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Psychiatry Newsletter - The bench. The bedside.

Hopkins BrainWise - Winter 2012

The bench. The bedside.

Date: January 2, 2012

Brief notes

A constant wash of the stress hormone cortisol increases body fat and risk of the evil trinity: diabetes, coronary artery disease and osteoporosis. That’s not to mention rearranging synapses, disturbing cognition and mood and lessening brain mass—all while thwarting nerve cell regrowth. Being able to measure a patient’s cortisol “burden” over time, then, is highly desirable—proof, for example, that life changes are in order. But a way to measure average cortisol levels over time is elusive because they fluctuate so, even within a single day. So Gary Wand’s team has hit on an indirect tactic. It’s based on the stress response gene, Fkpb5. The gene—which has a role in stress-sensitive psychiatric disease like PTSD—changes structurally during long-term cortisol exposure.

The team found that in mice with month-long artificially elevated cortisol, Fkpb5 showed matching epigenetic changes. The next step is to see if the changes hold in more realistic social stress situations. Call 410-614-0056.

Brain opioids take center stage in regulating feelings of pain and pleasure. They also influence alcohol’s effects and the desire to drink. But how? In new PET studies run by Betsy McCaul’s team, people dependent on alcohol were compared with social drinkers. The former clearly had a denser outlay of key opioid receptors in brain areas tied to alcohol reward, dependence and craving. What caused the receptor uptick? Was it alcohol withdrawal? Long-term excessive drinking/dependence? A person’s native genes? Childhood adversity or chronic stress? More research will tell, says McCaul. Call 410-955-9526.

Naltrexone cleanly blocks the effects of heroin and other opioids. And unlike the methadone or buprenorphine used as addiction therapy, you can’t overdose on it; it gives no “high.” Naltrexone would be ideal in addictions clinics if only patients would take it. Kenneth Silverman’s team, however, sees an opening, an option that could increase willingness. In a study of 38 detoxified dependent adults, the team offered the added option of training in a workplace situation and being paid in redeemable vouchers. One group had to take (new extended-release) naltrexone in order to work. The other half could earn vouchers, but getting naltrexone was optional. Result? Those compelled to take naltrexone in order to work stayed with the therapy far longer.  Call 410-550-2694.

Binge eating not only changes brain chemistry, but bouts of overeating fats and sugars may change it in a way that, ironically, encourages the problem. To clarify what’s going on, Angela Guarda has studied the distribution of cannabinoid receptors—yes, like that cannabis, though the cannabinoids involved here are self-generated—in brain areas tied to food intake and body weight. Her team worked with rats offered sweetened Crisco under various conditions that reflect aspects of human binge eating or dieting habits in patients with eating disorders. The rat brains showed characteristic decreases in the density of these receptors in key brain regions, depending on the lardy treat’s availability. Call 410-955-3863.

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