Mclean Hospital

Launching Careers With Coveted K Awards

October 23, 2019

K awards, which are part of the National Institutes of Health (NIH) Research Career Development Awards, support the next generation of scientists focused on addressing the country’s most pressing biomedical challenges.

These awards serve to provide both salary and research for intensive, focused, and expertly supervised research training and career mentorship. K-level mechanisms are most often used to provide a foundation for successful transition into a newly independent research position or to support an individual’s desire to gain extensive and expert training in a new field of specialty.

“Importantly, K awards have proven to allow early-career and new investigators to demonstrate their fundability and facilitate their progression on their academic career path,” explained McLean Chief Scientific Officer Kerry J. Ressler, MD, PhD. “These awards comprise a unique opportunity for scientists in transition to independence to gain expert mentorship from proven NIH mentors and protected time and resources, which serve as a powerful launchpad for continued success in the biomedical sciences.”

A Thoughtful Approach to Eating Disorders Research

The study of eating disorders tends to receive less attention than many other fields within psychiatry, despite the prevalence of these disorders and the impact they have on people’s lives. Kristin N. Javaras, DPhil, PhD, is hoping her research will lead to more effective treatments for these conditions that are far deeper than simple lifestyle choices.

An assistant psychologist in the Division of Women’s Mental Health at McLean Hospital, and initially trained as a statistician, Javaras said her career path was influenced by a desire to combine her analytic skill set with a fascination with psychological and psychiatric research. Collaborating with McLean clinical researchers James I. Hudson, MD, ScD, and Harrison G. Pope Jr., MD, MPH, to help analyze their data on eating disorders prompted her to add a degree in psychology and embark on a clinical and research pathway to better understand conditions such as anorexia nervosa, bulimia nervosa, and binge eating disorder.

Kristin N. Javaras, PhD, DPhil
Kristin N. Javaras, DPhil, PhD

As with many other behavioral health conditions, eating disorders have roots in stress and potential genetic preconditions

“In the real world, stressors or negative emotions can precipitate an increase in eating disorder symptoms,” she explained. “And in my own experience as a clinician, it can be hard to break the link between negative emotions and eating disorder symptoms. It is difficult enough for all of us to make changes when we’re in a sort of neutral mood, but it becomes even harder to implement a different strategy when you’re upset.”

Javaras’ recent work is focused on how to better identify what areas of the brain are involved when someone has an eating disorder. Her hope is that by better understanding the brain circuits involved, the field will be able to develop treatments that are better tailored to the disorder and more effective.

“I’m interested in better understanding how eating disorders affect decision-making—for example, how that might differ in a person with an eating disorder from someone without an eating disorder,” said Javaras. “Understanding how individuals with eating disorders make decisions is crucial for developing treatments that help people make everyday choices to promote recovery.”

One important feature of Javaras’ research on decision-making is her focus on including people not just from the clinic, but people from the community, who may or may not be in treatment. That way, the research will be relevant—and hopefully helpful—to a broader array of individuals with eating disorders.

Exploring How Metabolism Affects Cognitive Function

The gastrointestinal system and the brain interact to play a key role in our health and well-being. This GI-brain axis goes far beyond the expression of “gut” feelings. It was this interaction that attracted Rachel A. Ross, MD, PhD, to psychiatric neuroscience.

“The GI system itself is kind of thought of as the second brain,” she said. “It has a lot of the same neurotransmitters. It has a lot of the same neurons [that are also found in the brain]. Signals from the gut are sensed by the brain and can influence behavior.”

Aided by a grant from the National Institutes of Diabetes and Digestive and Kidney Diseases, she is now exploring the relationship between hunger and cognitive function as an assistant neuroscientist in the Neurobiology of Fear Laboratory and a staff psychiatrist at McLean Hospital.

“There is a lot of work that shows that people have abnormal responses to feelings of hunger or feelings of fullness, depending on which side of the spectrum you’re looking at,” she said. “And that is probably related to the biological signals that come from the gut and are interpreted by the brain.

Rachel A. Ross, MD, PhD
Rachel A. Ross, MD, PhD

Working with mice and using cues gleaned from her clinical practice, Ross is building on existing research that found that an impairment of cognitive function is associated with a reduction in activity in the medial prefrontal cortex.

Using a genetic model that enables her to home in on neuropeptides—the small protein-like molecules used by neurons to communicate with each other—she is exploring what drives cognitive function related to food intake behavior and metabolism.

“The receptor for this neuropeptide system is found in numerous regions throughout the brain, and what it’s doing is not well understood,” beyond the fact that it responds to two neuropeptides that have opposite effects on food intake, she said. In particular, the search is to understand what role it might play in decision-making.

The growing subspecialty of psychiatric neuroscience aims to better understand how biological and cognitive factors interact to develop targeted treatment of psychiatric illness, such as anorexia, that often lead to medical complications or suicide.

“In the past, it was hard to appreciate how the study of the brain in a biological manner might actually help us understand what was happening in that person,” she said. “But now, with newer tools, that’s becoming more accessible, so I think this is a field that has been growing and hopefully will come up with some really useful direction for improving how we understand psychiatric illness.”

