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New Studies Outline Different Approaches to Understanding and Perhap Treating Depression—Neuroscience 2013

When treating debilitating mental disorders, researchers look not only to the brain, but also to the body for answers. A new study in mice shows that levels of the inflammatory cytokine interleukin-6 (IL-6), a molecule that is produced and secreted by white blood cells of the immune system, can be used to predict how animals might react to social stress. The findings were presented at Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health. 30,000 scientists are attending this meeting. More than 350 million people worldwide suffer from clinical depression and between 5 and 25 percent of adults suffer from generalized anxiety, according to the World Health Organization. The resulting emotional and financial costs to people, families, and society are significant. Further, antidepressants are not always effective and often cause severe side effects. Social stress is one of the most significant contributors to depression in humans, yet some individuals experience no adverse effects, while others are vulnerable. Understanding the differences could drastically affect how depression is treated. In the IL-6 study, the researchers found that higher levels of IL-6 released by stimulation of the white blood cells before a defeat experience predicted depression-like behavior, while lower levels predicted stress-resistance. They also showed that reducing IL-6 in the body made mice immune to social stress. Conversely, increasing IL-6 with a bone marrow transplant from a stress-susceptible mouse had the opposite effect, provoking depression-like behavior. The results suggest that measuring stimulated IL-6, a chemical easily found in the blood, could serve as a biomarker for stress sensitivity. Furthermore, treatments to reduce IL-6 in the body might be effective in treating depression and related disorders. “This study changes the way we understand the relationship between our immune system and stress responses that can lead to depression. We now know that a specific reaction in the immune system actually predates, predicts, and can shape how we’ll respond to stress,” said the study’s lead author Georgia Hodes, Ph.D., of the Ichan School of Medicine at Mount Sinai (Georgia Hodes, Ph.D., abstract 542.1). “This may represent a legitimate biomarker for depression and could represent a new chapter in the effort to accurately diagnose and better treat mood disorders.” Additional important depression-related findings were also described at a Monday, November 11 press conference organized by Neuroscience 2013. “Today’s (reported) findings represent our rapidly growing understanding of the individual molecules and brain circuits that may contribute to depression and anxiety,” said press conference moderator Lisa Monteggia, Ph.D., of the University of Texas Southwestern Medical Center, an expert on mechanisms of antidepressant action. “These exciting discoveries represent the potential for significant changes in how we diagnose and treat these illnesses that touch millions.” Today’s additional new findings show that: decreasing a chemical signal in the amygdala, a brain area associated with emotional processing, produces antidepressant-like effects in mice (Yann Mineur, Ph.D., abstract 504); microRNAs, tiny molecules that alter gene expression, correlate with how mice respond to socially stressful situations that cause depressive-like behavior. The findings may help determine why some people are more likely to suffer from depression than others (Karen Scott, Ph.D., abstract 731.2); a pathway between two brain regions, the amygdala and the hippocampus, plays a significant role in anxiety. Shutting down this connection can decrease anxiety-like behavior in mice (Ada Felix-Ortiz, M.S., presentation 393.01); and aversive experiences can change how humans, particularly those with anxiety disorders, perceive stimuli. After a severe negative incident, patients with anxiety disorders over-generalize the experience and have increased emotional responses to subsequent similar situations (Rony Paz, Ph.D., presentation 295.05). The scientific presentations of these studies will be given on Tuesday, November 12, 9–10 a.m. PST. [Neuroscience 2013 Program] [Neuroscience 2013 Meeting]