Dysregulation of dopamine receptors linked to suicide, study finds

New research published in Neuropsychopharmacology suggests that an imbalance of dopamine receptors in certain regions of the brain is associated with suicide.

In the study, researcher analyzed brain tissue from 34 deceased individuals. Half of the subjects had died from suicide, while the other half had died from other causes. The researchers examined the individuals’ striatum, a dopamine-rich region of the brain involved in processing rewards.

PsyPost interviewed the study’s corresponding author, Megan L. Fitzgerald of Columbia University. Read her responses below:

PsyPost: Why were you interested in this topic?

Fitzgerald: Suicide is the most devastating endpoint of any psychiatric disease, but it is very difficult to study. There are no animal ‘models’ of suicide, and it is impossible to know in advance if a person will take their own life. Therefore, the best way to currently study the neurobiology of suicide is to conduct postmortem research on the brains of people who have died by suicide.

In this study, we used a technique called autoradiography, which is a fully quantitative and anatomical approach, to determine if levels of proteins and receptors in the brain differ in suicide.

What should the average person take away from your study?

For a long time, many researchers and physicians hypothesized that suicide and depression could be affected by altered levels of dopamine or dopamine receptors in the brain, because of dopamine’s significant effects on mood. However, a number of studies, including ours, showed no change in the overall levels of dopamine transporter or dopamine receptors in major depressive disorder or suicide.

What is unique about our study is that we looked at two different dopamine receptors (D1 and D2 receptors) as well as the dopamine transporter in tissue from the same brains. This let us examine not only the absolute binding levels but also the correlation between dopamine receptor binding levels in the same individual. When we did this, we found an imbalance in dopamine D1 and D2 receptor binding in suicides. This is important because it indicates that non-depressed people may be able to regulate the relative expression levels of these two types of dopamine receptors, but that depressed people who commit suicide may not do so effectively.

Are there any major caveats? What questions still need to be addressed?

Yes, there is a major caveat to this work. Although the individuals in our study were not on anti-depressants at the time of their deaths, many of those who died by suicide had been on anti-depressants at some point during their lives. These medications might, in the long term, alter dopamine receptor binding in the brain. Therefore, it is difficult to truly determine whether the imbalance in D1 and D2 receptors in suicide is due to depression itself or a lifetime of treatment with antidepressants. This question should be addressed in the future, perhaps using mouse models or PET studies.

Another important question that needs to be addressed is: What makes some individuals with depression more susceptible to suicide? The majority of the suicides in our study suffered from major depressive disorder. Therefore, in this study, we were not able to tease apart any possible brain differences between suicide and major depressive disorder. We are currently addressing this by adding to our studies a group of individuals with major depressive disorder who did not die by suicide.

Is there anything else you would like to add?

Yes. Our data also hinted that adversity in early life, such as abuse or neglect, could cause changes in the relationship between the dopamine transporter and the D1 receptor. This finding recalls the idea that life’s early circumstances can alter the function of the brain in a way that endures even after the hardship has passed.

Whether stemming from the environment, or genetics, or a combination thereof, depression and suicide have a very real biological basis in the brain. This study is just a very small piece in the much larger puzzle of how the brain is altered in mood disorders. I hope that these types of studies help anyone reading them understand why depression must be treated like any other biological illness, and help to reduce the stigma for those who suffer.

The study, “Dysregulation of Striatal Dopamine Receptor Binding in Suicide“, was also co-authored by Suham A Kassir, Mark D Underwood, Mihran J Bakalian, J John Mann and Victoria Arango.