New Clues to the Cause of Schizophrenia

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A research study published Aug 25th on Nature Genetics online has found 22 genetic risk loci for schizophrenia, 13 of which are new discoveries. Genes at these loci suggest involvement of two pathways- the calcium signaling pathway and the “micro-RNA 137” pathway. Calcium plays a major role in normal cell functioning. It is a signaling molecular involved in synaptic activity (the junction between nerve cells where neurotransmitters like serotonin are released), cell to cell communication and cell adhesion. In the brain, calcium is fundamental in the control of synaptic activity and memory formation. Calcium signaling disturbances are already known to be involved in different brain diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. The Micro-RNA 137 pathway is involved in neuronal development. This association of development and regulation of brain nerve cell genes with schizophrenia may further understanding and help with new treatments for the disease.

The lead author of the study, Patrick F. Sullivan, MD , commented:

“This study gives us the clearest picture to date of two different pathways that might be going wrong in people with schizophrenia,” Sullivan said. “Now we need to concentrate our research very urgently on these two pathways in our quest to understand what causes this disabling mental illness.”

The link to the study is here:

http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2742.html

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Can We Predict Who Will Attempt Suicide?

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Scientists at the Indiana University School of Medicine are looking to answer this question by analyzing proteins in the blood of patients who have mood disorders such as bipolar disorder and schizophrenia/schizoaffective disorder.  They looked at the amount of these proteins in the blood when the person was in a suicidal state vs. a non-suicidal state. A significant difference in expression was found for proteins coded for by the genes SAT1, PTEN, MARCKS and MAP3K3.  SAT1 is involved in the Omega-3 signaling pathway. MARCKS is involved in sleep–wake cycles, as well as mood regulation. PTEN is involved in regulation of the cell cycle and MAP3K3 directly regulates the stress-activated protein kinase SAPK.

Their conclusion was that “suicidality may be underlined, at least in part, by biological mechanisms related to stress, inflammation and apoptosis.” Apoptosis is the natural programmed cycle of cell death. The researchers wrote “our results have implications for the understanding of suicide, as well as for the development of objective laboratory tests and tools to track suicidal risk and response to treatment.” At some point this information could be used to predict and differentiate future and past hospitalizations due to suicidality in patients with bipolar disorder and psychosis (schizophrenia/schizoaffective disorder).

 

The link to the complete article is here:

http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201395a.html

Potential Genetic Testing For Schizophrenia

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A type of genetic testing may be useful for detecting schizophrenia.  A study published July 14th in the journal Human Molecular Genetics demonstrated a significance difference between the number of rare copy variants (CNVs) in patients with schizophrenia vs. the general population.  CNVs are duplications or deletions of small parts of the genome.  The  test for them, called a microarray, has only been around for about 10 years,and is becoming standard of care for people with autism and intellectual disabilities.. This study found a CNV detection rate of about 1 in 13 patients with schizophrenia- about 8%, which is a similar detection rate to some clinical CNV studies on autism.

The study excluded deletions in chromosome area 22q11.2, which are already known to be associated with condition that can include schizophrenia, birth defects and intellectual disabilities. The patients in this study had no obvious physical or mental disabilities.

This is the first study to implicate the area 2q13  as having a significant risk for schizophrenia. Information gained from further study of CNVs may help with medical and/or psychiatric management. This information can be used right now to help families understand reproductive implications for siblings and patients themselves.

Here is the link to the abstract:

http://www.ncbi.nlm.nih.gov/pubmed/23813976