Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an ...independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO. We find that genetic variation with concordant effects in both phenotypes shows significant SNP-based heritability enrichment, higher polygenic contribution in females, and positive covariance with mental disorders such as depression, anxiety, attention-deficit hyperactivity disorder, alcohol dependence, and autism. Conversely, genetic variation with discordant effects only contributes to schizophrenia risk in males and is negatively correlated with those disorders. Mendelian randomization analyses demonstrate a plausible bi-directional causal relationship between LNL-ISO and schizophrenia, with a greater effect of LNL-ISO liability on schizophrenia than vice versa. These results illustrate the genetic footprint of LNL-ISO on schizophrenia.
Common genetic variation has been associated with multiple phenotypic features in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this ...highly heterogeneous phenotypic spectrum is limited. Here, we developed and implemented a structural equation modelling framework to directly model genomic covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent with a case-only design. We identified three independent genetic factors most strongly linked to language performance, behaviour and developmental motor delay, respectively, studying an autism community sample (N = 5331). The three-factorial structure was largely confirmed in independent ASD-simplex families (N = 1946), although we uncovered, in addition, simplex-specific genetic overlap between behaviour and language phenotypes. Multivariate models across cohorts revealed novel associations, including links between language and early mastering of self-feeding. Thus, the common genetic architecture in ASD is multi-dimensional with overarching genetic factors contributing, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.
Schizophrenia is a debilitating psychiatric disorder associated with a reduced fertility and decreased life expectancy, yet common predisposing variation substantially contributes to the onset of the ...disorder, which poses an evolutionary paradox. Previous research has suggested balanced selection, a mechanism by which schizophrenia risk alleles could also provide advantages under certain environments, as a reliable explanation. However, recent studies have shown strong evidence against a positive selection of predisposing loci. Furthermore, evolutionary pressures on schizophrenia risk alleles could have changed throughout human history as new environments emerged. Here in this study, we used 1000 Genomes Project data to explore the relationship between schizophrenia predisposing loci and recent natural selection (RNS) signatures after the human diaspora out of Africa around 100,000 years ago on a genome-wide scale. We found evidence for significant enrichment of RNS markers in derived alleles arisen during human evolution conferring protection to schizophrenia. Moreover, both partitioned heritability and gene set enrichment analyses of mapped genes from schizophrenia predisposing loci subject to RNS revealed a lower involvement in brain and neuronal related functions compared to those not subject to RNS. Taken together, our results suggest non-antagonistic pleiotropy as a likely mechanism behind RNS that could explain the persistence of schizophrenia common predisposing variation in human populations due to its association to other non-psychiatric phenotypes.
Abstract
Schizophrenia is a biologically complex disorder with multiple regional deficits in cortical brain morphology. In addition, interindividual heterogeneity of cortical morphological metrics is ...larger in patients with schizophrenia when compared to healthy controls. Exploiting interindividual differences in the severity of cortical morphological deficits in patients instead of focusing on group averages may aid in detecting biologically informed homogeneous subgroups. The person-based similarity index (PBSI) of brain morphology indexes an individual’s morphometric similarity across numerous cortical regions amongst a sample of healthy subjects. We extended the PBSI such that it indexes the morphometric similarity of an independent individual (eg, a patient) with respect to healthy control subjects. By employing a normative modeling approach on longitudinal data, we determined an individual’s degree of morphometric dissimilarity to the norm. We calculated the PBSI for sulcal width (PBSI-SW) in patients with schizophrenia and healthy control subjects (164 patients and 164 healthy controls; 656 magnetic resonance imaging scans) and associated it with cognitive performance and cortical sulcation index. A subgroup of patients with markedly deviant PBSI-SW showed extreme deficits in cognitive performance and cortical sulcation. Progressive reduction of PBSI-SW in the schizophrenia group relative to healthy controls was driven by these deviating individuals. By explicitly leveraging interindividual differences in the severity of PBSI-SW deficits, neuroimaging-driven subgrouping of patients is feasible. As such, our results pave the way for future applications of morphometric similarity indices for subtyping of clinical populations.
Abstract
Sex differences in the development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal ...depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, gyral span, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants 2 scans, 104 three scans, age range: 16–70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. Although hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and lower variability for sulcal width. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.
The 7-item Functionality Appreciation Scale (FAS) measures the extent of an individual’s appreciation of their body for what it can do and is capable of doing. Although the FAS has been widely used ...in diverse linguistic contexts, it has not been previously translated into Spanish. Here, we examined the psychometric properties of a novel Spanish translation of the FAS in Colombian adults. A total of 1420 university students from Colombia (804 women, 616 men) completed the FAS, as well as additional validated measures. Exploratory and confirmatory factor analyses in separate subsamples supported a unidimensional model of FAS scores. The FAS evidenced scalar invariance across gender identity, with men having significantly higher FAS scores than women (Cohen’s d = 0.18). FAS scores were also found to have adequate composite reliability, as well as adequate convergent (significant associations with body appreciation, appearance evaluation, and eating disorder psychopathology) and concurrent validity (significant associations with self-esteem, life satisfaction, and gratitude). Functionality appreciation incrementally predicted life satisfaction in women, but not in men. Overall, these results suggest that the Spanish FAS is a psychometrically valid and reliable tool for the assessment of functionality appreciation in university-aged populations from Colombia.
•Functionality Appreciation Scale (FAS) has unidimensional structure in Colombian adults.•FAS is invariant across gender, with men having higher scores than women.•FAS scores have adequate composite reliability, and convergent and concurrent validity.•Evidence of incremental validity supported in women, but not men.
Se evaluó el efecto de la temperatura sobre el contenido de trans-β-caroteno (caroteno), como factor de calidad, en uchuva (Physalis peruviana L.). Las muestras de uchuva fueron almacenadas en ...incubadoras a temperaturas entre 4,0 y 40,0 ± 0,1°C por espacio de 15 a 18 días, durante los cuales se realizó el seguimiento del contenido de caroteno. A partir de la información obtenida por cromatografía líquida de alta resolución (CLAR) con detección por ultravioleta-visible, se determinaron los parámetros cinéticos: orden de reacción (n), constante de velocidad (k), tiempo de vida media (t1/2) y energía de activación (Ea). El modelo aplicado permitió establecer que en la uchuva, la degradación del caroteno, por efecto de la temperatura, presentó una cinética de primer orden, una energía de activación de 22,91 ± 1,25 kJ/mol y un tiempo de vida media del caroteno de 57,8 días a 4,0 ± 0,1°C. El fenómeno de la carotenogénesis fue observado en la uchuva en la etapa pos-cosecha.
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