A biologically informed polygenic score of neuronal plasticity moderates the association between cognitive aptitudes and cortical thickness in adolescents.

Although many studies of the adolescent brain identified positive associations between cognitive abilities and cortical thickness, little is known about mechanisms underlying such brain-behavior relationships. With experience-induced plasticity playing an important role in shaping the cerebral cortex throughout life, it is likely that some of the inter-individual variations in cortical thickness could be explained by genetic variations in relevant molecular processes, as indexed by a polygenic score of neuronal plasticity (PGS-NP). Here, we studied associations between PGS-NP, cognitive abilities, and thickness of the cerebral cortex, estimated from magnetic resonance images, in the Saguenay Youth Study (SYS, 533 females, 496 males: age=15.0 ± 1.8 years of age; cross-sectional), and the IMAGEN Study (566 females, 556 males; between 14 and 19 years; longitudinal). Using Gene Ontology, we first identified 199 genes implicated in neuronal plasticity, which mapped to 155,600 single nucleotide polymorphisms (SNPs). Second, we estimated their effect sizes from an educational attainment meta-GWAS to build a PGS-NP. Third, we examined a possible moderating role of PGS-NP in the relationship between performance intelligence quotient (PIQ), and its subtests, and the thickness of 34 cortical regions. In SYS, we observed a significant interaction between PGS-NP and object assembly vis-à-vis thickness in male adolescents (p = 0.026). A median-split analysis showed that, in males with a 'high' PGS-NP, stronger associations between object assembly and thickness were found in regions with larger age-related changes in thickness (r = 0.55, p = 0.00075). Although the interaction between PIQ and PGS-NP was non-significant (p = 0.064), we performed a similar median-split analysis. Again, in the high PGS-NP males, positive associations between PIQ and thickness were observed in regions with larger age-related changes in thickness (r = 0.40, p = 0.018). In the IMAGEN cohort, we did not replicate the first set of results (interaction between PGS-NP and cognitive abilities via-a-vis cortical thickness) while we did observe the same relationship between the brain-behaviour relationship and (longitudinal) changes in cortical thickness (Matrix reasoning: r = 0.63, p = 6.5e-05). No statistically significant results were observed in female adolescents in either cohort. Overall, these cross-sectional and longitudinal results suggest that molecular mechanisms involved in neuronal plasticity may contribute to inter-individual variations of cortical thickness related to cognitive abilities during adolescence in a sex-specific manner.

Integration of 3D nuclear imaging in 3D mapping system for ventricular tachycardia ablation in patients with implanted devices: Perfusion/voltage retrospective assessment of scar location.

Background: The identification of low-voltage proarrhythmic areas for catheter ablation of scar-mediated ventricular tachycardia (VT) remains challenging. Integration of myocardial perfusion imaging (single-photon emission computed tomography/computed tomography; SPECT/CT) and electroanatomical mapping (EAM) may improve delineation of the arrhythmogenic substrate. Objective: To assess the feasibility of SPECT/CT image integration with voltage maps using the EnSite Precision system (Abbott) in patients undergoing scar-mediated VT ablation. Methods: Patients underwent SPECT/CT imaging prior to left ventricular (LV) EAM with the EnSite Precision mapping system. The SPECT/CT, EAM data, and ablation lesions were retrospectively co-registered in the EnSite Precision system and exported for analysis. Segmental tissue viability scores were calculated based on SPECT/CT perfusion and electrogram bipolar voltage amplitude. Concordance, specificity, and sensitivity between the 2 modalities as well as the impact of SPECT/CT spatial resolution were evaluated. Results: Twenty subjects (95% male, 67 ± 7 years old, left ventricular ejection fraction 36% ± 11%) underwent EAM and SPECT/CT integration. A concordance of 70% was found between EAM and SPECT/CT for identification of cardiac segments as scar vs viable, with EAM showing a 68.5% sensitivity and 76.4% specificity when using SPECT/CT as a gold standard. Projection on low-resolution 3D geometries led to an average decrease of 38% ± 22% of the voltage points used. Conclusion: The study demonstrated the feasibility of integrating SPECT/CT with EAM performed retrospectively for characterization of anatomical substrates during VT ablation procedures.

