The protective effect of vitamin D supplementation as adjunctive therapy to antidepressants on brain structural and functional connectivity of patients with major depressive disorder: a randomized controlled trial.

BACKGROUND: Growing evidence points to the pivotal role of vitamin D in the pathophysiology and treatment of major depressive disorder (MDD). However, there is a paucity of longitudinal research investigating the effects of vitamin D supplementation on the brain of MDD patients. METHODS: We conducted a double-blind randomized controlled trial in 46 MDD patients, who were randomly allocated into either VD (antidepressant medication + vitamin D supplementation) or NVD (antidepressant medication + placebos) groups. Data from diffusion tensor imaging, resting-state functional MRI, serum vitamin D concentration, and clinical symptoms were obtained at baseline and after an average of 7 months of intervention. RESULTS: Both VD and NVD groups showed significant improvement in depression and anxiety symptoms but with no significant differences between the two groups. However, a greater increase in serum vitamin D concentration was found to be associated with greater improvement in depression and anxiety symptoms in VD group. More importantly, neuroimaging data demonstrated disrupted white matter integrity of right inferior fronto-occipital fasciculus along with decreased functional connectivity between right frontoparietal and medial visual networks after intervention in NVD group, but no changes in VD group. CONCLUSIONS: These findings suggest that vitamin D supplementation as adjunctive therapy to antidepressants may not only contribute to improvement in clinical symptoms but also help preserve brain structural and functional connectivity in MDD patients.

The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Dysregulated neural activity between the thalamus and cerebral cortex mediates cortical reorganization in cervical spondylotic myelopathy.

Neuroimaging research has revealed significant changes in brain structure and function in patients with cervical spondylotic myelopathy(CSM). The thalamus plays a crucial role in this process, although its mechanisms of action remain incompletely understood. This study aimed to investigate whether spinal cord compression leads to alterations in the functional connectivity between the thalamus and the cerebral cortex, and to determine if such changes are associated with structural and functional remodeling of the brain in patients with CSM, and to identify potential neuroimaging biomarkers for classification. The study included 40 patients with CSM and 34 healthy controls(HCs) who underwent resting-state functional magnetic resonance imaging(fMRI) and structural MRI scans. Brain structural and functional metrics were quantified using functional connectivity(FC), fractional amplitude of low-frequency fluctuations(fALFF), surface-based morphometry(SBM), and independent component analysis(ICA) based on functional and structural MRI. Patients with CSM exhibited significantly reduced fALFF in the bilateral lateral lingual gyrus, bilateral calcarine fissure, left precentral gyrus and postcentral gyrus, left middle and superior occipital gyrus, left superior marginal gyrus, left inferior parietal gyrus, and right Rolandic operculum. ICA results revealed weakened functional connectivity between the sensorimotor network (SMN) and the left and right frontoparietal network(FPN), and lateral visual network (lVN), along with decreased connectivity between lVN and rFPN, and increased connectivity between lFPN and rFPN. Patients with CSM also had decreased sulcus depth in the bilateral insula, left precentral and postcentral gyrus, and right lingual gyrus and calcarine fissure. Furthermore, cervical spondylotic myelopathy patients showed decreased functional connectivity between the left ventral posterolateral nucleus (VPL) of the thalamus and the right middle occipital gyrus (MOG). Finally,multimodal neuroimaging with support vector machine(SVM) classified patients with CSM and healthy controls with 86.00% accuracy. Our study revealed that the decrease in functional connectivity between the thalamus and cortex mediated by spinal cord compression leads to structural and functional reorganization of the cortex. Features based on neuroimaging markers have the potential to become neuroimaging biomarkers for CSM.

Brain function mediates the association between low vitamin D and neurocognitive status in female patients with major depressive disorder.

