Psychiatric illness and drug addiction may have a high frequency of comorbidity because of a common cause in the amygdala, according to an article in the December issue of Behavioral Neuroscience.

Researchers identified developmental changes in the amygdala, a region associated with fear and other emotions.

Lead author Andrew Chambers, MD, cited clinical reports that at least half of the people who seek help with addiction or mental-health treatment have co-occurring disorders. Epidemiological data indicate that from 2 to 5 of every 10 anxious or depressed people, and from 4 to 8 of every 10 people with schizophrenia, bipolar disorder, or antisocial personality, have some type of addiction.

To find the scientific basis for this complex, seemingly intractable pairing, Chambers' team at the Indiana University medical school compared the adult mood- and drug-related behavior of two groups of adult rats: those whose amygdalas were surgically damaged in infancy and those whose amygdalas were left intact but who underwent a sham surgery to equalize treatment.

Rats with damaged (lesioned) amygdalas grew up abnormally under-responsive to ambiguous or potentially threatening stimuli. Not showing normal caution, they moved significantly more in response to novelty, showed significantly less fear in an elevated maze, and kept socializing even when exposed to the scent of a predator.

Crucially, these same rats also were significantly more sensitive to cocaine after just one exposure. In addition, rats given repeated cocaine injections later showed even stronger expressions of the enduring changes in behavior - suggesting an overall hypersensitivity to the addictive process.

Given that the experimental and control rats were raised in the same tightly controlled conditions, the only difference brain status, researchers concluded that the integrity of the amygdala was the root cause of both impaired fear behavior and heightened drug response.

"Brain conditions may alter addiction vulnerability independently of drug history," said Chambers. He and his colleagues concluded that someone's greater vulnerability to addiction, rather than a given drug's ability to alter the symptoms of mental illness for better or worse (usually worse), more fully explains the high rates of dual diagnosis.

For these reasons, and given the lab evidence and the fact that dual diagnosis patients do less well on psychiatric medication than other patients, Chambers wondered whether the underlying problems in the brain - what he calls "neural inflexibility" -- make it harder for these people to respond.