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Blue Genes

© John McManamy, ESQ

"We have a treasure trove of new genes to explore."

"We wish to suggest a structure for the salt of deoxyribose nucleic acid (DNA)," began a one-page paper published in Nature 50 years ago. With what can only be called hyperbolic understatement, the article went on to say: "This structure has novel features which are of considerable biological interest." The authors were James Watson and Francis Crick, the structure was the double helix, and biological science would never be the same.

April's American Journal of Psychiatry commemorates the fiftieth anniversary of the publication of Watson and Crick's groundbreaking paper, with several articles devoted to "the genomic era," which, according to an editorial, "is about much more than 'finding genes.' It is about understanding how they get turned on, or turned off. It is about examining the complex interactions between genes and the huge array of nongenetic factors that influence their effects. It is about our capacity as scientists and clinicians to improve diagnosis, treatment, and, ultimately, prevention."

So far, the literature concerning genes and the brain has focused on less than one percent of the genome, representing a mere 300 or so genes. Yet our research on mice tells us 55 percent of our genes (roughly 16,500 genes) are expressed in the brain. According to Thomas Insel MD and Francis Collins MD, PhD, directors of the NIMH and Human Genome Project, respectively: "We have a treasure trove of new genes to explore, including many that may prove more important than the few neurotransmitters and intracellular signaling molecules that have been studied so intensively these past 50 years."

The hunt for mood genes can be likened to searching for pieces of hay in a haystack. There is no one gene that is likely to stand out. Instead, we're searching for what are probably common and fairly humdrum mutations to what may be more than ten genes, each with a modest effect. The search is further confounded by the fact that unlike say diabetes, a mood disorder leaves no discernible biological footprint equivalent to blood glucose. Not surprisingly, our efforts to link social wallflower genes to phantom footprint symptoms - or "phenotype" - by studying twins and families and isolated populations have been disappointing, yielding at best some possible suspects.

Accordingly, researchers are thinking outside the DSM box to the underlying biology of "endophenotype," such as sleep and circadian rhythms and appetite regulation. Intriguingly, some of the suspect genes we have identified may be responsible for more than one illness, raising such possibilities as schizophrenia and bipolar patients sharing some of the same psychosis genes. Should our enquiries down these paths bear fruit, we could eventually redefine mental illness according to "genotype" that would render the DSM obsolete. As Insel and Collins conclude:

The copyright of the article Blue Genes in Depression is owned by John McManamy, ESQ. Permission to republish Blue Genes in print or online must be granted by the author in writing.