Increased grey matter volumes in the temporal lobe and its relationship with cognitive functioning in euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is characterized by episodic mood dysregulation, although a significant portion of patients suffer persistent cognitive impairment during euthymia. Previous magnetic resonance imaging (MRI) research suggests BD patients may have accelerated brain aging, observed as lower grey matter volumes. How these neurostructural alterations are related to the cognitive profile of BD is unclear. METHODS: We aim to explore this relationship in euthymic BD patients with multimodal structural neuroimaging. A sample of 27 euthymic BD patients and 24 healthy controls (HC) underwent structural grey matter MRI and diffusion-weighted imaging (DWI). BD patient's cognition was also assessed. FreeSurfer algorithms were used to obtain estimations of regional grey matter volumes. White matter pathways were reconstructed using TRACULA, and four diffusion metrics were extracted. ANCOVA models were performed to compare BD patients and HC values of regional grey matter volume and diffusion metrics. Global brain measures were also compared. Bivariate Pearson correlations were explored between significant brain results and five cognitive domains. RESULTS: Euthymic BD patients showed higher ventricular volume (F(1, 46) = 6.04; p = 0.018) and regional grey matter volumes in the left fusiform (F(1, 46) = 15.03; pFDR = 0.015) and bilateral parahippocampal gyri compared to HC (L: F(1, 46) = 12.79, pFDR = 0.025/ R: F(1, 46) = 15.25, pFDR = 0.015). Higher grey matter volumes were correlated with greater executive function (r = 0.53, p = 0.008). LIMITATIONS: We evaluated a modest sample size with concurrent pharmacological treatment. CONCLUSIONS: Higher medial temporal volumes in euthymic BD patients may be a potential signature of brain resilience and cognitive adaptation to a putative illness neuroprogression. This knowledge should be integrated into further efforts to implement imaging into BD clinical management.

Disrupted network switching in euthymic bipolar disorder: Working memory and self-referential paradigms.

BACKGROUND: Patients with bipolar disorder (BD) frequently suffer from neurocognitive deficits that can persist during periods of clinical stability. Specifically, impairments in executive functioning such as working memory and in self-processing have been identified as the main components of the neurocognitive profile observed in euthymic BD patients. The study of the neurobiological correlates of these state-independent alterations may be a prerequisite to develop reliable biomarkers in BD. METHODS: A sample of 27 euthymic BD patients and 25 healthy participants (HC) completed working memory and self-referential functional Magnetic Resonance Imaging (fMRI) tasks. Activation maps obtained for each group and contrast images (i.e., 2-back > 1-back/self > control) were used for comparisons between patients and HC. RESULTS: Euthymic BD patients, in comparison to HC, showed a higher ventromedial prefrontal cortex activation during working memory, a result driven by the lack of deactivation in BD patients. In addition, euthymic BD patients displayed a greater dorsomedial and dorsolateral prefrontal cortex activation during self-reference processing. LIMITATIONS: Pharmacotherapy was described but not included as a confounder in our models. Sample size was modest. CONCLUSION: Our findings revealed a lack of deactivation in the anterior default mode network (aDMN) during a working memory task, a finding consistent with prior research in BD patients, but also a higher activation in frontal regions within the central executive network (CEN) during self-processing. These results suggest that an imbalance of neural network dynamics underlying external/internal oriented cognition (the CEN and the aDMN, respectively) may be one of the first reliable biomarkers in euthymic bipolar patients.

Altered white matter volumes in first-episode depression: Evidence from cross-sectional and longitudinal voxel-based analyses.

BACKGROUND: Major depressive disorder (MDD) is accompanied by atypical brain structure affecting grey and white matter from the early stages. Neuroimaging studies of first-episode depression (FED) have provided evidence on this regard, but most of the studies are cross-sectional. The aim of this longitudinal study was to test potential changes in grey matter (GM) and white matter (WM) volumes in FED. METHODS: Thirty-three untreated FED patients (DSM-IV criteria) and 33 healthy controls (HC) underwent a 3T structural magnetic resonance imaging (sMRI) at baseline and after 2 years. Depressive symptoms were assessed at baseline and throughout the study with the 17-item Hamilton Depressive Rating Scale (HDRS-17). Recurrences of FED patients were also collected along the follow-up. To analyze GM and WM differences, whole-brain voxel-based morphometry (VBM, SPM12) was employed (FWE corrected). RESULTS: FED patients showed significant reductions compared to HC in WM volumes of prefrontal cortex (left anterior corona radiata). No differences were found in GM volumes. Full factorial longitudinal analysis of the whole sample revealed no significant effect in GM nor in WM, while the full factorial longitudinal analysis comparing recurrent and non-recurrent patients showed increments in WM volumes of left posterior corona radiata and right posterior thalamic radiation in the recurrent group. LIMITATIONS: Limited sample size, especially in the follow-up. CONCLUSIONS: The present findings provided some new evidence of the role of white matter alterations in the early stages of MDD and in the progression of the illness.

Cognitive predictors of illness course at 12 months after first-episode of depression.

Major Depressive Disorder (MDD) entails cognitive dysfunction in many cognitive domains, but it is still uncertain whether such deficits are present in the early stages. The purpose of the study is to determine the cognitive performance in first episode depression (FED) exploring the presence of different cognitive profiles, and the role of cognition in FED at baseline and long-term. Ninety subjects (18-50 years) were included, 50 patients with a FED and 40 healthy controls. Participants were assessed with a neuropsychological battery, covering language, attention, verbal memory, processing speed and executive domains. Neuropsychological group comparisons were performed with MANOVAs. A hierarchical cluster analysis was run to identify clusters of patients with similar neuropsychological performance. Two generalized linear models were built to predict baseline HDRS-17 and changes at 12 months. Patients performed significantly worse than healthy controls in language, attention/working memory, verbal memory, processing speed and executive functioning, with moderate to large effect sizes (0.5 - 1). Two clusters were found: cognitively preserved patients (n=37) and cognitively impaired patients (n=13). Large effect sizes of cognitive impairment in FED were observed between the two cognitive clusters (preserved and impaired). Depressive symptoms at baseline were predicted by verbal memory (p=0.003), while 12-month changes were predicted by executive function (p=0.041) and language (p=0.037). Cognitive performance predicted depressive symptoms at baseline and at follow-up, pointing to the usefulness of cognitive assessment even at the commencement of the illness.