Visceral adiposity is associated with metabolic profiles predictive of type 2 diabetes and myocardial infarction.

Background: Visceral fat (VF) increases risk for cardiometabolic disease (CMD), the leading cause of morbidity and mortality. Variations in the circulating metabolome predict the risk for CMD but whether or not this is related to VF is unknown. Further, CMD is now also present in adolescents, and the relationships between VF, circulating metabolome, and CMD may vary between adolescents and adults. Methods: With an aim to add understanding to the metabolic variations in visceral obesity, we tested associations between VF, measured directly with magnetic resonance imaging, and 228 fasting serum metabolomic measures, quantified with nuclear magnetic resonance spectroscopy, in 507 adults (36-65 years) and 938 adolescents (12-18 years). We further utilized data from published studies to estimate similarities between VF and CMD-associated metabolic profiles. Results: Here we show that VF, independently of body mass index (BMI) or subcutaneous fat, is associated with triglyceride-rich lipoproteins, fatty acids, and inflammation in both adults and adolescents, whereas the associations with amino acids, glucose, and intermediary metabolites are significant in adults only. BMI-adjusted metabolomic profile of VF resembles those predicting type 2 diabetes in adults (R 2 = 0.88) and adolescents (R 2 = 0.70), and myocardial infarction in adults (R 2 = 0.59) and adolescents (R 2 = 0.40); this is not the case for ischemic stroke (adults: R 2 = 0.05, adolescents: R 2 = 0.08). Conclusions: Visceral adiposity is associated with metabolomic profiles predictive of type 2 diabetes and myocardial infarction even in normal-weight individuals and already in adolescence. Targeting factors contributing to the emergence and maintenance of these profiles might ameliorate their cumulative effects on cardiometabolic health.

Electroanatomical Navigation to Minimize Contrast Medium or X-Rays During Stenting: Insights From an Experimental Model.

Stents can be effectively implemented with no x-rays or contrast medium. Modified stents were successfully implanted in 9 of 11 attempted targets (82%) (7 carotid and 4 coronary arteries) using an impedance-sensitive navigation system and optical coherence tomography. Electroanatomical navigation systems can be used to assist interventionalists in performing arterial stenting while minimizing x-ray and contrast use, thereby potentially enhancing safety for both patients and catheterization laboratory staff members.

Peripheral Interventions Radiation Exposure Reduction Using a Sensor-Based Navigation System: A Proof-of-Concept Study.

BACKGROUND: Intravascular catheter positioning is done with radiography imaging. Increasing evidence indicates excessive ionizing radiation exposure for patients and physicians during catheterization procedures, making solutions to reduce radiation exposure a priority. This study evaluated the feasibility and impact of using sensor-based magnetic navigation on (i) fluoroscopy time and (ii) positioning accuracy and safety of a peripheral angioplasty balloon catheter. METHODS: All patients (n = 10) underwent a balloon-positioning protocol using 2 navigation methods sequentially: (i) magnetic navigation with minimal fluoroscopy; (ii) fluoroscopic navigation. The navigation method order was randomized, and 4 consecutive placements per method were performed. A target vascular bifurcation was used as a fiduciary landmark for both methods to determine accuracy. RESULTS: Balloon placements were successful with both navigation methods in all subjects, and no adverse events occurred. Magnetic guidance led to significant reductions in fluoroscopy time (0.37 ± 1.5 vs 15.0 ± 8.1 seconds, P < 0.001) and dose (0.3 ± 1.2 vs 24.1 ± 23.8 µGy.m2, P < 0.01). The time duration for balloon alignment was similar for the 2 navigation methods (4.8 ± 1.4 vs 4.8 ± 2.3 seconds, P = 0.89), and the accuracy was almost identical (0.51 ± 0.41 vs 0.51 ± 0.32 mm, P = 0.97). CONCLUSIONS: These results demonstrate the feasibility of using sensor-based magnetic guidance during simple peripheral interventional procedures; a significant reduction in ionizing radiation was achieved, with excellent positioning accuracy and safety. The clinical applications of magnetic guidance for device navigation during more complex percutaneous procedures should be evaluated.

