Cognitive and neural abnormalities: working memory deficits in bipolar disorder offspring

• Published in: Psychological medicine Vol. 55; p. e130
• Main Authors: Xie, Ye, Zou, Wenjin, Shang, Yuanqi, Lu, Weicong, Li, Xiaoyue, Chen, Qi, Shao, Robin, Ku, Yixuan, Lin, Kangguang
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 02.05.2025
• Subjects: Adolescent; Adult; Age; Analysis of covariance; Bipolar disorder; Bipolar Disorder - complications; Bipolar Disorder - physiopathology; Brain research; Case-Control Studies; Child of Impaired Parents - psychology; Cognitive Dysfunction - physiopathology; Cognitive impairment; Cognitive systems; Cortex; Cortex (frontal); Early intervention; Emotional regulation; False alarms; Female; Frontal gyrus; Functional magnetic resonance imaging; Genetic susceptibility; Humans; Information processing; Magnetic Resonance Imaging; Male; Memory; Memory, Short-Term - physiology; Mental disorders; Neuroimaging; Offspring; Original; Original Article; Performance evaluation; Physiological psychology; Postcentral gyrus; Precentral gyrus; Prefrontal cortex; Sensory integration; Sensory processes; Short term memory; Somatosensory cortex; Task performance; Young Adult; BD offspring; bipolar disorder; working memory; prefrontal cortex; functional magnetic resonance imaging
• ISSN: 0033-2917; 1469-8978; 1469-8978
• DOI: 10.1017/S0033291725001060

Offspring of parents with bipolar disorder (BD offspring) face elevated risks for emotional dysregulation and cognitive deficits, particularly in working memory. This study investigates working memory deficits and their neural correlates in BD offspring. We assessed 41 BD offspring and 25 age-matched healthy controls (HCs) using a spatial N-back task and task-related functional magnetic resonance imaging (fMRI). Compared to HCs, BD offspring exhibit reduced accuracy and lower signal-detection sensitivity ( ') on the 1-back task. fMRI reveals hyperactivation in the right intracalcarine cortex/lingual gyrus (ICC/LG) in BD offspring, particularly during the 1-back condition. Psychophysiological interaction (PPI) analyses show reduced connectivity between the right ICC/LG and the left postcentral gyrus in BD offspring as task load increases from 0-back to 1-back. This connectivity positively correlates with 1-back task performance in HCs but not in BD offspring. Additionally, using bilateral dorsolateral prefrontal cortex (DLPFC) as regions of interest, PPI analyses show diminished condition-dependent connectivity between the left DLPFC and the left superior frontal gyrus/paracingulate cortex, and between the right DLPFC and the left postcentral gyrus/precentral gyrus in BD offspring as the task load increases. These findings suggest that BD offspring exhibit working memory deficits and impaired neural connectivity involving both sensory processing and higher-order cognitive systems. Such deficits may emerge at a genetically predisposed stage of bipolar disorder, underscoring the significance of early identification and intervention strategies.