Absence of Causal Relationship Between Levels of Unsaturated Fatty Acids and ADHD: Evidence From Mendelian Randomization Study.

OBJECTIVE: Previous research suggests a potential link between unsaturated fatty acids (UFAs) and ADHD, but the causal relationship remains uncertain. This study aims to investigate the causal association between ADHD and UFAs using Mendelian randomization (MR) analysis. METHODS: Summary data from genome-wide association studies were used to estimate the concentration of circulating UFAs, including Monounsaturated Fatty Acids (MUFAs), Polyunsaturated Fatty Acids (PUFAs), Omega-3 PUFAs, Omega-6 PUFAs, Linoleic Acid (LA), and Docosahexaenoic Acid (DHA). Data from the Psychiatric Genomics Consortium, including both childhood and adult ADHD, were respectively used to examine the relationship between genetically predicted UFAs levels and ADHD. Various MR methods, including Inverse-variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier, MR-Egger, weighted median, and weighted mode, were employed to assess heterogeneity and pleiotropy. RESULTS: The IVW revealed only nominal evidence suggesting a potential causal relationship between genetically predicted PUFAs (OR = 0.92, 95% CI [0.85, 0.99], p = .031), Omega-6 PUFAs (OR = 0.90, 95% CI [0.83, 0.98], p = .020), and LA levels (OR = 0.90, 95% CI [0.82, 0.98], p = .021) with childhood ADHD risk. However, after false discovery rate correction, the p-values for PUFAs, Omega-6 PUFAs, and LA levels all exceeded the threshold for significance. For adult ADHD, we did not find any significant associations between the six circulating UFA levels and adult ADHD. CONCLUSION: Our findings do not support a causal relationship between UFAs levels and ADHD. This suggests that UFAs supplements may not be effective in improving ADHD symptoms and importantly, it appears that UFAs levels may not have a long-term effect on ADHD.

Similarities and differences between post-traumatic stress disorder and major depressive disorder: Evidence from task-evoked functional magnetic resonance imaging meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are psychiatric disorders that can present with overlapping symptoms and shared risk factors. However, the extent to which these disorders share common underlying neuropathological mechanisms remains unclear. To investigate the similarities and differences in task-evoked brain activation patterns between patients with PTSD and MDD. METHODS: A coordinate-based meta-analysis was conducted across 35 PTSD studies (564 patients and 543 healthy controls) and 125 MDD studies (4049 patients and 4170 healthy controls) using anisotropic effect-size signed differential mapping software. RESULTS: Both PTSD and MDD patients exhibited increased neural activation in the bilateral inferior frontal gyrus. However, PTSD patients showed increased neural activation in the right insula, left supplementary motor area extending to median cingulate gyrus and superior frontal gyrus (SFG), and left fusiform gyrus, and decreased neural activation in the right posterior cingulate gyrus, right middle temporal gyrus, right paracentral lobule, and right inferior parietal gyrus relative to MDD patients. CONCLUSION: Our meta-analysis suggests that PTSD and MDD share some similar patterns of brain activation, but also have distinct neural signatures. These findings contribute to our understanding of the potential neuropathology underlying these disorders and may inform the development of more targeted and effective treatment and intervention strategies. Moreover, these results may provide useful neuroimaging targets for the differential diagnosis of MDD and PTSD.

Effects of antidepressant on FKBP51 mRNA expression and neuroendocrine hormones in patients with panic disorder.

OBJECTIVE: The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). METHODS: Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. RESULTS: At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). CONCLUSIONS: The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.

Potential of niacin skin flush response in adolescent depression identification and severity assessment: a case-control study.

BACKGROUND: The diagnosis of adolescent Depressive Disorder (DD) lacks specific biomarkers, posing significant challenges. This study investigates the potential of Niacin Skin Flush Response (NSFR) as a biomarker for identifying and assessing the severity of adolescent Depressive Disorder, as well as distinguishing it from Behavioral and Emotional Disorders typically emerging in childhood and adolescence(BED). METHODS: In a case-control study involving 196 adolescents, including 128 Depressive Disorder, 32 Behavioral and Emotional Disorders, and 36 healthy controls (HCs), NSFR was assessed. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and anxious symptoms with the Generalized Anxiety Disorder 7-item scale (GAD-7). Pearson correlation analysis determined the relationships between NSFR and the severity of depression in DD patients. Receiver Operating Characteristic (ROC) was used to identify DD from BED integrating NSFR data with clinical symptom measures. RESULTS: The adolescent Depressive Disorder group exhibited a higher rate of severe blunted NSFR (21.4%) compared to BED (12.5%) and HC ( 8.3%). Adolescent Depressive Disorder with psychotic symptoms showed a significant increase in blunted NSFR (p = 0.016). NSFR had negative correlations with depressive (r = -0.240, p = 0.006) and anxious (r = -0.2, p = 0.023) symptoms in adolescent Depressive Disorder. Integrating NSFR with three clinical scales improved the differentiation between adolescent Depressive Disorder and BED (AUC increased from 0.694 to 0.712). CONCLUSION: The NSFR demonstrates potential as an objective biomarker for adolescent Depressive Disorder, aiding in screening, assessing severity, and enhancing insights into its pathophysiology and diagnostic precision.

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis developed after ovarian cancer cytoreduction surgery: a case report and literature review.

BACKGROUND: Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis (AE), is often found associated with tumors such as thymoma, lung cancer, ovarian tumors, and breast cancer, and the tumors were generally detected during the screening process after the encephalitis initiated. The tumor is considered a trigger of AE, but the mechanism remains unclear. CASE PRESENTATION: A 53-year-old woman presented short-term memory loss two days after the primary cytoreduction for high-grade serous ovarian cancer (HGSOC, FIGO stage IC3). Cell-based assay found AMPAR CluA2 IgG positive in both serum (1:3.2) and cerebrospinal fluid (1:32). Moreover, mild AMPAR GluA1 and strong GluA2 expressions were also found positive in the paraffin sections of ovarian tumor tissue, indicating the ovarian cytoreduction surgery might stimulate the release of receptor antigens into the circulation system. The patient's condition deteriorated within two weeks, developing consciousness and autonomic dysfunction, leading to ICU admission. With oral steroids, intravenous immunoglobulin, plasmapheresis, and rituximab treatment, the patient's consciousness markedly improved after three months. CONCLUSION: We presented the first case of anti-AMPAR encephalitis developed right after the primary cytoreduction of a patient with HGSOC and retrieved paraneoplastic anti-AMPAR encephalitis cases (n = 66). Gynecologists should pay attention to patients who develop cognitive dysfunction or psychiatric symptoms shortly after the ovarian tumor resection and always include AE in the differentiation diagnosis.

Common and distinct patterns of task-related neural activation abnormalities in patients with remitted and current major depressive disorder: A systematic review and coordinate-based meta-analysis.

Whether remitted major depressive disorder (rMDD) and MDD present common or distinct neuropathological mechanisms remains unclear. We performed a meta-analysis of task-related whole-brain functional magnetic resonance imaging (fMRI) using anisotropic effect-size signed differential mapping software to compare brain activation between rMDD/MDD patients and healthy controls (HCs). We included 18 rMDD studies (458 patients and 476 HCs) and 120 MDD studies (3746 patients and 3863 HCs). The results showed that MDD and rMDD patients shared increased neural activation in the right temporal pole and right superior temporal gyrus. Several brain regions, including the right middle temporal gyrus, left inferior parietal, prefrontal cortex, left superior frontal gyrus and striatum, differed significantly between MDD and rMDD. Meta-regression analyses revealed that the percentage of females with MDD was positively associated with brain activity in the right lenticular nucleus/putamen. Our results provide valuable insights into the underlying neuropathology of brain dysfunction in MDD, developing more targeted and efficacious treatment and intervention strategies, and more importantly, providing potential neuroimaging targets for the early screening of MDD.

Brain-derived neurotrophic factor blood levels after electroconvulsive therapy in patients with mental disorders: A systematic review and meta-analysis.

OBJECTIVE: Multiple studies have indicated that electroconvulsive therapy (ECT) could increase brain-derived neurotrophic factor (BDNF) concentrations in patients with different mental disorders. The aim of this synthesis was to evaluate post-ECT BDNF concentrations in patients with various mental disorders. METHODS: The Embase, PubMed and Web of Science databases were systematically searched for studies in English comparing BDNF concentrations before and after ECT through 11/2022. We extracted the pertinent information from the included studies and evaluated their quality. The standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated to quantify BDNF concentration differences. RESULTS: In total, 35 studies assessed BDNF concentrations in 868 and 859 patients pre and post-ECT treatment, respectively. Post-ECT-treatment BDNF concentrations were significantly higher than the pretreatment concentrations (Hedges'g = -0.50, 95% CI (-0.70, -0.30), heterogeneity I2 = 74%, p < 0.001). The analysis that combined both ECT responders and non-responders demonstrated a marked increase in total BDNF levels subsequent to ECT treatment (Hedges'g = -0.27, 95% CI (-0.42, -0.11), heterogeneity I2 = 40%, p = 0.0007). CONCLUSION: Irrespective of the effectiveness of ECT, Our study shows that peripheral BDNF concentrations increase significantly after the entire course of ECT, which may enhance our comprehension of the interplay between ECT treatment and BDNF levels. However, BDNF concentrations were not associated with the effectiveness of ECT, and abnormal concentrations of BDNF may be linked to the pathophysiological process of mental illness, necessitating more future research.

Heart rate variability in generalized anxiety disorder, major depressive disorder and panic disorder: A network meta-analysis and systematic review.

BACKGROUND: Heart rate variability (HRV) in patients with emotional disorders and healthy controls (HCs) has been investigated in many studies but the difference between these emotional disorders was unclear. METHODS: The PubMed, Embase, Medline and Web of Science databases were systematically searched for studies published in English that compared HCs with generalized anxiety disorder (GAD), major depressive disorder (MDD), panic disorder (PD) patients in HRV. We conducted a network meta-analysis to compare HRV in patients with GAD, MDD, PD and HCs. HRV outcomes, including time domain indices (the standard deviation of NN intervals (SDNN) and the root mean square of the successive differences between normal heartbeats (RMSSD)), and frequency domain indices (High-frequency (HF), Low-frequency (LF) and the ratio of LF to HF (LF/HF)) were obtained. A total of 4008 participants from 42 studies were included. RESULTS: The results of pairwise meta-analysis showed that compared with controls, GAD, PD and MDD patients exhibited significantly reduced HRV. Similar findings were also confirmed in network meta-analysis. The most important finding from network meta-analysis was that GAD patients had significantly lower SDNN than PD patients (SMD = -0.60, 95 % CI [-1.09, -0.11]). CONCLUSION: Our findings provided a potential objective biological marker to distinguish between GAD and PD. In the future, a large sample of research is needed to directly compare HRV of various mental disorders, which is crucial for finding biomarkers to distinguish them.

The effect of mindfulness-based interventions during pregnancy on postpartum mental health: A meta-analysis.

BACKGROUND: Mindfulness helps reduce negative emotions, but its ability to prevent postpartum psychological problems remains unclear. This study aimed to assess the effects of mindfulness-based interventions (MBIs) during pregnancy on postpartum mental health, especially postpartum depression. METHODS: Online databases regarding the effect of mindfulness on pregnancy were searched and a meta-analysis was conducted. RESULTS: Eight randomized controlled trials (RCTs) and a self-controlled study were included. We found consistent results showing that MBIs significantly improve the depressive symptoms of all pregnant women in both the case-control (SMD = -0.90, 95 % CI (-2.71, -1.82), p = 0.01) and self-control (SMD = 1.24, 95 % CI (0.37, 2.11), p = 0.005) comparisons. However, MBIs were ineffective for high-risk pregnant women with severe depressive symptoms before delivery in both the case-control (SMD = -1.07, 95 % CI (-3.40, 1.25), p = 0.36) and self-control comparisons (SMD = 2.10, 95 % CI (-0.26, 4.47), p = 0.08). Furthermore, MBIs did not have significant advantages over other intervention methods (SMD = -0.45, 95 % CI (-1.17, 0.28), p = 0.23). LIMITATIONS: There were few high-quality RCTs, and the sample size was small. CONCLUSION: MBIs can relieve maternal depressive and anxiety symptoms, especially for the prevention of postpartum depression in healthy pregnant women. However, MBIs do not have significant advantages over other interventions and may not be useful for all pregnant women. These findings contribute to the optimization of perinatal mental health intervention programs and the improvement of pregnancy outcomes, playing an important guiding role in clinical decision-making.

The homeostasis model assessment of insulin resistance is a judgment criterion for metformin pre-treatment before IVF/ICSI and embryo transfer cycles in patients with polycystic ovarian syndrome.

Purpose: The aim of this study was to explore the value of the homeostasis model assessment of IR (HOMA-IR) as a judgment criterion for metformin pre-treatment before in vitro fertilization/intracellular sperm injection (IVF/ICSI) and embryo transfer (ET) for polycystic ovarian syndrome (PCOS) patients. Materials and methods: The clinical and laboratory information of PCOS patients who received IVF/ICSI-ET from January 2017 to September 2021 was retrospectively analyzed. We compared the clinical pregnancy rate (primary outcome) and controlled ovarian stimulation (COS)-related parameters (secondary outcomes) between patients with and without metformin pre-treatment for all PCOS patients not grouped by HOMA-IR, PCOS patients with HOMA-IR < 2.71, and PCOS patients with HOMA-IR ≥ 2.71. Results: A total of 969 PCOS patients who received the GnRH-antagonist protocol were included in this study. For all PCOS patients, the metformin group showed comparable clinical pregnancy rates in fresh ET cycles and frozen ET cycles compared with the control group (55.9% vs. 57.1%, p = 0.821 and 63.8% vs. 60.9%, p = 0.497). For PCOS patients with HOMA-IR < 2.71, the clinical pregnancy rates in both fresh ET cycles and frozen ET cycles were statistically similar between the two groups (61.5% vs. 57.6%, p = 0.658 and 70.6% vs. 66.7%, p = 0.535). For PCOS patients with HOMA-IR ≥ 2.71, the clinical pregnancy rate in fresh ET cycles was comparable between the two groups (51.5% vs. 56.3, p = 0.590), but it was statistically higher in the metformin group than in the control group in frozen ET cycles (57.1% vs. 40.0%, p = 0.023). The metformin group had less oocytes retrieved, a lower cleaved oocyte rate, a lower available D3 embryo rate, a lower blastocyst formation rate, and a lower available blastocyst rate than the control group. Conclusion: HOMA-IR is a judgment criterion for metformin pre-treatment before IVF/ICSI-ET in patients with PCOS. Metformin pre-treatment could be added for PCOS patients with HOMA-IR ≥ 2.71 during frozen IVF/ICSI-ET cycles to improve the clinical pregnancy rate.

A new model for the treatment of type 2 diabetes mellitus based on rhythm regulations under the framework of psychosomatic medicine: a real-world study.

