Event-related potential alterations in fragile X syndrome

Fragile X Syndrome (FXS) is the most common form of X-linked intellectual disability (ID), associated with a wide range of cognitive and behavioral impairments. FXS is caused by a trinucleotide repeat expansion in the FMR1 gene located on the X-chromosome. FMR1 is expected to prevent the expression of the “fragile X mental retardation protein (FMRP)”, which results in altered structural and functional development of the synapse, including a loss of synaptic plasticity. This review aims to unveil the contribution of electrophysiological signal studies for the understanding of the information processing impairments in FXS patients. We discuss relevant event-related potential (ERP) studies conducted with full mutation FXS patients and clinical populations sharing symptoms with FXS in a developmental perspective. Specific deviances found in FXS ERP profiles are described. Alterations are reported in N1, P2, Mismatch Negativity (MMN), N2, and P3 components in FXS compared to healthy controls. Particularly, deviances in N1 and P2 amplitude seem to be specific to FXS. The presented results suggest a cascade of impaired information processes that are in line with symptoms and anatomical findings in FXS

Psychological risk in long-term survivors of childhood acute lymphoblastic leukemia and its association with functional health status : A PETALE cohort study

Background: Recent research has suggested that long-term pediatric cancer survivors were at risk of important physical and psychological morbidities. To date, we do not know to what extent functional health status contributes to psychological risk and which domains are most important. The aim of this study was to systematically explore which functional domain could explain anxiety, depression, and distress symptoms. Procedure: We used data available for 105 adolescents and 182 adults successfully treated for childhood acute lymphoblastic leukemia at two Canadian sites part of the PETALE cohort. Participants were ≥5 years postdiagnosis, aged 22 ± 6 years, 52% female, and 49% acute lymphoblastic leukemia high-risk status. The contribution of health functional status (15D/16D questionnaires) to self-reported anxiety, depression, and distress (Beck scales and distress thermometer) was evaluated using adjusted logistic regression models. Results: Prevalence rates found for mild-severe anxiety, depression, and distress were 14%, 21%, and 30% among adolescents and 27%, 20%, and 19% among adults. Frequent health domains associated with psychological risk were sleeping and breathing in adolescents, and vitality/fatigue, discomfort/symptoms, mental function, and sleeping in adults. Mental function was systematically associated with psychological risk across age groups (median OR = 10.00, 95% CI 3.01-33.71). Exploratory mediation bootstrapping analyses suggested that the effect on psychological risk of overall health status and mental function problems was partly explained by social/work/school functioning. Conclusion: The results identified important functional health domains that could be targeted for interventions preventing psychological risk: vitality/fatigue, discomfort/symptoms, sleeping, and mental function issues. Health domains probably affect mood partly by limiting social/work/school functioning

Impact of brain overgrowth on sensorial learning processing during the first year of life

Macrocephaly is present in about 2–5% of the general population. It can be found as an isolated benign trait or as part of a syndromic condition. Brain overgrowth has been associated with neurodevelopmental disorders such as autism during the first year of life, however, evidence remains inconclusive. Furthermore, most of the studies have involved pathological or high-risk populations, but little is known about the effects of brain overgrowth on neurodevelopment in otherwise neurotypical infants. We investigated the impact of brain overgrowth on basic perceptual learning processes (repetition effects and change detection response) during the first year of life. We recorded high density electroencephalograms (EEG) in 116 full-term healthy infants aged between 3 and 11 months, 35 macrocephalic (14 girls) and 81 normocephalic (39 girls) classified according to the WHO head circumference norms. We used an adapted oddball paradigm, time-frequency analyses, and auditory event-related brain potentials (ERPs) to investigate differences between groups. We show that brain overgrowth has a significant impact on repetition effects and change detection response in the 10–20 Hz frequency band, and in N450 latency, suggesting that these correlates of sensorial learning processes are sensitive to brain overgrowth during the first year of life

Managing Polyploidy in Ex Situ Conservation Genetics: The Case of the Critically Endangered Adriatic Sturgeon (Acipenser naccarii)

While the current expansion of conservation genetics enables to address more efficiently the management of threatened species, alternative methods for genetic relatedness data analysis in polyploid species are necessary. Within this framework, we present a standardized and simple protocol specifically designed for polyploid species that can facilitate management of genetic diversity, as exemplified by the ex situ conservation program for the tetraploid Adriatic sturgeon Acipenser naccarii. A critically endangered endemic species of the Adriatic Sea tributaries, its persistence is strictly linked to the ex situ conservation of a single captive broodstock currently decimated to about 25 individuals, which represents the last remaining population of Adriatic sturgeon of certain wild origin. The genetic variability of three F1 broodstocks available as future breeders was estimated based on mitochondrial and microsatellite information and compared with the variability of the parental generation. Genetic data showed that the F1 stocks have only retained part of the genetic variation present in the original stock due to the few parent pairs used as founders. This prompts for the urgent improvement of the current F1 stocks by incorporating new founders that better represent the genetic diversity available. Following parental allocation based on band sharing values, we set up a user-friendly tool for selection of candidate breeders according to relatedness between all possible parent-pairs that secures the use of non-related individuals. The approach developed here could also be applied to other endangered tetraploid sturgeon species overexploited for caviar production, particularly in regions lacking proper infrastructure and/or expertise

Pre-attentive processing in children with early and continuously-treated PKU. Effects of concurrent Phe level and lifetime dietary control

Sixty-four children, aged 7 to 14 years, with early-treated PKU, were compared with control children on visual evoked potential (VEP) amplitudes and latencies and auditory mismatch negativity (MMN) amplitudes. It was further investigated whether indices of dietary control would be associated with these evoked potentials parameters. There were no significant differences between controls and children with PKU in VEP- and MMN-indices. However, higher lifetime Phe levels were, in varying degree and stronger than concurrent Phe level, related to increased N75 amplitudes, suggesting abnormalities in attention, and longer P110 latencies, indicating a reduction in speed of neural processing, possibly due to deficits in myelination or reduced dopamine levels in brain and retina. Similarly, higher lifetime Phe levels and Index of Dietary Control (IDC) were associated with decreased MMN amplitudes, suggesting a reduced ability to respond to stimulus change and poorer triggering of the frontally mediated attention switch. In summary, the present study in children with PKU investigated bottom-up information processing, i.e., triggered by external events, a fundamental prerequisite for the individual’s responsiveness to the outside world. Results provide evidence that quality of dietary control may affect the optimal development of these pre-attentive processes, and suggest the existence of windows of vulnerability to Phe exposure

Effects of eight neuropsychiatric copy number variants on human brain structure

peer reviewedMany copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. © 2021, The Author(s)

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions