Imagine that a psychiatrist sees two new patients. The first says she's having trouble sleeping, isn't interested in eating, and can't find joy in activities she once loved. The second also reports that he doesn't enjoy the things he once did, but his other symptoms are the opposite of the first patient's: he's having a hard time getting out of bed, can't stop eating, and has gained weight. Eventually, both are diagnosed with depression and started on similar courses of treatment.

Like patients with depression, people who have autism spectrum disorder can also experience varying symptoms that fall under the same diagnosis. While one person with autism might be nonverbal and have an IQ of 30, another might have an IQ 100 points higher and speak cogently — but repeat a lot of what he or she says, obsess about specialized topics like trains or the weather and have trouble connecting with peers. What unites them are deficits in their social interactions, sensory processing, learning and memory, and verbal and non-verbal communication.

This variability in clinical presentation isn't the only similarity between autism and depression. Some of the root causes of both may be similar, says Dr. Conor Liston'08, an assistant professor of neuroscience in the Feil Family Brain and Mind Research Institute — and understanding what drives each condition is key to developing targeted therapies. "For both depression and autism, our long-term goal is to customize treatments rather than taking a one-size-fits-all approach," says Dr. Liston. "We're at the basic science level today, but in the not so distant future, the work we're doing might lead to personalized medicine for neuropsychiatric conditions."

For years, Dr. Liston has focused his studies on how nerve cells within the prefrontal cortex — an area that supports cognition, socialization and emotion recognition — communicate with each other and ultimately drive behavior. He theorizes that when there are misfires within these pathways and neural circuits subsequently fail to reconnect — especially during the transition from adolescence to adulthood — depression and other psychiatric conditions may result. Although autism is often diagnosed in childhood rather than adolescence, it too may link back to problems with connections within communication circuits in the brain, Dr. Liston says.

To test this hypothesis, Dr. Liston will revisit an approach he earlier used to identify subtypes of depression. For that work, which is currently in journal review, he studied more than 700 fMRI brain scans of depressed patients gathered from labs at Cornell, Stanford and Emory universities, and discovered distinct patterns. "We found that patients with depression have abnormal connectivity in circuits throughout different regions of the brain," he says. "Basically, in the depressed brain, the wiring is off." He grouped the scans that looked alike, and noted that they corresponded to patients with similar clinical symptoms. The result is what's called a biomarker: a measurable variable — in this case abnormal brain circuitry — that's tied to the same disease process. Ultimately, doctors might be able to discern from a brain scan whether a patient suffers from depression, what sub-type it is, how it might present clinically — and the optimal way to treat it. "Right now, some antidepressants only work in one-third of the people who take them," Dr. Liston notes. "We can do better."

Dr. Liston points out that this work is so challenging — and so important — in part because science still knows relatively little about how the brain works. But new technologies are giving researchers unprecedented insights into its processes, potentially offering great leaps in understanding about neuropsychiatric diseases and how to treat them. To describe the current state of knowledge, Dr. Liston offers an analogy to a computer. The brain's physical structure is the hardware, and when something goes wrong — like the development of a tumor — it's easily detectible on an MRI. But "software" problems are a different matter. "In a person with depression, you can't look at their brain and see anything structurally abnormal about it," Dr. Liston says. "There's something about the software — or the computations being performed by the brain — that is causing a problem."

For his new work on autism, Dr. Liston will use funding from his recent Hartwell Foundation Individual Biomedical Research Award, a grant of $300,000 over three years. His data set: brain scans and clinical information from 1,000 kids with autism, which affects an estimated one in 68 children in the United States. Because he typically studies adolescence and young adulthood, he'll focus on scans from patients aged 10 to 16, scrutinizing them for atypical patterns in neural connectivity within the prefrontal cortex. From there, as in the depression study, he'll try to link the atypical connectivity patterns to specific symptoms. Given the diversity of how autism presents, it's no small task; Dr. Liston predicts the project will require the entire three-year Hartwell Award term. "Once we've identified subtypes of these disorders, we can try to figure out what's going wrong in patients' brain circuits, what molecules are causing these wiring mistakes, and what drugs might be used to rewire them in a more functional way," Dr. Liston says. "With better tools, drugs and interventions, we'll hopefully reach the end goal: to improve each patient's quality of life."