We aimed to explore a new treatment model for type 2 diabetes mellitus (DM) based on rhythm regulation under the framework of psychosomatic medicine. Using psychotropics as rhythm regulators, 178 patients with DM were evaluated and divided into three groups: the antidiabetic treatment group (AT group), psychotropic treatment group (PT group), and combined antidiabetic + psychotropic treatment group (combined group), for a course of 16 weeks. The West China Psychiatry Association (WCPA) Somatic Symptom Classification Scale (SSCS) was used to evaluate each patient. The levels of hormones in the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid axes and of blood glucose and glycosylated hemoglobin (HbA1c) were evaluated both before and after treatment. After the treatment, the blood glucose and HbA1c levels in all three groups were lower than those at baseline. Furthermore, the incidence of the abnormal HPA axis in the PT group was significantly decreased (P = 0.003), while the incidence of the abnormal HPA axis in the combined group was 0.0%. The five factor scores of the SSCS in the PT and combined groups after treatment were both significantly low (P < 0.01). Both the incidence of abnormal neuroendocrine axes and SSCS scores in the AT group showed no significant difference before and after treatment. "Blood glucose control + rhythm regulation" should be considered as optimised treatment goals for DM. Moreover, some psychotropics could be used as biorhythm regulators, which have good potential value for clinical application.Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Reinterpretation of mechanism and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis. The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).

Heart rate variability changes in patients with obstructive sleep apnea: A systematic review and meta-analysis.

Obstructive sleep apnea is a common sleep breathing disorder related to autonomic nervous function disturbances. Heart rate variability is an important non-invasive indicator of autonomic nervous system function. The PubMed, Embase, Medline and Web of Science databases were systematically searched for English literature comparing patients with obstructive sleep apnea with controls up to May 2021. Heart rate variability outcomes, including integrated indices (parasympathetic function and total variability), time domain indices (the standard deviation of NN intervals and the root mean square of the successive differences between normal heartbeats) and frequency domain indices (high-frequency, low-frequency, very-low-frequency and the ratio of low-frequency to high-frequency) were derived from the studies. Twenty-two studies that included 2565 patients with obstructive sleep apnea and 1089 healthy controls were included. Compared with controls, patients with obstructive sleep apnea exhibited significantly reduced parasympathetic function. For the obstructive sleep apnea severity subgroup meta-analysis, patients with severe obstructive sleep apnea had significantly lower parasympathetic function, high-frequency, root mean square of the successive differences between normal heartbeats and standard deviation of NN intervals, and higher low-frequency and ratios of low-frequency to high-frequency. However, only the ratio of low-frequency to high-frequency was significantly higher in patients with moderate obstructive sleep apnea than in controls. Finally, for the collection time analysis, patients with obstructive sleep apnea had significantly higher low-frequency and ratio of low-frequency to high-frequency at night, significantly lower parasympathetic function, high-frequency, root mean square of the successive differences between normal heartbeats and standard deviation of NN intervals, and a higher ratio of low-frequency to high-frequency during the day than controls. Autonomic function impairment was more serious in patients with severe obstructive sleep apnea. During sleep, low-frequency can well reflect the impairment of autonomic function in obstructive sleep apnea, and the ratio of low-frequency to high-frequency may play an important role in obstructive sleep apnea diagnosis.

Integrated genome-wide methylation and expression analyses provide predictors of diagnosis and early response to antidepressant in panic disorder.

BACKGROUND: We investigated differentially methylated and expressed genes between panic disorder (PD) and healthy controls (HCs) to determine whether DNA methylation and expression level of candidate genes can be used as biomarkers for diagnosis and early response. METHODS: Illumina infiniun Methylation EPIC (850 k) Beadchip for genome-wide methylation screening and mRNA sequencing was conducted in a discovery set (30 patients with PD and 30 matched HCs). The candidate gene loci methylation and expression were verified in an independent validation sample (101 PD patients and 107 HCs). RESULTS: In the discovery set, there were 3613 differentially methylated cytosine phosphate guanosine sites and these differential methylation positions were located within 1938 unique genes, including 1758 hypermethylated genes, 150 hypomethylated genes, and the coexistence of hypermethylation and hypomethylation sites were found in 30 genes. There were 1111 differential transcripts in PD compared to normal controls (850 down-regulated and 261 up-regulated). Further, 212 differentially expressed genes were screened (40 up-regulated and 172 down-regulated). In the validation set, compared with HCs, there was no significant difference in DNA methylation level of Casitas B-lineage lymphoma (CBL) gene loci (cg07123846). The expression level of CBL gene in PD patients was lower (vs. HCs). After four weeks' treatment, the baseline expression level of CBL gene in the responders was higher than nonresponders. LIMITATIONS: The sample size was limited. We only chose CBL as a candidate gene. Follow-up periods were short. CONCLUSIONS: There are differences in genome-wide DNA methylation and mRNA expression between PD patients and HCs. The changes in expression level of CBL gene may be an important molecular marker for PD diagnosis and early response.

