Association between polygenic risk for schizophrenia, neurocognition and social cognition across development

Abstract

Breakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8–21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk. Schizophrenia polygenic risk was estimated for each participant based on summary statistics from the most recent schizophrenia genome-wide association analysis (Psychiatric Genomics Consortium 2014). After correction for multiple comparisons, greater schizophrenia polygenic risk was significantly associated with reduced speed of emotion identification and verbal reasoning. These associations were significant by age 9 years and there was no evidence of interaction between schizophrenia polygenic risk and age on neurocognitive performance. We then looked at the association between schizophrenia polygenic risk and emotion identification speed in the Harvard/MGH Brain Genomics Superstruct Project sample (695 participants ages 18–35 years), where we replicated the association between schizophrenia polygenic risk and emotion identification speed. These analyses provide evidence for a replicable association between polygenic risk for schizophrenia and a specific aspect of social cognition. Our findings indicate that individual differences in genetic risk for schizophrenia are linked with the development of aspects of social cognition and potentially verbal reasoning, and that these associations emerge relatively early in development.

The neuroimaging and genetics of emotion perception in schizophrenia

“…Recently, a large polygenic study has shown that deficits in emotion recognition are significantly associated with SCZ polygenic risk across development, supporting the notion that impaired processing of facial expressions may constitute a link between genetic risk for SCZ and development of psychosis (Germine et al, 2016b). Notwithstanding the important findings from this study, Germine and colleagues utilized an emotion tasks with static pictures as stimuli, consequently decreasing ecological validity and examining different underlying mechanisms compared to naturalistic, dynamic displays of emotion (Arsalidou et al, 2011;Palumbo and Jellema, 2013).…”

“…Emotion perception and the brain networks involved are considered viable endophenotypes for SCZ, encompassing all the features above (Bediou et al, 2007;Germine et al, 2016a;Lavoie et al, 2013;Martin et al, 2014). A meta-analysis by Lavoie et al (2013) has shown evidence for emotion perception ability to be genetically related to SCZ and state-independent.…”

“…However, no imaging polygenic study to date has explored the association between polygenic risk and neural correlates of emotion perception. Notably, a recent longitudinal polygenic study (Germine et al, 2016a), examining the association between SCZ polygenic risk and neurocognition in over 4000 healthy individuals, found the most significant and reliable relationship to be with emotion recognition ability. Germine and colleagues (2016) concluded that emotion recognition represents a potential link between genetic risk for SCZ and the development of psychosis, highlighting the significance of emotion perception as an endophenotype.…”

“…Meanwhile, genetic studies have identified SCZ common risk variants to be related to emotion perception deficits across development (Germine et al, 2016a) and to abnormal emotion perception neural circuitry (Curcic-Blake et al, 2012;Mothersill et al, 2014). In this thesis, I expand on the current literature by investigating naturalistic emotion perception and the underlying aberrant neurophysiological factors in SCZ.…”

“…Robust evidence has emerged identifying emotion perception as a viable endophenotype for SCZ, as deficits in emotion perception are heritable, associated with SCZ risk genes, and apparent before illness onset (Bediou et al, 2007;Germine et al, 2016b). It is thus of importance to investigate the specific processes and neurobiological underpinnings of emotion perception and their relationship with risk genes, as such research would lead to a clearer understanding of the pathway from genotype to clinical phenotype.…”