scholarly journals Functional Connectivity between Task-Positive Networks and the Left Precuneus as a Biomarker of Response to Lamotrigine in Bipolar Depression: A Pilot Study

2021 ◽  
Vol 14 (6) ◽  
pp. 534
Author(s):  
Marieke Martens ◽  
Nicola Filippini ◽  
Charles Masaki ◽  
Beata R. Godlewska

Treatment of bipolar depression poses a significant clinical challenge. Lamotrigine is one of a few efficacious drugs, however, it needs to be titrated very slowly and response can only be assessed after 10–12 weeks. With only a proportion of patients responding, an exploration of factors underlying treatment responsivity is of paramount clinical importance, as it may lead to an allocation of the drug to those most likely to respond to it. This study aimed at identifying differences in patterns of pre-treatment resting state functional connectivity (rsFC) that may underlie response to lamotrigine in bipolar depression. After a baseline MRI scan, twenty-one patients with bipolar depression were treated with lamotrigine in an open-label design; response, defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score, was assessed after 10–12 weeks of treatment. Twenty healthy controls had a baseline clinical assessment and scan but did not receive any treatment. Fifteen out of 21 (71%) patients responded to lamotrigine. Treatment responsivity was associated with enhanced pre-treatment rsFC of the right fronto-parietal network (FPN) and dorsal attention network (DAN) with left precuneus. The lack of treatment response was additionally characterised by reduced rsFC: of the DAN with right middle temporal gyrus; of the default mode network (DMN) with left precuneus; of the extended sensory-motor area with areas including the left hippocampus/left amygdala and left subcallosal cortex/nucleus accumbens; and of the left FPN with left inferior temporal gyrus/occipital fusiform gyrus/lateral occipital cortex. The results suggest that preserved rsFC between the FPN and DAN, the networks involved in cognitive control, and the hub of the posterior DMN, the left precuneus, may be critical for good response to lamotrigine as an add-on treatment in patients with bipolar depression. The study also suggests a more general decrease in rsFC to be related to poor treatment responsivity.

Author(s):  
Marieke A. G. Martens ◽  
Nicola Filippini ◽  
Catherine J. Harmer ◽  
Beata R. Godlewska

Abstract Rational With no available response biomarkers, matching an appropriate antidepressant to an individual can be a lengthy process. Improving understanding of processes underlying treatment responsivity in depression is crucial for facilitating work on response biomarkers. Objectives To identify differences in patterns of pre-treatment resting-state functional connectivity (rsFC) that may underlie response to antidepressant treatment. Methods After a baseline MRI scan, thirty-four drug-free patients with depression were treated with an SSRI escitalopram 10 mg daily for 6 weeks; response was defined as ≥ 50% decrease in Hamilton Depression Rating Scale (HAMD) score. Thirty-one healthy controls had a baseline clinical assessment and scan. Healthy participants did not receive treatment. Results Twenty-one (62%) of patients responded to escitalopram. Treatment responsivity was associated with enhanced rsFC of the right fronto-parietal network (FPN)—with the posterior DMN, somatomotor network (SMN) and somatosensory association cortex. The lack of treatment response was characterized by reduced rsFC: of the bilateral FPN with the contralateral SMN, of the right FPN with the posterior DMN, and of the extended sensorimotor auditory area with the inferior parietal lobule (IPL) and posterior DMN. Reduced rsFC of the posterior DMN with IPL was seen in treatment responders, although only when compared with HC. Conclusions The study supports the role of resting-state networks in response to antidepressant treatment, and in particular the central role of the frontoparietal and default mode networks.


2020 ◽  
Author(s):  
Nili Solomonov ◽  
Lindsay W. Victoria ◽  
Katharine Dunlop ◽  
Matteo Respino ◽  
Matthew Hoptman ◽  
...  