Persistent hiccups due to aripiprazole: a case report and review of the literature.

Introduction: Aripiprazole, a commonly prescribed antipsychotic, has been rarely associated with the onset of hiccups. This study aims to elucidate the prevalence, risk factors, and management of aripiprazole-induced hiccups. Methods: We report a case of aripiprazole-induced hiccups in a 32-year-old male diagnosed with Somatic Symptom Disorder per DSM-5 criteria.A comprehensive literature review was conducted, identifying 29 case reports of aripiprazole-induced hiccups. Patient demographics, dosage, onset and duration of hiccups, and management strategies were analyzed. Results: Aripiprazole-induced hiccups predominantly affected adolescents and middle-aged male patients (86.7%). The majority of hiccups developed within 1-2 days post-prescription (90.9%) and resolved within 1-4 days after discontinuation of aripiprazole. Discontinuation of aripiprazole was the most effective management strategy (51.7%). Co-administration with benzodiazepines was identified as a significant risk factor. Discussion: The findings suggest that clinicians should be vigilant for the onset of hiccups during the early stages of aripiprazole treatment, especially in male patients and those co-administered with benzodiazepines. Conclusion: Clinicians should be vigilant for hiccups during early aripiprazole treatment. Considering personality and psychological factors is crucial in managing hiccups in psychiatric patients.

Nomogram to predict postoperative complications after cytoreductive surgery for advanced epithelial ovarian cancer: A multicenter retrospective cohort study.

Objective: To establish nomograms to predict the risk of postoperative complications following cytoreductive surgery in patients with advanced epithelial ovarian cancer (AEOC). Methods: A multicenter retrospective cohort study that included patients with FIGO stage IIIC-IV epithelial ovarian cancer who underwent cytoreductive surgery was designed. By using univariate and multivariate analyses, patient preoperative characteristics were used to predict the risk of postoperative complications. Multivariate modeling was used to develop Nomograms. Results: Overall, 585 AEOC patients were included for analysis (training cohort = 426, extrapolation cohort = 159). According to the findings, the training cohort observed an incidence of postoperative overall and severe complications of 28.87% and 6.10%, respectively. Modified frailty index (mFI) (OR 1.96 and 2.18), FIGO stage (OR 2.31 and 3.22), and Surgical Complexity Score (SCS) (OR 1.16 and 1.23) were the clinical factors that were most substantially associated to the incidence of overall and severe complications, respectively. The resulting nomograms demonstrated great internal discrimination, good consistency, and stable calibration, with C-index of 0.74 and 0.78 for overall and severe complications prediction, respectively. A satisfactory external discrimination was also indicated by the extrapolation cohort, with the C-index for predicting overall and severe complications being 0.92 and 0.91, respectively. Conclusions: The risk of considerable postoperative morbidity exists after cytoreductive surgery for AEOC. These two nomograms with good discrimination and calibration might be useful to guide clinical decision-making and help doctors assess the probability of postoperative complications for AEOC patients.

Re-interpretation of the mechanism of type 2 diabetes mellitus based on a framework of psychosomatic medicine: a real-world study.

