The Identification of Potential Anti-Depression/Anxiety Drug Targets by Stress-Induced Rat Brain Regional Proteome and Network Analyses.

Depression and anxiety disorders are prevalent stress-related neuropsychiatric disorders and involve multiple molecular changes and dysfunctions across various brain regions. However, the specific and shared pathophysiological mechanisms occurring in these regions remain unclear. Previous research used a rat model of chronic mild stress (CMS) to segregate and identify depression-susceptible, anxiety-susceptible, and insusceptible groups; then the proteomes of six distinct brain regions (the hippocampus, prefrontal cortex, hypothalamus, pituitary, olfactory bulb, and striatum) were separately and quantitatively analyzed. To gain a comprehensive and systematic understanding of the molecular abnormalities, this study aimed to investigate and compare differential proteomics data from the six regions. Differentially expressed proteins (DEPs) were identified in between specific regions and across all regions and subjected to a series of bioinformatics analyses. Regional comparisons showed that stress-induced proteomic changes and corresponding gene ontology and pathway enrichments were largely distinct, attributable to differences in cell populations, protein compositions, and brain functions of these areas. Additionally, a notable degree of overlap in the significantly enriched terms was identified, potentially suggesting strong connections in the enrichment across different regions. Furthermore, intra-regional and inter-regional protein-protein interaction networks and drug-target-DEP networks were constructed. Integrated analysis of the three association networks in the six regions, along with the DisGeNET database, identified ten DEPs as potential targets for anti-depression/anxiety drugs. Collectively, these findings revealed commonalities and differences across different brain regions at the protein level induced by CMS, and identified several novel protein targets for the development of new therapeutics for depression and anxiety.

Association between cytokines and symptoms of depression and anxiety in patients with type 1 narcolepsy.

BACKGROUND: Symptoms of depression and anxiety are common complications of narcolepsy. Earlier studies have shown that narcolepsy type 1 (NT1) is an autoimmune inflammatory disease and symptoms of depression and anxiety are closely related to fluctuations in inflammatory cytokines. The objective of the current research was to investigate the potential correlation between cytokines and symptoms of depression and anxiety in patients with NT1. METHODS: We collected demographic and clinical data and information on cytokine levels from 50 patients with NT1 and used Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) to assess the severity of depression and anxiety symptoms. Patients with SDS scores ≥ 53 points were defined as depressive narcolepsy type 1 (D-NT1) and those with SDS scores < 53 points as non-depressive narcolepsy type 1 (ND-NT1). Patients with SAS scores ≥ 50 points were defined as anxious narcolepsy type 1 (A-NT1) and those with SAS scores < 50 points as non-anxious narcolepsy type 1 (NA-NT1). A binary logistic regression model was employed to identify the influencing factors of depressive and anxiety symptoms. RESULTS: Levels of IL-10 (p = 0.02), IL-4 (p = 0.049) and disease duration (p = 0.049) were decreased, while SAS scores (p < 0.001) and total sleep duration (p = 0.03) were increased in D-NT1 relative to ND-NT1 patients. A-NT1 patients had higher SDS scores (p < 0.001) compared to NA-NT1 patients. Binary logistic regression analysis revealed associations of longer disease duration (OR=0.83; 95 % CI: 0.70-0.97) and increased IL-10 (OR=0.40; 95 % CI: 0.17-0.90) with reduced risk of depression and worsening anxiety (SAS score; OR=1.17; 95 % CI: 1.06-1.30) with increased risk of depression in patients with NT1. Consistently, worsening depression (SDS score; OR=1.22; 95 % CI: 1.07-1.39) was correlated with increased risk of anxiety in the NT1 group. CONCLUSION: Our finding that higher IL-10 levels correlate with a lower risk of depression in NT1 patients provides a reference for further exploration of the pathophysiological mechanisms of depressive symptoms in NT1 patients.

Cell-based vs enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy.

