Association between schizophrenia polygenic risk and neural correlates of emotion perception.

The neural correlates of emotion perception have been shown to be significantly altered in schizophrenia (SCZ) patients as well as their healthy relatives, possibly reflecting genetic susceptibility to the disease. The aim of the study was to investigate the association between SCZ polygenic risk and brain activity whilst testing perception of multisensory, dynamic emotional stimuli. We created SCZ polygenic risk scores (PRS) for a sample of twenty-eight healthy individuals. The PRS was based on data from the Psychiatric Genomics Consortium and was used as a regressor score in the neuroimaging analysis. The results of a multivariate brain-behaviour analysis show that higher SCZ PRS are related to increased activity in brain regions critical for emotion during the perception of threatening (angry) emotions. These results suggest that individuals with higher SCZ PRS over-activate the neural correlates underlying emotion during perception of threat, perhaps due to an increased experience of fear or neural inefficiency in emotion-regulation areas. Moreover, over-recruitment of emotion regulation regions might function as a compensation to maintain normal emotion regulation during threat perception. If replicated in larger studies, these findings may have important implications for understanding the neurophysiological biomarkers relevant in SCZ

Variation of the gene coding for DARPP-32 (PPP1R1B) and brain connectivity during associative emotional learning

Associative emotional learning, which is important for the social emotional functioning of individuals and is often impaired in psychiatric illnesses, is in part mediated by dopamine and glutamate pathways in the brain. The protein DARPP-32 is involved in the regulation of dopaminergic and glutaminergic signaling. Consequently, it has been suggested that the haplotypic variants of the gene PPP1R1B that encodes DARPP-32 are associated with working memory and emotion processing. We hypothesized that PPP1R1B should have a significant influence on the network of brain regions involved in associative emotional learning that are rich in DARPP-32, namely the striatum, prefrontal cortex (comprising the medial frontal gyrus and inferior frontal gyrus (IFG)), amygdala and parahippocampal gyrus (PHG). Dynamic causal models were applied to functional MRI data to investigate how brain connectivity during an associative emotional learning task is affected by different single-nucleotide polymorphisms (SNPs) of PPP1R1B: rs879606, rs907094 and rs3764352. Compared to heterozygotes, homozygotes with GTA alleles displayed increased intrinsic connectivity between the IFG and PHG, as well as increased excitability of the PHG for negative emotional stimuli. We have also elucidated the directionality of these genetic influences. Our data suggest that homozygotes with GTA alleles involve stronger functional connections between brain areas in order to maintain activation of these regions. Homozygotes might engage a greater degree of motivational learning and integration of information to perform the emotional learning task correctly. We conclude that PPP1R1B is associated with the neural network involved in associative emotional learning

Dopaminergic Genes Predictive of Unmotivated Confirmation Bias are not Predictive of Motivated Confirmation Bias

Confirmation bias is persistently devastating to rational judgment and decision-making. Previous research supports cognitive and behavioral distinctions between two types of confirmation bias: motivated confirmation bias and unmotivated confirmation bias. Motivated confirmation bias is a member of the larger class of motivated reasoning biases. These often occur when one’s individual or group identity is tied up in certain beliefs or propositions that command one’s assent. Prior research has shown that even when individuals possess cognitive problem-solving skills such as high numeracy, these skills offer no benefit to rational thinking or judgment in the face of motivated reasoning problem sets. Prior research has also shown that dopaminergic genes DRD2, DARPP-32, and COMT are predictive of susceptibility to unmotivated confirmation bias; however, the role of these genes in motivated confirmation bias had yet to be tested. The present investigation examined the possible connection. Participants were 200 university students who completed questionnaires and tasks assessing motivated confirmation bias, numeracy, political philosophy and party identification. Logistic regression modeled the association of these measures with accuracy on a bias detection task. Numeracy predicted accuracy; however, genotypes and political measures did not. These results suggest that distinct genetic determinants are responsible for motivated and unmotivated confirmation bias. Further, the findings replicated previous research demonstrating that accuracy is much diminished in the motivated scenario compared to an unmotivated control. However, contrary to this earlier work, the current findings suggest that numeracy confers a benefit in both motivated and unmotivated conditions, rather than just in motivated situations. Overall, these findings suggest continued research is needed to uncover the neurobiological determinants of motivated confirmation bias