OBJECTIVE: Using bipolar disorder (BD) as a control, we explored the possible developmental process of impaired glucose metabolism rhythm. METHODS: In total, 441 subjects (77, 162, 134, 54, and 14 in the pre-diabetes [pre-DM], DM, BD, BD + pre-DM, and BD + DM groups, respectively) and 160 controls were included. All subjects were assessed using the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes were measured. RESULTS: Cluster analysis showed that the BD, BD + DM, and DM groups were classified as the 'disease group, the BD + pre-DM group as the 'mixed period group', and the pre-DM group as the 'pre-disease group'. The conscientiousness factor scores of the NEO-FFI in the 'disease group' were higher than the norm but lower than the norm in the 'pre-disease group'. The scores of neurotic factors in the 'pre-disease' and 'mixed period' groups were both significantly higher than that in the 'disease group' (corrected p < 0.001). The incidences of the abnormal HPA axis decreased gradually from the 'pre-disease group' to the 'mixed period group' then to the 'disease group', while those of the HPT axis slightly increased at first and then significantly decreased. The overall prediction rate of the multiple logistic regression model was 92.7%. CONCLUSION: This study suggests that progression of pre-diabetes to DM is a continuous process from local abnormalities to rhythm disorder of glucose metabolism. This understanding can be applied to the whole course management and early intervention of DM and to the future development of optimised treatment based on rhythm regulation. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Identify and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis (Registration date: 24/10/2018). The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).

Task-related neural activation abnormalities in patients with remitted major depressive disorder: A coordinate-based meta-analysis.

Major depressive disorder (MDD) patients demonstrate abnormal neural activation even after complete remission. Many task-related functional magnetic resonance imaging (fMRI) studies have focused on changes in brain function in individuals with remitted MDD (rMDD). We conducted a meta-analysis of these studies to explore differences in brain activation between patients with rMDD and healthy controls (HCs). Our meta-analysis included 13 studies, encompassing 18 experiments, 304 rMDD patients and 321 HCs. Patients with rMDD showed increased neural activation in the left inferior parietal gyrus and right fusiform gyrus and decreased neural activation in the left superior frontal gyrus, right middle temporal gyrus and right Heschl gyrus. Meta-regression analysis revealed that patient age and the number of depressive episodes were negatively associated with brain activity in the left superior frontal gyrus. Our findings suggest abnormal brain function, especially in areas involved in cognitive function, emotion regulation and perception, in rMDD patients; alterations of these regions may be the primary or secondary neurophysiological mechanisms underlying MDD and provide potential neuroimaging targets for early screening.

Associations of DNA methylation of HPA axis-related genes and neuroendocrine abnormalities in panic disorder.

OBJECTIVE: The purpose of this study was to investigate the role of aberrant DNA methylation of hypothalamic-pituitary-adrenal (HPA) axis-related genes (CRHR1, CRHR2, CRH, FKBP5, HSP90AA1, NR3C1, and POMC) in panic disorder (PD) development. We investigated the correlation among gene methylation levels, adrenocorticotropic hormone (ACTH), cortisol, and PD severity in patients. METHODS: We compared the methylation levels of HPA axis-related genes between 178 patients with PD and 184 healthy controls using MethylTarget. We then measured ACTH and cortisol levels using chemiluminescence. Disease severity was assessed using the Panic Disorder Severity Scale. RESULTS: Compared with healthy controls, patients with PD displayed significantly higher levels of ACTH and cortisol, and significantly reduced methylation levels of CRHR1, FKBP5, HSP90AA1, and NR3C1 after correcting for multiple testing using the false discovery method. A significant positive correlation was observed between the methylation of CRHR1, CRHR2, and NR3C1 and ACTH levels in patients with PD, and methylation levels of CRHR1 and NR3C1 were significantly positively related to cortisol levels. In addition, a negative correlation was observed between PD severity and the methylation of CRH, CRHR1, CRHR2, and HSP90AA1. CONCLUSION: Aberrant methylation of HPA axis-related genes may predict PD development and impact ACTH and cortisol levels.

Subjective health status: an easily available, independent, robust and significant predictive factor at the prometaphase of vaccination programs for the vaccination behavior of Chinese adults.

