Better late than never. Happy and relieved to share a final published version of one of my PhD projects in which we uncovered a fascinating genetic link between language ability, psychiatric risk and creativity. 🧵
nature.com/articles/s41598-022-26845-0
Endophenotypes are at the heart of human genetics research. They not only help discover disease genes, but they can also inform about the disease's pathophysiology, signs, symptoms etc.
Unfortunately in the field of psychiatric genetics, we are not blessed with as many endophenotypes as scientists in other areas such as cardiology, metabolism and immunology are blessed with.
We try to make the best out of the minimum that we are able to observe/measure in the patients. In this project, we look at the cognitive profile of six major psychiatric disorders through the lens of school performance at around 14-17 yrs of age.
14-17 yrs of age is a critical developmental time point in humans as the brain is still developing briskly, and it is when most psychiatric disorders lying dormant within susceptible humans start showing their real face.
Thanks to iPSYCH, a Danish register-based cohort that offers a unique opportunity to link genotypes with phenotypes that span nearly the entire life course of its participants through the extensive linkage to national registers.
nature.com/articles/mp2017196
We asked a simple question. How did the iPSYCH participants (who later in their life developed or didn't develop psychiatric disorders) fare in the school?
Particularly, we were interested in how they performed in specific subjects namely language and mathematics that might require proper functioning of different cognitive domains.
I believe I don't have to convince any of you that some of us are good at math but bad at language, some of us are good at language but bad at math and a lucky few are good at everything, and these inclinations have a genetic basis.
So, what did we find? We found that everyone who had a psychiatric diagnosis (except those with anorexia) performed poorly in mathematics compared to controls (those without disorders). But this might not come as a surprise to most of us.
What was surprising though is that we found no deficits in language grades (Danish and English) in any of the groups except ADHD. Even in ADHD, the language deficits were only modest compared to the magnitude of the math deficits.
Not only we found a lack of language deficits, but in some groups namely ASD, bipolar disorder and anorexia, we also found evidence for enhanced language performance.
And this whole pattern was true even among the controls when you correlate their subject performances with their genetic risks for psychiatric disorders (measured polygenic scores)
Even individuals who never developed any psychiatric disorders (within the follow-up period) but had a high genetic risk for the disorders performed poorly in math and better in language exams.
The contrast was most striking for schizophrenia polygenic risk: individuals with high genetic risk for schizophrenia were very good in language but bad in math and those with lower schizophrenia risk showed the opposite pattern. We replicate this in an independent cohort (TEDS)
So, it appears that psychiatric disorders start disrupting cognitive developments early in life (in some, long before the first symptoms appear). But interestingly they do not disrupt all cognitive domains similarly. Some domains (such as language skills) seem to be spared.
And based on the genetic analysis, we think that, like how all humans lie on a continuum of risk for psychiatric disorders, the impact of the psychiatric risk on cognitive functioning, too, follows a continuum.
So, some of you might wonder how the early tuning of cognitive development by psychiatric risk affects one's life trajectory, for example, in terms of their career choices.
To find out that we did a polygenic risk score analysis in an independent cohort (Million Veteran Program biobank) and uncovered something extremely fascinating.
We found that individuals with genetic tendencies to perform poorly in math but better in the language in school, more often chose a career that requires high creativity skills (writing, acting, singing, dancing etc.)
However, we cannot confidently tell that these individuals took these professions because of their enhanced language skills. It could also be that they simply chose such careers because as they suited well to their poor math skills.
Either way, we were able to show a positive link between psychiatric risk and creativity that is known for centuries and was also shown previously via genetic analysis.
nature.com/articles/nn.4040
To conclude, using an extraordinarily unique genetic resource from Denmark (the iPSYCH cohort), we discovered a fascinating genetic link connecting language ability, psychiatric risk and creativity.
Thanks to my supervisors @DemontisDitte,
@AndersBorglum and all the co-authors for helping me to bring this project to the finish line.