— Anne Machalinski

This story first appeared in Weill Cornell Medicine, Vol. 14, No.3.

A new program explores the lingering effects of Superstorm Sandy

Those are some of the questions that a recently launched service project hopes to answer. "There's emerging data out of New Orleans after Hurricane Katrina that the mental health effects are long-standing," says the project's designer, Dr. Jo Anne Sirey, an associate professor of psychology in psychiatry, who explains that major storms strike especially hard at adults over 60 who have pre-existing mental health conditions. "But even individuals who may not be suffering from depression, anxiety or alcohol abuse watch the news, and when we head into another hurricane season it brings back a kind of anniversary response and they worry."Three years after the floodwaters of Superstorm Sandy receded, it's not only homes that remain unrepaired. Less visibly, the lives of many New Yorkers disrupted by the stress and physical destruction of that epic event are nowhere near back to normal. Especially impacted were senior citizens. How many are still suffering? What services do they need?

Dr. Sirey estimates that at least 10 percent of the 500,000 older residents in the five boroughs may still suffer Sandy aftereffects. By interviewing as many as 2,000 New Yorkers, the project — dubbed Sandy Mobilization, Assessment, Referral and Treatment-Mental Health (SMART-MH) — is designed to assess how well older residents displaced by the storm are doing, and help connect those in need with appropriate services and counseling.

With $1.4 million in FEMA funds, SMART-MH has hired and trained an interdisciplinary team of two dozen outreach workers. Many are bilingual, speaking such languages as Spanish, Cantonese, Mandarin, Russian, Japanese and Farsi. Armed with dedicated mobile phones and notebook computers, these clinicians, social workers, and student trainees can enter data on the spot and, when merited, make immediate referrals for counseling or support services. The outreach began last fall, and by year's end had assessed more than 100 individuals; the project runs through September 2016.

In addition to documenting the ongoing concerns of Sandy victims — and essentially putting them on an emergency services map should another storm strike — another goal of SMART-MH is to function as a social services matchmaker. One of those contacted is Birdella McGreachy, a 70-year-old African American and lifelong New Yorker. McGreachy spent two days without power or running water in her 16th-floor Coney Island apartment, which is located a block from the beach and boasts views of the Atlantic. She moved in with her sister in an unflooded part of Brooklyn, but relations grew tempestuous as her stay pushed into the second week. Nor did finally putting the key in her own front door return McGreachy's life to normal. The elevators to her building weren't working for the first couple of days, so she had to take the stairs, carrying up food from the Red Cross truck parked across the street. "I look at the ocean every day and I think, it's so beautiful but so deadly," she says. "That storm put the fear of God in me. It was like the beach came to the people instead of the people going to the beach. The other day, when it was raining so hard and they were calling it a Nor'easter, that was nothing. But I'm always watching that water."

McGreachy and her SMART-MH outreach worker have discussed the possibility of counseling, and he put her in touch with a city social worker to address a difficult family issue unrelated to the storm. He's also arranging for assistance in cleaning her apartment and getting groceries; before the storm, she got shopping help from a nearby senior center, which only recently reopened. "As we're meeting with senior centers, mental health providers, and faith-based communities, we're hoping we'll leave behind some connections that didn't exist before," Dr. Sirey says. "We're creating relationships that may live on beyond this program."

— John Grossmann

A version of this story first appeared in Weill Cornell Medicine,Vol. 14, No. 1.

A rule proposed in 2014 that would have likely reduced the number of prescription antidepressant drugs available to Medicare patients would have had little impact on clinical care had the policy gone into effect, a new study from Weill Cornell Medical College suggests.

As a cost-saving measure, the Centers for Medicare and Medicaid Services (CMS) proposed removing special protections for antidepressants, which require insurers to cover nearly all drugs in that class. Comparative effectiveness research found no significant differences on average between antidepressant drugs within the same subclass. The CMS proposal sought support from this evidence and would have allowed Medicare Part D prescription drug plans to cover as few as two of some 30 related antidepressants within each subclass. Patient groups, the pharmaceutical industry, insurers and policymakers opposed the rule — which CMS eventually abandoned — arguing that the changes would harm millions of older and disabled Americans by restricting their drug choices.