CONTEXTE: Le positionnement d'un cathéter intravasculaire fait appel à l'imagerie radiographique. De plus en plus de données probantes indiquent que les patients et les médecins subissent une surexposition aux rayonnements ionisants pendant le cathétérisme, ce qui fait des solutions de réduction de l'irradiation une priorité. Cette étude a permis d'évaluer la faisabilité du guidage magnétique par capteur et son effet sur (i) la durée de la fluoroscopie et (ii) la précision et la sécurité du positionnement d'un cathéter d'angioplastie périphérique à ballonnet. MÉTHODOLOGIE: Chez tous les patients (n = 10), le positionnement du ballonnet a été effectué en fonction d'un protocole fondé sur deux méthodes de guidage mises en œuvre séquentiellement : (i) guidage magnétique avec fluoroscopie minimale; (ii) guidage fluoroscopique. L'ordre dans lequel les méthodes de guidage ont été mises en œuvre a été randomisé, et quatre positionnements consécutifs par méthode ont été effectués. Une bifurcation vasculaire cible a servi de repère de fond de chambre afin de déterminer la précision des deux méthodes. RÉSULTATS: Les deux méthodes de guidage ont permis un positionnement adéquat du ballonnet chez tous les patients, et aucun événement indésirable n'est survenu. Le guidage magnétique a entraîné des réductions significatives de la durée de la fluoroscopie (0,37 ± 1,5 vs 15,0 ± 8,1 secondes, p < 0,001) et de la dose de rayonnement (0,3 ± 1,2 vs 24,1 ± 23,8 µGy.m2, p < 0,01). La durée de l'alignement du ballonnet était similaire lors de la mise en œuvre des deux méthodes de guidage (4,8 ± 1,4 vs 4,8 ± 2,3 secondes, p = 0,89), et la précision était presque identique (0,51 ± 0,41 vs 0,51 ± 0,32 mm, p = 0,97). CONCLUSIONS: Ces résultats démontrent la faisabilité du guidage magnétique par capteur dans le cadre d'angioplasties périphériques simples. L'exposition aux rayonnements ionisants a été réduite de façon significative, et la précision ainsi que la sécurité du positionnement se sont avérées excellentes. Les applications cliniques du guidage magnétique dans le contexte d'interventions percutanées plus complexes représentent une avenue de recherche à explorer.

Predictors of participation restriction over a 9-year period in adults with myotonic dystrophy type 1.

PURPOSE: For slowly progressive neuromuscular disease, prognostic approach and long-term monitoring of participation is a crucial part of rehabilitation services. To improve the prognostic approach, professionals must identify individuals at risk of having higher participation restriction. This study aimed to identify personal and environmental predictors of participation restriction over nine years in adults with myotonic dystrophy type 1 (DM1). METHODS: A secondary analysis of a longitudinal design comparing baseline with a follow-up nine years later was used with a multidimensional assessment of participation and personal and environmental factors. Based on theoretical models, multiple linear regressions were used. RESULTS: One hundred and fourteen adults with DM1 were included in the study (63.2% women; 78.9% adult onset; mean (SD) age of 43.5 (10.4) years). When age, sex, phenotype, and education were controlled for, participation restriction was predicted by a longer time to stand and walk, lower grip strength, higher body mass index, absence of perceived impact of myotonia in daily living, use of adapted transportation from community services, and perception of obstacle in physical environment (p < 0.001, adjusted R2 = 0.50). CONCLUSIONS: The majority of predictors of participation restriction can be advantageously modified by rehabilitation and environmental changes, such as politics targeting community services provision or physical environment and services accessibility.Implications for rehabilitationPredictors could better inform rehabilitation professional to recognize individuals at risk of higher participation restriction over time and to target specific interventions based on a prognostic approach.Rehabilitation professionals could inform the people living with myotonic dystrophy type 1 and their relatives of the multifactorial nature of occurrence of participation restriction to diminish the "fatality" associated with a genetic progressive disorder.Predictors allow professionals to assess and intervene in the management of specific factors depending on the rehabilitation goal.Identifying individual with myotonic dystrophy with higher risk of participation restriction could help implement a long-term community based rehabilitation intervention plan targeting both personal and environmental factors.

