Australian researchers' experiments with mice resulted in the first experimental demonstration that babies of older males are at increased risk of de novo (new) copy number variants, or CNVs in their DNA.
It's the first time there has been proof of the biological mechanism responsible. It has long been known that children of older fathers are more likely to develop schizophrenia or autism, and now the link is evident.
De novo mutations, according to a research study, are more frequent in individuals with schizophrenia. These are genetic mistakes observed in people with a medical condition, that are not found in their parents.
Guy A. Rouleau, M.D., Ph.D. of the University of Montreal, credits the occurrence of these de novo mutations, found in the study, as partly responsible for the high worldwide incidence of schizophrenia.
The World Health Organization estimates as many as 24 million people worldwide have schizophrenia, and over half of them don't receive appropriate care to relieve their symptoms.
Without listing the numerical counterpoints of the copy number variants, I will however state that CNVs are now recognized to have a prominent role in the etiology of schizophrenia and other neuropsychiatric disorders such as autism.
A large two-stage genome-wide scan of rare CNVs yielded significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications were detected in 29 of 8,290 (0.35 percent) patients versus 2 of 7,431 (0.03 percent) controls in the combined sample.
The duplications overlapped or were significantly close to the vasoactive intestinal peptide receptor gene VIPR2. The findings suggest the VPAC2 receptor could be a potential target for the development of new antipsychotic drugs.
In other news:
The premise that has long indicated that people with schizophrenia smoke more heavily than the general public has led researchers to posit the nicotine possibly acts as a treatment for some of the symptoms of schizophrenia.
Individuals with schizophrenia have fewer low affinity nicotinic receptors that contain what is called the alpha 7-subunit.
Graham Williams, M.D. and colleagues at Yale University and AstraZeneca discovered that administering very lose dose of AZD0328, a novel drug that acts as an alpha-7 agonist, in healthy monkeys, produced both acute and persistent improvements in their performance on a spatial working memory task.
This finding indicates that the neuronal nicotinic alpha-7 receptor has a critical role in the core cognitive function of working memory. Working memory is a key indication of outcome in individuals with schizophrenia.
Another team of researchers, led by Jason Tregellas, Ph.D., examined the effects of DMXB-A, a novel alpha-7 partial agonist, on the brain's "default network" in people with schizophrenia.
The result? The DMXB-A altered schizophrenia patients' default network activity in a pattern consistent with improved function of the network.
The two studies, taken together, suggest the possibility for a novel pharmacologic tactic to treat cognitive impairments in schizophrenia.
