Recently evolved human-specific methylated regions are enriched in schizophrenia signals

Banerjee, Niladri; Polushina, Tatiana; Bettella, Francesco; Giddaluru, Sudheer; Steen, Vidar M.; Andreassen, Ole A.; Hellard, Stéphanie Le

doi:10.1101/113175

Cited by 6 publications

(4 citation statements)

References 68 publications

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“…This postulated connection between the emergence of our enhanced cross-modal abilities and (clinical) conditions in which these abilities are found impaired is in line with the significant enrichment of, specifically, candidates for ASD and SZ in genes that have been positively selected in our species (e.g. [44,79,80]), particularly, in genes involved in the evolution of our distinctive skull/brain (see [81, Table 2] and in our species-specific distinctive patterns of brain activity (see [82, Table 1].…”

Section: Cross-modality and Aggression: Two Dimensions Impaired In Disorders Implicating Problems With Languagesupporting

confidence: 58%

Language evolution: examining the link between cross-modality and aggression through the lens of disorders

Benítez‐Burraco

Progovac

2021

Phil. Trans. R. Soc. B

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We demonstrate how two linguistic phenomena, figurative language (implicating cross-modality) and derogatory language (implicating aggression), both demand a precise degree of (dis)inhibition in the same cortico-subcortical brain circuits, in particular cortico-striatal networks, whose connectivity has been significantly enhanced in recent evolution. We examine four cognitive disorders/conditions that exhibit abnormal patterns of (dis)inhibition in these networks: schizophrenia (SZ), autism spectrum disorder (ASD), synaesthesia and Tourette's syndrome (TS), with the goal of understanding why the two phenomena altered reactive aggression and altered cross-modality cluster together in these disorders. Our proposal is that enhanced cross-modality (necessary to support language, in particular metaphoricity) was a result, partly a side-effect, of self-domestication (SD). SD targeted the taming of reactive aggression, but reactive impulses are controlled by the same cortico-subcortical networks that are implicated in cross-modality. We further add that this biological process of SD did not act alone, but was engaged in an intense feedback loop with the cultural emergence of early forms of language/grammar, whose high degree of raw metaphoricity and verbal aggression also contributed to increased brain connectivity and cortical control. Consequently, in conjunction with linguistic expressions serving as approximations/‘fossils’ of the earliest stages of language, these cognitive disorders/conditions serve as confident proxies of brain changes in language evolution, helping us reconstruct certain crucial aspects of early prehistoric languages and cognition, as well as shed new light on the nature of the disorders. This article is part of the theme issue ‘Reconstructing prehistoric languages’.

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Section: Cross-modality and Aggression: Two Dimensions Impaired In Disorders Implicating Problems With Languagesupporting

confidence: 58%

Language evolution: examining the link between cross-modality and aggression through the lens of disorders

Benítez‐Burraco

Progovac

2021

Phil. Trans. R. Soc. B

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“…An explanation might be that higher genetic risk for schizophrenia but not having schizophrenia may be advantageous for performance in SPEM velocity gain. Genes associated with schizophrenia were found to be favoured by evolution which implies that they might be advantageous for (cognitive) functioning, at least to a certain degree (Banerjee et al, 2018;Srinivasan et al, 2016). However, it is unclear why those advantages should only exist in performance in one but not other oculomotor endophenotypes.…”

Section: Discussionmentioning

confidence: 99%

Polygenic risk scores for schizophrenia are associated with oculomotor endophenotypes

Coors

Imtiaz²,

Boenniger³

et al. 2021

Psychol. Med.

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Background Schizophrenia is a heterogeneous disorder with substantial heritability. The use of endophenotypes may help clarify its aetiology. Measures from the smooth pursuit and antisaccade eye movement tasks have been identified as endophenotypes for schizophrenia in twin and family studies. However, the genetic basis of the overlap between schizophrenia and these oculomotor markers is largely unknown. Here, we tested whether schizophrenia polygenic risk scores (PRS) were associated with oculomotor performance in the general population. Methods Analyses were based on the data of 2956 participants (aged 30–95) of the Rhineland Study, a community-based cohort study in Bonn, Germany. Genotyping was performed on Omni-2.5 exome arrays. Using summary statistics from a recent meta-analysis based on the two largest schizophrenia genome-wide association studies to date, we quantified genetic risk for schizophrenia by creating PRS at different p value thresholds for genetic markers. We examined associations between PRS and oculomotor performance using multivariable regression models. Results Higher PRS were associated with higher antisaccade error rate and latency, and lower antisaccade amplitude gain. PRS showed inconsistent patterns of association with smooth pursuit velocity gain and were not associated with saccade rate during smooth pursuit or performance on a prosaccade control task. Conclusions There is an overlap between genetic determinants of schizophrenia and oculomotor endophenotypes. Our findings suggest that the mechanisms that underlie schizophrenia also affect oculomotor function in the general population.

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“…As discussed in the literature on psychometrics, there seem to be discontinuous populations when comparing IQ and creativity: creativity would be higher in individuals above a certain IQ score [45]; analogous non-steady relationships might also be postulated when stratifying IQ by genetic risk for psychosis: perhaps only above a given schizophrenia PGRS value, individuals would transition to psychosis and display cognitive alterations. Also, considering genetic evidence on schizophrenia as a by-product of human evolution [46,47], one could postulate that the schizophrenia PGRS may confer some evolutionary advantages here manifested as increased cognitive performance.…”

Section: Discussionmentioning

confidence: 99%

Effects of autozygosity and schizophrenia polygenic risk on cognitive and brain developmental trajectories

et al. 2018

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Cognitive and brain development are determined by dynamic interactions between genes and environment across the lifespan. Aside from marker-by-marker analyses of polymorphisms, biologically meaningful features of the whole genome (derived from the combined effect of individual markers) have been postulated to inform on human phenotypes including cognitive traits and their underlying biological substrate. Here, estimates of inbreeding and genetic susceptibility for schizophrenia calculated from genome-wide data-runs of homozygosity (ROH) and schizophrenia polygenic risk score (PGRS)-are analyzed in relation to cognitive abilities (n = 4183) and brain structure (n = 516) in a general-population sample of European-ancestry participants aged 8-22, from the Philadelphia Neurodevelopmental Cohort. The findings suggest that a higher ROH burden and higher schizophrenia PGRS are associated with higher intelligence. Cognition-ROH and cognition-PGRS associations obtained in this cohort may, respectively, evidence that assortative mating influences intelligence, and that individuals with high schizophrenia genetic risk who do not transition to disease status are cognitively resilient. Neuroanatomical data showed that the effects of schizophrenia PGRS on cognition could be modulated by brain structure, although larger imaging datasets are needed to accurately disentangle the underlying neural mechanisms linking IQ with both inbreeding and the genetic burden for schizophrenia.

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Recently evolved human-specific methylated regions are enriched in schizophrenia signals

Abstract: Background: Despite the reduced fertility of patients, schizophrenia has a prevalence of ~1% in the

Cited by 6 publications

References 68 publications

Language evolution: examining the link between cross-modality and aggression through the lens of disorders

Language evolution: examining the link between cross-modality and aggression through the lens of disorders

Polygenic risk scores for schizophrenia are associated with oculomotor endophenotypes

Effects of autozygosity and schizophrenia polygenic risk on cognitive and brain developmental trajectories

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