Brain Biology

December 04, 2023 Translational Epidemiologist receives JKBF Award at ISSR

Once again JKBF partnered with the International Academy of Suicide Research (IASR) and the American Foundation for Suicide Prevention (AFSP) to award an early career scientist investigating biological factors that may contribute to suicidal behaviors. At the 2023 International Summit on Suicide Research the third James Kirk Bernard Foundation Award for Excellence in the Biological Exploration of Suicide was presented to Milenna van Dijk in recognition of her presentation "Differences in White Matter Structural Networks in Family Risk of Major Depressive Disorder and Suicide: A Connectome Analysis." Selected from a pool of early career researchers, Dr. van Dijk was chosen for her work looking at factors that differentiate suicidal behaviors from Major Depression, and consider resilience. Dr. van Dijk was selected on the basis of merit and innovation, and the award committee was particularly encouraged by her work to separate suicide from major depressive disorder. The award was bestowed by Dr. Holly Wilcox, President of IASR, during the awards ceremony at the October 2023 conference in Barcelona. Milenna van Dijk is a postdoctoral fellow in translational epidemiology at Columbia University. The goal of Dr. van Dijk’s research program is to understand mechanisms underlying intergenerational transmission of depression and suicidality across generations. Since not all individuals who have a high family risk of depression or suicide develop psychopathology, she also studies what determines susceptibility versus resilience. Dr. van Dijk is a transdisciplinary and translational scientist, uniquely trained in rodent models, MRI imaging, epidemiology, assessment of human psychopathology and (functional) genomics. She has obtained independent funding through a Young Investigator Award from AFSP as well as an NIMH K99/R00 award, has published papers in journals such as JAMA Psychiatry, Neuron and Biological Psychiatry, and has received several travel awards from professional societies, including from AFSP and ACNP. We wish Dr. van Dijk success in her efforts and look forward to her future contributions in suicide prevention research. JKBF appreciates the collaboration with IASR and AFSP and the efforts of  Jill Harkavy-Friedman and Holly Wilcox in the  in making this award possible. Dr. van Dijk received an honorarium and will receive an award featuring a piece of Jamie's art. 

 

From the Scientist:

What are the neurobiological signatures associated with familial risk for suicidality? Why do some individuals die by suicide while others with similar background risks remain resilient?

by Milenna van Dijk

For this project I was interested in trying to understand how family risk for suicide is passed across generations, and to understand some of the neurobiological and early life risk factors for suicidality. I also wanted to understand if there are differences between individuals with high family risk who do not have personal psychopathology (“resilient”) and those who develop personal suicidality (“susceptible”). Better understanding neurobiological mechanisms can lead to future targets for preventative and treatment strategies to restore neural function in individuals at highest risk for suicidality. Especially with the increases in adolescent mood disorders and suicidality in recent years, it is paramount to be able to pinpoint children at highest risk of developing psychopathology in the face of adversity and to understand mechanisms of resilience to harness in personalized prevention efforts.

I utilized a unique longitudinal 40-year, three-generation study of families at high and low risk for depression which my postdoctoral mentor, Dr. Myrna Weissman, began in 1982. This study consists of one group of participants with moderate to severe depression, and one control group of individuals from the local community. Importantly, their children and later, their grandchildren, were also included to assess how depression is passed on in families. The study team performed regular clinical interviews with the participants to understand psychopathology, and the participants filled out many surveys to gain detailed information about topics including parenting styles and parent-child bonding, child temperament, and social functioning. There were measures on cognition and memory and, importantly, participants underwent MRI scanning to study the brain and DNA was obtained to understand genetics. Because the study is longitudinal, it can relate prospectively acquired early child factors to outcomes in adulthood, without the memory bias that often occurs in retrospective reports.

