High levels of a specific enzyme in fetuses linked to anxiety

July 24, 2013

Mouse embryos with the human enzyme CYP2C19 in the brain develop a smaller hippocampus and anxiety-like behaviour as adults. The results of this new study, which is published in the journal Molecular Psychiatry, agree in principle with earlier genetic findings in humans, and can improve science's understanding of the genetic factors behind depression and anxiety disorders and contribute to the development of new anti-anxiety drugs.

Scientists have long been searching for the genetic reasons for the great differences in sensitivity that people show towards depression and anxiety disorders. Now, researchers at Karolinska Institutet have taken a closer look at the CYP2C19 enzyme, which plays an important part in the of psychoactive substances, such as antidepressants (e.g. SSRI drugs). CYP2C19 also operates on endogenous substances that affect the central nervous system. Interestingly, there is a between humans, since mutations of the CYP2C19 gene leave people with no, low, normal or high levels of the enzyme.

The present study was conducted on , which had copies of the human CYP2C19 gene inserted into their DNA so that the researchers could examine if the expression of CYP2C19 affected brain function and behaviour. It was discovered that the enzyme was found in the brain of the mouse fetus, which developed differently to that of normal mice. The behaviour of the mice was then examined using a battery of four behavioural tests.

"We found behavioural changes indicating anxiety and a higher stress sensitivity," says research group leader Magnus Ingelman-Sundberg from the Department of Physiology and Pharmacology. "These findings can tell us more about the of anxiety and the transgenic mice can hopefully be used to develop new anxiolytic drugs."

The expression of CYP2C19 in the fetus produced that had a smaller, stress-hypersensitive hippocampus, an area of the brain essential to learning and memory, adaption and sensitivity to stress and emotional response. A dysfunctional hippocampus in humans is thought to play an important part in the development of both depression and anxiety disorders.

In an earlier study on twins conducted with epidemiologists from Karolinska Institutet, the group observed that individuals lacking the CYP2C19 enzyme display a less depressed base state, a finding that is supported in principle by the present study on mice. The researchers now plan to study what effects genetic variations of CYP2C19 have on the development of the human brain.

"If we can see similar changes in humans, it would improve our understanding of how changes in the developing fetal brain can increase the risk of depression and later in life," says Anna Persson, in whose doctoral project the study is included.

Explore further: Analysis does not support genetic test before use of anti-clotting drug

More information: "Decreased hippocampal volume and increased anxiety in a transgenic mouse model expressing the human CYP2C19 gene " Molecular Psychiatry, online 23 July 2013

Related Stories

In the brain, broken down 'motors' cause anxiety

February 7, 2013

When motors break down, getting where you want to go becomes a struggle. Problems arise in much the same way for critical brain receptors when the molecular motors they depend on fail to operate. Now, researchers reporting ...

Drug prevents post-traumatic stress-like symptoms in mice

June 5, 2013

When injected into mice immediately following a traumatic event, a new drug prevents the animals from developing memory problems and increased anxiety that are indicative of post-traumatic stress disorder (PTSD).

Recommended for you

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.