Altered regional homogeneity in patients with somatic depression: A resting-state fMRI study

Geng, Jiting; Yan, Rui; Shi, Jiabo; Chen, Yu; Mo, Zhaoqi; Shao, Junneng; Wang, Xinyi; Yao, Zhijian; Lü, Qing

doi:10.1016/j.jad.2018.12.066

Cited by 56 publications

(41 citation statements)

References 64 publications

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“…Previous studies have proved that the changes of ReHo mainly concentrated in prefrontal cortex in patients with MDD. 35 , 36 The PFC plays a key role in reward and emotion regulation network. The ReHo and FC of PFC have been considered to be major neurobiological basis related to the pathogenesis of MDD.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED; Combined rs‐fMRI study on brain functional imaging and mechanism of RAGE‐DAMPs of depression: Evidence from MDD patients to chronic stress‐induced depression models in cynomolgus monkeys and mice

Yan

Xie

et al. 2021

Clinical & Translational Med

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More and more evidence show that major depressive disorder (MDD) is closely related to inflammation caused by chronic stress, which seriously affects human physical and mental health. However, the inflammatory mechanism of depression and its effect on brain function have not been clarified. Based on resting‐state functional magnetic resonance imaging (rs‐fMRI), we investigated change of brain functional imaging and the inflammatory mechanism of damage‐related molecular patterns (DAMPs)—receptor of advanced glycation protein end product (RAGE) in MDD patients and depressive‐like cynomolgus monkeys and mice models induced by chronic stress. The regional homogeneity (ReHo) and functional connectivity (FC) were analyzed using MATLAB and SPM12 software. We detected the expression of DAMPs‐RAGE pathway‐related proteins and mRNA in MDD peripheral blood and in serum and brain tissue of cynomolgus monkeys and mice. Meanwhile, RAGE gene knockout mice, RAGE inhibitor, and overexpression of AVV9 RAGE adeno‐associated virus were used to verify that RAGE is a reliable potential biomarker of depression. The results showed that the ReHo value of prefrontal cortex (PFC) in MDD patients and depressive‐like cynomolgus monkeys was decreased. Then, the PFC was used as a seed point, the FC of ipsilateral and contralateral PFC were weakened in depressive‐like mice. At the same time, qPCR showed that RAGE and HMGB1 mRNA were upregulated and S100β mRNA was downregulated. The expression of RAGE‐related inflammatory protein in PFC of depressive‐like monkeys and mice were consistent with that in peripheral blood of MDD patients. Moreover, the results were confirmed in RAGE –/– mice, injection of FPS‐ZM1, and overexpression of AAV9 RAGE in mice. To sum up, our findings enhance the evidence that chronic stress‐PFC‐RAGE are associated with depression. These results attempt to establish the links between brain functional imaging, and molecular targets among different species will help to reveal the pathophysiological mechanism of depression from multiple perspectives.

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Section: Discussionmentioning

confidence: 99%

RETRACTED; Combined rs‐fMRI study on brain functional imaging and mechanism of RAGE‐DAMPs of depression: Evidence from MDD patients to chronic stress‐induced depression models in cynomolgus monkeys and mice

Yan

Xie

et al. 2021

Clinical & Translational Med

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“…Finally, through further mediation analyses, we found that the relationship between the CACNA1C rs11832738 polymorphism and depression severity was mediated by the altered spontaneous activity of MFG_R. The MFG, a region of the ventral lateral prefrontal cortex, is responsible for the top-down regulation of emotional processing and numerous cognitive functions, such as decision-making, working memory, and attentional processing, and its contribution to MDD has been documented (21,22). Compared to the left side, MFG_R could modulate the cognitive shift between the internal and external environments due to the link between the ventral attention network and the dorsal attention network (21), and lesions in this area could lead to negatively biased attention in patients with MDD (23,24).…”

Section: Discussionmentioning

confidence: 81%

“…The MFG, a region of the ventral lateral prefrontal cortex, is responsible for the top-down regulation of emotional processing and numerous cognitive functions, such as decision-making, working memory, and attentional processing, and its contribution to MDD has been documented (21,22). Compared to the left side, MFG_R could modulate the cognitive shift between the internal and external environments due to the link between the ventral attention network and the dorsal attention network (21), and lesions in this area could lead to negatively biased attention in patients with MDD (23,24). Importantly, considerable research has, to date, supported the idea that negatively biased attention predicts prolonged mood persistence in patients with MDD and future increases in depression severity (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