A variant near DHCR24 associates with microstructural properties of white matter and peripheral lipid metabolism in adolescents.

Visceral adiposity has been associated with altered microstructural properties of white matter in adolescents. Previous evidence suggests that circulating phospholipid PC(16:0/2:0) may mediate this association. To investigate the underlying biology, we performed a genome-wide association study (GWAS) of the shared variance of visceral fat, PC(16:0/2:0), and white matter microstructure in 872 adolescents from the Saguenay Youth Study. We further studied the metabolomic profile of the GWAS-lead variant in 931 adolescents. Visceral fat and white matter microstructure were assessed with magnetic resonance imaging. Circulating metabolites were quantified with serum lipidomics and metabolomics. We identified a genome-wide significant association near DHCR24 (Seladin-1) encoding a cholesterol-synthesizing enzyme (rs588709, p = 3.6 × 10-8); rs588709 was also associated nominally with each of the three traits (white matter microstructure: p = 2.1 × 10-6, PC(16:0/2:0): p = 0.005, visceral fat: p = 0.010). We found that the metabolic profile associated with rs588709 resembled that of a TM6SF2 variant impacting very low-density lipoprotein (VLDL) secretion and was only partially similar to that of a HMGCR variant. This suggests that the effect of rs588709 on VLDL lipids may arise due to altered phospholipid rather than cholesterol metabolism. The rs588709 was also nominally associated with circulating concentrations of omega-3 fatty acids in interaction with visceral fat and PC(16:0/2:0), and these fatty acid measures showed robust associations with white matter microstructure. Overall, the present study provides evidence that the DHCR24 locus may link peripheral metabolism to brain microstructure, an association with implications for cognitive impairment.

Sex continuum in the brain and body during adolescence and psychological traits.

Many traits of the brain and body show marked sex differences, but the distributions of their values overlap substantially between the two sexes. To investigate variations associated with biological sex, beyond binary differences, we create continuous sex scores capturing the inter-individual variability in phenotypes. In an adolescent cohort (n = 1,029; 533 females), we have generated three sex scores based on brain-body traits: 'overall' (48 traits), 'pubertal' (26 traits) and 'non-pubertal' (22 traits). We then conducted sex-stratified multiple linear regressions (adjusting for age) using sex scores to test associations with sex hormones, personality traits and internalizing-externalizing behaviour. Higher sex scores (that is, greater 'femaleness') were associated with lower testosterone in males only, as well as lower extraversion, higher internalizing and lower externalizing in both sexes. The associations with testosterone, internalizing and externalizing were driven by pubertal sex scores, underscoring the importance of adolescence in shaping within-sex individual variability.

Adiposity-related insulin resistance and thickness of the cerebral cortex in middle-aged adults.

The thickness of the cerebral cortex decreases with ageing. Recent research suggests that obesity and type 2 diabetes mellitus may accelerate this cortical thinning, and that obesity-related insulin resistance may be a shared mechanistic pathway. Ageing of the cerebral cortex demonstrates sex-specific trajectories, with a gradual shift towards accelerated thinning beginning in midlife. Here, we investigated whether adiposity-related insulin resistance is associated with lower thickness of the human cerebral cortex in a community-based sample of middle-aged adults. We studied 533 adult participants (36-65 years) from the Saguenay Youth Study. Adiposity was assessed with bioimpedance, and insulin resistance was evaluated from a fasting blood sample with the homeostatic model assessment of insulin resistance (HOMA-IR). Associations between adiposity-related insulin resistance (adiposity/IR) and cortical thickness were assessed with linear models, separately in males and females younger or older than 50 years. Potential biological underpinnings were investigated with virtual histology. Adiposity/IR was associated with lower cortical thickness in females older than 50 years but not in males or younger females. The strength of the association varied across the cerebral cortex, with regions of the lateral frontal and parietal cortices and the superior temporal cortex demonstrating most pronounced thinning. Based on virtual histology, adiposity/IR-related cortical thinning may involve neurones, astrocytes, oligodendrocytes and ependymal cells acting so that they lower the cortical potential for synaptogenesis, formation of dendritic spines, production of extracellular matrix and myelination. Adiposity-related insulin resistance is associated with lower cortical thickness in middle-aged women older than 50 years. This aspect of thinning may involve neuronal and glial cells in a way that lowers the capacity of the cerebral cortex for neuronal plasticity and maintenance of myelination.