Background: Problem solving therapy (PST) and “Engage”, a reward-exposure” based therapy, are important treatment options for late-life depression, given modest efficacy of antidepressants in this disorder. Abnormal function of the reward and default mode networks has been observed during depressive episodes. This study examined whether resting state functional connectivity (rsFC) of reward and DMN circuitries is associated with treatment outcomes. Methods: Thirty-two older adults with major depression (mean age = 72.7) were randomized to 9-weeks of either PST or “Engage”. We assessed rsFC at baseline and Week 6. We placed seeds in three a priori regions of interest: subgenual cingulate (sgACC), dorsal anterior cingulate cortex (dACC), and nucleus accumbens (NAcc). Outcome measures included the Hamilton Depression Rating Scale (HAMD) and the Behavioral Activation for Depression Scale (BADS).Results: In both PST and “Engage”, higher rsFC between the sgACC and middle temporal gyrus at baseline was associated with greater improvement in depression severity (HAMD). Preliminary findings suggested that in “Engage” treated participants, lower rsFC between the dACC and DMPFC at baseline was associated with HAM-D improvement. Finally, in Engage only, increased rsFC from baseline to Week 6 between NAcc and Superior Parietal Cortex was associated with increased BADS scores.Conclusion: The results suggest that patients who present with higher rsFC between the sgACC and a structure within the DMN may benefit from behavioral psychotherapies for late life depression. ‘Engage’ may lead to increased rsFC within the reward system reflecting a reconditioning of the reward systems by reward exposure.


2010 ◽  
Vol 10 ◽  
pp. 321-328 ◽  
Author(s):  
Natalie L. Rasgon ◽  
Heather A. Kenna ◽  
Katherine E. Williams ◽  
Bevin Powers ◽  
Tonita Wroolie ◽  
...  

A number of cross-sectional studies have suggested an association between insulin resistance (IR) and affective disorders. However, limited data exist on potential changes in IR in a prospective treatment of depression. The present pilot study tested the hypothesis that improvement of IR with the addition of an insulin-sensitizing agent would improve mood in nondiabetic patients with unipolar or bipolar depression, who had surrogate blood markers suggestive of IR. Surrogate IR-criteria blood markers were fasting plasma glucose >100 mg/dl or triglyceride (TG) to high density lipoprotein (HDL) ratio >3.0. Open-label rosiglitazone, titrated to a dose of 8 mg/day, was administered for 12 weeks to 12 patients with depressive disorder receiving treatment as usual (TAU). Eight patients who completed the 12-week study exhibited significant declines in both depression severity by the Hamilton Depression Rating Scale and the Clinical Global Impression scale, with moderate effect sizes noted. Modest improvement in Matsuda Index scores was also noted at 12 weeks, yet declines in depression severity scores were not associated with improvements in the endocrine markers (Matsuda Index, TG/HDL ratio, and body mass index). These results suggest the potential novel use for an insulin-sensitizing agent in the treatment of depressive disorders. Larger placebo-controlled studies are warranted.


2021 ◽  
Vol 15 ◽  
Author(s):  
Seira Taniguchi ◽  
Yuichiro Higashi ◽  
Hirotaka Kataoka ◽  
Hiroshi Nakajima ◽  
Tetsuya Shimokawa

The aim of this study was to identify the functional connectivity and networks utilized during tool-use in real assembly workers. These brain networks have not been elucidated because the use of tools in real-life settings is more complex than that in experimental environments. We evaluated task-related functional magnetic resonance imaging in 13 assembly workers (trained workers, TW) and 27 age-matched volunteers (untrained workers, UTW) during a tool-use pantomiming task, and resting-state functional connectivity was also analyzed. Two-way repeated-measures analysis of covariance was conducted with the group as a between-subject factor (TW > UTW) and condition (task > resting) as a repeated measure, controlling for assembly time and accuracy as covariates. We identified two patterns of functional connectivity in the whole brain within three networks that distinguished TW from UTW. TW had higher connectivity than UTW between the left middle temporal gyrus and right cerebellum Crus II (false discovery rate corrected p-value, p-FDR = 0.002) as well as between the left supplementary motor area and the pars triangularis of the right inferior frontal gyrus (p-FDR = 0.010). These network integrities may allow for TW to perform rapid tool-use. In contrast, UTW showed a stronger integrity compared to TW between the left paracentral lobule and right angular gyrus (p-FDR = 0.004), which may reflect a greater reliance on sensorimotor input to acquire complex tool-use ability than that of TW. Additionally, the fronto-parietal network was identified as a common network between groups. These findings support our hypothesis that assembly workers have stronger connectivity in tool-specific motor regions and the cerebellum, whereas UTW have greater involvement of sensorimotor networks during a tool-use task.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengchao Dong ◽  
Michael F. Grunebaum ◽  
Martin J. Lan ◽  
Vashti Wagner ◽  
Tse-Hwei Choo ◽  
...  

