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Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence.
Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder.
Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers.
No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
Restless legs syndrome (RLS) is very common in older subjects, particularly in Western countries such as the United States. RLS can lead to severe insomnia and subsequent daytime hypersomnia. RLS resulted in the first successful results from a genome-wide association study (GWAS) in the field of sleep disorders. Insomnia can present as a primary disorder or as a symptom of comorbid conditions such as chronic pain. Comorbid insomnia is more common in older adults, which in part is a reflection of higher prevalence of comorbid medical conditions and significant progress has been made in identifying the genetic basis of some forms of sleep disorder such as RLS and narcolepsy, the genetic basis of obstructive sleep apnea (OSA) remains to be determined. In the sleep disorders, progress has been made in understanding the etiology of narcolepsy and RLS largely through the application of genome-wide association studies to the phenotypes.
This chapter discusses the diagnosis and epidemiology of panic disorder (PD). Genetic studies, while instrumental, cannot alone address the etiological complexities of most psychiatric disorders. The chapter turns to two integrative approaches that combine genetics with other clinical or biological methods to target the underlying mechanisms. First, it discusses exploiting the relationship between psychiatric and non-psychiatric medical manifestations (the expanded spectrum approach). This approach is particularly relevant to PD, where the panic attacks are accompanied by a range of physiological responses that may be central to the etiology. Second, the chapter describes neurobiological phenotypes, and in particular, on using measures of brain structure and function to identify genetic variation, and studies the mechanisms via which genes can impact behavior. The chapter concludes with an overview of imaging genetic studies of PD, and particularly, of how data from imaging studies can be used to enhance the tractability of genetic targets.