Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

Exosomes: potential targets for the diagnosis and treatment of neuropsychiatric disorders.

The field of neuropsychiatry is considered a middle ground between neurological and psychiatric disorders, thereby bridging the conventional boundaries between matter and mind, consciousness, and function. Neuropsychiatry aims to evaluate and treat cognitive, behavioral, and emotional disorders in individuals with neurological conditions. However, the pathophysiology of these disorders is not yet fully understood, and objective biological indicators for these conditions are currently lacking. Treatment options are also limited due to the blood-brain barrier, which results in poor treatment effects. Additionally, many drugs, particularly antipsychotic drugs, have adverse reactions, which make them difficult to tolerate for patients. As a result, patients often abandon treatment owing to these adverse reactions. Since the discovery of exosomes in 1983, they have been extensively studied in various diseases owing to their potential as nanocellulators for information exchange between cells. Because exosomes can freely travel between the center and periphery, brain-derived exosomes can reflect the state of the brain, which has considerable advantages in diagnosis and treatment. In addition, administration of engineered exosomes can improve therapeutic efficacy, allow lesion targeting, ensure drug stability, and prevent systemic adverse effects. Therefore, this article reviews the source and biological function of exosomes, relationship between exosomes and the blood-brain barrier, relationship between exosomes and the pathological mechanism of neuropsychiatric disorders, exosomes in the diagnosis and treatment of neuropsychiatric disorders, and application of engineered exosomes in neuropsychiatric disorders.

The association of childhood trauma with suicidality in adult psychiatric patients: The mediating role of NSSI and the moderating role of self-esteem.

BACKGROUND: The contribution of specific childhood trauma subtypes to suicidal thoughts and the associated mechanisms remains unclear, particularly in psychiatric patients. METHODS: Face-to-face interviews were conducted with 449 psychiatric patients aged 18-73. Childhood trauma, self-esteem, nonsuicidal self-injury (NSSI), and suicidality were assessed retrospectively. Regression and moderated mediation model were employed to examine these relationships. RESULTS: Emotional and sexual abuse were independently associated with suicidality. Female patients reported higher levels of emotional and sexual abuse, lower self-esteem, and a heightened risk of suicide. Self-esteem moderated the links between childhood trauma and NSSI, as well as between NSSI and suicidality. NSSI served as a mediator between childhood trauma and suicidality. CONCLUSIONS: Suicide prevention in mentally ill patients should involve targeted programs addressing specific childhood trauma. Additionally, psychological interventions to enhance self-esteem and assist individuals engaging in NSSI behavior are crucial.

Somatic symptoms and related disorders in a large cohort of people with epilepsy: A cohort study.

OBJECTIVE: This study was undertaken to characterize somatic symptoms and related disorders (SSD) in epilepsy. METHODS: Adults with epilepsy under active follow-up at a tertiary epilepsy center were consecutively enrolled. The diagnosis of SSD was performed by an experienced psychologist based on the structured clinical interview for Statistical Manual of Mental Disorders, 5th edition. Detailed social/demographic data, epilepsy features, psychiatric features, life quality, disability, and economic burden were collected and compared between people with SSD and those without. Bodily distress syndrome checklist, Somatic Symptom Disorder-B Criteria Scale, Patient Health Questionnaire-9, and Generalized Anxiety Disorder seven-item scale (GAD-7) were used to evaluate SSD individuals' somatic symptoms, symptom-related psychological distress, and depressive and anxious symptoms. Quality of life and disability were assessed by Quality of Life in Epilepsy Inventory 31 (QOLIE-31) and World Health Organization Disability Assessment Schedule V.2.0 (WHO DAS 2.0). A risk prediction nomogram was generated using least absolute shrinkage and selection operator (LASSO) analysis and validated. RESULTS: One hundred fifty of 631 participants (24%) were diagnosed with SSD. In people with SSD, the top three most common somatic symptoms were memory impairment, headache, and dizziness (85%, 80%, and 78%, respectively), and multiple systems were involved in most (82%) people with SSD. Compared with people without SSD, those with SSD had lower QOLIE-31 total scores, and higher WHO DAS 2.0 scores and disease economic burdens. LASSO analysis suggested that a history of severe traumatic brain injury, hippocampal sclerosis, low seizure worry and medication effects scores on QOLIE-31, multiple systems affected by somatic symptoms, and a high GAD-7 score were risk factors of SSD. The nomogram was validated for good accuracy in the training and testing cohorts. SIGNIFICANCE: SSD are likely to be a common comorbidity in epilepsy and harm epilepsy prognosis. Our risk prediction nomogram was successfully developed but needs further validation in larger cohorts.

