Gene Variant Linked to Psychotic Symptoms of Bipolar Disorder

the Psychiatry Advisor take:

Researchers have identified a variant of the sorting nexin 7 (SNX7) gene that may be linked to both cognitive impairment and psychotic symptoms in people with bipolar disorder, according to research published in Molecular Psychiatry. 

The study, led by Mikael Landén, MD, PhD, senior researcher at Karolinska Institutet’s Department of Medical  Epidemology and Biostatistics and the Sahlgrenska Academy’s Department of Neuroscience and Physiology at Gothenburg University in Sweden, has also identified a mechanism that could explain how the gene variant affects protein levels in the brain and produces clinical symptoms of bipolar disorder.

“The link to cognitive symptoms is particularly interesting, since there are no treatments currently available to improve problems with attention, memory, and concentration, which impact heavily on functional outcome and recoverability,” said Dr Landén.

The study included participants with bipolar disorder from the St. Göran project in Stockholm and Gothenburg. The researchers carefully mapped each participant’s symptoms, tested their cognitive abilities, and measured the levels of proteins in their blood and cerebrospinal (CSF) fluids. After performing a genome-wide association study (GWAS), the researchers discovered a genetic variant of the SNX7 gene associated with both elevated levels of kynurenic acid and symptoms of bipolar disorder.

Dr Landén and colleagues performed a series of further experiments in an effort to identify a potential signal pathway. “The pathway mainly involves signaling via the brains’ immune cells,” Dr Landén explained. “We’re hoping … that the new mechanisms we’ve discovered will help the development of more targeted drugs.”

While all study participants were people with bipolar disorder, the researchers believe that the mechanisms discovered may also have implications for other psychotic disorders, including schizophrenia.

dna biopolar disorder gene variant
The genetic variant of the SNX7 gene has been linked to the disease symptoms of bipolar disorder.

Researchers at Karolinska Institutet, and the Sahlgrenska Academy at Gothenburg University in Sweden have identified a gene variant linked to psychotic symptoms and cognitive impairment in people with bipolar disorder. The study, which is published in the journal Molecular Psychiatry, describes a possible mechanism for how the gene variant produces clinical symptoms by affecting levels of specific proteins in the brain.

"We've identified a gene variant linked to specific psychotic symptoms and cognitive impairment in people with bipolar disorder," says Mikael Landén, researcher at Karolinska Institutet's Department of Medical Epidemiology and Biostatistics and the Sahlgrenska Academy's Department of Neuroscience and Physiology. "The link to cognitive symptoms is particularly interesting, since there are no treatments currently available to improve problems with attention, memory and concentration, which impact heavily on functional outcome and recoverability."

Bipolar disorder and schizophrenia can largely be attributed to inherited factors. In recent years, scientists have identified specific gene variants that increase the risk of these diseases, but these risk variants only go some way to explaining why some people are afflicted by the disease and others are not. We currently do not know how these genetic risk factors affect the chemistry of the brain and cause specific symptoms, so it is not yet possible for scientists to design drugs to relieve symptoms shown by people with a particular genetic variant. To link, at a molecular level, a gene variant with biochemical changes and clinical symptoms related to a heritable psychiatric disorder, as in this present study, is therefore something of a breakthrough.

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