A cure for fear?

GlobalPost
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SYDNEY, Australia — Men and women process fear differently. Females are twice as likely to suffer from anxiety — but why that is remains a mystery.

And there is also no explanation for why, despite considerable advancements in the treatment of anxiety, relapses are still common.

But groundbreaking research by a young Australian scientist and clinical psychologist on how the brain stores memories could ultimately lead to a cure for anxiety.

At just 25, Bronwyn Graham, a postdoctoral research fellow at the University of New South Wales, has discovered that a neurotransmitter in the brain, called fibroblast growth factor 2, may be important in storing memories.

When she gave fibroblast growth factor 2 to rats, it greatly enhanced their ability to form a new memory — which therapists call a ‘‘fear extinction’’ memory — and could provide a breakthrough treatment.

Scientists have essentially reached what Graham calls a ‘‘therapeutic impasse’’ on anxiety treatment.

Exposure therapy is used to treat anxiety disorders by gradually exposing a person to their fear and teaching them how to cope with it.

For it to be effective, patients must form new memories (fear extinction memories) and anxiety sufferers are not good at this. Thus there are high levels of relapse, indicating some type of dysfunction in their neural circuitry, she said.

Neuroscientists around the world are working to identify structural changes to the brain that underlie how memories are formed and what causes them and Graham is the first to discover that fibroblast growth factor 2 plays a factor.

Next year, Graham, whose doctoral thesis results are due in September, will move to America to continue her research under a $25,000 Neurological Fellowship by the American Australian Association. She will work at the Department of Psychiatry at Harvard Medical School and at Massachusetts General Hospital.

At Harvard, she will examine possible sex differences in the neural circuitry underlying fear inhibition. In particular, she will study the effect of women’s menstrual cycles on fear and anxiety levels.

‘‘Women are twice as likely as men to develop anxiety disorders but we don’t know why this is,’’ Graham said.

‘‘There’s something about women that makes us more vulnerable,’’ she said.

Graham suspects it may have something to do with fluctuations in estrogen — namely, a vulnerability when levels are low.

‘‘There are a lot of estrogen receptors in the neural circuitry and women have more estrogen and we also have fluctuations in the estrogen cycle [due to pregnancy, menopause and the menstrual cycle],’’ she said.

Graham is at the cutting edge of psychology — juggling the demands of lab work at the University of New South Wales while also seeing patients at her Sydney-based clinical practice.

Her posting to the United States came about after she met Harvard’s associate professor Mohammed Milad at the Society for Neuroscience conference in Chicago last year and he invited her to present her research on fibroblast growth factor 2 in Boston.

‘‘Two hours after she presented I got an email from them saying is Bronwyn as good as she seems she is and I emailed back and said actually she’s better,’’ said her supervisor, Rick Richardson.

‘‘Being able to get across these two fields is really remarkable and I think it’s the future of psychology and hopefully she’ll be a leader in the field,’’ he said.

At Harvard, she intends to use a method developed by Milad in which images of the brain are taken while a person is being trained to overcome the fear they are experiencing.

She hopes to define which brain structures are important in "fear extinction." The use of fibroblast growth factor 2, which occurs naturally in the body, is still in human clinical trials in the United States.

Current anti-anxiety drugs are designed to reduce the fear a person feels but do not help them process the information causing that fear so that a better memory is formed.

Milad has already experimented with rats and discovered that when estrogen levels are low the animals are more susceptible to fear and anxiety and that can be alleviated with regular injections of the hormone.

‘‘What that suggests is that estrogen might actually be protective,’’ Graham said.

If Graham is able to prove that estrogen plays an important role in anxiety disorders, this could also lead to a breakthrough treatment for both women and men.

The Harvard lab is one of very few places in the world that specializes in ‘‘translational research’’ — translating findings from animal research to treatments in humans at the one site.

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