BACKGROUND: Vitamin D is engaged in various neural processes, with low vitamin D linked to depression and cognitive dysfunction. There are gender differences in depression and vitamin D level. However, the relationship between depression, gender, vitamin D, cognition, and brain function has yet to be determined. METHODS: One hundred and twenty-two patients with major depressive disorder (MDD) and 119 healthy controls underwent resting-state functional MRI and fractional amplitude of low-frequency fluctuations (fALFF) was calculated to assess brain function. Serum concentration of vitamin D (SCVD) and cognition (i.e. prospective memory and sustained attention) were also measured. RESULTS: We found a significant group-by-gender interaction effect on SCVD whereby MDD patients showed a reduction in SCVD relative to controls in females but not males. Concurrently, there was a female-specific association of SCVD with cognition and MDD-related fALFF alterations in widespread brain regions. Remarkably, MDD- and SCVD-related fALFF changes mediated the relation between SCVD and cognition in females. CONCLUSION: Apart from providing insights into the neural mechanisms by which low vitamin D contributes to cognitive impairment in MDD in a gender-dependent manner, these findings might have clinical implications for assignment of female patients with MDD and cognitive dysfunction to adjuvant vitamin D supplementation therapy, which may ultimately advance a precision approach to personalized antidepressant choice.

Compensatory thalamocortical functional hyperconnectivity in type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is associated with brain damage and cognitive decline. Despite the fact that the thalamus involves aspects of cognition and is typically affected in T2DM, existing knowledge of subregion-level thalamic damage and its associations with cognitive performance in T2DM patients is limited. The thalamus was subdivided into 8 subregions in each hemisphere. Resting-state functional and structural MRI data were collected to calculate resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each thalamic subregion in 62 T2DM patients and 50 healthy controls. Compared with controls, T2DM patients showed increased rsFC of the medial pre-frontal thalamus, posterior parietal thalamus, and occipital thalamus with multiple cortical regions. Moreover, these thalamic functional hyperconnectivity were associated with better cognitive performance and lower glucose variability in T2DM patients. However, there were no group differences in GMV for any thalamic subregions. These findings suggest a possible neural compensation mechanism whereby selective thalamocortical functional hyperconnectivity facilitated by better glycemic control help to preserve cognitive ability in T2DM patients, which may ultimately inform intervention and prevention of T2DM-related cognitive decline in real-world clinical settings.

The Relationship Between Vitamin D, Clinical Manifestations, and Functional Network Connectivity in Female Patients With Major Depressive Disorder.

Evidence suggests the pivotal role of vitamin D in the pathophysiology of major depressive disorder (MDD) via its effects on the brain. Gender differences exist in both depression and vitamin D level. Our objective was to investigate the association between gender, vitamin D, clinical manifestations, and functional network connectivity in a large sample of MDD patients and healthy controls. Resting-state functional MRI data were collected from 122 patients and 119 controls, with independent component analysis adopted to examine large-scale inter- and intranetwork functional connectivity. Serum concentration of vitamin D (SCVD) and clinical manifestations were also assessed. MDD patients exhibited lower SCVD than controls in females but not males. Moreover, we identified a female-specific association between lower SCVD and poorer cognitive performance. Concurrently, MDD-related functional network connectivity changes were correlated with SCVD in females as well as depression and anxiety symptoms in female patients. Remarkably, MDD- and SCVD-related functional network connectivity alterations mediated the associations between SCVD and cognition in females. Aside from providing evidence for a female-specific neurobiological mechanism whereby low vitamin D might contribute to MDD and its associated clinical characteristics, our findings inform a novel conceptualization that adjuvant vitamin D supplementation therapy may yield clinical benefits in improving treatment outcomes in female patients with MDD.

Fecal Transplantation from db/db Mice Treated with Sodium Butyrate Attenuates Ischemic Stroke Injury.

