The combined association of adherence to recommended physical activity and glycemic control with depression: an exploratory study with mediation and moderation models.

BACKGROUND: Both physical activity and dysglycemia are associated with depression. However, the combined association of adherence to recommended physical activity (RPA) and glycemic control with depression is unknown. Moreover, the extent to which glycemic control mediates the association between physical activity and depression is not established. METHODS: The sample included 31,302 adults from the National Health and Nutrition Examination Survey 2007-08 to 2017-18. Adherence to RPA for aerobic activity was defined according to the WHO 2020 guidelines. HbA1c was classified as < 5.7%, 5.7-6.4%, 6.5-6.9%, and ≥ 7.0%. Depression was evaluated according to the 9-item Patient Health Questionnaire. The odds ratio for depression stratified by adherence to RPA and HbA1c level were estimated by logistic regressions. Mediation analysis was performed to estimate the direct associations (not through glycemic control) and indirect associations (through glycemic control). RESULTS: A total of 2871 participants were diagnosed with depression. Compared to participants with HbA1c level < 5.7% who adhere to RPA, those with HbA1c level < 5.7%, 5.7-6.4%, 6.5-6.9%, and ≥ 7.0% who did not adhere to RPA had increased odds ratio for depression, especially in women and older adults. Individuals with HbA1c ≥ 7.0% still had an increased odds ratio for depression even though they were physically active. The results of the mediation analysis were insignificant. CONCLUSION: There was a combined association of adherence to RPA and glycemic control with depression in women and older adults. We did not find out evidence of glycemic control mediation on the pathway from physical activity to depression.

The FXR mediated anti-depression effect of CDCA underpinned its therapeutic potentiation for MDD.

Emerging evidence from animal and human studies has suggested that small microbial metabolites generated in the gut influence host mood and behavior. Our previous study reported that patients with major depressive disorder (MDD) reduced the abundance of genera Blautia and Eubacterium, the microbials critically regulating cholesterol and bile acid metabolism in the gut. In this study, we further demonstrated that the levels of plasma bile acid chenodeoxycholic acid (CDCA) were significantly lower in Chinese MDD patients (142) than in healthy subjects (148). Such low levels of plasma CDCA in MDD patients were rescued in remitters but not in nonremitters following antidepressant treatment. In a parallel animal study, Chronic Social Defeat Stress (CSDS) depressed mice reduced the plasma CDCA and expression level in prefrontal cortex (PFC) of bile acid receptor (FXR) protein, which is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. We found that CDCA treatment restored the level of FXR in the CSDS mice, suggesting the involvement of bile acid receptors in MDD. We observed that CDCA decreased the activity of the NLRP3 inflammasome and caspase-1 and subsequently increased the levels of phosphorylation and expression of PFC glutamate receptors (GluA1) in the PFC. In addition, CDCA showed antidepressant effects in the tests of sucrose preference, tail suspension, and forced swimming in CSDS mouse model of depression. Finally, in agreement with this idea, blocking these receptors by a FXR antagonist GS abolished CDCA-induced antidepressant effect. Moreover, CDCA treatment rescued the increase of IL-1ß, IL-6, TNF α and IL-17, which also were blocked by GS. These results suggest that CDCA is a biomarker and target potentially important for the diagnosis and treatment of MDD.

Guidance on the conversion of the Chinese versions of the Quick Inventory of Depressive Symptomatology-Self-Report (C-QIDS-SR) and the Montgomery-Asberg Scale (C-MADRS) in Chinese patients with major depression.

BACKGROUND: The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) is a newly introduced screening tool, while the Montgomery-Asberg Scale (MADRS) is commonly used in research and clinical practice in China. Converting the total scores between the two instruments could facilitate the comparison of different studies. METHODS: This study included 1164 patients with major depressive disorder (MDD). The diagnosis was established using the Mini International Neuropsychiatric Interview (MINI). The severity of depressive symptoms was assessed with the Chinese versions of MADRS (C-MADRS) and QIDS-SR (C-QIDS-SR) at baseline and 6 weeks later (exit point). Total scores of both scales were converted using Item Response Theory (IRT) analysis. RESULTS: At baseline, the C-MADRS and C-QIDS-SR were not unifactorial, therefore the conversion between them could not be performed. At exit, the C-MADRS and C-QIDS-SR were unifactorial, meeting the unidimensionality assumption of the IRT approach. Depression severity thresholds for the QIDS-SR are suggested as 6-10 for mild, 11-15 for moderate, 16-20 for severe, 21+ for very severe depression and ≤ 5 for remission (www.ids-qids.org). Based on the results of this study, the corresponding C-MADRS thresholds are 9-17 for mild, 18-24 for moderate, 25-33 for severe, 34+ for very severe depression and ≤ 7 or 8 (7.5) for remission. CONCLUSIONS: The conversion of C-QIDS-SR and C-MADRS total scores would help researchers understand findings across different studies using these scales.

Psychometric properties of the Chinese versions of the Quick Inventory of Depressive Symptomatology - Clinician Rating (C-QIDS-C) and Self-Report (C-QIDS-SR).

BACKGROUND: Developing accurate and time-efficient tools to measure depressive symptoms is important for research and clinical practice. This study aimed to test the psychometric properties of the Chinese version of the 16-item Quick Inventory of Depressive Symptomatology - Clinician Rating (C-QIDS-C) and Self-Report (C-QIDS-SR). METHODS: This study included 998 patients with major depressive disorder (MDD) established using the Mini International Neuropsychiatric Interview (MINI). The severity of depressive symptoms was assessed using the Hamilton Rating Scale for Depression (HAMD), C-QIDS-C and C-QIDS-SR at baseline and 6 weeks later. RESULTS: Internal consistency (Cronbach's alpha) ranged from 0.73 to 0.82 for C-QIDS-C and C-QIDS-SR at both the baseline and exit. The involvement and energy domains at baseline, and sad mood, concentration/decision making, self outlook, involvement and agitation/retardation domains at exit had the highest item-total correlations across the two C-QIDS scales. The C-QIDS-C and C-QIDS-SR total scores were highly correlated with the HAMD total score at both baseline (r=0.61, p<0.01 and r=0.54, p<0.01, respectively) and exit (r=0.75, p<0.01 and r=0.72, p<0.01, respectively). The C-QIDS-C, C-QIDS-SR and HAMD were equally sensitive to change of depressive symptoms, suggesting high concurrent validity. The C-QIDS-C and C-QIDS-SR showed uni-dimensional measurement properties in exploratory factor analyses at both baseline and exit. CONCLUSIONS: The C-QIDS-C and C-QIDS-SR have excellent psychometric properties and are sensitive measurement of symptom severity in MDD.