Funded by the National Institute of Mental Health and the National Institutes of Health Clinical and Translational Science Awards program, investigators from Weill Cornell and the University of Pittsburgh sought to quantify the effects the proposed policy would have on patient care. The findings, published Jan. 21 in JAMA Psychiatry, found that few patients would have been affected by the policy change had it been implemented.

For the study, the investigators examined patient records of more than 47,000 Medicare beneficiaries who were treated for depression in 2009 and 2010 and found that only 4 percent of them tried more than two antidepressants over the course of treatment.

"More importantly, we found that 76 percent of patients used only one drug throughout treatment," said lead author Dr. Yuhua Bao, an associate professor of healthcare policy and research at Weill Cornell. "This suggests a disconnect between actual clinical practice and compelling scientific evidence of the benefits of at least two antidepressant drug trials for a vast majority of patients."

Implemented in 2006, Medicare Part D give special protections to six drug classes, including the five subclasses of antidepressants. The U.S. Affordable Care Act in 2010 authorized CMS to propose changes to the prescription drug program's "protected status" requirement, based on certain care quality and cost-savings criteria.

Dr. Bao believes the current debate detracts from a probably more important discussion about gaps in depression treatment.

"Comprehensive drug coverage alone is not enough to improve the quality of depression management," Dr. Bao said. "Ultimately, better outcomes are achieved when doctors and patients work together throughout the course of treatment, which may include regular monitoring of a patient's symptoms and response to medication and adjustment of their antidepressant regimens to maximize the benefits of treatment."

Exercise is key to improving health outcomes for patients who suffer from cardiovascular disease and depression, according to new research findings from Weill Cornell Medical College investigators.

Previous research has shown that patients who have both cardiovascular disease and depression have as much as a two times greater risk for adverse events, such as heart attacks and death, and frequently present with other chronic diseases, though the biological reasons behind this are not fully understood. With recent scientific literature suggesting that physical inactivity may be at the root of that increased risk, the Weill Cornell investigators set out to see if exercise would tangibly improve these patients' health.

Dr. Janey Peterson. Photo credit: Faye Osgood

Their findings, published Nov. 13 in the journal Clinical Therapeutics, shed light on the biological mechanics of those improved health outcomes, and offers a threshold for just how much physical activity is needed to reduce risk.

"This study allowed us to dig deep into the biological mechanisms underlying why exercise helps decrease morbidity and mortality," said first author Dr. Janey Peterson, an associate professor of clinical epidemiology in medicine, in cardiothoracic surgery and in integrative medicine. "That's what is so exciting about this."

Researchers have recognized the connection between cardiovascular disease and depression in increasing the risk of adverse health outcomes for three decades, but previous attempts to improve clinical outcomes in this population have proven disappointing, Dr. Peterson said. Scientists have examined several strategies to treat these patients, such as using antidepressants to improve depressive symptoms and thereby reduce morbidity and mortality, but none of them have ultimately been successful, Dr. Peterson said.

In their study, the Weill Cornell investigators enrolled 242 patients who had recently undergone a non-surgical procedure to open narrow or blocked coronary arteries — 89 of whom had high levels of depressive symptoms — in a randomized, 12-month clinical trial evaluating the efficacy of exercise on this population. A subset of 54 patients agreed to participate in a biological measures sub-study.

Patients' physical activity, demographic, psychosocial characteristics and depressive symptoms were evaluated at the beginning of the trial to establish a baseline; patients in the biological study also gave blood. Participants were asked to increase their physical activity to the equivalent of walking about 4.2 miles per week.

While all of the patients were given an educational workbook about cardiovascular disease and how to live with it, half of the participants received an induction of positive affect intervention. Positive affect, a feeling of happiness and wellbeing, has been shown in non-clinical studies to enhance positive feelings, lead to higher self-efficacy, increase intrinsic motivation and promote flexible thinking and healthier behaviors. Weill Cornell investigators are credited as the first group to translate and develop induction of positive affect for use in clinical patient groups, which Dr. Peterson and her colleagues have recently employed to successfully motivate physical activity and other health behaviors, such as medication adherence.