DNA methylation at the DMPK gene locus is associated with cognitive functions in myotonic dystrophy type 1.

Aim: Myotonic dystrophy type 1 (DM1) is caused by an unstable trinucleotide (CTG) expansion at the DMPK gene locus. Cognitive dysfunctions are often observed in the condition. We investigated the association between DMPK blood DNA methylation (DNAm) and cognitive functions in DM1, considering expansion length and variant repeats (VRs). Method: Data were obtained from 115 adult-onset DM1 patients. Molecular analyses consisted of pyrosequencing, small pool PCR and Southern blot hybridization. Cognitive functions were assessed by validated neuropsychological tests. Results: For patients without VRs (n = 103), blood DNAm at baseline independently contributed to predict cognitive functions 9 years later. Patients with VRs (n = 12) had different DNAm and cognitive profiles. Conclusion: DNAm allows to better understand DM1-related cognitive dysfunction etiology.

Sex Differences in Blood Pressure Hemodynamics in Middle-Aged Adults With Overweight and Obesity.

High blood pressure (BP) is the strongest modifiable risk factor for cardiovascular disease. Overweight/obesity is a major risk factor of high BP. Multiple sex differences exist in mechanistic pathways that increase BP in overweight/obesity. They may result in a sex-specific pattern of BP hemodynamics-males and females may vary in the relative contributions of stroke volume, total peripheral resistance (TPR), and heart rate to higher BP. We investigated this possibility in a population-based sample of middle-aged adults (36-65 years). The total sample (n=618) included 289 males and 329 females; 79% of males and 66% of females were overweight. In all, we measured BP, stroke volume, TPR, and heart rate beat-by-beat during a 52-minute protocol that included changes in posture and mental stress. We assessed the relative contributions of stroke volume, TPR, and heart rate to BP at each minute of the protocol. We observed marked sex differences in BP hemodynamics in overweight/obese individuals: the main determinant of higher BP was TPR in males (49% versus only 35% in females, P=0.008), whereas it was stroke volume in females (51% versus only 35% in males, P=0.006). These sex differences were most apparent when standing or sitting at rest. No such differences were seen in normal-weight individuals in whom the main determinant of higher BP was TPR in both sexes. Our study suggests that, in middle-aged adults, marked sex differences exist in BP hemodynamics, contributing to high BP in overweight/obese but not normal-weight individuals. As such, this study may contribute to precision medicine in hypertension.

Novel Genetic Locus of Visceral Fat and Systemic Inflammation.

CONTEXT: Visceral fat (VF), more than fat elsewhere in the body [mostly subcutaneous fat (SF)], promotes systemic inflammation and related disease. The mechanisms of preferentially visceral accumulation of body fat are largely unknown. OBJECTIVE: To identify genetic loci and mechanistic pathways of preferential accumulation of VF and associated low-grade systemic inflammation. DESIGN: Genome-wide association study (GWAS). SETTING AND PARTICIPANTS: Population-based cohort of 1586 adolescents (aged 12 to 19 years) and adults (aged 36 to 65 years). MAIN OUTCOME MEASURES: Abdominal VF and SF were measured with MRI, total body fat (TBF) was assessed with bioimpedance, and low-grade systemic inflammation was examined by serum C-reactive protein (CRP) measurement. RESULTS: This GWAS of preferential accumulation of VF identified a significant locus on chromosome 6 at rs803522 (P = 1.1 × 10-9 or 4.3 × 10-10 for VF adjusted for SF or TBF, respectively). The major allele was associated with more VF; the association was similar in adolescents and adults. The allele was also associated with higher CRP level, but this association was stronger in adults than adolescents (P for interaction = 4.5 × 10-3). In adults, VF was a significant mediator (P = 1.9× 10-4) in the association between the locus and CRP, explaining 30% of the mediation. The locus was near ATG5, encoding an autophagy molecule reported to modulate adipocyte size and macrophage polarization. CONCLUSION: A genetic locus near ATG5 regulates preferential accumulation of VF (vs SF) in youth and adulthood and contributes to the development of systemic inflammation in adulthood.

