Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

Evidence for similar structural brain anomalies in youth and adult attention-deficit/hyperactivity disorder: a machine learning analysis

Attention-deficit/hyperactivity disorder (ADHD) affects 5% of children world-wide. Of these, two-thirds continue to have impairing symptoms of ADHD into adulthood. Although a large literature implicates structural brain differences of the disorder, it is not clear if adults with ADHD have similar neuroanatomical differences as those seen in children with recent reports from the large ENIGMA-ADHD consortium finding structural differences for children but not for adults. This paper uses deep learning neural network classification models to determine if there are neuroanatomical changes in the brains of children with ADHD that are also observed for adult ADHD, and vice versa. We found that structural MRI data can significantly separate ADHD from control participants for both children and adults. Consistent with the prior reports from ENIGMA-ADHD, prediction performance and effect sizes were better for the child than the adult samples. The model trained on adult samples significantly predicted ADHD in the child sample, suggesting that our model learned anatomical features that are common to ADHD in childhood and adulthood. These results support the continuity of ADHD’s brain differences from childhood to adulthood. In addition, our work demonstrates a novel use of neural network classification models to test hypotheses about developmental continuity

Caring About Errors: Effects of Simulated Interpersonal Touch and Trait Intrinsic Motivation on the Error-Related Negativity

These data form the basis of the article: Tjew-A-Sin, M., Tops, M., Heslenfeld, D. J., & Koole, S. L. (2016). Effects of simulated interpersonal touch and trait intrinsic motivation on the error-related negativity. Neuroscience letters, 617, 134-138. Abstract: The error-related negativity (ERN or Ne) is a negative event-related brain potential that peaks about 20 to 100 ms after people perform an incorrect response in choice reaction time tasks. Prior research has shown that the ERN may be enhanced by situational and dispositional factors that promote intrinsic motivation. Building on and extending this work the present authors hypothesized that simulated interpersonal touch may increase task engagement and thereby increase ERN amplitude. To test this notion, a group of participants (N= 20) performed a Go/No-Go task while holding a teddy bear or a same-sized cardboard box. As expected, the ERN was significantly larger when participants held a teddy bear rather than a cardboard box. The latter effect was especially pronounced for people high (rather than low) in trait intrinsic motivation. These findings highlight simulated interpersonal touch as a motivational factor that may influence error processing, especially among people with high intrinsic motivation to perform a task. These data are referenced by: Tjew-A-Sin, M., Tops, M., Heslenfeld, D. J., & Koole, S. L. (2016). Data on simulated interpersonal touch, individual differences and the error-related negativity. Data in Brief, 7, 1327-1330

Caring About Errors: Effects of Simulated Interpersonal Touch and Trait Intrinsic Motivation on the Error-Related Negativity

These data form the basis of the article: Tjew-A-Sin, M., Tops, M., Heslenfeld, D. J., & Koole, S. L. (2016). Effects of simulated interpersonal touch and trait intrinsic motivation on the error-related negativity. Neuroscience letters, 617, 134-138. Abstract: The error-related negativity (ERN or Ne) is a negative event-related brain potential that peaks about 20 to 100 ms after people perform an incorrect response in choice reaction time tasks. Prior research has shown that the ERN may be enhanced by situational and dispositional factors that promote intrinsic motivation. Building on and extending this work the present authors hypothesized that simulated interpersonal touch may increase task engagement and thereby increase ERN amplitude. To test this notion, a group of participants (N= 20) performed a Go/No-Go task while holding a teddy bear or a same-sized cardboard box. As expected, the ERN was significantly larger when participants held a teddy bear rather than a cardboard box. The latter effect was especially pronounced for people high (rather than low) in trait intrinsic motivation. These findings highlight simulated interpersonal touch as a motivational factor that may influence error processing, especially among people with high intrinsic motivation to perform a task. These data are referenced by: Tjew-A-Sin, M., Tops, M., Heslenfeld, D. J., & Koole, S. L. (2016). Data on simulated interpersonal touch, individual differences and the error-related negativity. Data in Brief, 7, 1327-1330