The complication of type 2 diabetes (T2D) exacerbates brain infarction in acute ischemic stroke (AIS). Because butyrate-producing bacteria are decreased in T2D and butyrate has been reported to be associated with attenuated brain injury in AIS, we hypothesize that administering butyrate could ameliorate T2D-associated exacerbation of brain infarction in AIS. Therefore, we first validated that Chinese AIS patients with T2D comorbidity have significantly lower levels of fecal butyrate-producing bacteria and butyrate than AIS patients without T2D. Then, we performed a 4-week intervention in T2D mice receiving either sodium butyrate (SB) or sodium chloride (NaCl) and found that SB improved the diabetic phenotype, altered the gut microbiota, and ameliorated brain injury after stroke. Fecal samples were collected from T2D mice after SB or NaCl treatment and were transplanted into antibiotic-treated C57BL/6 mice. After 2 weeks of transplantation, the gut microbiota profile and butyrate level of recipient mice were tested, and then the recipient mice were subjected to ischemic stroke. Stroke mice that received gut microbiota from SB-treated mice had a smaller cerebral infarct volume than mice that received gut microbiota from NaCl-treated mice. This protection was also associated with improvements in gut barrier function, reduced serum levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and proinflammatory cytokines, and improvements in the blood-brain barrier. IMPORTANCE Ischemic stroke is a major global health burden, and T2D is a well-known comorbidity that aggravates brain injury after ischemic stroke. However, the underlying mechanism by which T2D exacerbates stroke injury has not been completely elucidated. A large amount of evidence suggests that the gut microbiota composition affects stroke outcomes. Our results showed that the gut microbiota of T2D aggravated brain injury after ischemic stroke and could be modified by SB to afford neuroprotection against stroke injury. These findings suggest that supplementation with SB is a potential therapeutic strategy for T2D patients with ischemic stroke.

The Relationship Between Serum Concentration of Vitamin D, Total Intracranial Volume, and Severity of Depressive Symptoms in Patients With Major Depressive Disorder.

Background: Depression has been linked to vitamin D deficiency. However, little attention was paid to the neural substrate underlying this association. Methods: Fifty patients with major depressive disorder (MDD) were enrolled in this study. High-resolution structural magnetic resonance imaging was performed to calculate total intracranial volume (TIV). Peripheral venous blood samples were collected to measure serum vitamin D concentration. Hamilton Rating Scale for Depression (HAMD) was used to assess severity of depression symptoms. The relationship among TIV, serum vitamin D concentration, and HAMD score was examined using correlation, linear regression, and mediation analyses. Results: In patients with MDD, HAMD score was negatively correlated with TIV and serum vitamin D concentration, and TIV was positively correlated with serum vitamin D concentration. Linear regression analyses showed that TIV and serum vitamin D concentration were significant predictors of HAMD score. Importantly, mediation analysis revealed that TIV significantly mediated the relationship between serum vitamin D concentration and HAMD score. Conclusion: Our findings suggest that TIV may serve as a potential neural biomarker for monitoring responses to adjuvant therapy of vitamin D in patients with MDD.

Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia.

Background: Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown. Methods: 89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups. Results: Whole gray matter CBF-FCS coupling was decreased in schizophrenia patients relative to healthy controls. In schizophrenia patients, the decreased CBF/FCS ratio was predominantly located in cognitive- and emotional-related brain regions, including the dorsolateral prefrontal cortex, insula, hippocampus and thalamus, whereas an increased CBF/FCS ratio was mainly identified in the sensorimotor regions, including the putamen, and sensorimotor, mid-cingulate and visual cortices. Conclusion: These findings suggest that the neurovascular decoupling in the brain may be a possible neuropathological mechanism of schizophrenia.

Cerebral blood flow alterations specific to auditory verbal hallucinations in schizophrenia.

