The purpose of this NIMH Mentored Patient-Oriented Research Career Development (K-23) Award application is to support my long-term career objective of integrating innovative neuroimaging techniques and mechanisms of emotion regulation to understand the neurodevelopment of Bipolar Disorder (BD). My previous training is in the phenomenology and Magnetic Resonance Imaging (MRI) morphometric analyses of children at familial risk for developing BD. One limitation of previous neuroimaging studies in bipolar offspring is the inadequate assessment of the potential underlying mechanisms of emotion regulation in this vulnerable cohort, independent of confounds associated with illness onset, such as co-occurring psychiatric conditions, medication exposure, and substance use. Therefore, to achieve my career goal of maximizing the application of in vivo neuroimaging techniques to at-risk clinical populations, I propose to gain expertise integrating pediatric investigations of emotion regulation and dysregulation, functional (fMRI), magnetic resonance spectroscopy (MRS), statistical analyses, and the ethical conduct of research by participating in course work, didactic readings, mentoring, and experiential learning activities that complement the proposed research activities. BD is a prevalent, life-long, progressive disease that typically begins in adolescence or early adulthood. A cardinal symptom of BD is emotion dysregulation. Brain and cerebellar regions, including the prefrontal cortex, ventral striatum, amygdala, hippocampus, and cerebellar vermis have been shown to modulate emotional processes in children and adolescents with, and at familial risk for, BD. My short-term goal is to apply fMRI and MRS, in conjunction with reward and information-processing paradigms used in affective neuroscience, to elucidate the functional and neurochemical bases for emotion regulation in preadolescent children at familial risk for developing BD. Data obtained in this project will inform future longitudinal studies to facilitate the advancement of our understanding of risk and protective factors that are involved in the development of this illness. The proposed integrated research and training programs, together with the strong research environment of Stanford University, will foster my development into an independent investigator in the field of the neurodevelopment of BD.

Public Health Relevance

Despite major improvements in the identification of pediatric bipolar disorder (BD), key indicators of treatment response and outcome have remained unchanged or worsened over the past decade. Given increasing rates of clinical diagnosis of BD in youth, it is clear that new conceptual approaches are required to achieve gains in favorable long-term outcomes in these populations. The proposed research will help to identify modifiable risk factors for BD that could prevent adverse outcomes for children and their families.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Avenevoli, Shelli A
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Stanford University
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United States
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Park, Min-Hyeon; Garrett, Amy; Boucher, Spencer et al. (2015) Amygdalar volumetric correlates of social anxiety in offspring of parents with bipolar disorder. Psychiatry Res 234:252-8
LeMoult, Joelle; Ordaz, Sarah J; Kircanski, Katharina et al. (2015) Predicting first onset of depression in young girls: Interaction of diurnal cortisol and negative life events. J Abnorm Psychol 124:850-9
Singh, Manpreet K; Kelley, Ryan G; Chang, Kiki D et al. (2015) Intrinsic Amygdala Functional Connectivity in Youth With Bipolar I Disorder. J Am Acad Child Adolesc Psychiatry 54:763-70
Park, Min-Hyeon; Chang, Kiki D; Hallmayer, Joachim et al. (2015) Preliminary study of anxiety symptoms, family dysfunction, and the brain-derived neurotrophic factor (BDNF) Val66Met genotype in offspring of parents with bipolar disorder. J Psychiatr Res 61:81-8
Singh, Manpreet K; Chang, Kiki D; Kelley, Ryan G et al. (2014) Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder. Bipolar Disord 16:678-89
Singh, Manpreet K (2014) Preparing and presenting effective abstracts and posters in psychiatry. Acad Psychiatry 38:709-15
Singh, Manpreet K; Gotlib, Ian H (2014) The neuroscience of depression: implications for assessment and intervention. Behav Res Ther 62:60-73
Singh, Manpreet K; Kelley, Ryan G; Howe, Meghan E et al. (2014) Reward processing in healthy offspring of parents with bipolar disorder. JAMA Psychiatry 71:1148-56
Whitney, Jane; Howe, Meghan; Shoemaker, Virginia et al. (2013) Socio-emotional processing and functioning of youth at high risk for bipolar disorder. J Affect Disord 148:112-7
Singh, Manpreet K; Kesler, Shelli R; Hadi Hosseini, S M et al. (2013) Anomalous gray matter structural networks in major depressive disorder. Biol Psychiatry 74:777-85

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