Schizophrenia is one of the most illusive psychiatric disorders. Over the years NIH has doled out millions to research groups pursuing various mechanistic models. The dopaminergic model is the most popular and is the target of most (if not all) antipsychotic medications. Less popularized but still empirically validated models include the GABAergic model (the subject of my personal research) and a prenatal infection model.
Findings that schizophrenia is alarmingly heritable are widely reproduced; for example a recent twin study found 20/49 monozygotic twins both developed schizophrenia versus 3/57 dizigotic twins. However, despite expansive genomic screening for aberration only a few were implicated and even they only show up in an average of 10% of schizophrenia patients (SZP).
In this study, researchers combed the genomes of 150 schizophrenia sufferers and 268 healthy individuals for never-before-seen copy number variations (CNVs)—mutations that result in large swaths of DNA encompassing multiple genes either being deleted or duplicated. Some such mutations have been found to be benign, but others have been implicated in ailments such as autism and cancer. The team of scientists, from research facilities across the U.S., found novel gene alterations in 5 percent of the healthy volunteers and 15 percent of the schizophrenia patients; new CNVs showed up in 20 percent of those subjects who developed symptoms at or before the age of 18.
Furthermore these SNPs were “overwhelmingly linked to changes in pathways responsible for communication between and within nerve cells” including some genes that have long been suspect in the pathophisiology of schizophrenia (SciAm, 2008).
While doubtful that SNPs will explain every instance of schizophrenia it may very well account for the previously mysterious genetic component.
King says the next step is to screen the 20 suspect genes to pinpoint specific defects common among large groups of schizophrenia patients.
Sebat acknowledges that the data presented is merely consistent with the rare mutation gene model and not direct proof of it. “It’s premature to say that these findings have diagnostic value [right now],” he says. “But, that’s exactly where we’re headed.”
I’m rather excited. Walsh et al. are onto something and I’ll anxiously anticipate their future findings. Schizophrenia research is rarely so concrete.
On a side note: Jeffrey Schaler, a psychologist and professor of law, was quoted in my last post as saying “Schizophrenia and depression refer to behavior, not to cellular abnormalities.” These findings highlight how silly that statement is.