The Neural Basis of Pain Modulation in Depression

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DESCRIPTION (provided by applicant): Pain and depression are common, often co-occur in the same patient, and result in significant disability. Over 75% of patients with depression suffer from pain symptoms and between 30-60% of pain patients report significant depressive symptoms. Importantly, the comorbidity between pain and depression contributes significantly to (1) poorer outcomes and (2) increased cost of treatment. The primary goal of this proposal is to prepare the candidate to develop into an expert in the neural mechanisms underlying the comorbidity of pain and depression. The purpose of the training plan is to enhance the candidate knowledge in: 1) neurobiology and clinical manifestation of mood disorders; 2) identification and formulation of clinically relevant research problems in the area of mood disorders and pain; 3) the ability to develop clinically driven neuroscience system models of pain-mood interactions. The secondary goal is to strengthen the candidate's expertise in functional Magnetic Resonance Imaging (fMRI) to better develop paradigms and techniques to delineate the neural substrates that are important for pain-mood interaction assessment. The research plan aims to examine the inter-relationship between pain and depression addressing the question, "do depression and pain share common neural substrates?" These studies will extend the current research interests of the applicant. Recent evidence indicates that the integrity of the neural circuits that provide top-down pain modulation is compromised in patients with mood disorders. Two cognitive/affective mechanisms that are important for this top-down modulation include: (1) Pain Anticipation, which enables the brain to alter the processing of pain intensity and its affective quality; and (2) Distraction, which is used by top-down neural substrates to attenuate the experience of pain. The integrity of these processes will be examined using Functional Magnetic Resonance Imaging (fMRI) by comparing individuals with current Major Depressive Disorder (MOD) to healthy comparison subjects. The specific aims of research plan are: 1) To assess sensory and affective responses to pain in subjects with current MOD; 2) To determine which neural substrates underlie anticipation of painful stimulus in subjects with current MOD; 3) To establish which neural substrates underlie pain modulation by distraction in subjects with current MDD. Understanding how pain and depression interaction will have profound implications for (1) the development of assessments of pain in people at risk for depression; (2) the development of biomarkers for treatment outcomes of pain in depression, (3) the quantification of the emotional effects on pain processes and their susceptibility to treatment. Given the frequent comorbidity of pain and depression, results of this study may fundamentally alter how psychiatrists approach depression and its neurobiological underpinnings.