Visceral fat-related systemic inflammation and the adolescent brain: a mediating role of circulating glycerophosphocholines.

OBJECTIVE: Life-long maintenance of brain health is important for the prevention of cognitive impairment in older age. Low-grade peripheral inflammation associated with excess visceral fat (VF) may influence brain structure and function. Here we examined (i) if this type of inflammation is associated with altered white-matter (WM) microstructure and lower cognitive functioning in adolescents, and (ii) if recently identified circulating glycerophosphocholines (GPCs) can index this type of inflammation and associated variations in WM microstructure and cognitive functioning. SUBJECTS: We studied a community-based sample of 872 adolescents (12-18 years, 48% males) in whom we assessed VF and WM microstructure with magnetic resonance imaging, processing speed with cognitive testing, serum C-reactive protein (CRP, a common marker of peripheral inflammation) with a high-sensitivity assay, and serum levels of a panel of 64 GPCs with advanced mass spectrometry. RESULTS: VF was associated with CRP, and CRP in turn was associated with "altered" WM microstructure and lower processing speed (all p < 0.003). Further, "altered" WM microstructure was associated with lower processing speed (p < 0.0001). Of all 64 tested GPCs, 4 were associated with both VF and CRP (at Bonferroni corrected p < 0.0004). One of them, PC16:0/2:0, was also associated with WM microstructure (p < 0.0001) and processing speed (p = 0.0003), and mediated the directed associations between VF and both WM microstructure (p < 0.0001) and processing speed (p = 0.02). As a mediator, PC16:0/2:0 explained 21% of shared variance between VF and WM microstructure, and 22% of shared variance between VF and processing speed. Similar associations were observed in an auxiliary study of 80 middle-aged adults. CONCLUSIONS: Our results show that VF-related peripheral inflammation is associated with "altered" WM microstructure and lower cognitive functioning already in adolescents, and a specific circulating GPC may be a new molecule indexing this VF-related peripheral inflammation and its influences on brain structure and function.

Inter-Regional Variations in Gene Expression and Age-Related Cortical Thinning in the Adolescent Brain.

Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2). Across 34 cortical regions (Desikan-Killiany parcellation), age-related cortical thinning varied as a function of mRNA expression levels of NR3C1 in males (R2 = 0.46) and females (R2 = 0.30) and AR in males only (R2 = 0.25). Cortical thinning did not vary as a function of expression levels of PGR, ESR1, or ESR2 in either sex; this might be due to the observed low consistency of expression profiles of these 3 genes across donors. Inter-regional levels of the NR3C1 and AR expression interacted with each other vis-à-vis cortical thinning: age-related cortical thinning varied as a function of NR3C1 mRNA expression in brain regions with low (males: R2 = 0.64; females: R2 = 0.58) but not high (males: R2 = 0.0045; females: R2 = 0.15) levels of AR mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.

Cell-Specific Gene-Expression Profiles and Cortical Thickness in the Human Brain.

