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Transforming the understanding
and treatment of mental illnesses.

Riya Dange, Winner of the 2020 Three-Minute Talks Competition

Watch on YouTube.

Transcript

Riya Dange: Psychiatric disorders like schizophrenia are often complicated to diagnose and treat because a wide variety of symptoms fall under their umbrella. In addition to core symptoms such as hallucinations, delusions, and cognitive dysfunction people experience symptoms of anxiety and depression at higher rates than the general population. 

We wanted better to understand the genetic and neural underpinnings of these symptoms, so we collected fMRI and genetic data from 765 participants who fell into three categories: patients with schizophrenia, their siblings who did not have schizophrenia, and healthy volunteers. 

On the genetic level we investigated whether patients and their siblings had genetic variation that predisposed them to anxiety and depressive symptoms, and in order to do that we used polygenic risk scores, which are imputed measures of genetic risk for a particular trait calculated from large genome-wide association studies. 

Meanwhile, on the neural level, we assessed whether the brain activity in certain regions was different in patients and their siblings compared to healthy volunteers. And in order to gauge that, we used this emotional processing task and then we analyzed correlations in certain key emotion modulation regions of the brain, including and especially the insula. 

Now of course, the genetic and neural levels don't operate separately. Genes influence neural structure and function, and both contribute to psychiatric symptoms, so we used our analyses on both levels to answer one question: Does brain activity in patients, and their siblings vary as a function of polygenic risk for anxiety and depression? 

And we found that it did; specifically, with the higher polygenic risk for anxiety shown in our participants, the lower activation across four brain regions, the left amygdala, the right and left orbital frontal area, and the left insula. Now patients with schizophrenia showed the strongest negative correlations, while healthy volunteers showed virtually no correlation, unaffected siblings meanwhile fell somewhere in between. 

Now, we also found that same correlation for one brain region with regard to polygenic risk for depression and that was the right insula. Interestingly, the insula was the only region that appeared across both polygenic risk scores. It's been shown to play an important role in emotion modulation and abnormal insula activity has been associated with anxiety, depression, and several symptoms of schizophrenia. 

So, from our analyses at the intersection of genetics and neural biology we were able to conclude that polygenic risk for anxiety and depression modulates in selectivity differently based on schizophrenia diagnosis. These connections open the door to a variety of possibilities including being able to detect these symptoms early in patients with schizophrenia so we can help them seek out and develop personalized treatment strategies. 
We have a lot of work ahead of us, but the possibilities are nothing short of exhilarating.