Neurodevelopmental biology, coupled with the application of advanced histological, imaging, molecular, cellular, biochemical, and genetic approaches, has provided new insights into these intricate genetic, cellular, and molecular events. During telencephalic development, specific neural progenitor cells (NPCs) proliferate, differentiate into numerous cell types, migrate to their apposite positions, and form an integrated circuitry. Critical disturbance to this dynamic process via genetic and environmental risk can cause neurological disorders and disability. The phosphatidylinositol-3-OH kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling cascade contributes to mediate various cellular processes, including cell proliferation and growth, and nutrient uptake. In light of its critical function, dysregulation of this node has been regarded as a root cause of several neurodevelopmental diseases, such as megalencephaly (“big brain”), microcephaly (“small brain”), autism spectrum disorders, intellectual disability, schizophrenia, and epilepsy. In this review, particular emphasis will be given to the PI3K-Akt-mTOR signaling pathway and their paramount importance in neurodevelopment of the cerebral neocortex, because of its critical roles in complex cognition, emotional regulation, language, and behaviors.

BackgroundWe conducted this meta-analysis to address the open question of a possible association between maternal socioeconomic status and congenital heart defects (CHDs).MethodsWe searched MEDLINE and EMBASE from their inception to January 1, 2014 for case-control and cohort studies that assessed the association between maternal socioeconomic status and the risk of CHDs. Study-specific relative risk estimates were polled according to random-effect or fixed-effect models.ResultsFrom 3343 references, a total of 31 case-control studies and 2 cohort studies were enrolled in this meta-analysis, including more than 50,000 cases. We observed that maternal educational attainment, family income and maternal occupation were negatively associated with an 11% (pooled RR = 1.11, 95% CI: 1.03, 1.21), 5% (pooled RR = 1.05, 95% CI: 1.01, 1.09) and 51% (pooled RR = 1.51, 95% CI: 1.02, 2.24) increased risk of CHDs, respectively. In a subgroup analysis by geographic region, the results were inconsistent for the European region (RR = 1.29, 95% CI: 0.99–1.69) and USA/Canada region (RR = 1.06, 95% CI: 0.97, 1.16) in maternal educational attainment.ConclusionIn summary, this meta-analysis suggests that a lower degree of maternal socioeconomic status is modestly associated with an increased risk of CHDs. However, further investigations are needed to confirm the association.

ObjectiveTo determine if APOE ε4 influences the association between white matter hyperintensities (WMH) and cognitive impairment in Alzheimer disease (AD) and dementia with Lewy bodies (DLB).MethodsA total of 289 patients (AD = 239; DLB = 50) underwent volumetric MRI, neuropsychological testing, and APOE ε4 genotyping. Total WMH volumes were quantified. Neuropsychological test scores were included in a confirmatory factor analysis to identify cognitive domains encompassing attention/executive functions, learning/memory, and language, and factor scores for each domain were calculated per participant. After testing interactions between WMH and APOE ε4 in the full sample, we tested associations of WMH with factor scores using linear regression models in APOE ε4 carriers (n = 167) and noncarriers (n = 122). We hypothesized that greater WMH volume would relate to worse cognition more strongly in APOE ε4 carriers. Findings were replicated in 198 patients with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI-I), and estimates from both samples were meta-analyzed.ResultsA significant interaction was observed between WMH and APOE ε4 for language, but not for memory or executive functions. Separate analyses in APOE ε4 carriers and noncarriers showed that greater WMH volume was associated with worse attention/executive functions, learning/memory, and language in APOE ε4 carriers only. In ADNI-I, greater WMH burden was associated with worse attention/executive functions and language in APOE ε4 carriers only. No significant associations were observed in noncarriers. Meta-analyses showed that greater WMH volume was associated with worse performance on all cognitive domains in APOE ε4 carriers only.ConclusionAPOE ε4 may influence the association between WMH and cognitive performance in AD and DLB.