Striatal Functional Alterations Link to Distinct Symptomatology Across Mood States in Bipolar Disorder.

BACKGROUND: As a central hub in cognitive and emotional brain circuits, the striatum is considered likely to be integrally involved in the psychopathology of bipolar disorder (BD). However, it remains unclear how alterations in striatal function contribute to distinct symptomatology of BD during different mood states. METHODS: Behavioral assessment (i.e., emotional symptoms and cognitive performance) and neuroimaging data were collected from 125 participants comprising 31 (hypo)manic, 31 depressive, and 31 euthymic patients with BD, and 32 healthy control participants. We compared the functional connectivity (FC) of striatal subregions across BD mood states with healthy control participants and then used a multivariate data-driven approach to explore dimensional associations between striatal connectivity and behavioral performance. Finally, we compared the FC and behavioral composite scores, which reflect the individual weighted representation of the associations, among different mood states. RESULTS: Patients in all mood states exhibited increased FC between the bilateral ventral rostral putamen and ventrolateral thalamus. Bipolar (hypo)mania uniquely exhibited increased ventral rostral putamen connectivity and superior ventral striatum connectivity. One latent component was identified, whereby increased FCs of striatal subregions were associated with distinct psychopathological symptomatology (more manic symptoms, elevated positive mood, less depressive symptoms, and worse cognitive performance). Patients with bipolar (hypo)mania had the highest FC and behavioral composite scores while bipolar patients with depression had the lowest scores. CONCLUSIONS: Our data demonstrated both trait features of BD and state features specific to bipolar (hypo)mania. The findings underscored the fundamental role of the striatum in the pathophysiological processes underlying specific symptomatology across all mood states.

Intrinsic functional connectivity correlates of cognitive deficits involving sustained attention and executive function in bipolar disorder.

BACKGROUND: The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further investigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the different relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs). METHODS: Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic resonance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clinical assessment. A seed-based approach was used to evaluate the intrinsic FC alterations in three core neurocognitive networks (the default mode network [DMN], the central executive network [CEN] and the salience network [SN]). Finally, we examined the relationship between FC and cognitive performance by using linear regression analyses. RESULTS: Decreased FC was observed within the DMN, in the DMN-SN and DMN-CEN and increased FC was observed in the SN-CEN in BD. The alteration direction of regional FC was consistent with that of FC at the brain network level. Decreased FC between the left posterior cingulate cortex and right anterior cingulate cortex was associated with longer WCST completion time in BD patients (but not in HCs). CONCLUSIONS: These findings emphasize the dominant role of the DMN in the psychopathology of BD and provide evidence that cognitive deficits in BD may be associated with aberrant FC between the anterior and posterior DMN.

Eight-week antidepressant treatment changes intrinsic functional brain topology in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: A recent study revealed disrupted topological organization of whole-brain networks in patients with major depressive disorder (MDD); however, these results were mostly driven by recurrent MDD patients, rather than first-episode drug-naïve (FEDN) patients. Furthermore, few longitudinal studies have explored the effects of antidepressant therapy on the topological organization of whole-brain networks. METHODS: We collected clinical and neuroimaging data from 159 FEDN MDD patients and 152 normal controls (NCs). A total of 115 MDD patients completed an eight-week antidepressant treatment procedure. Topological features of brain networks were calculated using graph theory-based methods and compared between FEDN MDD patients and NCs, as well as before and after treatment. RESULTS: Decreased global efficiency, local efficiency, small-worldness, and modularity were found in pretreatment FEDN MDD patients compared with NCs. Nodal degrees, betweenness, and efficiency decreased in several networks compared with NCs. After antidepressant treatment, the global efficiency increased, while the local efficiency, the clustering coefficient of the network, the path length, and the normalized characteristic path length decreased. Moreover, the reduction rate of the normalized characteristic path length was positively correlated with the reduction rate of retardation factor scores. LIMITATIONS: The interaction effects of groups and time on the topological features were not explored because of absence of the eighth-week data of NC group. CONCLUSIONS: The topological architecture of functional brain networks is disrupted in FEDN MDD patients. After antidepressant therapy, the global efficiency shifted toward recovery, but the local efficiency deteriorated, suggesting a correlation between recovery of retardation symptoms and global efficiency.