White matter microstructure in youth with and at risk for bipolar disorder

Abstract

Objectives Bipolar disorder (BD) and familial risk for BD have been associated with aberrant white matter (WM) microstructure in the corpus callosum and fronto‐limbic pathways. These abnormalities might constitute trait or state marker and have been suggested to result from aberrant maturation and to relate to difficulties in emotion regulation. Methods To determine whether WM alterations represent a trait, disease or resilience marker, we compared youth at risk for BD (n = 36 first‐degree relatives, REL) to youth with BD (n = 36) and healthy volunteers (n = 36, HV) using diffusion tensor imaging. Results Individuals with BD and REL did not differ from each other in WM microstructure and, compared to HV, showed similar aberrations in the superior corona radiata (SCR)/corticospinal tract (CST) and the body of the corpus callosum. WM microstructure of the anterior CC showed reduced age‐related in‐creases in BD compared to REL and HV. Further, individuals with BD and REL showed in‐creased difficulties in emotion regulation, which were associated with the microstructure of the anterior thalamic radiation. Discussion Alterations in the SCR/CST and the body of the corpus callosum appear to represent a trait marker of BD, whereas changes in other WM tracts seem to be a disease state marker. Our findings also support the role of aberrant developmental trajectories of WM microstructure in the risk architecture of BD, although longitudinal studies are needed to confirm this association. Finally, our findings show the relevance of WM microstructure for difficulties in emotion regulation—a core characteristic of BD.

Structural brain abnormalities associated with cognitive impairments in bipolar disorder

“…Global or regional white matter disruptions have consistently been reported in BD patients, both recently diagnosed, 49 patients with longer duration of illness 80 and young first‐degree relatives of patients with BD 81,82 . Our demonstration of lower cerebral white matter volume in CI patients extends previous findings by suggesting these deficits may be specific to cognitively impaired patients.…”

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study

“…The anterior corpus callosum carried left and right ventral prefrontal cortex connections engaging in cognitive processing and emotional regulation 43 , 44 . Abnormalities in the corona radiata, which connects brainstem with prefrontal regions including the ventrolateral prefrontal cortex (VLPFC) and dorsolateral prefrontal cortex (DLPFC) 45 , 46 , are repeatedly reported in patients with BD 47 , 48 . This finding of increased FA in the WM might suggest signs of compensatory reactions to the subthreshold mood symptoms manifested in the bipolar offspring as we previously observed 25 , 26 .…”

Evaluating endophenotypes for bipolar disorder

“…Another possible explication of the negative results of this follow-up study is that evidence indicates that in individuals at-risk for BD, WMA has been found in specifically brain regions (i.e. superior corona radiata (SCR)/corticospinal tract (CST) and the body of the corpus callosum) whereas changes in other WM tracts seem to be a disease state marker (Linke et al 2020 ).…”

“…Regarding co-segregation of WMA with the genetic risk of BD, there is compelling evidence that are more frequent in URs compared to controls. Widespread FA reductions and significant lower FA values have been found in BD patients and their URs respect to healthy control subjects particularly in corpus callosum, the dorsal part of the right cingulum bundle, the hippocampal part of the cingulum bundle bilaterally, and the uncinate fasciculus (Sprooten et al 2013 , 2016 ; Mahapatra et al 2017 ; Linke et al 2020 ). Of note, a 2-year follow-up study identified similar trajectories of FA reductions for controls and high-risk young adults and failed to find differences in FA among URs of BD patients and healthy controls, suggesting that difference in WM integrity could occur in earlier childhood and be a necessary but not sufficient condition to develop future BD (Ganzola et al 2017 ).…”