Nanoparticles-based delivery system and its potentials in treating central nervous system disorders.

Central nervous system (CNS) disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become severe health concern worldwide. The treatment of the CNS diseases is of great challenges due largely to the presence of the blood-brain barrier (BBB). On the one hand, BBB protects brain from the harmful exogenous molecules via inhibiting their entry into the brain. On the other hand, it also hampers the transport of therapeutic drugs into the brain, resulting in the difficulties in treating the CNS diseases. In the past decades, nanoparticles-based drug delivery systems have shown great potentials in overcoming the BBB owing to their unique physicochemical properties, such as small size and specific morphology. In addition, functionalization of nanomaterials confers these nanocarriers controlled drug release features and targeting capacities. These properties make nanocarriers the potent delivery systems for treating the CNS disorders. Herein, we summarize the recent progress in nanoparticles-based systems for the CNS delivery, including the conventional and innovative systems. The prerequisites, drawbacks and challenges of nanocarriers (such as protein corona formation) in the CNS delivery are also discussed.

RPS6KA5 methylation predict response to 6-week treatment for adolescent MDD patients.

OBJECTIVE: We aimed to investigate the effect of differentially methylated genes and chronic childhood stress on the development of depressive symptoms in Chinese adolescents, as well as to test whether methylation at baseline can be used as a predictor of remission at follow-up after six weeks of treatment. METHODS: After recruiting 87 MDD patients and 53 healthy controls, we compared demographic and baseline clinical characteristics. The Childhood Chronic Stress Questionnaire was used to assess stress caused by early-life events. MDD patients underwent six weeks of treatment, and response to treatment was assessed using the Beck Depression Inventory-II. In addition, four MDD patients and five controls were randomly chosen for genome-wide methylation analysis. RESULTS: The gene RPS6KA5 showed significant methylation differences between the two groups. Severity of chronic childhood stress was significantly associated with increased risk of depression in adolescents, but not with treatment response. Baseline RPS6KA5 methylation can predict remission after six weeks of treatment. We did not observe any interaction between RPS6KA5 methylation and chronic childhood stress. CONCLUSIONS: Our results suggest that RPS6KA5 methylation can be used as a predictor of response to treatment in adolescent MDD patients. Here we offer new evidence for the role of epigenetics in early response to treatment of depression. TRIAL REGISTRATION: ChiCTR, ChiCTR2000033402, 31/05/2020, http://www.chictr.org.cn/index.aspx.

Plasma levels of interleukin-8 and response to paroxetine in patients with major depressive disorder.

OBJECTIVES: Immune dysregulation plays a key role in major depressive disorder (MDD). However, little is known about the complicated involvement of various interleukins in MDD. This study was performed to investigate the correlation between plasma interleukin-8 (IL-8) levels and treatment outcome of paroxetine (a selective serotonin reuptake inhibitor) in patients with MDD. METHODS: A total of 115 hospitalized patients (36 males and 79 females), aged from 18 to 72 years, were enrolled. Plasma levels of IL-8 were measured before treatment initiation (baseline) and at 8 weeks after oral paroxetine treatment. Efficacy of paroxetine was evaluated by use of the Hamilton Depression Rating Scale (HAMD-17). Baseline IL-8 levels were compared between responders and non-responders to paroxetine treatment. RESULTS: Plasma IL-8 levels decreased significantly after an 8-week antidepressant treatment in responders, in association with a dramatic decrease in HAMD-17 scores. In non-responders, plasma IL-8 levels did not change significantly at 8 weeks after antidepressant treatment. Baseline plasma IL-8 levels were found to be significantly lower in responders than in non-responders, showing a correlation between IL-8 and antidepressant response to paroxetine. CONCLUSIONS: These results indicate that plasma IL-8 levels were related to treatment outcome of paroxetine, and therefore suggest that IL-8 could be a promising predicator of treatment response in individual patients with MDD.

