White Matter Microstructural Changes and Episodic Memory Disturbances in Late-Onset Bipolar Disorder.

Background: Bipolar disorder (BD) has been associated with distributed network disruption, but little is known on how different clinical subtypes, particularly those with an earlier and later onset of disease, are related to connectivity changes in white matter (WM) tracts. Methods: Diffusion tensor imaging (DTI) and volumetric measures were carried out in early-onset bipolar patients [(EOD) (n = 16)], late-onset bipolar disorder [(LOD)(n = 14)] and healthy controls (n = 32). We also computed ROI analysis of gray matter (GM) and white matter (WM) volumes using the regions with significant group differences in the DTI parameters. Cognitive and behavior measurements were analyzed between groups. Results: Lower fraction of anisotropy (FA) in the right hemisphere comprising anterior thalamic radiation, fornix, posterior cingulate, internal capsule, splenium of corpus callosum was observed in the LOD in comparison with EOD; additionally, lower FA was also found in the LOD in comparison with healthy controls, mostly in the right hemisphere and comprising fibers of the splenium of the corpus callosum, cingulum, superior frontal gyrus and posterior thalamic radiation; LOD also showed worse episodic memory performance than EOD; no statistical significant differences between mood symptoms, WM and GM volumes were found between BD groups. Conclusion: Even after correcting for age differences, LOD was associated with more extensive WM microstructural changes and worse episodic memory performance than EOD; these findings suggest that changes in the WM fiber integrity may be associated with a later presentation of BD, possibly due to mechanisms other than neuroprogression. However, these findings deserve replication in larger, prospective, studies.

Cortical thinning in bipolar disorder and schizophrenia.

Although schizophrenia (SZ) and bipolar disorder (BD) share some clinical features such as psychotic symptoms and cognitive dysfunctions, little is known about possible pathophysiological similarities between both diseases. Therefore, we investigated the potential topographical overlap and segregation of cortical thickness abnormalities in SZ and BD patients. We analyzed 3D-anatomical magnetic resonance imaging datasets with the FreeSurfer 5.1.0 software to examine cortical thickness and volumes in three groups of participants: n=34 BD patients, n=32 SZ patients and n=38 healthy controls. We observed similar bilateral cortical thickness reductions in BD and SZ patients predominantly in the pars opercularis of the inferior frontal gyrus and in the anterior and posterior cingulate. We also found disease-specific cortical reductions in the orbitofrontal cortex for BD patients and in dorsal frontal and temporal areas for SZ. Furthermore, inferior frontal gyrus cortical thinning was associated with deficits in psychomotor speed and executive functioning in SZ patients and with age at onset in both groups. Our findings support the hypothesis that thinning of the frontal cortex may represent a biological feature shared by both disease groups. The associations between cognitive deficits and the reported findings in SZ and to a lesser degree in BD patients add to the functional relevance of our results. However, further studies are needed to corroborate a model of shared pathophysiological disease features across BD and SZ.

Association between age of disease-onset, cognitive performance and cortical thickness in bipolar disorders.

OBJECTIVES: Neuroimaging studies in patients with bipolar disorder (BD) have indicated a number of structural brain changes, including reduced cortical thickness. However, the effects of the course of illness, clinical and cognitive variables on cortical thickness in BD patients have not yet been evaluated. METHODS: A total of 67 individuals (32 patients with euthymic BD and 35 healthy and age-matched controls) underwent 3D-anatomical magnetic resonance imaging (MRI). Whole-brain cortical thickness and group differences were assessed using the Freesurfer software. Course of disease variables, clinical and cognitive parameters were correlated with cortical thickness measures. RESULTS: We found reduced cortical thickness in BD patients compared with controls in the frontal and temporal lobes and in several limbic areas. We also report significant associations between cortical thickness and age of disease-onset, speed of cognitive processing, executive function and depression severity in BD patients. CONCLUSIONS: Cortical thickness reduction across frontal and limbic areas is a structural correlate of affective symptom severity and cognitive impairments in BD as well of age of disease-onset. We may assume that frontal lobe structural abnormalities are present in bipolar disorder, and might lead to dysfunctional cognitive functioning. The causality and functional relevance beyond mere correlation, however, is yet to be established. Our findings encourage further longitudinal studies in BD patients and in healthy at-risk subjects in order to discern the temporal order and development of morphological changes and clinical symptoms.

Episodic memory impairments in bipolar disorder are associated with functional and structural brain changes.

OBJECTIVES: We combined multimodal functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging to probe abnormalities in brain circuits underpinning episodic memory performance deficits in patients with bipolar disorder (BD). METHODS: We acquired whole-brain fMRI data in 21 patients with BD and a matched group of 20 healthy controls during a non-verbal episodic memory task, using abstract shapes. We also examined density of gray matter, using voxel-based morphometry (VBM), and integrity of connecting fiber tracts, using diffusion tensor imaging (DTI) and tract-based spatial statistics, for areas with significant activation differences. RESULTS: Patients with BD remembered less well than controls which shapes they had seen and had lower activation levels during the encoding stage of the task in the anterior cingulate gyrus, the precuneus/cuneus bilaterally, and the left lingual gyrus, and higher activation levels during the retrieval stage in the left temporo-parietal junction. Patients with BD showed reduced gray matter volumes in the left anterior cingulate, the precuneus/cuneus bilaterally, and the left temporo-parietal region in comparison with controls. DTI revealed increased radial, axial, and mean diffusivity in the left superior longitudinal fascicle in patients with BD compared with controls. CONCLUSIONS: Changes in task-related activation in frontal and parietal areas were associated with poorer episodic memory in patients with BD. Compared with data from single imaging modalities, integration of multimodal neuroimaging data enables the building of more complete neuropsychological models of mental disorders.

Verbal episodic memory deficits in remitted bipolar patients: a combined behavioural and fMRI study.

BACKGROUND: Episodic memory deficits affect the majority of patients with bipolar disorder (BD). AIMS: The study investigates episodic memory performance through different approaches, including behavioural measures, physiological parameters, and the underlying functional activation patterns with functional neuroimaging (fMRI). METHODS: 26 Remitted BD patients and a matched group of healthy controls underwent a verbal episodic memory test together with monitored autonomic response, psychopathological ratings and functional magnetic resonance imaging (fMRI) during the verbal episodic memory test. RESULTS: Compared to healthy controls, BD patients performed significantly worse during the episodic memory task. The results further indicate that verbal episodic memory deficits in BD are associated with abnormal functional activity patterns in frontal, occipital and limbic regions, and an increase in stress parameters. LIMITATIONS: We aimed to minimise sample heterogeneity by setting clear criteria for remission, based on the scores of a depression (BDI II) and mania scale (BRMAS) and on the DSM IV criteria. However, our patients were not symptom-free and scored higher on BDI II scores than the control group. CONCLUSIONS: The results are of interest for the treatment of cognitive symptoms in BD patients, as persistent cognitive impairment may hamper full rehabilitation.