Topologically convergent and divergent functional connectivity patterns in unmedicated unipolar depression and bipolar disorder

Abstract

Bipolar disorder (BD), particularly BD II, is frequently misdiagnosed as unipolar depression (UD), leading to inappropriate treatment and poor clinical outcomes. Although depressive symptoms may be expressed similarly in UD and BD, the similarities and differences in the architecture of brain functional networks between the two disorders are still unknown. In this study, we hypothesized that UD and BD II patients would show convergent and divergent patterns of disrupted topological organization of the functional connectome, especially in the default mode network (DMN) and the limbic network. Brain resting-state functional magnetic resonance imaging (fMRI) data were acquired from 32 UD-unmedicated patients, 31 unmedicated BD II patients (current episode depressed) and 43 healthy subjects. Using graph theory, we systematically studied the topological organization of their whole-brain functional networks at the following three levels: whole brain, modularity and node. First, both the UD and BD II patients showed increased characteristic path length and decreased global efficiency compared with the controls. Second, both the UD and BD II patients showed disrupted intramodular connectivity within the DMN and limbic system network. Third, decreased nodal characteristics (nodal strength and nodal efficiency) were found predominantly in brain regions in the DMN, limbic network and cerebellum of both the UD and BD II patients, whereas differences between the UD and BD II patients in the nodal characteristics were also observed in the precuneus and temporal pole. Convergent deficits in the topological organization of the whole brain, DMN and limbic networks may reflect overlapping pathophysiological processes in unipolar and bipolar depression. Our discovery of divergent regional connectivity that supports emotion processing could help to identify biomarkers that will aid in differentiating these disorders.

Aberrant brain network topology in fronto‐limbic circuitry differentiates euthymic bipolar disorder from recurrent major depressive disorder

“…These findings indicate that the aforementioned nodes are more integrated into the brain network of BD patients than in networks of individuals not suffering from BD, possibly leading to a disturbed perception of emotions in BD. Changes in the limbic system supporting our results were both found in resting‐state paradigms (Ambrosi et al, ; Anand et al, ; Lois, Linke, & Wessa, ; Wang, Wang, Jia, Zhong, Zhong et al, ) as well as in task‐based paradigms (Gruber et al, ; Strakowski, Adler, Holland, Mills, & DelBello, ; Thermenos et al, ; Townsend & Altshuler, ). In most studies, irregularities were registered in the frontal lobes along with temporal and subcortical regions such as hippocampus and basal ganglia.…”

“…Overall, comparing our results to other studies utilizing graph theory to examine differences between BD and MDD is difficult as these studies are still rare and results among them vary. While a previous study reported a significantly higher global CC mean value (He et al, ) between a group of BD patients in mixed states (mainly depressed) and a group of acutely depressed MDD patients, another study comparing depressed BD and MDD individuals (Wang, Wang, Jia, Zhong, Zhong et al, ) did not detect any significant differences in global CC. They instead reported significantly higher global PL and lower EF mean values for both acutely depressed BD and MDD patients compared to HC.…”

“…Other studies (e.g. Goya‐Maldonado et al, ; Wang, Wang, Jia, Zhong, Zhong et al, ) observed differences between patients and HC as well as between BD and MDD using a diversity of FC analysis procedures. Most studies showed differences between affective disorders and HC mainly in the limbic circuitry as well as in prefrontal regions which are known to have an impact on the emotion regulation process (Blond, Fredericks, & Blumberg, ; Strakowski et al, ).…”

“…Recently, graph analysis using graph theoretical measures has been applied to explore brain network properties in individuals with psychiatric disorders (Bassett & Bullmore, ; He et al, ; Manelis et al, ; Wang, Wang, Jia, Zhong, Niu et al, ; Wang, Wang, Jia, Zhong, Zhong et al, ). Using graph analysis, the brain is modulated as a network of nodes (most commonly a priori defined regions) that are connected by edges resembling functional connections between these regions (Bassett & Bullmore, ).…”

“…They predominantly reported alterations of regional topological properties while findings are inconsistent regarding global changes. GT studies comparing both affective disorders are scarce and most of them so far have only focused on currently depressed BD and MDD patients (Lord et al, ; Meng et al, ; Roberts et al, ; Wang, Wang, Jia, Zhong, Zhong et al, ; Ye et al, ; Zhang et al, ). Lately, researchers have investigated state‐dependent differences between not only depressed, but also euthymic individuals suffering from BD and MDD.…”