Imaging Biomarker Predicts Response to Rapid Antidepressant

Signals Dysfunction in Brain System Targeted by Scopolamine – NIH Study A telltale boost of activity at the back of the brain while processing emotional information predicted whether depressed patients would respond to an experimental rapid-acting antidepressant, a National Institutes of Health study has found. NIMH’s Dr. Maura Furey talks about scopolamine research “We have discovered a potential neuroimaging biomarker that may eventually help to personalize treatment selection by revealing brain-based differences between patients,” explained Maura Furey, Ph.D., of NIH’s National Institute of Mental Health (NIMH). Furey, NIMH’s Carlos Zarate, M.D., and colleagues, reported on their functional magnetic resonance imaging (fMRI) study of a pre-treatment biomarker for the antidepressant response to scopolamine, Jan. 30, 2013, online in JAMA Psychiatry. Scopolamine, better known as a treatment for motion sickness, has been under study since Furey and colleagues discovered its fast-acting antidepressant properties in 2006. Unlike ketamine, scopolamine works through the brain’s acetylcholine chemical messenger system. The NIMH team’s research has demonstrated that by blocking receptors for acetylcholine on neurons, scopolamine can lift depression in many patients within a few days; conventional antidepressants typically take weeks to work. But not all patients respond, spurring interest in a predictive biomarker Alcoholism and Drug Abuse Counselors Continuing Education The acetylcholine system plays a pivotal role in working memory, holding information in mind temporarily, but appears to act by influencing the processing of information rather than through memory. Imaging studies suggest that visual working memory performance can be enhanced by modulating acetylcholine-induced activity in the brain’s visual processing area, called the visual cortex, when processing information that is important to the task. Since working memory performance can predict response to conventional antidepressants and ketamine, Furey and colleagues turned to a working memory task and imaging visual cortex activity as potential tools to identify a biomarker for scopolamine response. Depressed patients have a well-known tendency to process and remember negative emotional information. The researchers propose that this bias stems from dysregulated acetylcholine systems in some patients. They reasoned that such patients would show aberrant visual cortex activity in response to negative emotional features of a working memory task. They also expected to find that patients with more dysfunctional acetylcholine systems would respond better to scopolamine treatment. Before receiving scopolamine, participants performed a working memory task while their brain activity was monitored via fMRI. For some trials, it required that they pay attention to, and remember, the emotional expression (sad, happy, etc.) of faces flashing on a computer monitor. For other trials, they had to pay attention to only the identity, or non-emotional feature, of the faces. After scanning, and over the following several weeks, 15 patients with depression and 21 healthy participants randomly received infusions of a placebo (salt solution) and/or scopolamine. Mood changes were monitored with depression rating scales. Overall, scopolamine treatment reduced depression symptoms by 63 percent, with 11 of the patients showing a significant clinical response. The strength of this response correlated significantly with visual cortex activity during key phases of the working memory task – while participants were paying attention to the emotional content of the faces. There was no such correlation for trials when they attended to the identity of the faces. The findings suggest that acetylcholine system activity drives visual cortex activity that predicts treatment response – and that differences seen between depressed patients and controls may be traceable to acetylcholine dysfunction. Overall, patients showed lower visual cortex activity than controls during the emotion phase of the task. Patients showing activity levels most dissimilar to controls experienced the greatest antidepressant response to scopolamine treatment. Visual cortex activity in patients who didn’t respond to scopolamine more closely resembled that of controls. As hypothesized, the pretreatment level of visual cortex activity appears to reflect the extent of patients’ acetylcholine system dysfunction and to predict their response to the experimental medication, say the researchers. Preliminary evidence suggests that such visual cortex activity in response to emotional stimuli may also apply to other treatments and may prove to be a shared biomarker of rapid antidepressant response, according to Furey. The level of increased activity in left and right visual cortex (blue), while attending to emotional faces in a working memory task, predicted depressed patients’ responsiveness to the experimental antidepressant scopolamine. View from the back of the brain shows fMRI data superimposed on anatomical MRI scan