Dopamine Linked to ‘Anxious’ Amygdalas


by Jim Schnabel

December 31, 2008

Easily stressed? Your amygdala might not be getting the right amount of dopamine, according to a recent study led by German researchers. The findings suggest a new approach to anxiety disorders, which are said to affect nearly 20 percent of adults in the United States. The dopamine connection might also help to explain why excess anxiety has been linked to Parkinson’s disease and other conditions involving disruptions of the brain’s dopamine circuitry.

“One can imagine in the distant future the development of a drug that selectively enhances dopamine signaling in the amygdala, leading to decreased anxiety,” says Ahmad Hariri, a neuroimaging expert at the University of Pittsburgh School of Medicine who participated in the study.

The amygdala is an almond-shaped structure nestled in both the left and right temporal lobes. Much remains to be learned about its various subregions and functions, but it seems to have evolved largely to help animals connect the events and situations of life with appropriate emotional reactions.

Although the amygdala appears to be involved in processing positive emotions, it is better known for its role in processing fearful and anxious emotional states associated with potential threats to survival. Animals whose amygdalas are experimentally damaged often lose their usual caution in the presence of strangers, even predators. In the classic demonstration, a rat whose amygdala has been removed will calmly approach even a sleeping cat. Humans with damaged amygdalas also show a blunted ability to react to things in the environment that would normally produce an emotional reaction.

On the other hand, excess anxiety doesn’t appear to be caused simply by a hyperactive amygdala. Recent research has suggested that problems in the way the prefrontal cortex and other brain regions respond to the amygdala’s activation may be more important.

“In simple terms, the amygdala is working to let you know that there’s something out there that may or may not be important for your survival,” says Hariri, “whereas the prefrontal cortex, once stimulated by the amygdala and also receiving feedback from your autonomic responses, is charged with determining what the best course of action is and, in doing so, quieting the amygdala.” 

In the recent study, published Nov. 2 in Nature Neuroscience, a group including Hariri and led by Thomas Kienast at the Charite Hospital in Berlin decided to look at how this amygdala–prefrontal cortex network is affected by the neurotransmitter dopamine. Nerve circuits originating in the midbrain are known to provide inputs of dopamine to the amygdala. As elsewhere in the brain, this dopamine signal appears to indicate the importance or “saliency” of a given event. The researchers wondered whether the levels of dopamine ready to be pumped from these nerve terminals inside the amygdala would help to determine how well the amygdala and prefrontal cortex communicate.

To find out, they first used positron emission tomography (PET) with a radioactive dopamine-like tracer to measure storage levels of the neurotransmitter in the amygdalas of 13 adult male volunteers. Then, using functional magnetic resonance imaging (fMRI), they studied changes in the activity of the amygdala, and a linked prefrontal region called the anterior cingulate cortex (ACC), when the same volunteers were shown a standard set of emotion-evoking images.

Kienast and his colleagues found that those with greater dopamine stores in the left amygdala—which seems to represent fear more reliably than the right amygdala—also tended to show greater and better ACC-linked left-amygdala responses in fMRI scans. Those with less amygdala-ACC integration were more likely to score higher on a psychological test for “trait anxiety”—the baseline anxiety level that comes with one’s personality.

In other words, says Hariri, “as the functional coupling between these brain regions increases, in part reflecting dopamine’s boosting effects on amygdala reactivity, the general tendency to experience events in your life as more stressful and anxiety-provoking decreases.”

Dopamine storage capacity in the amygdala is just one thing that can influence anxiety levels, Hairiri emphasizes, and more research is needed to spell out this and other influences.

However, such research could some day broadly affect our understanding of anxiety. In one recent study, for example, Japanese researchers found that dopamine storage in the amygdala and related regions declines with age, which raises the possibility that aging itself might disrupt the brain’s ability to process emotional states appropriately, including controlling excess anxiety. Other researchers have noted a strong association between anxiety and Parkinson’s disease—in which the supply of dopamine to some brain regions is lost. Kienast and some of his colleagues from the present study also published a paper in 2007 showing, among other things, an association between reduced dopamine storage in the amygdala and worse symptoms in people with schizophrenia.

Anxiety also is common in drug-addiction withdrawal, notes George Koob, an expert on the neurobiology of addiction at the Scripps Research Institute in La Jolla, Calif. For example, Koob says, “binging on cocaine may ultimately lead to more and more anxiety-like responses that persist into protracted abstinence.” The findings of Kienast, Hariri and colleagues are consistent with the idea that drug-induced disruptions of dopamine signaling can bring about such long-term shifts towards greater anxiety, Koob adds.