Patients with bipolar disorder (BPD) were once thought to achieve complete inter-episode recovery, particularly with regard to cognitive dysfunction. More recent data suggest a persistent, trait-like pattern of neurocognitive impairments in BPD, even during periods of affective remission. At the group level, the severity of these deficits is 3/4 to 1 full standard deviation below average, which is significantly less severe than deficits noted in schizophrenia (SZ). Recent evidence, however, suggests that the frequency of cognitive impairment in euthymic BPD patients is ~40-60%, with a substantial proportion of patients characterized as cognitively- spared. This contrasts with the relative homogeneity of this phenotype in SZ where > 90% of patients demonstrates significant impairment. A better understanding of the cognitive heterogeneity in BPD, why some patients develop significant cognitive difficulties while others do not, is critical toward optimizing patiets' quality of life. The current proposal aims to determine the clinical and biological predictors of cognitive impairment in 350 patients with BPD using a novel approach. We will empirically test for homogeneous subgroups within the sample based neurocognitive performance and test a cassette of clinical features and biomarkers as potential predictors of impairment. We will also investigate the relationship between neurocognitive functioning and everyday functional capacity in the areas of occupational, social and independent living ability. Data will provide important information on the underlying structure of neurocognition in BPD and its etiology, guiding future efforts to target these disabling symptoms with treatment.

Public Health Relevance

Converging evidence suggests that patients with bipolar disorder (BPD) have persistent neurocognitive impairment, despite remission of acute affective symptoms that contribute directly to functional disability in social, occupational, and residential status. The current study aims to identify subgroups of BPD patients based on their cognitive performance and to identify clinical features and biomarkers that are associated with cognitive dysfunction and functional disability. Ultimately, data derived from this project could serve to 1) identify groups of BPD patients who are at increased risk for developing cognitive problems~ and 2) guide future efforts toward developing novel and effective treatments for these disabling symptoms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
4R01MH100125-04
Application #
9065620
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Rumsey, Judith M
Project Start
2013-08-05
Project End
2018-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Van Rheenen, Tamsyn E; Lewandowski, Kathryn E; Lipschitz, Jessica M et al. (2018) Conducting clinical studies targeting cognition in psychiatry: guiding principles and design. CNS Spectr :1-6
Ospina, L H; Nitzburg, G C; Shanahan, M et al. (2018) Social cognition moderates the relationship between neurocognition and community functioning in bipolar disorder. J Affect Disord 235:7-14
Nitzburg, George C; Cuesta-Diaz, Armando; Ospina, Luz H et al. (2017) Organizational Learning Strategies and Verbal Memory Deficits in Bipolar Disorder. J Int Neuropsychol Soc 23:358-366
Russo, M; Van Rheenen, T E; Shanahan, M et al. (2017) Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings. Psychol Med 47:2892-2905
Trampush, J W; Yang, M L Z; Yu, J et al. (2017) GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium. Mol Psychiatry 22:336-345
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Van Rheenen, T E; Lewandowski, K E; Tan, E J et al. (2017) Characterizing cognitive heterogeneity on the schizophrenia-bipolar disorder spectrum. Psychol Med 47:1848-1864
Howrigan, D P; Simonson, M A; Davies, G et al. (2016) Genome-wide autozygosity is associated with lower general cognitive ability. Mol Psychiatry 21:837-43
Ospina, Luz H; Russo, Manuela; Nitzburg, George M et al. (2016) The effects of cigarette smoking behavior and psychosis history on general and social cognition in bipolar disorder. Bipolar Disord 18:528-538
Nitzburg, George C; Russo, Manuela; Cuesta-Diaz, Armando et al. (2016) Coping strategies and real-world functioning in bipolar disorder. J Affect Disord 198:185-8

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