Caleb Gardner

Effects of negative stressors on DNA methylation in the brain: Implications for mood and anxiety disorders

Stress is a major contributor to anxiety and mood disorders. The recent discovery of epigenetic changes in the brain resulting from stress has enhanced our understanding of the mechanism by which stress is able to promote these disorders. Although epigenetics encompasses chemical modifications that occur at both DNA and histones, much attention has been focused on stress‐induced DNA methylation changes on behavior. Here, we review the effect of stress‐induced DNA methylation changes on physiological mechanisms that govern behavior and cognition, dysregulation of which can be harmful to mental health. A literature review was performed in the areas of DNA methylation, stress, and their impact on the brain and psychiatric illness. Key findings center on genes involved in the hypothalamic‐pituitary‐adrenal axis, neurotransmission and neuroplasticity. Using animal models of different stress paradigms and clinical studies, we detail how DNA methylation changes to these genes can alter physiological mechanisms that influence behavior. Appropriate levels of gene expression in the brain play an important role in mental health. This dynamic control can be disrupted by stress‐induced changes to DNA methylation patterns. Advancement in other areas of epigenetics, such as histone modifications and the discovery of the novel DNA epigenetic mark, 5‐hydroxymethylcytosine, could provide additional avenues to consider when determining the epigenetic effects of stress on the brain.

The land of the lotus eaters

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Shadowing: pediatric heart surgery in El Salvador.

In September 2009, the year before the author began medical school, he accompanied a team of doctors, nurses, and technicians from the nonprofit organization Heart Care International (HCI) on a trip to El Salvador. Founded in 1994 by the heart surgeon Robert Michler, HCI strives to provide care to children with congenital heart disease in developing countries. In addition to El Salvador, HCI has worked in Guatemala and the Dominican Republic, leaving behind lasting local programs and always looking to the future for new opportunities.

A Moment’s Thought: How to Tell a True Medical Story

O NE OF THE FIRST PATIENTS I INTERVIEWED ON MY own in medical school was a warm and energetic man in his mid-90s who, having slipped on a patch of ice the week before, had come to get a few stitches taken out of his lower lip. I was halfway through my first year and my heart sank as I looked at his list of medications and past health problems; for most of them, I knew just enough to know that I didn’t know anything. It was the second week of clinic and I had no idea where to begin trying to help this man who had outlived his wife and daughter and was now waiting, more patiently than I could have expected, for the physician across the hall to finish. So we just ended up talking for 15 minutes, about his life at first, but, later, also about Baltimore and medical school and the path that had brought me there. The importance of stories, or narrative, in clinical medicine is so commonly expressed that the idea often seems in danger of being reduced to a tagline. Clearly there is no question that stories are important. Among many other potential benefits, they help health professionals understand, categorize, and treat diseases and enable patients to come to terms with and find meaning in their experiences. If a story is important, then telling it well is important too. But telling a story well is not easy, and its truth is not communicated solely through fidelity to factual occurrence. The way in which a story is told is inextricable from the meaning it ultimately produces, and, as Yeats implied when he wrote “A line will take us hours maybe;/Yet if it does not seem a moment’s thought,/Our stitching and unstitching has been naught,” there are no shortcuts around the work required to get the words just right. The world of medicine is, by its nature, filled with events so dramatic, powerful, and laden with the universal elements of life and death, happiness and loss, that the form of any story is easily overshadowed by the content. From the scripting of “patient encounters” and rigidly structured reflective writing assignments in medical school, to clichéd accounts of patient distress and clinician selflessness, formulas make stories easier, or at least faster to tell, but they often feel untrue. Issues of form and content in medical narrative had been in my thoughts since the beginning of school, but it was an unexpected influence, a statistics-driven class on patient safety, that recently moved them to the forefront of my mind. Peter Pronovost, MD, director of the quality and safety research group at Johns Hopkins, gave the first lecture of the class, during which he showed a video clip from a meeting of physicians discussing an emergency case that had gone poorly. In response to what he would have done differently, one of the physicians replied that he would have pushed harder. However, was that the real problem? Had the patient not made it to the operating room in time simply because the physician did not urge the rest of the team to work quickly enough? Of course not. The real problem (an overfilled elevator, miscommunication among clinicians, misplaced equipment) was probably more complicated, involving multiple factors and traceable to various origins. Pronovost presented this clip as an example of well-intentioned but narrow-minded and self-centered thinking. I see it also as fundamentally a problem of poor narrative. The formula for the story was right there: a young physician honorably admitting to and learning from his mistake, doubling his efforts to save the next patient singlehandedly, and because it was a familiar explanation, because it “fit,” because it required no further thought from those listening, it was accepted. In his chapter on patient narratives, or “the life story,” psychiatrist Paul McHugh reminds us of Tolstoy’s take on history and describes his emphasis on the innumerable factors contributing to any single event. Equally compelling here, I think, is Tolstoy’s related notion of the fallacy of attributing any occurrence to the will of one person. Pronovost calls the idea of looking for causality beyond conventional sources (such as ourselves) “systems thinking,” and, like Tolstoy’s theory of history, it is a way of saying that reality is complicated and often ambiguous, as is our perception of reality; that understanding the world depends not only on understanding objective events, but