9 Dec 2016

Gene code for brain changes in schizophrenia

Dr Caroline Gurvich and a colleague
by Anne Crawford

Researchers from the Monash Alfred Psychiatry research centre (MAPrc) and Central Clinical School, in collaboration with Swinburne University and the Baker IDI, have identified a link between a gene encoding a particular dopamine receptor and schizophrenia symptoms in healthy individuals.

The researchers were investigating the D1 receptor gene which is involved in the regulation of dopamine – a neurotransmitter implicated in schizophrenia – in people with schizotypy.

Schizotypy refers to the subclinical spectrum of psychosis-like behaviours, such as unusual perceptual experiences, odd beliefs and suspiciousness, that are observed in the general population. According to the continuum theory of psychosis the personality characteristics and symptoms associated with psychosis lie on a spectrum, with healthy individuals on one end and a diagnosable psychotic illness, like schizophrenia, at the extreme end.

“This project was looking at people with different clinical symptoms within the healthy end of that continuum,” explained first author Dr Caroline Gurvich, an NHMRC Early Career Research Fellow and clinical neuropsychologist at MAPrc.

“They might have odd beliefs, strange thoughts or slightly off perceptual experiences when they see something that’s not a clear-cut hallucination but a slightly distorted view of reality,” Dr Gurvich said. “There’s also research that links these groups of people to creativity and other benefits. They function completely normally.”

Dr Gurvich said there were several advantages to studying symptoms in people with schizotypy rather than those with schizophrenia, which the researchers are also studying in related projects.

People with high levels of schizotypy are thought to be at high risk of developing schizophrenia but they don’t have the confounding factors that go with schizophrenia such as being socially isolated or taking many medications, Dr Gurvich said.

“It’s a ‘pure’ way of looking at some of the symptoms at a much less severe end of the spectrum, so we can try to work out what the risk factors are for developing schizophrenia and also what the protective factors are because these people are healthy and functioning well,” she said.

“The other advantage is the potential to reduce some of the stigma that’s associated with schizophrenia. Unlike depression where you can feel blue or have clinical depression, schizophrenia is always seen as a very severe mental illness, which it is, but if we recognise that there’s some sort of continuum it might lessen the stigma.”

The researchers explored the association between the D1 receptor, encoded by the DRD1 gene, and schizotypy in a non-clinical sample of 127 healthy adults. They found that people with this gene have higher levels of ‘negative’ types of schizotypy symptoms such as lack of motivation, drive, energy and enthusiasm.

The gene codes for dopamine, primarily in the prefrontal cortex of the brain: there were many D1 dopamine receptors in that region, Dr Gurvich said.

“This is a piece of the puzzle in trying to understand what’s changing in the brain that’s leading to these symptoms,” she said. “It’s novel – this particular linking hasn’t been found before.”

The study’s findings add to the growing body of evidence that schizotypy and schizophrenia share a common biological basis related to genetic susceptibility, as well as shared pathological processes regarding dysregulation of dopamine functioning.

The research, which is ongoing, is part of a broader project looking at genes and cognition across the schizophrenia continuum. The team is now analysing data looking at the same gene in people with schizophrenia.

Gurvich C, Bozaoglu K, Neill E, Van Rheenen TE, Tan EJ, Louise S, Rossell SL. The dopamine D1 receptor gene is associated with negative schizotypy in a non-clinical sample. Psychiatry Res. 2016 Jan 30;235:213-4. doi: 10.1016/j.psychres.2015.11.051. Epub 2015 Dec 2.


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