N-methyl-D-aspartate glutamate-receptor (NMDAR) antagonists such as ketamine have demonstrated efficacy in both major depressive disorder (MDD) and bipolar disorder depression (BP-D). We have previously reported that reduction in Glx (glutamate + glutamine) in the ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC), measured by proton magnetic resonance spectroscopy (1H MRS) at 3T during a ketamine infusion, mediates the relationship of ketamine dose and blood level to improvement in depression. In the present study, we assessed the impact of D-cycloserine (DCS), an oral NMDAR antagonist combined with lurasidone in BP-D on both glutamate and Glx. Subjects with DSM-V BP-D-I/II and a Montgomery-Asberg Depression Rating Scale (MADRS) score>17, underwent up to three 1H MRS scans. During Scan 1, subjects were randomized to receive double-blind lurasidone 66 mg or placebo. During Scan 2, all subjects received single-blind DCS 950 mg + lurasidone 66 mg, followed by 4 weeks of open label phase of DCS+lurasidone and an optional Scan 3. Five subjects received lurasidone alone and three subjects received placebo for Scan 1. Six subjects received DCS+lurasidone during Scan 2. There was no significant baseline or between treatment-group differences in acute depression improvement or glutamate response. In Scan 2, after a dose of DCS+lurasidone, peak change in glutamate correlated negatively with improvement from baseline MADRS (r = −0.83, p = 0.04). There were no unexpected adverse events. These preliminary pilot results require replication but provide further support for a link between antidepressant effect and a decrease in glutamate by the NMDAR antagonist class of antidepressants.


2021 ◽  
Author(s):  
Ruxue WANG ◽  
Jiangtao GONG ◽  
Chenying ZHAO ◽  
Yingqing XU ◽  
Bo HONG

In the absence of visual input, occipital 'visual' cortex of blind people has been found to be engaged in non-visual higher cognitive tasks. Although the increased functional connectivity between 'visual' cortex and frontal cortex in the blind has been observed, the specific organization and functional role of this connectivity change remain to be elucidated. Here, we tested resting-state functional connectivity for primary 'visual' cortex (V1) and higher-tier lateral occipital cortex (LOC) in people with acquired blindness, and found an enhanced connectivity between the LOC but not V1 and typical frontal language areas - the inferior frontal cortex (IFC). In fact, the left-lateralized LOC-IFC connectivity strength predicted blind individuals' natural Braille reading proficiency. Furthermore, an increased bidirectional information flow between the left LOC and IFC was observed during a natural Braille reading task. In particular, the task-relevant modulation of the top-down communication from left IFC to LOC was significantly stronger than that of the bottom-up communication. Altogether, our study identified a distinctive neural nexus, LOC-IFC connection, and its behavioral significance in the acquired blind, revealing the neural correlates of the crossmodal plasticity in their 'visual' cortex underlying natural Braille reading.


2021 ◽  
Author(s):  
Ziqing Zhu ◽  
You Wang ◽  
Way Lau ◽  
Xinhua Wei ◽  
Yingjun Liu ◽  
...  

Abstract BackgroundDisrupted whole-brain resting-state functional connectivity (RSFC) of the posterior cingulate (PCC) has been highlighted to associate with cognitive and affective dysfunction in major depressive disorder (MDD). However, prior findings showed certain inconsistency about the RSFC of the PCC in MDD. This study aims to investigate the aberrant RSFC of the PCC in MDD using anisotropic effect-size version of seed-based d mapping (AES-SDM). MethodsWeb of Science and PubMed were searched for studies investigating PCC-based RSFC in MDD. A total of 17 studies, involving 804 patients and 724 healthy controls (HCs), fit our selection criteria. Additionally, to seek for the link between functional and structural differences, we did a meta-analysis on the studies in conjunction with Voxel-based morphology (VBM) analysis. ResultsThe PCC showed higher RSFC with the left middle temporal gyrus (MTG) and the right middle frontal gyrus (MFG), and lower RSFC with the left superior frontal gyrus (SFG) and the left precuneus in patients with MDD than HCs. Notably, the left MTG and the left MFG were the overlapped regions of aberrant VBM and RSFC results.ConclusionsOur results indicated that the aberrant RSFC between the PCC and brain regions sub-serving cognitive control and emotional regulation in patients with MDD. And such functional alterations may have structural basis. These findings may underlie the mechanisms of deficits in cognitive control and emotional regulation of MDD.


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