Depressive disorders are a major public health problem, both in terms of personal suffering and socioeconomic burden. Epidemiological studies have emphasized the roles of genetic vulnerability and environmental factors in the emergence of depression. Unfortunately, the causes and pathophysiology of major depressive disorder remain largely unknown. Moreover, progress in understanding the neurobiology of depression is hindered by the lack of objective measures of core depressive symptoms. The goals of the proposed work are: (1) to investigate the neurobiological underpinnings of stress-induced anhedonia - an emerging endophenotype of depression - and the moderating effects of candidate genes previously linked to increased vulnerability to depression and stress sensitivity on these mechanisms;(2) to test the hypothesis that decreased phasic dopaminergic transmission within mesolimbic regions plays a key role in the pathophysiology of major depression, which will be achieved by using functional magnetic resonance imaging (fMRI) in conjunction with a pharmacological challenge;and (3) to investigate dopamine transporter (DAT) function and its relation to reward deficits in MDD using positron emission tomography (PET) and fMRI techniques. By combining molecular genetics, functional neuroimaging, pharmacological challenges, endocrinological assessments, and molecular imaging techniques, the proposed study is expected to provide novel insights into the pathophysiology of depression, and thus might offer new targets for treatment strategies and disorder prevention.
The current project proposes a combination of behavioral probes, molecular genetics, and functional and molecular neuroimaging techniques to investigate the role of dopaminergic dysfunction in major depression and in the cardinal symptom anhedonia - the loss of pleasure. This interdisciplinary approach is expected to provide novel insights into putative pathways associated with increased vulnerability to depression and anhedonia, and might provide novel targets for treatment strategies and prevention measures.
|Kaiser, Roselinde H; Treadway, Michael T; Wooten, Dustin W et al. (2018) Frontostriatal and Dopamine Markers of Individual Differences in Reinforcement Learning: A Multi-modal Investigation. Cereb Cortex 28:4281-4290|
|Whitton, Alexis E; Mehta, Malavika; Ironside, Manon L et al. (2018) Evidence of a diurnal rhythm in implicit reward learning. Chronobiol Int 35:1104-1114|
|Moran, Lauren V; Stoeckel, Luke E; Wang, Kristina et al. (2018) Nicotine Increases Activation to Anticipatory Valence Cues in Anterior Insula and Striatum. Nicotine Tob Res 20:851-858|
|Whitton, Alexis E; Deccy, Stephanie; Ironside, Manon L et al. (2018) Electroencephalography Source Functional Connectivity Reveals Abnormal High-Frequency Communication Among Large-Scale Functional Networks in Depression. Biol Psychiatry Cogn Neurosci Neuroimaging 3:50-58|
|Dillon, Daniel G; Gonenc, Atilla; Belleau, Emily et al. (2018) Depression is associated with dimensional and categorical effects on white matter pathways. Depress Anxiety 35:440-447|
|Kumar, Poornima; Goer, Franziska; Murray, Laura et al. (2018) Impaired reward prediction error encoding and striatal-midbrain connectivity in depression. Neuropsychopharmacology 43:1581-1588|
|Treadway, Michael T; Admon, Roee; Arulpragasam, Amanda R et al. (2017) Association Between Interleukin-6 and Striatal Prediction-Error Signals Following Acute Stress in Healthy Female Participants. Biol Psychiatry 82:570-577|
|Der-Avakian, Andre; D'Souza, Manoranjan S; Potter, David N et al. (2017) Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats. Psychopharmacology (Berl) 234:1603-1614|
|Auerbach, Randy P; Pisoni, Angela; Bondy, Erin et al. (2017) Neuroanatomical Prediction of Anhedonia in Adolescents. Neuropsychopharmacology 42:2087-2095|
|Whitton, Alexis E; Van't Veer, Ashlee; Kakani, Pragya et al. (2017) Acute stress impairs frontocingulate activation during error monitoring in remitted depression. Psychoneuroendocrinology 75:164-172|
Showing the most recent 10 out of 103 publications