What myelination has to do with schizophrenia

As we all learned in physiology class, many of us may not yet have a fully myelinated prefrontal cortex.  Phylogenetically, the prefrontal cortex was one of the most recent regions of the brain to develop, and consequently one of the last to mature in all of us (Fuster, 2002). This area of our brain has been found to be involved in social behavior, decision-making, cognition, judgement and personality. When we are in our teens and very early twenties, we experience a large decrease in the grey matter in our prefrontal cortex. This late decrease in grey matter is unique to only the prefrontal cortex. According to Arnsten & Shansky (2004) and Lewis (1997), many risky behaviors such as alcohol, drug, and nicotine abuse, as well as psychiatric disorders, such as depression, bipolar disorder, and schizophrenia can develop during this prefrontal cortex developmental stage.

This is an image of the brain with the prefrontal cortex shown and labeled in purple, just anterior to the basal forebrain. 

Harris et al. (2009) performed a study in which they looked at the difference in gene expression in the prefrontal cortex of 48 subjects from ages 0 to 49 who had already passed away. The researchers specifically looked at late adolescents in order to determine the difference in susceptibility to psychiatric disorders, such as schizophrenia. According to Castle and Murray (1993), schizophrenia is usually seen in the age range of 15-25, precisely when myelination of the prefrontal cortex is occurring. The gene, NRG1 (specifically increased isoform 1, and potentially isoform 4) seems to be linked with schizophrenia (Harris et al. 2009). Harris et al. found that gene expression for oxidative phosphorylation and glycolysis, transcription and translation are at their highest during this important adolescent stage. The researchers hypothesized that this may be due to the increased need for energy by the prefrontal cortex because of the ATP-dependent myelin synthesis occurring. The researchers found a similarity between gene regulations during late adolescence and genes that are not functioning correctly in schizophrenia patients. Based on their data, Harris et al. hypothesize that the schizophrenic brain is affected because of the lack of energy (ATP) provided to complete the process of myelination in the prefrontal cortex.

I very highly suggest reading the the journal article: Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia, as it highlights many physiological processes that we have discussed in class and that may be a major factor in the onset of schizophrenia.

http://www.biomedcentral.com/1755-8794/2/28/#B34

References:
1. Fuster JM. Frontal lobe and cognitive development. 2002. J Neurocytol. 31(3-5):373-385
2. Arnsten AF, Shansky RM. 2004. Adolescence: vulnerable period for stress-induced prefrontal cortical function? Introduction to part IV. Ann N Y Acad Sci. 1021:143-147.
3. Lewis DA. 1997. Development of the prefrontal cortex during adolescence: insights into vulnerable neural circuits in schizophrenia. 16(6):385-398.
4. Harris LW, Lockstone HE, Khaitovich P, Weickert CS, Webster MJ, Bahn S. 2009. Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia. BMC Medical Genomics. 2:28.