Bipolar disorder (BP) is one of the most debilitating and common illnesses worldwide. Individuals with BP frequently present to clinical services when depressed, but are often misdiagnosed with unipolar depression (UPD), leading to inadequate treatment and poor outcome. Increased accuracy in diagnosing BP, especially during depression, is therefore a key long term goal to help improve the mental health of individuals with BP. The attainment of this goal can be facilitated by identifying biomarkers reflecting pathophysiologic processes in BP - impaired emotion regulation, impaired attention and distractibility - that persist during depression and remission and are not common to UPD. As a first step toward this goal, this study employs a cross-sectional design and functional brain imaging to measure in individuals with the traditional BPI subtype functional abnormalities in brain systems underlying emotion processing (amygdala-centered) and working memory and attention (dorsolateral prefrontal cortex, DLPFC-centered) common to BPI depression and remission and BPI-specific. Second, we will employ a longitudinal design to measure relationships between changes in these brain system abnormalities and changes in depression severity over 6 months in BPI versus UPD. We will examine 1. 40 remitted BPI; 2. 40 depressed BPI; 3. 40 UPD; and 4. 40 healthy individuals. We will re- examine 20 individuals per group 6 months later. We will restrict medication combinations taken by patient participants to a small number to allow delineation of abnormal neural activity related to specific medications. We hypothesize that 1. BPI remitted and BPI depressed individuals will show abnormally increased amygdala and decreased DLPFC activity to positive and negative emotional stimuli, and decreased DLPFC activity during working memory; 2. UPD individuals will show increased amygdala activity to negative but not positive emotional stimuli; 3. decreased depression severity over time will be associated with decreased DLPFC activity during working memory in BPI, but with decreased amygdala activity to negative emotional stimuli in UPD. Relevance: BPI is a common, debilitating and potentially fatal disorder, often misdiagnosed as UPD. This study is directed at identifying biological markers of BPI that reflect pathophysiologic brain processes common to depression and remission and specific to BPI, as a first stage toward the long term goal of increasing diagnostic accuracy to help improve the mental heath of those with the disorder. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH076971-02
Application #
7474520
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Rumsey, Judith M
Project Start
2007-07-24
Project End
2012-06-30
Budget Start
2008-09-16
Budget End
2009-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$428,304
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Chase, Henry W; Fournier, Jay C; Aslam, Haris et al. (2018) Haste or Speed? Alterations in the Impact of Incentive Cues on Task Performance in Remitted and Depressed Patients With Bipolar Disorder. Front Psychiatry 9:396
Hibar, D P; Westlye, L T; Doan, N T et al. (2018) Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Mol Psychiatry 23:932-942
Scola, Gustavo; Versace, Amelia; Metherel, Adam H et al. (2018) Alterations in peripheral fatty acid composition in bipolar and unipolar depression. J Affect Disord 233:86-91
Sun, Zhong Yi; Houenou, Josselin; Duclap, Delphine et al. (2017) Shape analysis of the cingulum, uncinate and arcuate fasciculi in patients with bipolar disorder. J Psychiatry Neurosci 42:27-36
Quevedo, Karina; Ng, Rowena; Scott, Hannah et al. (2017) Ventral Striatum Functional Connectivity during Rewards and Losses and Symptomatology in Depressed Patients. Biol Psychol 123:62-73
Manelis, Anna; Almeida, Jorge R C; Stiffler, Richelle et al. (2016) Anticipation-related brain connectivity in bipolar and unipolar depression: a graph theory approach. Brain 139:2554-66
Chase, Henry W; Phillips, Mary L (2016) Elucidating neural network functional connectivity abnormalities in bipolar disorder: toward a harmonized methodological approach. Biol Psychiatry Cogn Neurosci Neuroimaging 1:288-298
Ham, Byung-Joo; Greenberg, Tsafrir; Chase, Henry W et al. (2016) Impact of the glucocorticoid receptor BclI polymorphism on reward expectancy and prediction error related ventral striatal reactivity in depressed and healthy individuals. J Psychopharmacol 30:48-55
Fournier, Jay C; Chase, Henry W; Almeida, Jorge et al. (2016) Within- and Between-Session Changes in Neural Activity During Emotion Processing in Unipolar and Bipolar Depression. Biol Psychiatry Cogn Neurosci Neuroimaging 1:518-527
Kerestes, Rebecca; Segreti, Anna Maria; Pan, Lisa A et al. (2016) Altered neural function to happy faces in adolescents with and at risk for depression. J Affect Disord 192:143-52

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