Neuroinflammation and white matter microstructure as mediators of cognitive deficits in offspring of parents with bipolar disorder.
Source: PubMed, NCBI / U.S. National Library of Medicine
Neuroinflammation and white matter disruptions have been implicated in cognitive impairments associated with bipolar disorder, particularly in information processing speed (IPS). These neurological factors may manifest in at-risk offspring, even prior to the full development of the disorder, emphasizing the importance of investigating their role in early cognitive changes associated with bipolar disorder. This study examines these associations in offspring with varying levels of risk for bipolar disorder. Offspring of parents with bipolar disorder were classified as asymptomatic (AO,= 41) or symptomatic (SO,= 35) groups and age-matched healthy controls (HCs,= 32). We assessed serum interleukin-6 (IL-6) levels, IPS performance and fractional anisotropy (FA) of the forceps major (FM) connecting the occipital lobes. Compared to AO, SO demonstrated significantly higher IL-6 levels, reduced FM FA and lower IPS performance, while the AO group exhibited preserved FM FA and IPS performance comparable to HCs. Serial mediation analysis revealed that symptomatic status among offspring at familial risk exerted a significant total indirect effect (= -3.83, 95% CI [-7.28, -0.84]) on IPS performance through the pathways involving IL-6 and FM FA. This indirect effect accounted for 42.46% of the total effect, indicating significant full mediation. Our findings suggest that neuroinflammation and FM microstructure mediate the association between symptomatic status for bipolar disorder offspring
Abstract
Neuroinflammation and white matter disruptions have been implicated in cognitive impairments associated with bipolar disorder, particularly in information processing speed (IPS). These neurological factors may manifest in at-risk offspring, even prior to the full development of the disorder, emphasizing the importance of investigating their role in early cognitive changes associated with bipolar disorder. This study examines these associations in offspring with varying levels of risk for bipolar disorder. Offspring of parents with bipolar disorder were classified as asymptomatic (AO,= 41) or symptomatic (SO,= 35) groups and age-matched healthy controls (HCs,= 32). We assessed serum interleukin-6 (IL-6) levels, IPS performance and fractional anisotropy (FA) of the forceps major (FM) connecting the occipital lobes. Compared to AO, SO demonstrated significantly higher IL-6 levels, reduced FM FA and lower IPS performance, while the AO group exhibited preserved FM FA and IPS performance comparable to HCs. Serial mediation analysis revealed that symptomatic status among offspring at familial risk exerted a significant total indirect effect (= -3.83, 95% CI [-7.28, -0.84]) on IPS performance through the pathways involving IL-6 and FM FA. This indirect effect accounted for 42.46% of the total effect, indicating significant full mediation. Our findings suggest that neuroinflammation and FM microstructure mediate the association between symptomatic status for bipolar disorder offspring and IPS deficits in offspring. This highlights potential neural mechanisms underlying cognitive dysfunction in pre-symptomatic and symptomatic stages of bipolar disorder.