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Genetic markers linked to five psychiatric disorders.


Genetic variants at four chromosomal positions have now been linked to five diverse childhood- and adult-onset psychiatric illnesses: schizophrenia, autism spectrum disorders, attention-deficit/hyperactivity disorder, bipolar disorder, and major depressive disorder.

Two of the four loci encode for transmembranal calcium ion transport, a physiologic finding that could become a treatment target, Dr. Jordan W. Smoller and his colleagues wrote (Lancet 2013 Feb. 28 [doi: 10.1016/S0140-6736(12)62129-1]).

"The finding that genetic variants have cross-disorder effects is an empirical step toward helping clinicians understand the common co-occurrence of clinical phenotypes in individual patients," wrote Dr. Smoller of the Massachusetts General Hospital, Boston, and his coauthors. "Our results implicate a specific biological pathway - voltage-gated calcium-channel signaling - as a contributor to the pathogenesis of several psychiatric disorders, and support the potential of this pathway as a therapeutic target."

The findings also could further the goal of "moving beyond descriptive syndromes in psychiatry and towards a nosology informed by disease cause," they noted.

The genome-wide association study analyzed single nucleotide polymorphisms (SNPs) for the five disorders among 33,332 cases and 27,888 controls, all of European ancestry. Four independent regions contained SNPs that were significantly related to the disorders. Three were related to all five disorders, and one to only bipolar disorder and schizophrenia.

The analysis also identified additional cross-disorder associations with a number of loci previously identified only with schizophrenia, although these associations were not as strong as those seen with the four primary regions, the authors said.

Two of the four loci are related to voltage-gated transmembranal calcium channels. One of these has been previously identified as a risk gene for schizophrenia, bipolar disorder, and major depressive disorder. The gene facilitates the passage of calcium ions into the plasma membrane.

"Thus, our results suggest that voltage-gated calcium signaling, and, more broadly, calcium channel activity, could be an important biological process in psychiatric disorders," Dr. Smoller and his colleagues wrote.

"Alterations in calcium channel signaling could represent a fundamental mechanism contributing to a broad vulnerability to psychopathology," the investigators noted.

The authors cited several possible limitations. For example, diagnostic misclassification in cases of schizophrenia and bipolar disorder could produce "spurious evidence of genetic overlap between disorders."

Dr. Smoller and his coauthors are members of the Cross-Disorder Group of the Psychiatric Genomics Consortium.


Major finding: Polymorphisms on four separate chromosomal locations are significantly associated with five separate psychiatric illnesses: schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, autism spectrum disorders, and bipolar disorder.

Data source: The genome-wide association study comprised 33,332 cases and 27,888 controls, all of European ancestry.

Disclosures: The work was sponsored by the National Institutes of Health; none of the authors had any financial disclosures.
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Title Annotation:MENTAL HEALTH
Author:Sullivan, Michele G.
Publication:Internal Medicine News
Date:Mar 15, 2013
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