There is a clear need for ongoing clinical research on bipolar disorder to identify more effective treatments. However, the primary affective symptoms, and deficits in insight and cognitive functioning that are often associated with this condition, may adversely affect the capacity of some patients to consent to participate in such research. With the exception of our preliminary data from a small circumscribed sample of middle-aged and older bipolar patients, there have been no published studies of capacity to consent to research among bipolar patients. The goals of the proposed longitudinal study are to identify the factors associated with the level and stability of capacity to consent to research among a clinically and demographically heterogeneous sample of 172 people with bipolar I or II disorder, as well as among 118 healthy comparison subjects (HCs). We will also evaluate the degree to which understanding of disclosed information can be improved through an interactive disclosure process. Using standard measures, decisional capacity, severity of psychopathology, insight deficits, and neuropsychological functioning will be systematically evaluated at baseline, 6-, 12-, and 26- week visits. We hypothesize that bipolar patients will show significant deficits in decisional capacity relative to HCs, but there will be considerable within-group heterogeneity;between person differences in decisional capacity will be more strongly related to level of cognitive deficits than to severity of psychopathology or insight deficits. However, within-person variability over time will be a function of changes in psychopathology and insight. We also hypothesize that the number of prior affective episodes will be related to worse decisional capacity, but that this relationship will be mediated by the deleterious effects of multiple affective episodes on cognitive functioning and that levels of understanding among all participants will improve through an iterative disclosure process. This study will have high public health and bioethical significance, as there remains a clear need for clinical research in bipolar disorder, but there is a lack of empirical data to guide policy and researchers regarding the ethical enrollment of such participants in terms of ensuring valid initial and continuing informed consent.

Public Health Relevance

Bipolar disorder is characterized by fluctuations in mental status which may be relevant to patients'capacity to give meaningful consent to research participation, but decision-making capacity for research among bipolar patients has received almost no empirical attention. Thus, patients, investigators, IRBs, stakeholder advocacy groups, and regulatory authorities lack essential empirical information to inform decisions such as if, when, and what form of additional protections may be warranted and effective to ensure ethical enrollment of patients in clinical research on bipolar disorder. The data collected in the proposed study will be a key component in filling this vital informational gap.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Special Emphasis Panel (ZRG1-HOP-E (90))
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Otey, Emeline M
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Veterans Medical Research Fdn/San Diego
San Diego
United States
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Harmell, Alexandrea L; Mausbach, Brent T; Moore, Raeanne C et al. (2014) Longitudinal study of sustained attention in outpatients with bipolar disorder. J Int Neuropsychol Soc 20:230-7
Depp, Colin A; Harmell, Alexandrea L; Savla, Gauri N et al. (2014) A prospective study of the trajectories of clinical insight, affective symptoms, and cognitive ability in bipolar disorder. J Affect Disord 152-154:250-5
Palmer, Barton W; Savla, Gauri N; Roesch, Scott C et al. (2013) Changes in capacity to consent over time in patients involved in psychiatric research. Br J Psychiatry 202:454-8
Thompson, Wesley K; Savla, Gauri N; Vahia, Ipsit V et al. (2013) Characterizing trajectories of cognitive functioning in older adults with schizophrenia: does method matter? Schizophr Res 143:90-6
Depp, C A; Savla, G N; de Dios, L A Vergel et al. (2012) Affective symptoms and intra-individual variability in the short-term course of cognitive functioning in bipolar disorder. Psychol Med 42:1409-16
Palmer, Barton W; Lanouette, Nicole M; Jeste, Dilip V (2012) Effectiveness of multimedia aids to enhance comprehension of research consent information: a systematic review. IRB 34:1-15
Harmell, Alexandrea L; Palmer, Barton W; Jeste, Dilip V (2012) Preliminary study of a web-based tool for enhancing the informed consent process in schizophrenia research. Schizophr Res 141:247-50
Savla, Gauri N; Twamley, Elizabeth W; Delis, Dean C et al. (2012) Dimensions of executive functioning in schizophrenia and their relationship with processing speed. Schizophr Bull 38:760-8
Burton, Cynthia Z; Twamley, Elizabeth W; Lee, Lana C et al. (2012) Undetected cognitive impairment and decision-making capacity in patients receiving hospice care. Am J Geriatr Psychiatry 20:306-16
Thorp, Steven R; Sones, Heather M; Glorioso, Danielle et al. (2012) Older patients with schizophrenia: does military veteran status matter? Am J Geriatr Psychiatry 20:248-56

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