BackgroundAuditory verbal hallucinations (AVHs) have been associated with deficits in auditory and speech-related networks. However, the resting-state cerebral blood flow (CBF) alterations specific to AVHs in schizophrenia remain unknown.AimsTo explore AVH-related CBF alterations in individuals with schizophrenia.MethodIn total, 35 individuals with schizophrenia with AVHs, 41 individuals with schizophrenia without AVHs and 50 controls underwent arterial spin labelling magnetic resonance imaging. The CBF differences were voxel-wise compared across the three groups.ResultsWe found AVH-specific CBF increase in the right superior temporal gyrus and caudate, and AVH-specific CBF decrease in the bilateral occipital and left parietal cortices. We also observed consistent CBF changes in both schizophrenia subgroups (i.e. those with and without AVHs) including decreased CBF in the bilateral occipital regions, the left lateral prefrontal and insular cortices, and the right anterior cingulate cortex and increased CBF in the bilateral lateral temporal regions and putamen, the left middle cingulate cortex and the right thalamus.ConclusionsThe AVH-specific CBF increases in the auditory and striatal areas and CBF reductions in the visual and parietal areas suggest that there exists a CBF redistribution associated with AVHs.

Efficacy and advantages of modified Traditional Chinese Medicine treatments based on "kidney reinforcing" for chronic aplastic anemia: a randomized controlled clinical trial.

OBJECTIVE: To compare the efficacy of modified treatments based on "kidney reinforcing" in the management of chronic aplastic anemia (CAA), and explore their advantages and specialties. METHODS: One hundred and eleven patients with CAA were randomly divided into three groups: kidney reinforcing alone (KA), "kidney reinforcing and Qi tonifying" (KQ), and "kidney reinforcing and blood circulation invigorating" (KC). Normal and positive control groups were also formed. All patients were treated for 6 months (two courses). Hemograms, Traditional Chinese Medicine (TCM) syndrome scores, and therapeutic effects were assessed, and changes in T-lymphocyte subsets, regulatory T cells and cytokines were detected. RESULTS: The KQ and KC groups had lower TCM syndrome scores than the positive control group after 6 months (P < 0.05). The KQ group had a higher overall efficacy than the positive control group after 3 months (P < 0.05), while platelet counts increased in the KC group after 6 months (P < 0.05). CD3+ T-lymphocyte ratios decreased only in the KQ group, while CD3 + CD4 + CD8 − Tlymphocytes increased only in the KC group after 6 months (P < 0.05). Levels of interferon-γ, tumor necrosis factor tor-α, interleukin (IL)-2 and IL-6 decreased and levels of IL-4 and IL-10 increased in all treated groups after 6 months. Levels of IL-6 in the KQ and KC groups were lower than those in the positive control group (P < 0.05). CONCLUSION: Treatments based on kidney reinforcing have a rebalancing effect on cytotoxic and T helper cells, and regulate expression of interferon- γ, IL-2, IL-6 and IL-4. KQ may be more effective in treating CAA, and KC may have an advantage in platelet recovery.

Multi-central clinical research into treating 80 cases of chronic thrombocytopenia with qi-supplementing and yin-nourishing therapy and western medicine.

OBJECTIVE: To probe the effects of qi-supplementing and yin-nourishing therapy (blood-increasing decoction and blood generating powder) on chronic thrombocytopenia. METHODS: Two hundred patients with chronic thrombocytopenia were randomly divided into control (n = 100) and test groups (n = 100) with Amino-polypeptide as a basic treatment for both. Test group patients consumed a blood-increasing decoction and blood-generating powder for 1-3 months. Improvements in platelet counts and TCM syndrome were observed. RESULTS: One hundred and sixty-four (80 in the test group and 84 in the control group) of 189 total participants were treated for 3 months. The total effective rate in improving TCM syndrome was 95.00% in the test group and 79.76% in the control group (P < 0.05). There was significant difference (P < 0.05) in the accumulated score of TCM syndrome between the two groups treated at different time points. The total effective rate of platelet counts was 86.25% in the test group and 59.52% in the control group (P < 0.05). There was a significant difference in platelet counts before and after treatment in the two groups (P < 0.05). There was no significant differences in platelet count between the two groups treated for 1-2 months; however, a significant difference was found between the two groups after treatment for 3 months (P < 0.05). CONCLUSIONS: After a 3-month treatment of chronic thrombocytopenia patients with qi-supplementing and yin-nourishing therapy, TCM syndrome was improved and platelet counts increased with no obvious side effects, and the quality of life of the participants was enhanced with noticeable long-term curative effects.