Preliminary Study Shows Polymorphism in Different Loci of Autism/Aspberger's Gene in Chronic Fatigue Syndrome.

Preliminary Study Shows Polymorphism in Different Loci of Autism/Aspberger's Gene in Chronic Fatigue Syndrome.

A preliminary study suggests that a polymorphism in the DISC1 gene is associated with chronic fatigue syndrome. These findings, if found to be true, have important implications for the conditon, as well as, may have an influence on research findings of other environmental illnesses. DISC1 is also known as Disrupted in Schizophrenia and has been associated with a number of mental health conditions including schizophrenia, bipolar disorder and major depression. Just recently the gene has also been implicated in playing a role, in addition to other genes, in autism. We have noted before that some experts believe that conditions such as ADHD and certain types of MCS are in fact, autism spectrum disorders. As one author points out, DISC1 is responsible for a number of physiological activities including the production of new neurons during brain development and adult neurogenesis. A defective DISC1 gene which has been demonstrated in schizophrenia could lead to a reduction in dendritic spines and also influence nerve cells to maintain weaker connections with neighboring neurons and for the purpose of simplification, reduce the "cross-talk" between neurons by influencing dopamine production. If similar disruptions through mutation in DISC1 were to occur, it does make sense it may be involved in the development of autism because of its effect on the central nervous system. (Tsai)


Of course, the idea that it plays a role in chronic fatigue syndrome is a novel finding. From my standpoint, the idea that DISC1 may play a role in CFS makes a lot of sense. As I have described in other blogs, a protein called GSK-3b is an on/off switch for Nrf2 which provides a protective role against endogenous threats that may negatively influence neurotransmission  in autism. Recently, it was demonstrated that the Wnt pathway is a pathway involved in ammonia and urea excretion that also involves the activities of GSK-3b. Biochemically, one researcher writes that DISC1 inhibits GSK-3b and therefore, this pathway has been suggested to play the important role in a number of mood disorders which we noted earlier. Like most anything in cell biology, too much activity or too little can have dramatic effects on function. In the case of GSK-3b, blocking its abherrant signaling has been associated with symptomatic benefits in MS, colitis, sepsis and arthritis and conditions involving inflammation. The latter implicates an inhibitory role of GSK-3b signaling on Nrf2. Elevations of GSK-3b activity are also present in patients with Parkinson's disease and Alzheimer's. A recent report from MIT demostrates that DISC1 knock-out present with behaviors including hyperactivity, a characteristic of schizophrenia and GSK-3b inhibitors reversed these behaviors. The author suggests that the scewed balance of neural cell development and alterations in signaling may lead to compromised cognition and behavior alterations. (Halber) A polymorphism in DISC1 that has been suggested in CFS could very well lead to abherrant signaling from GSK-3b, elevations in oxidative stress and uncontrolled expression of inflammatory proteins and changes in redox because of subsequent loss of Nrf2 signaling. Of course, other factors such as genetic SNPs in Nrf2 and suppression of gene expression should also be considered.

Citations and Original Document