STUDY OBJECTIVES: Narcolepsy type 1 is attributed to a deficiency in cerebrospinal fluid orexin and is considered linked to autoimmunity. The levels of anti-Tribbles homolog 2 (TRIB2) autoantibodies are elevated in the sera of some patients with narcolepsy with cataplexy. Additionally, injecting mice with serum immunoglobulin from patients with narcolepsy with positive anti-TRIB2 antibodies can induce hypothalamic neuron loss and alterations in sleep patterns. Consequently, we hypothesized the existence of a potential association between anti-TRIB2 antibodies and narcolepsy. To test this possibility, we used cell-based assays (CBAs) and enzyme-linked immunosorbent assays (ELISAs) to detect the presence of anti-TRIB2 antibodies in Chinese patients with narcolepsy. METHODS: We included 68 patients with narcolepsy type 1, 39 patients with other central disorders of hypersomnolence, and 43 healthy controls. A CBA and a conventional ELISA were used to detect anti-TRIB2 antibody levels in patients' sera. RESULTS: CBA was used to detect serum anti-TRIB2 antibodies in Chinese patients with narcolepsy, and the results were negative. However, when the ELISA was used, only 2 patients with narcolepsy type 1 had TRIB2 antibody titers higher than the mean titer plus 2 standard deviations of the healthy controls. CONCLUSIONS: In our study, ELISA identified TRIB2 autoantibodies in sera of patients with narcolepsy where CBA failed to demonstrate them. Contrary to our hypothesis, this intriguing finding deserves further research to elucidate the potential association between TRIB2 and narcolepsy type 1. Exploring the implications of TRIB2 autoantibodies in narcolepsy and disparate outcomes between ELISA and CBA could provide crucial insights. CITATION: Zhong X, Yuan Y, Zhan Q, et al. Cell-based vs enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy. J Clin Sleep Med. 2024;20(6):941-946.

Interaction between diabetes and body mass index on severe headache or migraine in adults: a cross-sectional study.

BACKGROUND: Research on the effects of body mass index (BMI) on severe headache or migraine is limited and controversial. The aim of this study was to explore the association between BMI and the prevalence of migraine, with particular interest in diabetes status difference. METHODS: The present study used analyzed data from people who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004. Logistic regression models and restricted cubic spline (RCS) models were applied to investigate the relationship between body mass index and migraine. RESULTS: A total of 10,074 adults aged 20 years or older were included in this study. Body mass index was positively related to migraine, and the corresponding odds ratio (OR; 95% CI) was 1.02 (1.01, 1.03; p < 0.001). And compared to participants in the lowest group of body mass index (< 25 kg/m2), the adjusted ORs for migraine in medium group (25-29.9 kg/m2), and highest group (≥ 30 kg/m2) were 1.14 (95% CI: 0.98-1.32, p = 0.09) and 1.30 (95% CI: 1.11-1.52, p = 0.0022), respectively. The relationship between BMI and migraine exhibited a linear in overall in the RCS. Our findings also suggested an interaction between BMI and diabetes. The relationship between BMI and migraine in adults with diabetes was non-linear. The OR of developing migraine was 1.30 (95% CI: 1.10-1.54) in individuals with BMI ≥ 29.71 kg/m2 in adults with diabetes. CONCLUSION: A higher body mass index is significantly associated with an increased prevalence of migraine, and diabetes status can modify the association between them.

Vitamin B6 and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999-2004.

Previous studies have shown that B vitamins can relieve migraine. However, the association between vitamin B6 and folate, 2 important B vitamins consumed in the diet, with migraine have received minimal attention. This study explored the independent relationships between dietary vitamin B6 and folate intake with migraine and the interaction effect of these 2 nutrients on migraine in US adults. We hypothesized that vitamin B6 and folate intake would be inversely associated with migraine. This study included cross-sectional data from participants aged 20 years and older who participated in the National Health and Nutrition Examination Survey from 1999 to 2004. We conducted multivariate logistic regression and restricted cubic spline regression to explore the association between dietary vitamin B6 and folate intake on migraine. Also, relative excess risk due to interaction, attributable proportion of interaction, and synergy index were used to assess additive interactions. A total of 7017 participants were included in this study, 1350 of whom were migraineurs. We determined that vitamin B6 and folate intake revealed a negative association with severe headache or migraine (0.66; 95% confidence interval [CI], 0.47-0.89; P = .01 and 0.57; 95% CI, 0.42-0.78; P = .002]), respectively. Also, a significant interaction effect between a high mass of vitamin B6 and folate intake was observed for a lower risk of migraine (relative excess risk due to interaction, 0.28 [95% CI, 0.05-0.51]; attributable proportion of interaction: 0.45 [95% CI, 0.05-0.86]; synergy index: 0.58 [95% CI, 0.40-0.83]). A high mass of vitamin B6 and folate intake (vitamin B6 intake ≥ 2.39 mg/day and folate intake ≥ 502.01 µg/day) presented a synergistic interaction with migraine, suggesting that these 2 nutrients might be beneficial in preventing migraine.

Association between dietary folate intake and severe headache among adults in the USA: a cross-sectional survey.

