Inhibitory deficits in euthymic bipolar disorder patients assessed in the human behavioral pattern monitor

Abstract

Background: Bipolar disorder (BD) is associated with inhibitory deficits characterized by a reduced ability to control inappropriate actions or thoughts. While aspects of inhibition such as exaggerated novelty-seeking and perseveration are quantified in rodent exploration of novel environments, similar models are rarely applied in humans. The human Behavioral Pattern Monitor (hBPM), a cross-species exploratory paradigm, has identified a pattern of impaired inhibitory function in manic BD participants, but this phenotype has not been examined across different BD phases. The objective of this study was to determine if euthymic BD individuals demonstrate inhibitory deficits in the hBPM, supporting disinhibition as an endophenotype for the disorder.

Methods: 25 euthymic BD outpatients and 51 healthy comparison subjects were assessed in the hBPM, where activity was recorded by a concealed videocamera and an ambulatory monitoring sensor.

Results: Euthymic BD individuals, similar to manic subjects, demonstrated increased motor activity, greater interaction with novel objects, and more frequent perseverative behavior relative to comparison participants. The quantity of locomotion was also reduced in BD individuals treated with mood stabilizers compared to other patients.

Limitations: Low sample size for treatment subgroups limits the evaluation of specific medication regimens.

Conclusions: Our results suggest that BD is distinguished by both trait- and state-dependent inhibitory deficits optimally assessed with sophisticated multivariate measures. These data support the use of the hBPM as a tool to elucidate the effects of BD across various illness states, facilitate the development of BD animal models, and advance our understanding of the neurobiology underlying the disorder.

Keywords: Behavioral pattern monitor; Bipolar disorder; Euthymic; Exploration; Impulsivity; Inhibition.

Figure 1

hBPM data for healthy comparison (HC, n = 51) and bipolar disorder (BD, n = 25) participants during the 15-minute session, including acceleration (A), distance traveled (B), sector transitions (C), spatial d (D), spatial CV (E), number of object interactions (F), and the percent of participants who engaged in multiple object interactions (MOI) (G) or perseverative object interactions (POI) (H). Data are represented as means ± SEM. Asterisks indicate significant group differences; * p < 0.05; *** p < 0.001.

Figure 2

15 minute hBPM data for BD participants currently treated with mood stabilizers (BDms, n = 15) compared to BD participants not treated with mood stabilizer medication (BDnt, n = 10), including acceleration (A), distance traveled (B), sector transitions (C), spatial d (D), spatial CV (E), number of object interactions (F). Data are represented as means ± SEM. ** p < 0.01; † p < 0.10.