BACKGROUND: The World Health Organization (WHO) proposed COVID-19 vaccination as an emergent and important method to end the COVID-19 pandemic. Since China started vaccination programs in December 2020, vaccination has spread to provinces and municipalities nationwide. Previous research has focused on people's vaccination willingness and its influencing factors but has not examined vaccination behavior. We examine the effectiveness of psychosocial factors in predicting vaccination behavior. METHODS: A cross-sectional online survey was performed among Chinese adults on 8 May and 4 June 2021. The statistical analysis of the data included univariate analysis, receiver operator characteristics (ROC) analysis and ordinal multiclassification logistic regression model analysis. RESULTS: Of the 1300 respondents, 761 (58.5%) were vaccinated. Univariate analysis showed that a high education level and good subjective health status were protective factors for vaccination behavior, while suffering from chronic diseases was a risk factor. ROC analysis showed that subjective health status (AUC = 0.625, 95% CI: 0.594-0.656, P < 0.001) was the best predictor of vaccination behavior. Logistic regression analysis with subjective health status as a dependent variable indicated that older age, female sex, depression, neurasthenia, obsession, hypochondriasis and chronic disease were significant risk factors, while positive coping tendencies were a significant protective factor. CONCLUSION: Our study found a simple and effective marker, subjective health status, that can predict vaccination behavior. This finding can guide future epidemic prevention work.

Gray Matter Abnormalities in Patients with Chronic Primary Pain: A Coordinate-Based Meta-Analysis.

BACKGROUND: Many structural magnetic resonance imaging (MRI) studies have used voxel-based morphometry (VBM) to identify gray matter abnormalities in patients with chronic primary pain (CPP), but the findings have been inconsistent. OBJECTIVES: To identify (a) gray matter differences between CPP patients or female patients and healthy individuals and (b) the effects of symptom duration and pain scores on gray matter. STUDY DESIGN: We conducted a meta-analysis. METHODS: VBM studies in PubMed, Cochrane Library, and Google Scholar, from November 2005 to June 2020, were thoroughly collected and carefully reviewed. Manual searches were performed using title and citation information. Gray matter VBM study comparing adult patients (18-65 years) with CPP to healthy controls was reviewed, and results, presented in Talairach or Montreal Neurological Institute coordinates, were included. The t value, peak coordinates, and basic clinical information of each study were reported in detail. Anisotropic effect-size signed differential mapping was used for voxel-based meta-analyses. RESULTS: Patients with CPP had decreased gray matter in the left anterior cingulate (z value = 2.950, P < 0.001), right median cingulate (z value = 1.858, P = 0.001), and the insula bilaterally (left: z value = 2.441, P < 0.001; right: z value = 2.113, P < 0.001 ), and increased gray matter in the right striatum (z value = 1.194, P < 0.001). Subgroup meta-analysis showed female patients with CPP also had decreased gray matter in the left anterior cingulate gyrus (z value = 2.622, P < 0.001). Meta-regression analyses revealed that pain symptom duration was positively associated with a large right brain region (z value = 2.110, P < 0.001), a negative association between pain symptom duration and gray matter was found in the right anterior cingulate (z value = 1.969, P < 0.001) and right middle frontal gyrus (z value = 1.849, P < 0.001). LIMITATIONS: Due to the lack of data from male patients, we were unable to perform a male subgroup analysis; therefore, we cannot thoroughly explore the difference in CPP from the perspective of gender. CONCLUSION: We identified gray matter changes in CPP patients and female patients, as well as a close relationship between CPP and mental disorders. With the chronicity of pain leads to changes in relevant brain regions, which makes treatment more challenging and may have synergistic effects with affective disorders. More prospective longitudinal structural MRI studies of CPP examining the associations between those variables and gray matter in a larger population should be conducted. Additional prospective longitudinal structural MRI studies of CPP with larger sample sizes to confirm the relationships between these variables and gray matter are needed as well as gender differences of CPP in brain structure and function.