Folate, also known as vitamin B9, is a water-soluble vitamin. Previous studies on dietary folate intake in severe headache patients were equivocal. Therefore, we conducted a cross-sectional study to elucidate the relationship between folate intake and severe headache. This cross-sectional study used data from participants over 20 years old who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The diagnosis of severe headache was made through participants' self-report in the NHANES questionnaire section. We performed multivariate logistic regression and restricted cubic spline (RCS) regression to explore the relationship between folate intake and severe headache. A total of 9859 participants took part in the study, 1965 of whom were severe headache patients and the rest were non-severe headache. We found that dietary folate intake was significantly and inversely associated with severe headache. Compared with participants with lower folate intake Q1 (≤ 229·97 ug/d), the adjusted OR values for dietary folate intake and severe headache in Q2 (229·98-337 ug/d), Q3 (337·01-485 ug/d) and Q4 (≥ 485·01 ug/d) were 0·81 (95 % CI: 0·67, 0·98, P = 0·03), 0·93 (95 % CI: 0·77, 1·12, P = 0·41) and 0·63 (95 % CI: 0·49, 0·80, P < 0·001), respectively. For women aged 20-50 years, there was a non-linear association between folate intake and severe headache in the RCS. Women aged 20-50 years should have higher awareness of dietary folate and increase their dietary intake of folate, which may aid in preventing severe headache.

Dietary niacin intake in relation to depression among adults: a population-based study.

BACKGROUND: Previous studies have shown that an antioxidant diet is a protective factor against depression. However, the association between niacin, an important antioxidant consumed from the diet, and depression has received little attention. Therefore, we explored the association between niacin intake and depression through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. METHODS: Depression was measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Niacin intake was assessed through 24-h dietary recall interviews. The relationship of niacin intake with depression among adults in US was assessed by using a weighted multiple logistic regression model with subgroup analysis. Non-linear associations were explored using restricted cubic spline models. And we used a two-piece-wise logistic regression model with smoothing to explore the threshold for association between them. RESULTS: A total of 16,098 adults were included in this study. Compared with individuals with lowest niacin intake Q1 (≤ 15.96 mg/day), the adjusted OR values for dietary niacin intake and depression in Q2 (15.97-22.86 mg/day), Q3 (22.87-32.28 mg/day) and Q4 (≥ 32.29 mg/day), were 0.92 (95% CI: 0.70-1.20), 0.76 (95% CI: 0.56-0.99,) and 0.68 (95% CI: 0.48-0.98), respectively. The results were not modified by sex, by age and by BMI. Furthermore, the relationship between dietary niacin intake and depression exhibited a U-shaped curve (nonlinear, p < 0.001). And depression risk was lowest when dietary consumption of niacin was around 36 mg/day. CONCLUSIONS: In present study, moderate niacin intake, but not high intake, was associated with lower odds of depression suggesting a U-shaped association.

Body mass index modifies the relationship between dietary iron intake and depressive symptoms among adults: A national population-based cohort.

BACKGROUND: Research on the effects of dietary iron intake on depression is limited and controversial. The aim of this study was to explore the association between iron intake and the prevalence of depressive symptoms. METHODS: The present study used cross-sectional data from people who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016. Logistic regression models and restricted cubic spline models were applied to investigate the relationship between iron intake and depressive symptoms. RESULTS: A total of 16,098 adults aged 20 years or older were included in this study. Compared with individuals with lowest iron intake Q1 (≤8.31 mg/day), the adjusted OR values for dietary iron intake and depression in Q2 (8.32-11.47 mg/day), Q3 (11.48-15.02 mg/day), Q4 (15.03-20.28 mg/day), and Q5 (≥20.29 mg/day) were 0.69 (95 % CI: 0.52-0.91), 0.68 (95 % CI: 0.50-0.94,), 0.59 (95 % CI: 0.42-0.82,), and 0.63 (95 % CI: 0.40-0.98), respectively. The relationship between iron intake and depressive symptoms exhibited a non-linear. Our findings suggested an interaction between body mass index (BMI) and iron intake (P = 0.03). Additionally, the relationship between dietary iron intake and depressive symptoms in adults with a BMI <25 kg/m2 was U-shaped. And the OR of developing depressive symptoms was 0.93 (95 % CI: 0.87-0.99) in individuals with iron intake ≤19.72 mg/day. LIMITATIONS: Cross-sectional study and relevant data was based on self-reports. CONCLUSION: A higher iron intake is significantly associated with a decreased prevalence of depressive symptoms, and different levels of BMI can modify the association between them.

Dietary zinc intake in relation to migraine among adults: a cross sectional study of NHANES 1999-2004.