CACNA1C Gene rs11832738 Polymorphism Influences Depression Severity by Modulating Spontaneous Activity in the Right Middle Frontal Gyrus in Patients With Major Depressive Disorder

et al. 2020

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Objectives: This study aimed to examine whether the CACNA1C gene rs11832738 polymorphism and major depressive disorder (MDD) have an interactive effect on the untreated regional amplitude of low-frequency fluctuation (ALFF) and to determine whether regional ALFF mediates the association between CACNA1C rs11832738 and MDD. Methods: A total of 116 patients with MDD and 66 normal controls (NCs) were recruited. The MDD and NC groups were further divided into two groups according to genotype: carriers of the G allele (G-carrier group, GG/GA genotypes; MDD, n = 61; NC, n = 26) and AA homozygous group (MDD, n = 55; NC, n = 40). MDD was diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Depression severity was assessed using the Hamilton Depression Scale-24 (HAMD-24) at baseline and followup (after 2 and 8 weeks of treatment). All subjects underwent functional MRI (fMRI) scans at baseline, and the ALFF was calculated to reflect spontaneous brain activity. The interactions between MDD and CACNA1C single nucleotide polymorphism rs11832738 were determined using two-way factorial analysis of covariance, with age, sex, education, and head motion as covariates. We performed mediation analysis to further determine whether regional ALFF strength could mediate the associations between rs11832738 and depression severity, MDD treatment efficacy. Results: MDD had a main effect on regional ALFF distribution in three brain areas: the right medial frontal gyrus (MFG_R), the left anterior cingulate cortex (ACC_L), and the right cerebellum posterior lobe (CPL_R); CACNA1C showed a significant interactive effect with MDD on the ALFF of MFG_R. For CACNA1C G allele carriers, the ALFF of MFG_R had a significant positive correlation with the baseline HAMD-24 score. Exploratory mediation

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“…An MDD that is accompanied by somatic symptoms, including fatigue, appetite and sleep disturbance, was defined by Silverstein as somatic depression (SD) (2). It has been found that SD differs from non-somatic depression (NSD) in regards to the gender ratio (3–5), developmental patterns (6), and awareness of behavioural errors (7). In addition, in the Star*D study, the response to biological-based treatments, including Citalopram, Sertraline, and others, was better for NSD than for SD (8).…”

Section: Introductionmentioning

confidence: 99%

“…The perpetuation of SD by the brain is still not well understood. However, Geng et al found that SD exhibits abnormal regional homogeneity in the frontal and temporal regions (5). Thus, the somatic-related differences in MDD may be linked to a stronger neurobiological diathesis.…”

Section: Introductionmentioning

confidence: 99%

Abnormal Alterations of Regional Spontaneous Neuronal Activity in Inferior Frontal Orbital Gyrus and Corresponding Brain Circuit Alterations: A Resting-State fMRI Study in Somatic Depression

et al. 2019

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Background: Major depressive disorders often involve somatic symptoms and have been found to have fundamental differences from non-somatic depression (NSD). However, the neural basis of this type of somatic depression (SD) is unclear. The aim of this study is to use the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) analyses to examine the abnormal, regional, spontaneous, neuronal activity and the corresponding brain circuits in SD patients. Methods: 35 SD patients, 25 NSD patients, and 27 matched healthy controls were selected to complete this study. The ALFF and seed-based FC analyses were employed, and the Pearson correlation was determined to observe possible clinical relevance. Results: Compared with NSD, the SD group showed a significant ALFF increase in the right inferior temporal gyrus; a significant ALFF decrease in left hippocampus, right inferior frontal orbital gyrus and left thalamus; and a significant decrease in the FC value between the right inferior frontal orbital gyrus and the left inferior parietal cortex ( p < 0.05, corrected). Within the SD group, the mean ALFF value of the right inferior frontal orbital gyrus was associated with the anxiety factor scores (r = –0.431, p = 0.010, corrected). Conclusions: Our findings suggest that abnormal differences in the regional spontaneous neuronal activity of the right inferior frontal orbital gyrus were associated with dysfunction patterns of the corresponding brain circuits during rest in SD patients, including the limbic-cortical systems and the default mode network. This may be an important aspect of the underlying mechanisms for pathogenesis of SD at the neural level.

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Altered regional homogeneity in patients with somatic depression: A resting-state fMRI study

Cited by 56 publications

References 64 publications

RETRACTED; Combined rs‐fMRI study on brain functional imaging and mechanism of RAGE‐DAMPs of depression: Evidence from MDD patients to chronic stress‐induced depression models in cynomolgus monkeys and mice

RETRACTED; Combined rs‐fMRI study on brain functional imaging and mechanism of RAGE‐DAMPs of depression: Evidence from MDD patients to chronic stress‐induced depression models in cynomolgus monkeys and mice

CACNA1C Gene rs11832738 Polymorphism Influences Depression Severity by Modulating Spontaneous Activity in the Right Middle Frontal Gyrus in Patients With Major Depressive Disorder

Abnormal Alterations of Regional Spontaneous Neuronal Activity in Inferior Frontal Orbital Gyrus and Corresponding Brain Circuit Alterations: A Resting-State fMRI Study in Somatic Depression

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