This application proposes to examine brain function associated with response to cognitive therapy (CT) for recurrent unipolar depression. Depression is a common, debilitating disorder and treatment of severe depression is often difficult. Rumination or involuntary elaboration on negative topics is a salient symptom linked to depressive severity and duration. Evidence from cognitive and affective neuroscience suggests that such sustained emotional information processing could result from decreased inhibition of brain areas that automatically process emotional information by brain areas responsible for executive control such as the prefrontal cortex. Initial data suggests that depressed individuals suffer from increased amygdala and decreased prefrontal activity, and that CT is likely to target these mechanisms. Yet, these links have not been tested directly. This proposal requests funds to examine whether increased and sustained limbic and ventromedial prefrontal activity during emotional information processing tasks and decreased dorso-lateral prefrontal cortex activity during cognitive tasks are associated with recovery from unipolar depression in CT. Recovery in CT is expected to be strongest for individuals who display pre-treatment disruptions in these functions, which are targeted by CT. Thus, CT is further expected to decrease limbic reactivity and improve executive control. 60 depressed individuals will be assessed using functional magnetic resonance imaging during tasks requiring cognitive and emotional information processing before and after 12-14 weeks of CT;21 healthy individuals will also be scanned twice to understand expected changes in brain activity overtime that are unrelated to recovery. Positive results could help to understand which individuals are likely to recover in CT, the mechanisms by which this efficacious intervention leads to recovery in depressed individuals, how cognitive and physiological aspects of depression are related to recovery, and validation for the proposed mechanisms of action for CT. Negative results would suggest that CT may depend on different mechanisms of action than have been proposed by the cognitive neuroscience community. This project will be executed in conjunction with an ongoing clinical trial through which the intervention will be provided.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
3R01MH074807-03S1
Application #
7774694
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Muehrer, Peter R
Project Start
2006-04-01
Project End
2011-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2009
Total Cost
$75,538
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Bruder, Gerard E; Haggerty, Agnes; Siegle, Greg J (2017) A quick behavioral dichotic word test is prognostic for clinical response to cognitive therapy for depression: A replication study. Psychiatry Res 248:13-19
Price, Rebecca B; Lane, Stephanie; Gates, Kathleen et al. (2017) Parsing Heterogeneity in the Brain Connectivity of Depressed and Healthy Adults During Positive Mood. Biol Psychiatry 81:347-357
Jones, Neil P; Siegle, Greg J; Mandell, Darcy (2015) Motivational and emotional influences on cognitive control in depression: A pupillometry study. Cogn Affect Behav Neurosci 15:263-75
Marsden, Karen E; Ma, Wei Ji; Deci, Edward L et al. (2015) Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive. Cogn Affect Behav Neurosci 15:276-86
Horner, Michelle S; Siegle, Greg J; Schwartz, Robert M et al. (2014) C'mon get happy: reduced magnitude and duration of response during a positive-affect induction in depression. Depress Anxiety 31:952-60
Lee, Kyung Hwa; Siegle, Greg J (2012) Common and distinct brain networks underlying explicit emotional evaluation: a meta-analytic study. Soc Cogn Affect Neurosci 7:521-34
Siegle, Greg J; Thompson, Wesley K; Collier, Amanda et al. (2012) Toward clinically useful neuroimaging in depression treatment: prognostic utility of subgenual cingulate activity for determining depression outcome in cognitive therapy across studies, scanners, and patient characteristics. Arch Gen Psychiatry 69:913-24
Siegle, Greg J; Steinhauer, Stuart R; Friedman, Edward S et al. (2011) Remission prognosis for cognitive therapy for recurrent depression using the pupil: utility and neural correlates. Biol Psychiatry 69:726-33
Zhou, Dongli; Thompson, Wesley K; Siegle, Greg (2009) MATLAB toolbox for functional connectivity. Neuroimage 47:1590-607
Tamburo, Robert J; Siegle, Greg J; Stetten, George D et al. (2009) Amygdalae morphometry in late-life depression. Int J Geriatr Psychiatry 24:837-46

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