CLOCKΔ19 mouse model elucidates cognitive deficits in bipolar disorder

Poster Session A - Saturday, April 13, 2024, 2:30 – 4:30 pm EDT, Sheraton Hall ABC

Dennis Arruda¹ (darruda@rwu.edu), Simrat Dhillon¹, Eden Fraatz¹, Giana Guerra¹, Brittany Martin¹, Samantha Soares¹, Victoria Heimer-McGinn¹; ¹Roger Williams University

Bipolar disorder (BD) is a neuropsychiatric disorder characterized by rapid mood cycling, fluctuations in energy, mania, and depressive episodes. The accompanying cognitive deficits of BD, however, are most predictive of patient psychosocial outcomes. Deficits in recognition memory and cognitive flexibility are two understudied symptoms that could potentially help refine BD endophenotypes. The CLOCKΔ19 transgenic mouse model has good construct, face, and predictive validity for BD and, notably, exhibits regular mood cycling between manic and euthymic behavior over 24 hours. The current study seeks to characterize various cognitive domains in CLOCKΔ19 mice. We compare the performance of 6 experimental groups (n=6 per group) on several tasks, with sex (male, female) and genotype (wildtype [+/+], homozygous [-/-], heterozygous [+/-]) as independent variables. The cognitive battery includes an open field maze (OFM), novel object recognition (NOR), novel object location (NOL), and attentional set-shifting tasks (AST). Preliminary data from OFM, NOR, and NOL show trends toward impairments similar to those observed in the human population. For example, a significant main effect of genotype was found in NOL. In AST, we have yet to discern any clear behavioral patterns with our limited sample size, although this is not surprising considering the complexity of the task. In upcoming experiments, we will also be testing these cognitive domains longitudinally to assess disease progression. These results will help elucidate the role of the clock gene in cognition and serve to further validate the model for translational studies of cognition in BD.

Topic Area: EXECUTIVE PROCESSES: Goal maintenance & switching