Neurobiological underpinnings of cortical thickness in the human brain are largely unknown. Here we use cell-type-specific gene markers to evaluate the contribution of 9 neural cell-types in explaining inter-regional variations in cortical thickness and age-related cortical thinning in the adolescent brain. Gene-expression data were derived from the Allen Human Brain Atlas (and validated using the BrainSpan Atlas). Values of cortical thickness/thinning were obtained with magnetic resonance imaging in a sample of 987 adolescents. We show that inter-regional profiles in cortical thickness relate to those in the expression of genes marking CA1 pyramidal cells, astrocytes, and microglia; taken together, the 3 cell types explain 70% of regional variation in cortical thickness. We also show that inter-regional profiles in cortical thinning relate to those in the expression of genes marking CA1 and S1 pyramidal cells, astrocytes and microglia. Using Gene Ontology analysis, we demonstrate that the difference in the contribution of CA1 and S1 pyramidal cells may relate to biological processes such as neuronal plasticity and potassium channel activity, respectively. This "virtual histology" approach (scripts provided) can be used to examine neurobiological underpinnings of cortical profiles associated with development, aging, and various disorders.

Income inequality, gene expression, and brain maturation during adolescence.

Income inequality is associated with poor health and social outcomes. Negative social comparisons and competition may involve the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in underlying some of these complex inter-relationships. Here we investigate brain maturation, indexed by age-related decreases in cortical thickness, in adolescents living in neighborhoods with differing levels of income inequality and household income. We examine whether inter-regional variations relate to those in glucocorticoid receptor (HPA) and androgen receptor (HPG) gene expression. For each sex, we used a median split of income inequality and household income (income-to-needs ratio) to create four subgroups. In female adolescents, the high-inequality low-income group displayed the greatest age-related decreases in cortical thickness. In this group, expression of glucocorticoid and androgen receptor genes explained the most variance in these age-related decreases in thickness across the cortex. We speculate that female adolescents living in high-inequality neighborhoods and low-income households may experience greater HPA and HPG activity, leading to steeper decreases in cortical thickness with age.

Cohort Profile: The Saguenay Youth Study (SYS).

The Saguenay Youth Study (SYS) is a two-generational study of adolescents and their parents (n = 1029 adolescents and 962 parents) aimed at investigating the aetiology, early stages and trans-generational trajectories of common cardiometabolic and brain diseases. The ultimate goal of this study is to identify effective means for increasing healthy life expectancy. The cohort was recruited from the genetic founder population of the Saguenay Lac St Jean region of Quebec, Canada. The participants underwent extensive (15-h) phenotyping, including an hour-long recording of beat-by-beat blood pressure, magnetic resonance imaging of the brain and abdomen, and serum lipidomic profiling with LC-ESI-MS. All participants have been genome-wide genotyped (with ∼ 8 M imputed single nucleotide polymorphisms) and a subset of them (144 adolescents and their 288 parents) has been genome-wide epityped (whole blood DNA, Infinium HumanMethylation450K BeadChip). These assessments are complemented by a detailed evaluation of each participant in a number of domains, including cognition, mental health and substance use, diet, physical activity and sleep, and family environment. The data collection took place during 2003-12 in adolescents (full) and their parents (partial), and during 2012-15 in parents (full). All data are available upon request.

Cognitive decline over time in adults with myotonic dystrophy type 1: A 9-year longitudinal study.

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease with multisystemic involvement including the central nervous system. The evolution of the cognitive profile is a matter of debate, whether an eventual decline could be global or process-specific. Study aims are to describe, compare and document the clinical relevance of the progression of cognitive abilities in DM1 patients with adult and late-onset phenotypes. A total of 115 DM1 patients (90 adult; 25 late-onset) were assessed twice within a 9-year period on cognitive abilities (language, memory, visual attention, processing speed, visuoconstructive abilities and executive functions) and intellectual functioning (WAIS-R 7). A significant worsening over time was observed for verbal memory, visual attention, and processing speed. The progression in cognitive scores correlated with age and disease duration, but not with nCTG, muscular impairment nor education at baseline. Intellectual functioning remained stable. The rate of decline was higher among the late-onset phenotype than in the adult phenotype. Results showed that executive functions, language, and visual memory are impaired earlier in adult life, while verbal memory, visual attention, and processing speed decline later. Globally, results suggest an early and accelerated normal ageing process. This longitudinal study was based on the largest sample and the longest time period studied to date. These findings are highly relevant for clinical practice and genetic counselling.