Connections between genetics, brain activity, and preference found

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Washington, August 7 : Experts at Massachusetts General Hospital (MGH) have established connections between genetics, brain activity, and preference.

The researchers say that they brain imaging, genetics and experimental psychology techniques to identify a connection between brain reward circuitry, a behavioural measurement of preference and a gene variant that appears to influence both.

Writing about their work in the journal Archives of General Psychiatry, the researchers said that their findings had implications for how genes might influence healthy or dysfunctional behaviour involving choices in many different areas.

"This work helps connect our psychological understanding of why we like some things and not others with the genetic mechanisms that define our range of behaviours," said Dr. Hans Breiter, senior and corresponding author of the study and principal investigator for the Phenotype Genotype Project in Addiction and Mood Disorders, an interdisciplinary project involving the MGH Departments of Radiology, Psychiatry, and Neurology.

"In the ongoing discussion about how much the environment versus genetics determine behaviour, this study points to how the interaction between these factors influences our judgment and decision-making," Dr. Breiter added.

The researchers have revealed that their current study connects molecular genetics with earlier studies of choice and preference and with investigations of the brain's reward circuitry.

They focused on a gene called CREB1 that has been implicated in animal studies of the brain's reward/aversion function.

Lead author Dr. Roy Perlis, medical director of the MGH Bipolar Program, says that it has been previously found that depressed men with a particular variation near the gene coding for CREB report greater difficulty suppressing anger.

Another study by Perlis' team associated the same variation with a threefold greater risk of suicidal thinking in major depressive disorder patients soon after beginning antidepressant therapy.

The 28 participants in the current study had no evidence of any psychiatric disorder or physical disorder that might influence brain activity.

The researchers analysed each participant's version of the CREB1 gene, and conducted a set of experiments.

As the participants viewed facial expressions reflecting different emotional states - happy, neutral, sad, fearful and angry - fMRI scans were taken to examine the activity of brain structures associated with processing pleasant or unpleasant experiences.

In another test, participants viewed the same pictures and could change how long they viewed an image by the way they pressed keys on a keyboard. Keypress responses reflected participants' judgment and decisions about how much or how little they preferred the facial expressions.

The researchers found that, during the viewing of angry faces, the activity of a structure called the insula, involved in the response to unpleasant situations, depended on which version of the CREB1 gene a participant inherited.

In the keypress experiment, responses indicating a preference against the angry expression paralleled the CREB1-affected fMRI activity seen in the insula in the first experiment and also differed depending on the CREB1 variant that had been inherited.

"We were surprised to see that variation in the CREB1 gene would account for more than 20 percent of the difference in how healthy participants weighed different options and expressed specific preferences. Our previous studies and the work of other groups suggested that variation in this gene could be important for judgment and decision-making by the brain, but we needed to connect this to a measurable decision-making effect in both behavior and brain activity," says Perlis.

Dr. Breiter adds: "This study connects quantitative measurements across three levels of observation - brain activity, genomic variation and the expression of preference. We now are investigating the potential role of other genes and will go on to assess how this relationship across three levels of observation may be affected by conditions such as depression and addiction."

ANI

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