Patients receiving induction of positive affect received small, unexpected gifts in the mail, such as fleece blankets or umbrellas. Researchers followed up with patients by phone at bimonthly intervals during the year; staff induced positive affect for patients in the intervention group at the end of each call.

Investigators found that patients who walked 4.2 miles or more per week for a year, regardless of what group they were in, had lower rates of cardiovascular morbidity and mortality. Patients with high depressive symptoms who achieved that physical activity benchmark were nearly nine times less likely to experience a major cardiac complication or death over the course of the study.

The biological study seems to confirm these findings. Researchers compared blood samples taken at baseline and at the end of the trial, measuring the amounts of a peptide (interleukin-6) and protein (C-reactive protein) that are implicated in inflammation and also examining activity in the parasympathetic branch of the autonomic nervous system, which is tasked with restraining a person's stress response. Higher activity is associated with reduced inflammation and better cardiovascular health.

Patients who met the physical activity benchmark had an increased ability to respond to stressors in a healthy way, a decrease in the biological markers of inflammation, interleukin-6 and C-reactive protein, Dr. Peterson said.

"The biological study provides strong evidence as to why physical activity works so well," she said. "We now have longitudinal data that we didn't have before. We can now show in a structural equation model, from baseline to a year later, how important physical activity benchmark is for patients with cardiovascular disease and the mechanisms."

A new care-management intervention developed by Weill Cornell Medical College investigators may provide relief to homebound older adults who suffer from moderate to severe depression.

The intervention trains nurses to both identify and manage clinically significant depressive symptoms. They do this by collaborating with the patient's physician to manage patients' anti-depressant adherence and side effects (nurses are not allowed to prescribe medications), provide a game plan designed to improve their symptoms — such as encouraging the patient to socialize and tend to their appearance — and educate their loved ones about their condition. Medical homecare nurses can integrate the technique into their routine practice and administer it while treating their patients for their primary medical conditions.

"The program provides nurses with a framework to deal with depression," said first author Dr. Martha Bruce, the DeWitt Wallace Senior Scholar and a professor of sociology in psychiatry at Weill Cornell. "It builds on their clinical skills and addresses nurses' observations that depression interferes with successful management of other medical problems."

The intervention could benefit more elderly, homebound people who need mental health services than are able to access them now. While older adults who are being treated at home for chronic diseases or physical disabilities are more likely to also have depression, a shortage of psychiatrically trained homecare nurses, compounded by the way Medicare covers care provided by such professionals, limits treatment options for affected patients, according to the study.

Dr. Bruce and her coauthors conducted a randomized clinical trial at six certified home-health agencies around the country to test the efficacy of the intervention, called Depression CAREPATH. Their study, published Nov. 10 in JAMA Internal Medicine, found that CAREPATH successfully relieved the symptoms of patients who have moderate to severe depression. The finding underscores the value of medical homecare nurses as care deliverers, as well as the need for improved homecare mental health services, Dr. Bruce said.

"We designed CAREPATH to reach as many patients as possible. We wanted something that would be effective but also flexible enough to fit in with different home-health organizations," Dr. Bruce said. "To put an intervention on top of an existing service is difficult since many agencies can’t afford the costs of sending an extra person to the home."

More than a quarter of all homebound patients receiving care through Medicare's home health program suffer from depression—a result consistent with the disability, chronic illnesses and other stresses that characterize the population — yet many don't receive mental health treatment. Medicare will typically only cover the cost of psychiatrically trained homecare nurses (a rare specialty) if patients' primary diagnosis is mental illness. Even if there are trained nurses available, Medicare's bundled payment schedule discourages home health agencies from authorizing extra home visits, Dr. Bruce said.

Working with researchers, homecare clinicians and administrators, Dr. Bruce and her colleagues developed CAREPATH to fill this void and mediate the financial and physical burdens that depression causes. CAREPATH provides nurses with instructions to follow given their patients’ depressive symptoms and a way to manage and identify their psychological state over time. Nurses can deliver the combination of approaches during their routine patient visits. The procedures are understandable and relatable to nurses, tapping into principles and terminology familiar to their practice.