Can Big Data Tell Us Why PTSD Exists?

Is there a genetic predisposition to post-traumatic stress disorder (PTSD)? Nikolaos P. Daskalakis, MD, PhD, director of the Neurogenomics and Translational Bioinformatics Laboratory at McLean Hospital, thinks the answer is yes. And he is committed to analyzing lots of data to confirm it.

Daskalakis is combining traditional medical training in behavioral neuroscience and neuroendocrinology with systems biology and “big data” computing to explore whether a person’s genetic makeup can play a role in the development and treatment of PTSD. This is a condition that affects up to 8% of the population at some point in their lives.

The principal factor of PTSD was and remains a traumatic event. But, said Daskalakis, “a genetic predisposition to psychiatric disease has long been recognized in schizophrenia and is now coming into focus for PTSD.”

Researchers can be hampered by difficulties in defining PTSD. Are all PTSDs the same? Since there are differences in trauma types, are there differences in PTSD types? Is PTSD caused by a car accident different from PTSD caused by a terrorist act?

The search for an answer to that question is at the heart of statistical genetics, a subspecialty that has developed over the past 20 years. It uses data gleaned from traditional medical biomarkers and now, increasingly, integrates data from postmortem brain samples.

Nikolaos P. Daskalakis, MD, PhD
Nikolaos P. Daskalakis, MD, PhD

“There is something in the genetic makeup of individuals, the genotype that people are conceived with from day zero or some epigenetic state they partially inherited or developed as they were growing, that could be positive or negative,” Daskalakis said.

“The genomic makeup will play out in how they will immediately respond or if they will be the ones who have the chronic sequelae of trauma-related symptoms.”

The genetic link to schizophrenia was established as researchers gained enough data to identify specific loci, or fixed positions on the chromosomes linked to the disease. Similar work on PTSD is underway using large genotype collections of disease, such as the PTSD working group of the Psychiatric Genetics Consortium, co-led by Kerry J. Ressler, MD, PhD, McLean’s chief scientific officer.

Expanding the scope of the data analysis to integrate functional genomic data derived from brain tissues, such as those collected by the Harvard Brain Tissue Resource Center, involves bioinformatic modeling and novel techniques of machine and deep learning using improved computing power.

Today’s statistical geneticists are trying to identify “genetic or genomic biomarkers that could help understand how many different types of PTSD exist,” he said, a discovery that could open the possibility of clinical trials, which haven’t been effective to date.

The multidisciplinary work involves the Harvard Paulson School of Engineering and Applied Science, the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL), and the Broad Institute.

Believing Survivors of Childhood Abuse Is a Global Ethical Issue

Nearly two-thirds of people in the United States have experienced at least one traumatic event during childhood. Of those, close to 10% will go on to develop post-traumatic stress disorder. A subset of those individuals, upwards of 3 million people in the US alone, experience a particular type of post-traumatic coping response called dissociative identity disorder (DID). DID, in particular, is associated with prolonged and severe childhood abuse and neglect, typically at the hands of caretakers.

Yet “the existence of DID and its associated symptoms have long been misunderstood and at times ignited controversy,” said Lauren A.M. Lebois, PhD, a cognitive psychologist and neuroscientist in the Dissociative Disorders and Trauma Research Program and Neurobiology of Fear Laboratory at McLean Hospital. She is working on research that tracks brain responses through functional magnetic resonance imaging (fMRI).

“Most treaters don’t assess for DID, and if someone happens to report these types of symptoms, some treaters may discount or even disbelieve them. This doubt lays the groundwork for a vicious cycle of stigmatization, misdiagnosis, and delayed healing.”

Dr. Lebois and her colleagues hope that by elucidating the neurobiology of DID, they will help destigmatize the disorder so that people can access the treatment they need. The research supported by her National Institute of Mental Health K award proposes to do just that by studying dissociative symptoms that are a hallmark of DID.

Lauren A.M. Lebois, PhD
Lauren A.M. Lebois, PhD

“One of the ways symptoms manifest for people with DID is sometimes when they look in the mirror, their reflection feels off or strange in some way. And sometimes it can feel like it’s someone else looking back at them in the mirror—even though they know it must be their own reflection.”

To study these symptoms, Dr. Lebois and her colleagues have designed a novel task in which participants with DID and a control group of people without DID are shown pictures of their own face while they measure brain activity through fMRI.

Their research to date has found that for people with DID, seeing their own face doesn’t elicit feelings of familiarity like it does for control participants. Preliminary fMRI findings support this, indicating that a number of brain regions that are typically active when someone looks at their own face aren’t active in someone with DID.

While expanding existing treatment options is a long-term goal, Lebois said the more urgent goal of her work is to raise awareness of DID—and the role of childhood trauma as a cause.

“It’s troubling—a global ethical issue, actually—that the most vulnerable people in our society, children, have these experiences of abuse and neglect. And, on top of that, as adults they can’t access the mental health treatment that would help them because there’s so little understanding in the medical, clinical, and lay communities.”