Altered Functional Connectivity Differences in Salience Network as a Neuromarker of Suicide Risk in Euthymic Bipolar Disorder Patients

Sobczak, Anna Maria; Bohaterewicz, Bartosz; Marek, Tadeusz; Fąfrowicz, Magdalena; Dudek, Dominika; Siwek, Marcin; Tereszko, Anna; Krupa, Anna; Bryll, Amira; Chrobak, Adrian Andrzej

doi:10.3389/fnhum.2020.585766

Cited by 7 publications

(4 citation statements)

References 71 publications

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“…These results are consistent with the results of our previous study that negative functional resting-state brain connectivity is disrupted in DMN-SN circuitry in individuals with PBD (36). Other MRI studies on individuals with bipolar disorder observed similar connectivity deficits (43)(44)(45).…”

Section: Resultssupporting

confidence: 92%

Neurite outgrowth deficits caused by rare PLXNB1 mutation in pediatric bipolar disorder

Yang

Parker

Gorsi

et al. 2022

Preprint

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Pediatric Bipolar Disorder (PBD) is a severe mood dysregulation condition experienced by 2 to 3% of children and teens in the United States. It is associated with recurrent episodes of psychosis and depression and an increased risk of suicidality. However, the genetics and neuropathology of PBD are largely unknown. Here, we used a combinatorial family-based approach to characterize the cellular, molecular, genetic, and network-level deficits associated with PBD. We recruited a PBD patient and three unaffected family members from a family with a history of psychiatric illnesses. Using resting-state functional magnetic resonance imaging (rs-fMRI), we detected altered resting-state functional connectivity in the patient as compared to the unaffected sibling. Using transcriptomic profiling of patient and control induced pluripotent stem cell (iPSC) derived telencephalic organoids, we found aberrant signaling in the molecular pathways related to neurite outgrowth. We corroborated the presence of neurite outgrowth deficits in patient iPSC-derived cortical neurons and identified a rare homozygous loss-of-function PLXNB1 variant (c.1360C>C; p.Ser454Arg) in the patient. Expression of wild-typePLXNB1, but not the variant, rescued neurite outgrowth deficit in patient neurons, and expression of the variant caused neurite outgrowth deficit in cortical neurons from PlxnB1knock-out mice.These results indicate that dysregulated PLXNB1signaling may contribute to an increased risk of PBD and other mood dysregulation-related disorders by disrupting neurite outgrowth and functional brain connectivity. Overall, the study established and validated a novel family-based combinatorial approach for studying cellular and molecular deficits in psychiatric disorders.

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Section: Resultssupporting

confidence: 92%

Neurite outgrowth deficits caused by rare PLXNB1 mutation in pediatric bipolar disorder

Yang

Parker

Gorsi

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Altered activities of the regions involved in DMN are linked to the suicide risk in mood disorders. 41 The precuneus is the core hub within DMN, which may be an important region for emotional processing, episodic memory, and self-reflection. [42][43][44] As such, the left precuneus is metabolically overactive in patients with refractory depression.…”

Section: Discussionmentioning

confidence: 99%

Altered resting-state cerebral blood flow and functional connectivity mediate suicidal ideation in major depressive disorder

Fan

Liu

et al. 2022

J Cereb Blood Flow Metab

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The relationships among cerebral blood flow (CBF), functional connectivity (FC) and suicidal ideation (SI) in major depressive disorder (MDD) patients have remained elusive. In this study, we characterized the changes in CBF and FC among 175 individuals including 47 MDD without SI (MDDNSI), 59 MDD with SI (MDDSI), and 69 healthy control (HC) who underwent arterial spin labeling and resting-state functional MRI scans. Then the voxel-wise CBF, seed-based FC and partial correlation analyses were measured. Mediation analysis was carried out to reveal the effects of FC on the association between CBF and behavioral performances in both subgroups. Results showed that CBF was higher in MDDSI patients in the bilateral precuneus compared to HC and MDDNSI participants. MDDSI patients exhibited enhanced FC in the prefrontal-limbic system and decreased FC in the sensorimotor cortex (SMC) relative to MDDNSI patients. CBF and FC were significantly correlated with clinical variables. More importantly, exploratory mediation analyses identified that abnormal FC can mediate the association between regional CBF and behavioral performances. These results highlight the potential role of precuneus gyrus, prefrontal-limbic system as well as SMC in the process of suicide and provide new insights into the neural mechanism underlying suicide in MDD patients.

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“…Altered functional connectivity between the bilateral dorsal anterior insula and left inferior parietal lobule, a key node of the frontoparietal executive control network, has been shown to be differentiated in BD patients with unipolar depression and healthy controls [ 51 , 52 ]. In the study of Sobczak et al [ 53 ], euthymic bipolar disorder patients revealed that the salience network, specifically the insular cortex, might be a key factor in suicidal risk propeness. The study showed that decreased connectivity between regions involved in the salience network has negative correlation with direct suicidal risk.…”

Section: Discussionmentioning

confidence: 99%

Time-Frequency Characterization of Resting Brain in Bipolar Disorder during Euthymia—A Preliminary Study

et al. 2021

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The goal of this paper is to investigate the baseline brain activity in euthymic bipolar disorder (BD) patients by comparing it to healthy controls (HC) with the use of a variety of resting state functional magnetic resonance imaging (rs-fMRI) analyses, such as amplitude of low frequency fluctuations (ALFF), fractional ALFF (f/ALFF), ALFF-based functional connectivity (FC), and r egional homogeneity (ReHo). We hypothesize that above-mentioned techniques will differentiate BD from HC indicating dissimilarities between the groups within different brain structures. Forty-two participants divided into two groups of euthymic BD patients (n = 21) and HC (n = 21) underwent rs-fMRI evaluation. Typical band ALFF, slow-4, slow-5, f/ALFF, as well as ReHo indexes were analyzed. Regions with altered ALFF were chosen as ROI for seed-to-voxel analysis of FC. As opposed to HC, BD patients revealed: increased ALFF in left insula; increased slow-5 in left middle temporal pole; increased f/ALFF in left superior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right putamen, and bilateral thalamus. There were no significant differences between BD and HC groups in slow-4 band. Compared to HC, the BD group presented higher ReHo values in the left superior medial frontal gyrus and lower ReHo values in the right supplementary motor area. FC analysis revealed significant hyper-connectivity within the BD group between left insula and bilateral middle frontal gyrus, right superior parietal gyrus, right supramarginal gyrus, left inferior parietal gyrus, left cerebellum, and left supplementary motor area. To our best knowledge, this is the first rs-fMRI study combining ReHo, ALFF, f/ALFF, and subdivided frequency bands (slow-4 and slow-5) in euthymic BD patients. ALFF, f/ALFF, slow-5, as well as REHO analysis revealed significant differences between two studied groups. Although results obtained with the above methods enable to identify group-specific brain structures, no overlap between the brain regions was detected. This indicates that combination of foregoing rs-fMRI methods may complement each other, revealing the bigger picture of the complex resting state abnormalities in BD.

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Altered Functional Connectivity Differences in Salience Network as a Neuromarker of Suicide Risk in Euthymic Bipolar Disorder Patients

Cited by 7 publications

References 71 publications

Neurite outgrowth deficits caused by rare PLXNB1 mutation in pediatric bipolar disorder

Neurite outgrowth deficits caused by rare PLXNB1 mutation in pediatric bipolar disorder

Altered resting-state cerebral blood flow and functional connectivity mediate suicidal ideation in major depressive disorder

Time-Frequency Characterization of Resting Brain in Bipolar Disorder during Euthymia—A Preliminary Study

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