Suicide and depression: what explains the contradictory effect of antidepressants?

October 25, 2023 – Lin Zhang’s doctoral research reveals for the first time that different molecular changes underlie suicide and depression.

Suicide is an important health problem. Globally, around 700,000 people die by suicide on an annual basis. In the Netherlands there are around 2,000 suicide victims annually. There is a taboo surrounding this topic, even though the number of suicides is three times higher than the number of road fatalities. In fact, the number of suicide attempts is 20 times higher meaning that there is a dire need for effective treatments.

In 90% of suicide victims, there are underlying psychiatric problems, such as depression, but also schizophrenia or other psychiatric disorders. Since suicide is so often associated with depression, it is frequently seen as one of its symptoms. However, antidepressants are not effective against suicide. In fact, they may increase the likelihood of suicide in early stages of treatment.

Specific changes related to suicide

On 25 Oct 2023, Lin Zhang, forensic pathologist, has received her PhD cum laude on the thesis ‘Molecular Pathology of Suicide: A postmortem study’. Her work was supervised by prof. dr. Dick F. Swaab (Netherlands Institute for Neuroscience, KNAW) and prof. dr. Paul Lucassen (SILS, University of Amsterdam). The research performed by Lin Zhang resulted in numerous novel findings regarding the molecular changes in the suicidal brain.

Zhang’s research showed that changes in so called ‘purine receptors’ in different brain regions and cell types are associated with the various stages of suicidal behaviour. These stages include suicidal thoughts, single or repeated suicidal attempts or suicide. The changes appeared to be suicide-specific and occurred in suicide by major depression, manic depression, and schizophrenia.

New therapeutic targets

For the first time in the world, the molecular basis of suicide has been examined in the brains of donors from the Dutch Brain Bank who died by legal euthanasia. Molecular patterns related to intense suicidal thoughts were identified. The molecular changes in donors resilient to suicide may serve as the foundation for therapeutic targets. This new research direction at the Netherlands Institute for Neuroscience could lead to the development of novel, effective medications for suicidal behaviour.

Lin Zhang: Molecular Pathology of Suicide: a Postmortem Study. Supervisors: Prof. P.J. Lucassen and Prof. D.F. Swaab. Zhang’s PhD defense ceremony will take place on Wednesday 25 October, at 11.00, in the Aula of de UvA.