MRI Studies of Folate-Related Genes, Diet and Development
Folate (folic acid) is a B vitamin linked to normal brain development and function. People with schizophrenia often exhibit reduced blood folate levels, low-functioning genetic variants in the folate metabolic pathway, or both. These markers have been correlated with symptom severity in schizophrenia, and several clinical trials conducted by our group suggest that folate supplementation can improve symptoms in certain schizophrenia patients. Through work supported by the National Institute of Mental Health, we are further investigating folate’s role in brain health by studying the relationships among folate intake, folate-related genes, and brain structure and function, in both healthy adults and patients with schizophrenia. Additional studies supported by the MQ Fellows program are determining whether early gestational exposure to folic acid confers protective effects on MRI markers of schizophrenia risk in children and adolescents, as a prelude to early intervention trials.
Effects of D1 signaling on networks that underlie working memory
Working memory impairment is a core feature of schizophrenia. Extensive work involving non-human primates and human brain imaging has implicated cortical dopamine signaling at the D1 receptor in the “tuning” of cortical networks to task-relevant stimuli. Using the world’s first simultaneous PET-MRI platform, we are determining in real time how individual variation in D1 signaling impacts cortical networks that mediate working memory. This work, supported by the Howard Hughes Medical Institute, may inform strategies to improve cognitive impairment in schizophrenia by optimizing cortical dopamine signaling.
Large scale imaging data sets are necessary to address complex questions regarding the relationship between brain and behavior. The Brain Genomics Superstruct Project, co-directed by Randy Buckner, Jordan Smoller, and Joshua Roffman, is a repository of uniformly-collected neuroimaging, behavior, cognitive, and personality data and DNA for over 4,000 human participants. Each neuroimaging data set includes one high-resolution Magnetic Resonance Imaging (MRI) acquisition and one or more resting-state functional MRI acquisitions. Each functional acquisition is accompanied by a fully-automated quality assessment and pre-computed brain morphometrics are also provided. MRI and cognitive data have been publicly released for the first 1,570 individuals. Holmes et al. (2015) provide an overview of the Superstruct’s initial data release.
Impact of Fetal Gene Expression on Adult Cortical Networks
Brain structure and function relies strongly on individual genetic differences. Further, genes exhibit different expression patterns over the lifespan. In a study supported by the Brain and Behavior Research Foundation, we are examining whether variation in genes that are expressed predominantly during fetal development exerts a stronger influence on brain structure and function than genes that are expressed either constitutively or predominantly later in life. We are also studying whether variation in fetal DNA methylation, a process that is influenced by folate status, influences MRI measures in early adulthood.