Bipolar depression, the depressive phase of bipolar disorder (BD), is a major therapeutic challenge and frequent cause of chronic impairment. Patients suffering from bipolar depression are often non-responsive to various therapeutic interventions. Abnormalities in fronto-limbic brain (FLB) mechanisms could account for their pathophysiology and relate to treatment response. We propose to test specific hypotheses about the involvement of FLB circuits in bipolar depression in BD type 1patients, and the relationship of FLB abnormalities to symptom remission and treatment response to mood stabilizing agents. Study Design and Methods: In vivo brain imaging methods (magnetic resonance imaging, MRI, and MRspectroscopy, MRS) will be utilized to measure and compare regional brain volumes and regional levels of Nacetyl Aspartate (NAA), a non-specific marker of neuronal viability and function, in prefrontal cortex and medial temporal lobe regions. 90 untreated depressed DSM-IV BD type I patients will undergo MRI and MRS scans at entry to the study, and after 4 and 16 weeks of medication treatment. 60 matched healthy controls will undergo MRS scan at entry, of which 20 will repeat these measures at weeks 4 and 16. The BD patients will be stratified into 3 groups, based on their responsiveness to treatments (>50% improvement in HAMD-21 item scores) during the 16-week period: (i) those who improve following 4 weeks of monotherapy with lithium, and remain improved until the end of the 16-week follow-up period, (ii) monotherapy non-responders who subsequently are responsive to an additional 12 weeks of combination treatment with lamotrigine and lithium, and (iii) patients with bipolar depression who do not respond to either monotherapy or combination therapy. Specific Hypotheses: I: Bipolar depression arises from impairment in neuronal survival in FLB circuits. II: Treatment with a mood-stabilizing agent has detectable effects of ameliorating or reversing prefrontal cortex (PFC) abnormalities. III: Amygdala abnormalities are related to decreased PFC inhibitory drive. IV: Therapeutic response to mood stabilizing agents is related to amelioration or reversal of FLB abnormalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH068766-03
Application #
7171496
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
2005-02-16
Project End
2010-01-31
Budget Start
2007-05-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$346,086
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Dandekar, Manoj P; Luse, Dustin; Hoffmann, Carson et al. (2017) Increased dopamine receptor expression and anti-depressant response following deep brain stimulation of the medial forebrain bundle. J Affect Disord 217:80-88
Passos, Ives Cavalcante; Mwangi, Benson; Cao, Bo et al. (2016) Identifying a clinical signature of suicidality among patients with mood disorders: A pilot study using a machine learning approach. J Affect Disord 193:109-16
Cao, Bo; Passos, Ives Cavalcante; Mwangi, Benson et al. (2016) Hippocampal volume and verbal memory performance in late-stage bipolar disorder. J Psychiatr Res 73:102-107
Cardoso, Taiane de A; Bauer, Isabelle E; Jansen, Karen et al. (2016) Effect of alcohol and illicit substance use on verbal memory among individuals with bipolar disorder. Psychiatry Res 243:225-231
Bauer, Isabelle E; Ouyang, Austin; Mwangi, Benson et al. (2015) Reduced white matter integrity and verbal fluency impairment in young adults with bipolar disorder: a diffusion tensor imaging study. J Psychiatr Res 62:115-22
Lijffijt, M; Rourke, E D; Swann, A C et al. (2014) Illness-course modulates suicidality-related prefrontal gray matter reduction in women with bipolar disorder. Acta Psychiatr Scand 130:374-87
Ghouse, Amna A; Sanches, Marsal; Zunta-Soares, Giovana B et al. (2014) Lifetime mood spectrum symptoms among bipolar patients and healthy controls: a cross sectional study with the Mood Spectrum Self-Report questionnaire. J Affect Disord 166:165-7
Nery, Fabiano G; Hatch, John P; Monkul, E Serap et al. (2013) Trait impulsivity is increased in bipolar disorder patients with comorbid alcohol use disorders. Psychopathology 46:145-52
Henna, Elaine; Hatch, John P; Nicoletti, Mark et al. (2013) Is impulsivity a common trait in bipolar and unipolar disorders? Bipolar Disord 15:223-7
Selek, Salih; Nicoletti, Mark; Zunta-Soares, Giovana B et al. (2013) A longitudinal study of fronto-limbic brain structures in patients with bipolar I disorder during lithium treatment. J Affect Disord 150:629-33

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