BACKGROUND: Previous studies have revealed that an antioxidant diet is a protective factor against migraine. However, the association between zinc, an important antioxidant obtained from the diet, and migraine has received little attention. The purpose of this study was to explore the association between zinc intake with migraine. METHODS: The present study used cross-sectional data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004. Logistic regression models and restricted cubic spline models were performed to explore the association between zinc intake and migraine. RESULTS: A total of 9849 adults aged 20 years or older were included in this study. Zinc intake was negatively associated with migraine. Compared to participants in the lowest group of dietary zinc intake Q1 (≤5.93 mg/day), the adjusted ORs for migraine in Q2 (5.94-8.38 mg/day), Q3 (8.39-11.26 mg/day), Q4 (11.27-15.75 mg/day), and Q5 (≥15.76 mg/day) were 0.73 (95% CI: 0.60-0.89, p = 0.004), 0.72 (95% CI: 0.55-0.95, p = 0.02), 0.76 (95% CI: 0.58-0.99, p = 0.04) and 0.73 (95% CI: 0.50-1.05, p = 0.08), respectively. Our findings also suggested an interaction between zinc intake and age (P for interaction = 0.007). Additionally, the relationship between zinc intake and migraine in adults with 20-50 years was non-linear. CONCLUSIONS: A higher zinc intake is significantly associated with a decreased prevalence of migraine, and age can modify the association between them.

Identification of autophagy-related genes in neuropathic pain through bioinformatic analysis.

BACKGROUND: Neuropathic pain (NP) is one of the most common types of chronic pain and significantly compromises the quality of life. Autophagy is an intracellular catabolic process that is required to maintain cellular homeostasis in response to various stresses. The role of autophagy-related genes in the diagnosis and treatment of neuropathic pain remains unclear. METHODS: We identified autophagy-related differentially expressed genes (ARDEGs) and differentially expressed miRNAs (DE-miRNAs) in neuropathic pain by bioinformatics analysis of the GSE145226 and GSE145199 datasets. These ARDEGs and their co-expressed genes were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and friends analysis. Meanwhile, we constructed TFs-ARDEGs, miRNA-ARDEGs regulatory network through ChIPBase database and the HTFtarget database, multiMir R package. Finally, we performed immune infiltration analysis of ARDEGs by Single Sample Gene Set Enrichment Analysis (ssGSEA). RESULTS: We identified 2 potential autophagy-related differentially expressed genes (Sirt2 and ST7) that may be closely associated with the pathogenesis of neuropathic pain. GO, KEGG and GSEA analysis revealed that these two ARDEGs were mainly enriched in pyridine nucleotide metabolic process, nicotinamide nucleotide metabolic process, Nicotinate and nicotinamide metabolism, NF-κB pathway, KRAS signaling, P53 pathway. In the TFs-ARDEGs and miRNA-ARDEGs regulatory network, miR-140-5p and Cebpb were predicted to be as crucial regulators in the progression of NP. For the ssGSEA results, Sirt2 was positively correlated with Eosinophil and Effector memory CD8+ T cell infiltration, which suggested that it may be involved in the regulation of neuroimmune-related signaling. CONCLUSION: Two autophagy-related differentially expressed genes, especially Sirt2, may be potential biomarkers for NP, providing more evidence about the crucial role of autophagy in neuropathic pain.

Effect of botulinum toxin type A on non-motor symptoms and quality of life in Meige syndrome.

Background: It has been shown in previous studies that botulinum toxin type A (BTX-A) can effectively relieve the motor symptoms of Meige syndrome. However, its effect on non-motor symptoms (NMS) and quality of life (QoL) has not been comprehensively studied. This study aimed to explore the effects of BTX-A on NMS and QoL and to clarify the relationship between changes in motor symptoms, NMS, and QoL after BTX-A. Methods: Seventy-five patients were recruited for the study. All patients were assessed by a series of clinical assessments before, one, and 3 months after BTX-A treatment. Dystonic symptoms, psychiatric disturbances, sleep disorders, and QoL were evaluated. Results: After 1 and 3 months of BTX-A treatment, the scores of motor symptoms, anxiety, and depression were significantly decreased (P < 0.05). Except for general health, the scores of the other 36-item short-form health survey QoL subitems were significantly improved after BTX-A (P < 0.05). After 1 month of treatment, the changes in anxiety and depression were not correlated with changes in motor symptoms (P > 0.05). Still, they were negatively correlated with changes in physical functioning, role-physical and mental component summary QoL (P < 0.05). Conclusions: BTX-A effectively improved motor symptoms, anxiety, depression, and QoL. Anxiety and depression improvement did not correlate with motor symptom changes after BTX-A, and QoL improvements were strongly associated with psychiatric disturbances.