Six home health agencies across the country piloted the program for the clinical trial, testing the effectiveness of CAREPATH compared to basic training to identify depression, but not on how to manage their symptoms.

During a regular homecare visit, nurses provided patients over 65 with a questionnaire gauging depression, with those identified as depressive receiving one of the two therapies on a randomized basis. The nurses treated them, and researchers conducted multiple follow-up interviews about their condition, for a year.

Dr. Bruce and her colleagues found that patients with more severe depression who were treated with CAREPATH had a more significant improvement in their conditions than those whose nurses had received basic training to identify depression. The outcome was the same whether or not patients were taking antidepressants, and did not require additional nurse visits or more nurse time in the home.

Cornell's Translational Research Institute for Pain in Later Life (TRIPLL), a New York City-based center to help older adults prevent and manage pain, has received a five-year, $1.95 million renewal grant from the National Institute on Aging.

The institute, formed in 2009 as one of 12 national Edward R. Roybal Centers for Translational Research on Aging, studies innovative, nonpharmacological methods to ease persistent pain, which is estimated to afflict nearly half of older Americans. TRIPLL unites social and psychological scientists at Cornell's Ithaca campus, Weill Cornell Medical College researchers and community-based health care partners.

With the grant renewal, TRIPLL adds a focus on behavior change science, seeking to apply insights from psychology, sociology, economics and communications to develop optimal pain management techniques. For instance, knowing how and why older adults decide on various medications, therapies, exercises and other methods to limit pain can help individuals and their caregivers to weigh their preferred treatments. TRIPLL investigators also plan to explore how new communication tools, including social media and smartphones, can be harnessed to manage pain.

"In spite of how widespread chronic pain is among older adults, there are relatively few tested interventions to help people reduce their pain," said TRIPLL Co-Director Dr. Karl Pillemer, the Hazel E. Reed Professor of Human Development in the College of Human Ecology and a professor of gerontology in medicine at Weill Cornell. "Our new focus is exciting because we hope to translate findings into more effective interventions by deepening our understanding of human behavior and decision- making."

More than 100 million Americans suffer from chronic pain, more than those affected by heart disease, diabetes and cancer combined. Yet relatively few researchers study pain management, with most focusing on well-known diseases. But untreated pain takes a physical, mental, social and economic toll on older adults, according to TRIPLL Co-Director Dr. Cary Reid, the Irving Sherwood Wright associate professor in geriatrics and an associate professor of medicine at Weill Cornell.

"Treating pain in older patients is challenging in many ways," Dr. Reid added. "There are few studies that enroll typical older patients that can help to guide management decisions. Older adults are more sensitive than younger adults to medication-related side effects, and many older individuals (along with their health care providers) believe that pain is supposed to be present in later life."

Despite these challenges, Dr. Reid said that preventive approaches are critical to lessen the many negative consequences — such as reduced mobility, depression and anxiety, sleep impairment and social isolation — of poorly controlled pain.

In its first five years, TRIPLL has funded 30 pilot studies on innovative treatments, policies and interventions for improved pain management. More than 100 investigators — faculty members and graduate students — have been mentored by TRIPLL investigators, including presentations of their work at monthly work-in-progress seminars.

The institute will continue to have strong community roots, said TRIPLL Co-Director Dr. Elaine Wethington, a professor of human development and of sociology. In Ithaca and New York City, TRIPLL researchers are partnering with health care providers, hospice and home nurse agencies and older adults themselves to match interventions to their needs. Its translational focus seeks to move evidence-based techniques directly into clinical practices, programs and policies.

"The involvement of community organizations in every aspect of research project development — from conceptualization, design, participant recruitment and eventual dissemination — is one of TRIPLL's strengths," said Dr. Wethington. "The input of community agencies and consumers leads to research that is more likely to be implemented successfully in diverse cultural settings."

Affiliated with Cornell's Bronfenbrenner Center for Translational Research, TRIPLL includes collaborating investigators at Weill Cornell Medical College, Cornell University (Ithaca campus) and the Hebrew Home at Riverdale. TRIPLL also maintains ongoing partnerships with Columbia University, the Hospital for Special Surgery, Memorial Sloan Kettering Cancer Center, Visiting Nurse Service of New York, and the Council of Senior Centers and Services of NYC.