Abstract
ObjectivesBipolar 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.MethodsTo 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.ResultsIndividuals 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.DiscussionAlterations 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.
Highlights
Bipolar disorder (BD), which is characterized by discrete, episodic changes in affect, motivation, cognition and behavior,[1] is a severe mental disorder with a prevalence of at least 1%2 and a high heritability of 60%-80%.3 To date, the pathophysiology of BD is still poorly understood impeding early and precise diagnosis,[4] and thereby detrimentally affecting the course of the disease.[5]
Studies in individuals at risk for BD before the first peak of onset that occurs between 21-25 years7) offer the possibility to identify adaptive functional changes associated with resilience and will further advance our etiological understanding of BD
12 studies were conducted in pediatric BD and, as in adult BD, reduced fractional anisotropy (FA) in the anterior corpus callosum (CC), cingulum bundle, UNC, SLF, corticospinal tract (CST) and ATR,[14] emerged as the most robust findings
Summary
Bipolar disorder (BD), which is characterized by discrete, episodic changes in affect, motivation, cognition and behavior,[1] is a severe mental disorder with a prevalence of at least 1%2 and a high heritability of 60%-80%.3 To date, the pathophysiology of BD is still poorly understood impeding early and precise diagnosis,[4] and thereby detrimentally affecting the course of the disease.[5]. | 164 and regulation.[6] to differentiate quantitative risk factors from markers of disease progression, it is necessary to study healthy individuals at high risk to develop bipolar disorder (ie, unaffected first-degree relatives of individuals with BD; REL). Seven studies in unaffected adult REL reported reduced FA in the CC,[15] cingulum bundle,[16] SLF,[16,17] ATR,[15,17] and UNC.[15,16,17] Based on these findings, it has been argued that altered WM microstructure might represent a quantitative risk marker for BD, meaning it plays an antecedent, possibly causal, role in the pathophysiology of BD.[13] the two studies that compared adolescent REL (n = 25-79, age: 15-21) to HV's yielded conflicting results.
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