Genetic Risk Followed by an Environmental Trigger Can Cause Disrupted Brain Function
A team of British researchers from Cambridge University has linked immune system abnormalities with neuropsychiatric disorders such as schizophrenia, major depressive disorder, bipolar disorder, autism spectrum disorder, and ADHD. Additionally, the research team discovered that environmental exposures (e.g., stress or infections) that generate an immune response are most likely risk factors in multiple neuropsychiatric diagnoses. The authors reached these conclusions using data from past genome-wide association studies (GWAS) searching for DNA risk factors within specific disorders. The majority of these risk variants found in GWAS studies were discovered in the non-coding portion of the genome. These variants can affect the epigenetic processes–biological processes in which molecular tags are added to or removed from the DNA double helix, resulting in the regulation of gene activity. The authors point out that their research is consistent with previous epidemiological studies, which found an increased risk of multiple psychiatric disorders following a wide range of infections. Their new research also supports the “two-hit” model of injury where the neuropsychiatric genetic risk variants (the first “hit”) are only revealed after T cell activation (the second “hit,” potentially due to stress or infection). In this research, the authors indicated that genetic variants capable of producing atypical T cells could impact the brain in two different ways. One possible route is when activated T cells alter the function of neurons, perhaps due to factors linked to inflammation. Another path is associated with brain development. T cells have an important role in normal childhood and adolescent programs of synaptic pruning: the essential process through which a super-abundance of nerve cells and connections between them are reduced as the very young brain matures. The authors propose that atypical T cells in the brain could lead to disrupted brain connectivity from atypical synaptic pruning, as seen in schizophrenia, autism, and other disorders. In the future, this research could lead to more investigations, including profiling the epigenetic profile of T cells in neuropsychiatric patient groups.
