This Mentored Research Scientist Development Award will support the candidate in transitioning into an independent investigator in translational research with a focus on mood disorders. With a background in animal research, the candidate proposes training in human functional magnetic resonance imaging (fMRI) to investigate brain activity associated with social rejection and acceptance. Social rejection (an explicit declaration that an individual is not liked) has powerful effects on emotion and behavior including lowered self- esteem, major depression, risk-taking behavior, substance abuse, and violence. A few fMRI studies have found increased activity in the anterior cingulate cortex using different paradigms for social rejection.
The first aim of the project is to test experimental manipulations for social rejection, explore its parameters, and adapt a stimulus presentation for use in fMRI experiments.
The second aim i s to use fMRI to examine neuronal pathways involved in social rejection. Based on anatomical pathways found in rats and monkeys, it is hypothesized that in addition to the anterior cingulate cortex, activation will be found in the periaqueductal gray, thalamus, amygdala, nucleus accumbens, and subgenual cortex. These structures are known to be involved in stress responses and major depression, as well as responding to rewards. An exploratory aim will assess behavioral responses to social rejection in patients with Major Depressive Disorder (MDD) without fMRI. Once the behavioral responses are studied, my long-term goal is to examine abnormal neuronal responses to social rejection in MDD with neuroimaging. Atypical depression, for example, is uniquely characterized by intense social rejection sensitivity. Identifying a unique biological profile for a depressive subtype may improve its definition, diagnosis, and treatment.

Public Health Relevance

Social rejection can lead to major depression and social anxiety. This proposal seeks to understand how the brain processes social rejection. The results may help us to identify those who are vulnerable to the effects of social rejection, and lead to innovative treatments and preventive measures.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Chavez, Mark
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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Yttredahl, Ashley A; McRobert, Erin; Sheler, Benjamin et al. (2018) Abnormal emotional and neural responses to romantic rejection and acceptance in depressed women. J Affect Disord 234:231-238
Jacobs, R H; Barba, A; Gowins, J R et al. (2016) Decoupling of the amygdala to other salience network regions in adolescent-onset recurrent major depressive disorder. Psychol Med 46:1055-67
Hsu, D T; Sanford, B J; Meyers, K K et al. (2015) It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder. Mol Psychiatry 20:193-200
Glaser, Yi G; Zubieta, Jon-Kar; Hsu, David T et al. (2014) Indirect effect of corticotropin-releasing hormone receptor 1 gene variation on negative emotionality and alcohol use via right ventrolateral prefrontal cortex. J Neurosci 34:4099-107
Hsu, D T; Sanford, B J; Meyers, K K et al. (2013) Response of the ?-opioid system to social rejection and acceptance. Mol Psychiatry 18:1211-7
PeciƱa, Marta; Mickey, Brian J; Love, Tiffany et al. (2013) DRD2 polymorphisms modulate reward and emotion processing, dopamine neurotransmission and openness to experience. Cortex 49:877-90
Hsu, D T; Sanford, B J; Meyers, K K et al. (2013) Social feedback activates the endogenous opioid system. Mol Psychiatry 18:1147
Hsu, David T; Mickey, Brian J; Langenecker, Scott A et al. (2012) Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene influences fMRI signal responses during emotional stimulus processing. J Neurosci 32:3253-60
Mickey, Brian J; Zhou, Zhifeng; Heitzeg, Mary M et al. (2011) Emotion processing, major depression, and functional genetic variation of neuropeptide Y. Arch Gen Psychiatry 68:158-66
Hsu, David T; Langenecker, Scott A; Kennedy, Susan E et al. (2010) fMRI BOLD responses to negative stimuli in the prefrontal cortex are dependent on levels of recent negative life stress in major depressive disorder. Psychiatry Res 183:202-8