NCAN geneIn the September issue of the American Journal of Psychiatry, researchers report a series of studies that suggest a strong association between one particular genetic variation and manic symptoms. (Studies in humans and mice implicate neurocan in the etiology of mania. Miró X, Meier S, Dreisow ML, Frank J, Strohmaier J, Breuer R, Schmäl C, Albayram O, Pardo-Olmedilla MT, Mühleisen TW, Degenhardt FA, Mattheisen M, Reinhard I, Bilkei-Gorzo A, Cichon S, Seidenbecher C, Rietschel M, Nöthen MM, Zimmer A. Am J Psychiatry, 2012 Sep 1;169(9):982-90.)

One arm of the study examined the genomes of large numbers of people with bipolar disorder, depression, and schizophrenia and compared them to the genomes of large numbers of control subjects (people without any psychiatric diagnoses). The results of this part of the study showed a high rate of association between a variation in the neurocan (NCAN) gene and symptoms of mania — particularly excessive activity, elevated mood, a decreased need for sleep, and reckless activity. These symptoms occurred more frequently in people with the NCAN gene variant, regardless of their diagnosis — it didn’t matter if they had bipolar disorder, depression, or schizophrenia.

In the second arm of the study, the researchers compared mice with this same gene variant to mice with the more typical gene form and found that these NCAN variant mice had many more mania-like behaviors than the mice with the typical NCAN gene. These behaviors included higher rates of motor activity, higher rates of risk taking and repetitive behaviors, and lower rates of depressive type behaviors, among others. Interestingly, these atypical behavior patterns returned to normal when the mice were given lithium.

The NCAN gene itself codes for extracellular building materials and processes, but how changes in this coding system would be related to manic symptoms remains unclear.

This is only one study among many looking for the genetic roots for bipolar disorder, and it must be repeated and further analyzed before it can be useful clinically. But it suggests a few important things, including the following:

  • Manic symptoms seem to have an association with this particular gene, but exactly how the genetic differences contribute to the development of these types of behaviors is unclear.
  • Manic symptoms occur with the gene variant regardless of the subject’s diagnostic label, so people with bipolar, depression, and schizophrenia who presented with manic symptoms all had similarly higher rates of this gene change. We may need to rethink our diagnostic categories as results from genetic studies clarify what’s really going on.
  • The mouse model of the genetic difference seems to be a good way to look at the human symptoms; behavioral and genetic changes are consistent between mice and humans.
  • Lithium had some beneficial effects on the behaviors related to this form of the NCAN gene.

It will be interesting to follow the development of further studies in this area with the goals of improving diagnostic accuracy and understanding and eventually developing different targets for treatment.

DNA photo available from Shutterstock