data. Source: Maura Furey, Ph.D., NIMH Experimental Therapeutics and Pathophysiology Branch Working memory task: Over several trials, participants were required to attend to either the identity (non-emotional feature) or the emotion of a face, remember it during a 9 second delay, and match the feature to a subsequent face. Neural activity in the visual cortex elicited by the emotion trials predicted a patient’s subsequent responsiveness to scopolamine treatment. Source: Maura Furey, Ph.D., NIMH Experimental Therapeutics and Pathophysiology Branch References Potential of Pretreatment Neural Activity in the Visual Cortex During Emotional Processing to Predict Treatment Response to Scopolamine in Major Depressive Disorder. Furey ML, Drevets WC, Hoffman EM, Frankel E, Speer AM, Zarate CA. JAMA Psychiatry. 2013 Jan 30:1-11. doi: 10.1001/2013.jamapsychiatry.60. [Epub ahead of print] PMID:23364679 Cholinergic Modulation of Cognition and Emotion in Mood Disorders ### The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Therapists phone it in and keep more patients

Telephone therapy retains more patients than face-to-face sessions and improves depression CHICAGO --- Phoning it in is more effective than the therapist's couch when it comes to keeping patients in psychotherapy. New Northwestern Medicine research shows patients who had therapy sessions provided over the phone were more likely to complete 18 weeks of treatment than those who had face-to-face sessions. The study, published in the June 6 issue of the Journal of the American Medical Association, is the first large trial to compare the benefits of face-to-face and telephone therapy. Phone therapy is a rapidly growing trend among therapists. About 85 percent of psychologists now deliver some of their services over the phone because competing demands, transportation time and other problems make it difficult for many patients to get to their offices social worker continuing education "Now therapists can make house calls," said David Mohr, the lead author and a professor of preventive medicine at Northwestern University Feinberg School of Medicine. "Our study found psychotherapy conveniently provided by telephone to patients wherever they are is effective and reduces dropout. This suggests these services now should be covered by insurance." While telephone therapy was as effective as face-to-face sessions in reducing depression during treatment, the improvement ebbed slightly six months after treatment ended compared to face-to-face therapy. The randomized control trial included 325 primary care patients with major depressive disorder. The results showed 20.9 percent of patients who had cognitive behavioral therapy over the phone dropped out compared to 32.7 percent for face-to-face therapy. Patients in both therapies showed equally good improvement in their depression when treatment ended. Six months after treatment ended, all patients remained much improved. However, patients who had the telephone therapy scored three points higher on a depression scale than those who had face-to-face sessions. "The three point difference is of questionable clinical significance but it raises the question whether some individuals are at risk of worsening after treatment with telephone therapy compared to face-to-face," Mohr said. It may be that the slight worsening seen in the telephone therapy after the end of treatment was because patients who had more mental health difficulties and who would have dropped out of face-to-face sessions were retained in telephone therapy, Mohr noted. Thus, this may not be a real finding. "But we can't rule out the possibility that it may be true and there is something about face-to-face treatment that creates better results for some people," Mohr said. "The physical presence of the therapist may be therapeutic in a way that helps some patients maintain their improvement in mood. There may be a unique quality about the human contact that increases resilience and maintains the skills learned to manage depression after treatment has ended." Mohr said he hopes the study results will encourage insurance providers including Medicare to reimburse telephone therapy sessions, which many companies currently don't cover. "There is good reason to reimburse these sessions," Mohr said. "Many people can't get to a therapist's office, but they want to talk to someone. Telephone therapy is highly effective and offers a solution to people with depression who otherwise would be left out." This is particularly true for disabled people or those who live where care is unavailable, such as in rural areas, he noted. Research shows people prefer talk therapy to antidepressant medication, but many quickly drop out of treatment or don't follow up on a referral from their primary care physicians, likely the result of obstacles that prevent them from getting to the therapist's office. ### Other Northwestern authors include: Joyce Ho, Jenna Duffecy, Michelle Nicole Burns, Ling Jin and Juned Siddique. This study was funded by the National Institute of Mental Health of the National Institutes of Health research grant NIMH R01-MH059708.