Research Projects
Research Projects
Eating Disorders
Identifying risk markers for eating disorders in adolescence through genetics, neuroimaging, and behavior
Eating disorders have a strong biological component and tend to have their onset during adolescence. Understanding risk factors prior to a diagnosis of an eating disorder can hold important clues for early intervention efforts and future treatment paths. This project aims to build biologically-informed predictive models of adolescent psychiatric disorders, using an array of multi-modal brain imaging, genomics and clinical/behavioral data, from two datasets. The first comes from the Adolescent Brain Cognitive Development (ABCD) Study, one of the largest studies of brain development of its kind, is following nearly 12,000 youth in the US from ages 9-11. This study collects brain imaging, cognitive, physical and mental health data over one to two-year intervals until participants reach early adulthood (ages 19-21). This project aims to predict eating disorder-related outcomes in adolescence from various markers in late childhood and early adolescence, including: brain imaging markers (brain structure, white matter organization, subcortical tissue microstructure, brain function during working memory and reward processing tasks), polygenic risk markers for eating disorders and related conditions, and an array of behavioral measures capturing cognition, temperament, and reward processing. The knowledge gained by this project will also be complemented and extended to clinical data collected at UCSD’s Eating Disorders Center, to better understand the impact of discovered predictors in a clinical setting.
PI: Dr. Carolina Makowski
Collaborators: Dr. Christina Wierenga (Department of Psychiatry, UCSD), Dr. Anders M. Dale (J Craig Venter Institute)
Funded by the National Institutes of Mental Health, K99/R00 MH132886.
Mapping premorbid profiles of adolescent eating disorders using the Norwegian Mother, Father and Child Cohort
Eating Disorders have a strong genetic and familial component. There is also evidence that risk factors for eating disorders are already present prior to their peak onset in adolescence. This project will leverage data from approximately 100,000 mother/father/child trios within the Norwegian Mother, Father and Child (MoBa) Cohort. The dataset is also linked to Norwegian health records, whereby approximately 2000 youth have been diagnosed with an eating disorder in adolescence. This project will investigate the different paths of behavioral and mental health traits in childhood that converge upon an eating disorder in adolescence, as well as the genetic factors that might influence these behavioral profiles.
PI: Dr. Carolina Makowski
Collaborators: Dr. Ole Andreassen (Oslo University), Dr. Christina Wierenga (Department of Psychiatry, UCSD)
Funded by the Brain Behavior Research Foundation.
Precision Functional Mapping during Treatment for Anorexia Nervosa
Anorexia nervosa is associated with widespread structural and functional brain changes that can rapidly change over the course of treatment. We are using “Precision Mapping” to advance our understanding of how the brain changes during treatment for Anorexia Nervosa at the individual level. By repeatedly sampling the same individual (hours of brain imaging data per subject, collected over many sessions), we can create precise, reliable functional activation and functional connectivity network maps for each person. This research has two specific aims. First, we aim to examine how brain structure and function changes over the course of treatment in individuals with Anorexia Nervosa. Second, we aim to determine which changes in brain structure and function are associated with symptom improvement and treatment response.
PIs: Dr. Deanna Greene, Emily Koithan (Department of Cognitive Science, UCSD)
Collaborators: Dr. Carolina Makowski, Dr. Christina Wierenga (Department of Psychiatry, UCSD)
Psychotic Disorders
Predicting psychotic-like experiences in adolescence
Psychotic-like experiences are subclinical mental health concerns that may confer vulnerability to psychiatric disorders later in adolescence and adulthood like schizophrenia, bipolar disorder, and depression. The BRIDGE lab is involved in several collaborations aiming to map risk factors for psychotic-like experiences in adolescence in an effort to better understand the biological and behavioral factors contributing to psychotic disorders, as well as identifying key developmental windows and measures that could be used to inform early intervention efforts. Two key large-scale cohorts are used to help tackle this research question: 1) the Adolescent Brain Cognitive Development (ABCD) Study, following nearly 12,000 youth in the US from ages 9-11 until early adulthood; 2) the Norwegian Mother, Father and Child (MoBa) Cohort, which has collected data on ~100,000 youth related to early-life temperament and mental health concerns, with linked health record data for mental health outcomes in adolescence.
ABCD collaborators: Dr. Nicole Karcher, Dr. Deanna Barch (Washington University in St. Louis); Dr. Terry Jernigan (Department of Cognitive Science, UCSD); Dr. Anders M. Dale (J Craig Venter Institute)
MoBa collaborators: Dr. Ole Andreassen, Viktoria Birknæs (Oslo University)
From episodic memory to functioning in schizophrenia and related psychoses: A neurocognitive model
Memory impairments are common in people with schizophrenia and related psychotic disorders, particularly in terms of remembering everyday events. Difficulty in this area is related to poorer clinical, functioning, and occupational outcomes, and greater brain abnormalities. No comprehensive model exists to help explain the strong associations between memory and these poor outcomes. This project aims to propose a model based on the role of specific brain regions involved in relational memory, which is a type of memory for everyday events that helps us to identify the relationship between different items or things. The study aims to recruit 300 individuals with schizophrenia and 150 non-clinical control participants from three different locations across Canada (Douglas Institute in Montreal, UBC in Vancouver, and the Royal's Institute of Mental Health Research site in Ottawa). A clinical research evaluation will gather data on i) socio-demographic and clinical variables, ii) social functioning and wellbeing, iii) social cognition and relational memory, and iv) images of the brain using magnetic resonance imaging. The project aims to identify relations between brain regions, memory, and functional outcomes and use this information to develop a computational approach to identify individuals at risk of having poorer functioning. Such an approach could be used in the future to stratify participants in intervention studies.
PIs: Martin Lepage (Douglas Institute; McGill University), Synthia Guimond (Royal Institute of Mental Health Research), Mahesh Menon (UBC), Todd S. Woodward (UBC)
Co-Investigators: Carolina Makowski, Michael D. Bodnar, Mallar M. Chakravarty, Stephan Heckers, Ridha Joober, Katie Lavigne, Bratislav Misic, Delphine Raucher-Chéné, Jai Shah
Funded by the Canadian Institutes of Health Research.
Mapping the genetic architecture of brain morphology and microstructure, and links to psychiatric disorders
We use various methods to boost discovery of variants contributing to the genetic architecture of complex human traits, including:
Integration of high resolution brain MRI and genetic data from large population cohorts, such as the UK Biobank and the ABCD Study
Careful consideration of brain imaging-derived measures to be included in genome-wide association studies
Application of novel statistical methods (such as conditional false discovery rate [see pleioFDR github from our Oslo collaborators]) and FEMA-long [see preprint]
Collaborators: Dr. Dennis van der Meer, Dr. Ole Andreassen (Oslo University); Dr. Anders M. Dale (JCVI)
Previously funded by the Canadian Institutes of Health Research, Fonds de recherche du Québec, and the Kavli Institute for Brain and Mind