Amygdala, Prefrontal Cortex Are Keys to Anxiety: Bringing That Knowledge to Neuroimaging Should Help Pinpoint Diagnosis, Treatment Response

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ORLANDO -- A complex interaction of genetics, childhood stress, neurocircuits, the amygdala, and prefrontal cortex structures determines how a person develops and copes with anxiety, according to a presentation at a psychopharmacology congress sponsored by the Neuroscience Education Institute.

"As a psychiatrist, you probably need to know where the amygdala and prefrontal cortex structures are--you can leave the rest of the brain to the neurologists," Dr. Stephen M. Stahl said.

Knowing this anatomy will come in handy, because in the near future, psychiatrists likely will routinely use neuroimaging to diagnose anxiety and monitor patient response to treatment, Dr. Stahl predicted. Another advance will be genotyping of buccal swabs to determine patients' risk for anxiety and/or their potential response to treatment.

"As time goes on, the neurobiology will fit with your clinical intuition," said Dr. Stahl, of the department of psychiatry at the University of California, San Diego.

Genetic factors centered on serotonin have been linked to susceptibility to anxiety disorders. For example, the serotonin transport gene SLC6A4 codes for a short or long allele--and those with the short version are at higher risk. "S means you get shortchanged--that is how I remember this. People with S get more anxiety. People with L get less.

"More people with the wrong genetic makeup will have anxiety," Dr. Stahl said. "But not all will, because some have backup systems that compensate."

Functional MRI studies suggest that people with the S allele fire their amygdala more than do people with the L allele, and a "jumpy" amygdala is associated with higher anxiety levels. In addition, carriers of S alleles make fewer serotonin pumps, so they have less serotonin available. All this information will have implications for treatment, Dr. Stahl predicted. For example, "if you have the wrong gene, you won't get clozapine (Clozaril). If you don't have the wrong gene, you won't need monitoring while on clozapine."

Genes code for proteins, not for psychiatric disorders or behaviors, Dr. Stahl said. Specifically, combinations of proteins can exert a significant control over behavior: "Proteins don't cause symptoms; they change the circuit. …


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