to examine the brains of people with MS who committed suicide or who attempted suicide. In addition to that, he would like to know more about the molecular background of various suicides. “That is totally uncharted territory.”

‘Alzheimer needs a very early intervention’

Swaab’s Alzheimer research focuses on the changes in the brain that show up the earliest: “If you want to stand a chance for treatment you need to be there at the earliest possible stage”. Although the first changes are visible – in the entorhinal cortex and the hippocampus (two brain areas that are important for memory) – seeing them requires a microscope. At that stage people do not yet experience any Alzheimer symptoms. “This may be due to the fact that the brain self-activates, directed by a couple of transcription factors and micro RNAs. We are currently looking into that.”

Swaab wants to know – for the sake of both depression research and Alzheimer research – whether epigenetic factors may be reversed. Do biological or social circumstances in the early stages of life play an important role when it comes to developing disorders? “Do children who suffered neglect or physical and/or sexual abuse at a young age by definition have a lifelong overactive stress-axis? If we discover how this works on the molecular level, we may be able to intervene. We know that bilingualism can delay Alzheimer by four years. How does such an epigenetic change work?” He smiles. “So many questions are interesting in neuroscience!”