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Polygenic scores for autism are associated with reduced neurite density in adults and children from the general population
Genetic variants linked to autism are thought to change cognition and behaviour by altering the structure and function of the brain. Although a substantial body of literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic variants are linked to changes in cortical macro- and micro-structure. We investigated this using neuroimaging and genetic data from adults (UK Biobank, N = 31,748) and children (ABCD, N = 4928). Using polygenic scores and genetic correlations we observe a robust negative association between common variants for autism and a magnetic resonance imaging derived phenotype for neurite density (intracellular volume fraction) in the general population. This result is consistent across both children and adults, in both the cortex and in white matter tracts, and confirmed using polygenic scores and genetic correlations. There were no sex differences in this association. Mendelian randomisation analyses provide no evidence for a causal relationship between autism and intracellular volume fraction, although this should be revisited using better powered instruments. Overall, this study provides evidence for shared common variant genetics between autism and cortical neurite density.
Light exposure differs by sex in the US, with females receiving less bright light
Light is the primary entraining cue for the circadian system and has other, non-circadian, effects on health. Sex differences in light exposure patterns could drive sex differences in health outcomes. Real-world light exposure (measured with wrist-worn ActiGraph GT3X+) was investigated in the 2011–2014 U.S.-based National Health and Nutrition Examination Survey (NHANES) with metrics reflecting duration in and timing of exposure at different light levels. Sex differences were tested using two-sample t-tests and linear regression models. Occupational and physical activity-related factors were also explored as contributing factors using linear regression models adjusted for age, season, and race/ethnicity. 11,314 NHANES participants (age range: 3–80+, 52.2% females) were included in the analysis. The results show males spending approximately 52% more time in bright light than females, with this sex difference beginning in childhood. While further research is needed, these findings may be due to sex differences in indoor vs. outdoor activities.
Accelerated differentiation of neo-W nuclear-encoded mitochondrial genes between two climate-associated bird lineages signals potential co-evolution with mitogenomes
There is considerable evidence for mitochondrial-nuclear co-adaptation as a key evolutionary driver. Hypotheses regarding the roles of sex-linkage have emphasized Z-linked nuclear genes with mitochondrial function (N-mt genes), whereas it remains contentious whether the perfect co-inheritance of W genes with mitogenomes could hinder or facilitate co-adaptation. Young (neo-) sex chromosomes that possess relatively many N-mt genes compared to older chromosomes provide unprecedented hypothesis-testing opportunities. Eastern Yellow Robin (EYR) lineages in coastal and inland habitats with different climates are diverged in mitogenomes, and in a ~ 15.4 Mb nuclear region enriched with N-mt genes, in contrast with otherwise-similar nuclear genomes. This nuclear region maps to passerine chromosome 1A, previously found to be neo-sex in the inland EYR genome. To compare sex-linked Chr1A-derived genes between lineages, we assembled and annotated the coastal EYR genome. We found that: (i) the coastal lineage shares a similar neo-sex system with the inland lineage, (ii) neo-W and neo-Z N-mt genes are not more diverged between lineages than are comparable non-N-mt genes, and showed little evidence for broad positive selection, (iii) however, W-linked N-mt genes are more diverged between lineages than are their Z-linked gametologs. The latter effect was ~7 times stronger for N-mt than non-N-mt genes, suggesting that W-linked N-mt genes might have diverged between lineages under environmental selection through co-evolution with mitogenomes. Finally, we identify a candidate gene driver for divergent selection, NDUFA12. Our data represent a rare example suggesting a possible role for W-associated mitochondrial-nuclear interactions in climate-associated adaptation and lineage differentiation.
Sex differences in the association between repetitive negative thinking and neurofilament light
Emerging evidence suggests that repetitive negative thinking (RNT; i.e., worry and ruminative brooding) is associated with biomarkers of Alzheimer’s disease. Given that women have a greater risk of many neurodegenerative diseases, this study investigated whether worry and brooding are associated with general neurodegeneration and whether associations differ by sex. Exploratory analyses examined whether allostatic load, a marker of chronic stress, mediates any observed relationships. Baseline data from 134 cognitively healthy older adults in the Age-Well clinical trial were utilised. Worry and brooding were assessed using questionnaires. Plasma neurofilament light chain (NfL), a biomarker of neurodegeneration, was quantified using a Meso Scale Discovery assay. We found a positive interaction between brooding and sex on NfL, with higher brooding associated with greater NfL levels in women. No associations were observed between worry/ruminative brooding and allostatic load. These results offer preliminary support that RNT is associated with worse brain health, specifically in women.
Spontaneous thought separates into clusters of negative, positive, and flexible thinking
The nature and frequency of spontaneous thoughts play a critical role in cognitive processes like perception, decision-making, attention, and memory. Deficits in these processes are also greatly associated with the development and maintenance of psychopathology. However, the underlying cognitive dynamics of free and stuck spontaneous thought remain unclear, as these often occur in the absence of measurable behaviors. Here, we analyze free word-association data using attractor-state dynamic modeling, which conceptualizes stuck spontaneous thought as navigating a multidimensional semantic space while in the presence of strong attractor locations. Word-association data was collected from an exploratory sample (N1 = 65), a first replication sample (N2 = 79), and, following pre-registration, a second replication sample (N3 = 222). After the data was embedded into a 3-dimensional semantic space and fit by our dynamic model, unsupervised learning consistently grouped data into four clusters across all independent samples. These clusters were characterized by two distinct patterns of stuck negative thinking, a pattern of protective positive thinking, and a pattern of flexible mind-wandering. Our results support a method for modeling spontaneous thought and isolate distinct sub-types that may not be accessible using retrospective self-report methods. We discuss implications for clinical and cognitive science.
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