This study is unique because the participants have been followed for so long with so much detail and precision. We realized that, not only did children and grandchildren of the original participants with depression have much higher rates of depression and other psychopathology themselves, there were also very high rates of suicidal ideation, attempts and, unfortunately, some completed suicides. This provided a unique chance to study how suicidality runs in families, what the brain mechanisms are, what kind of early life characteristics might be associated with later onset of suicidality. We also asked brain mechanisms associated with high risk for suicidality might differ from those associated with high risk for depression.

With a grant from the American Foundation for Suicide Prevention, I set out to answer these questions with help from my fantastic Master’s student, Nora Kelsall, MSc. Previously it had been shown there were structural brain differences in people who are at family risk for depression, as well as in people who have had personal suicidal thoughts and behaviors. The approach researchers have usually used to analyze brain data is to study each brain region or white matter tract as an independent unit. However, since the brain is an integrated network of regions, perturbations in one area might affect processing in the network as a whole.

Complex Networks, Risk and Resilience

Recently brain researchers have begun to adopt a network science approach, used to understand complex networks such as telecommunication and social networks leading to predictive models of these networks. We decided to use this integrated complex systems approach to understand white matter brain differences (connectivity) in people at high compared to low family risk for depression, and separately, at high and low family risk for suicide.

While there were only small differences between people at high and low risk for depression, we found that individuals at high family risk for suicidality had substantial decreases in a measure called global efficiency. This showed that brains of individuals with high family risk for suicide were less efficient at information exchange across the whole brain network. This decrease in global efficiency was evident in high-risk family members, whether or not participants had a personal history of suicidality.

We then investigated which subnetworks had decreased white matter connectivity between high and low risk for suicidality. We found decreased connectivity in cortical-subcortical connections, including those between the superior frontal cortex, thalamus, precuneus, and putamen. These regions have been thought to be involved in emotion regulation, rumination, and anhedonia. Our findings were independent of whether or not participants had a personal or family history of depression or personal history of suicidality, showing that the differences were due to having a family history of suicidality, not depression. Even when we performed the analysis only with participants who had a family risk of suicidality but were “resilient”, the results were very similar. These findings indicate that we found family risk factors for suicidality, not just signatures of psychopathology. Risk markers for suicidality can help us better understand the mechanisms involved in vulnerability, and in the future provide targets to harness for prevention.

With Master’s student, Elizabeth Bruno, I am currently examining if childhood factors such as temperament and social functioning are related to suicidal thoughts and behaviors in adulthood. For childhood temperament, we examined factors such as how irritable, distractable and adaptable the child was. The measures were prospectively acquired, when the children were young, which strengthens the research by removing bias. We are finding that higher childhood irritability and distractibility, and lower adaptability, are associated with suicidal thoughts and behaviors in adulthood, specifically in participants at high family risk for suicidality who are susceptible. Resilient high-risk participants were not different from low-risk controls. Our next steps will be to relate the childhood characteristics to our brain structure findings and see if they might be associated.

In summary, we found that family history of suicidality is associated with hypoconnectivity between subcortical and cortical regions, suggesting brain-wide impaired information processing, even in personally unaffected “resilient” individuals. However, while brain signatures were similar across susceptible and resilient individuals at high family risk for depression compared to low-risk individuals, resilient individuals had a childhood temperament that showed less irritability, less distractibility and more flexibility. This was similar to children at low risk for depression, suggesting that temperament might be an important early risk factor.

This does not mean that everyone with such a childhood temperament will go on to develop suicidality. But if confirmed in other studies, it might provide a future warning sign for children from families with suicidality, for parents and caretakers to keep an extra eye on these children. Better understanding of both neuroscientific and developmental risk factors can help us, in the future, to build profiles of children who are at highest risk for developing suicidal thoughts and behaviors so that we can intervene early before full-fledged psychopathology ensues.

Dr. van Dijk's recent work has been published: Differences in White Matter Structural Networks in Family Risk of Major Depressive Disorder and Suicidality: A Connectome Analysis  

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