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

Reversed hierarchy in the brain for general and specific cognitive abilities: A morphometric analysis

Intelligence is composed of a set of cognitive abilities hierarchically organized. General and specific abilities capture distinguishable, but related, facets of the intelligence construct. Here, we analyze gray matter with three morphometric indices (volume, cortical surface area, and cortical thickness) at three levels of the intelligence hierarchy (tests, first-order factors, and a higher-order general factor, g). A group of one hundred and four healthy young adults completed a cognitive battery and underwent high-resolution structural MRI. Latent scores were computed for the intelligence factors and tests were also analyzed. The key finding reveals substantial variability in gray matter correlates at the test level, which is substantially reduced for the first-order and the higher-order factors. This supports a reversed hierarchy in the brain with respect to cognitive abilities at different psychometric levels: the greater the generality, the smaller the number of relevant gray matter clusters accounting for individual differences in intelligent performance

[Non-autistic pervasive developmental disorders: Rett syndrome, disintegrative disorder and pervasive developmental disorder not otherwise specified],Transtornos invasivos do desenvolvimento nưao-autưisticos: sưindrome de Rett, transtorno desintegrativo da infưancia e transtornos invasivos do desenvolvimento sem outra especificaưcưao

Contains fulltext : 49657.pdf (publisher's version ) (Open Access)The category "Pervasive Developmental Disorders" includes autistic disorder, Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, and a residual category, named pervasive developmental disorder not otherwise specified. In this review, Rett's syndrome and childhood disintegrative disorder, which are well-defined categories, will be discussed, as well as the not well defined categories that have been included in the Pervasive Developmental Disorder Not Otherwise Specified group. Different proposals of categorization have been created, some of which based on descriptive phenomenological approach, and others based upon other theoretical perspectives, such as neuropsychology. Current proposals are presented and discussed, followed by critical appraisals on the clinical advantages and disadvantages of these concepts