Structural brain abnormalities associated with cognitive impairments in bipolar disorder

Abstract

Objective Cognitive impairment has been highlighted as a core feature of bipolar disorder (BD) that often persists during remission. The specific brain correlates of cognitive impairment in BD remain unclear which impedes efficient therapeutic approaches. In a large sample of remitted BD patients, we investigated whether morphological brain abnormalities within dorsal prefrontal cortex (PFC) and hippocampus were related to cognitive deficits. Methods Remitted BD patients (n = 153) and healthy controls (n = 52) underwent neuropsychological assessment and structural MRI. Based on hierarchical cluster analysis of neuropsychological test performance, patients were classified as either cognitively impaired (n = 91) or cognitively normal (n = 62). The neurocognitive subgroups were compared amongst each other and with healthy controls in terms of dorsal PFC cortical thickness and volume, hippocampus shape and volume, and total cerebral grey and white matter volumes. Results Cognitively impaired patients displayed greater left dorsomedial prefrontal thickness compared to cognitively normal patients and healthy controls. Hippocampal grey matter volume and shape were similar across patient subgroups and healthy controls. At a whole‐brain level, cognitively impaired patients had lower cerebral white matter volume compared to the other groups. Across all participants, lower white matter volume correlated with more impaired neuropsychological test performance. Conclusions Our findings associate cognitive impairment in bipolar disorder with cerebral white matter deficits, factors which may relate to the observed morphological changes in dorsomedial PFC possibly due to increased neurocognitive effort to maintain symptom stability in these remitted patients.

Alterações Neuropsicológicas no Transtorno Bipolar

“…O comprometimento cognitivo vem sendo estudado em pacientes com TB como uma das principais características. O estudo de Macoveanu (2021), testou uma amostra de pacientes em remissão da doença para investigar as anormalidades morfológicas cerebrais no hipocampo e no córtex pré-frontal dorsal, e se as mesmas estão relacionadas a déficits cognitivos.…”

Aberrant resting‐state functional connectivity underlies cognitive and functional impairments in remitted patients with bipolar disorder

“…These rsFC abnormalities may arise from disruption of structural connectivity due to white matter deficits that have been observed in CI relative to CN patients with mood disorders and HC. 52,53 Interestingly, an MRI study exploring the corpus callosum (CC) in children and adolescents with BD found a lower circularity of the splenium of the CC in a sample of pediatric patients with BD relative to HC, suggesting that such white matter abnormalities may occur early in the course of BD. 54 Indeed, this lends support to the hypothesis of an abnormal neurodevelopmental trajectory in BD.…”

“…Second, from a theoretical perspective, it is interesting that rsFC abnormalities were seen both within and between DMN and ECN in partially overlapping parietal and PCC areas. These rsFC abnormalities may arise from disruption of structural connectivity due to white matter deficits that have been observed in CI relative to CN patients with mood disorders and HC 52,53 . Interestingly, an MRI study exploring the corpus callosum (CC) in children and adolescents with BD found a lower circularity of the splenium of the CC in a sample of pediatric patients with BD relative to HC, suggesting that such white matter abnormalities may occur early in the course of BD 54 .…”

Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force

“…In keeping with this, recent fMRI studies that compared neuronal activity between cognitively impaired (with global cognition scores ≥1 SD below the mean of healthy controls) and cognitively normal people with BD found that cognitive impairments were associated with working memory(WM)‐related hypo ‐activity in the DPFC and parietal regions coupled with hyper ‐activity in the DMN 12,13 . At a structural level, cognitively impaired BD individuals were found to display lower cerebral white matter volume and greater DPFC volume or grey matter, respectively, than cognitively normal individuals and healthy participants 14,15 . In MDD, extensive white matter dysfunction has also been observed in globally cognitively impaired individuals relative to those with either selective impairments or normal cognition 16 .…”

“… 12 , 13 At a structural level, cognitively impaired BD individuals were found to display lower cerebral white matter volume and greater DPFC volume or grey matter, respectively, than cognitively normal individuals and healthy participants. 14 , 15 In MDD, extensive white matter dysfunction has also been observed in globally cognitively impaired individuals relative to those with either selective impairments or normal cognition. 16 However, other structural studies in BD revealed no differences between impaired and normal neurocognitive subgroups, 12 , 17 suggesting that task‐based fMRI could be a more sensitive assay of cognitive impairments.…”