Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders

Background: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown. Method/Principal Findings: 53 healthy individuals between 18–59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject’s sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 39 untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia. Conclusions: Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brai

Strengths of character, orientations to happiness, and life satisfaction

Why are certain character strengths more associated with life satisfaction than others? A sample of U.S. adults (N = 12,439) completed on-line surveys in English measuring character strengths, orientations to happiness (engagement, pleasure, and meaning), and life satisfaction, and a sample of Swiss adults (N = 445) completed paper-and-pencil versions of the same surveys in German. In both samples, the character strengths most highly linked to life satisfaction included love, hope, curiosity, and zest. Gratitude was among the most robust predictors of life satisfaction in the U.S. sample, whereas perseverance was among the most robust predictors in the Swiss sample. In both samples, the strengths of character most associated with life satisfaction were associated with orientations to pleasure, to engagement, and to meaning, implying that the most fulfilling character strengths are those that make possible a full life