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.

Anemia in pregnancy and sleep of 6-month-old infants: A prospective cohort study.

Objective: Anemia has been reported to adversely influence sleep in infants. However, the association between anemia in pregnancy and infant sleep remains unclear. We aimed to examine the association between maternal anemia in pregnancy and sleep parameters of 6-month-old infants. Methods: We enrolled 2,410 mother-infant pairs between 2018 and 2021 in Hefei. Data on maternal hemoglobin concentration were collected at 24-28 gestational weeks from the electronic medical records of the hospitals. Nocturnal and daytime sleep duration, number of night awakenings, nocturnal wakefulness, and sleep latency of infants aged 6 months were measured using the Brief Infant Sleep Questionnaire with five items. A restricted cubic spline model was used to examine the relationship between maternal hemoglobin concentration and infant nocturnal sleep duration after adjusting for potential confounders. Results: In our study, 807 (33.5%) mothers had anemia during pregnancy. Compared to infants born to mothers without anemia, infants born to mothers with anemia in pregnancy had shorter nocturnal sleep duration [mean (SD), 560.29 (79.57) mins vs. 574.27 (75.36) mins] at the age of 6 months. Subgroup analysis showed consistent significant differences in nocturnal sleep duration between infant born to anemic and non-anemic mothers, except in case of stratification by preterm birth [mean difference (mins), 2.03 (95% CI, -20.01, -24.07)] and pre-pregnancy obesity [mean difference (mins), -0.85 (95% CI, -16.86, -15.16)]. A J-shaped nonlinear correlation curve was observed between maternal hemoglobin concentration and infant nocturnal sleep duration. Compared with mothers without daily iron supplementation, mothers who had daily iron supplementation had higher hemoglobin concentrations [mean (SD), 112.39 (11.33) g/L vs. 110.66 (10.65) g/L] at delivery and their infants had longer nocturnal sleep duration [mean (SD), 565.99 (82.46) mins vs. 553.66 (76.03) mins]. Conclusion: Anemia in pregnancy may have an adverse influence on the sleep of 6-mon-old infants, and the relationship between maternal hemoglobin concentration and nocturnal sleep duration is nonlinear.

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.

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.

Vitamin D supplementation improves anxiety but not depression symptoms in patients with vitamin D deficiency.

OBJECTIVE: Epidemiological evidence indicated a relationship between vitamin D (VD) and depression with anxiety, but their therapeutic relationship has not been fully elucidated. This study aimed to examine whether VD supplementation would relieve symptoms in patients with depression and anxiety with low serum 25-hydroxy VD [25(OH) D] levels. METHOD: Participants with low 25(OH)D levels were randomized to control or daily VD group and were followed up for 6 months. Serum concentrations of 25(OH) D were measured using commercial kits. Psychological symptoms were evaluated with the Hamilton Depression Rating Scale-17 (HAMD-17), Revised Social Anhedonia Scale (RSAS), Revised Physical Anhedonia scale (RPAS), and Hamilton Anxiety Rating Scale-14 (HAMA-14). The trial was listed in the trial registration (http://www.medresman.org.cn/uc/index.aspx; NTR number: ChiCTR2000030130). RESULTS: In this clinical population, no significant difference in depression symptoms was detected between VD group and control group at both baseline and at the endpoint of our study. The HAMD-17, RSAS, and RPAS scores did not change significantly between VD and control groups from baseline to endpoint (all p > .05). However, there was a significant difference in time effect of the total HAMA-14 scores between the two groups (ß [95% Cl] = -2.235 [-3.818, -0.653], p = .006). CONCLUSIONS: Vitamin D supplementation could improve the anxiety symptoms but not depressive symptoms in depressive patients with low VD level after the 6-month intervention.

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.