Impact of non-pharmacological interventions on quality of life, anxiety, and depression scores in patients with colorectal cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Different non-pharmacological interventions have been considered and applied to patients with colorectal cancer to improve their quality of life and distress symptoms; however, there is little evidence comparing the effectiveness of these strategies. This review aimed at assessing the effect of non-pharmacological interventions on quality of life, anxiety, and depression scores among patients with colorectal cancer. METHODS: A systematic search for articles published until August 1, 2020, in the English language was performed in Medline, EMBASE, Web of Science, and the Cochrane Library; the reference lists of eligible articles were scanned for other potentially eligible publications. A meta-analysis was performed using random-effects models to estimate pooled effect sizes. RESULTS: Twenty studies were included, representing a total of 3438 patients with colorectal cancer. Non-pharmacological interventions were associated with a significant reduction in anxiety (standardized mean difference [SMD] = - 0.157; 95% confidence interval [CI], - 0.312-[- 0.002]) and depression (SMD = - 0.207; 95% CI, - 0.390-[- 0.024]) scores during 5-8 months of follow-up. Subgroup analyses revealed that interventions delivered face-to-face improved patients' quality of life during 1-4 months of follow-up. Moreover, interventions delivered face-to-face but without a behavioral component were associated with improved anxiety scores, whereas interventions with a behavioral component improved the depression scores during 5-8 months of follow-up. CONCLUSIONS: Non-pharmacological interventions were associated with reduced anxiety and depression scores, whereas interventions delivered face-to-face were associated with improved quality of life scores in patients with colorectal cancer. Given the few studies and patients included in this meta-analysis, these conclusions should be interpreted with caution.

[Association of CHRNA4 gene polymorphisms with response to antidepressant among ethnic Han Chinese].

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) CHRNA4 gene with response to selective serotonin re-uptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD). METHODS: For 304 patients receiving drug treatment for major depression, 2 SNPs, namely rs4522666 and rs4603829, of the CHRNA4 gene were determined by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th and 6th weeks treatment. RESULTS: The frequency of GG genotype/G allele for rs4522666 differed significantly from that of TT and GT genotypes/T allele between responders and non-responders (P=0.015 and P=0.006, respectively). No significant difference was found in genotypic and allelic frequencies of rs4603829 between the two groups (P> 0.05). CONCLUSION: SNPs of the CHRNA4 gene may play an important role in the response to antidepressant drugs among ethnic Han Chinese with MDD.

High rates of depression anxiety and suicidal ideation among inpatients in general hospital in China.

Objective: To investigate the prevalence rates of depression anxiety and suicidal ideation among Chinese general hospital inpatients and to identify the potential associations with sociodemographics. Method: A cross-sectional survey was applied in a Chinese general hospital. A questionnaire set, including sociodemographic variables, Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder Scale-7 (GAD-7), was completed by the participants. Clinically significant depression (CSD) and clinically significant anxiety (CSA) were defined as a score above 10 on the two scales. CSD and CSA are proxy measures but not specific diagnoses of mental disorders. Results: Data from 1329 patients were included in the final analysis. 422 (31.8%) reported clinically significant depressive symptoms, 83 (6.3%) reported frequent suicidal ideation, and 204 (15.3%) reported clinically significant anxiety. Household income was negatively associated with CSD. Inpatients with lower household incomes and educational levels had higher rates of CSA. Middle-aged inpatients were more prone to suicidal ideation, and stable marital status was related to less suicidal ideation. Conclusion: Depression, anxiety, and suicidal ideation were determined to be common psychological problems in Chinese inpatients. Chinese medical personnel must pay attention to the mental health conditions of inpatients, particularly inpatients with lower income, educational levels, and poor marital status. Key Points This is one of the first studies focusing on the prevalence of depression and anxiety in Chinese hospitalized inpatients in non-psychiatric departments of a general hospital. The PHQ-9 and GAD-7 were determined to be potential screening tools to aid Chinese medical workers in recognizing depression and anxiety in nonpsychiatric departments. The prevalence of depression, anxiety and suicidal ideation was observed to be relatively high in inpatients, which requires more attention from Chinese clinicians.

[Association of TPH2 gene polymorphism with response to antidepressant treatment among ethnic Han Chinese population].

OBJECTIVE: To assess the association of TPH2 gene polymorphisms with the response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs during treatment of major depressive disorder. METHODS: For 304 patients receiving SSRIs treatment for major depression disorder, 3 single nucleotide polymorphisms (SNPs) (rs1007023, rs1023990 and rs4570625) in the TPH2 gene were genotyped by MALDI-TOF mass spectrometry using a MassArray Analyzer 4 system. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th and 6th week of treatment. RESULTS: The frequency of GG genotype/G allele for rs4570625 differed significantly with the frequency of TT and GT genotypes/T allele between responders and non-responders (P=0.013 and 0.007, respectively). Genotypic and allelic frequencies of the other polymorphisms did not differ significantly between the two groups (P>0.05). No association of TPH2 gene polymorphism with remission was found with the 3 SNPs. CONCLUSION: The polymorphisms of TPH2 gene may play an important role in response to antidepressant drug therapy.

The development and validation of Huaxi emotional-distress index (HEI): A Chinese questionnaire for screening depression and anxiety in non-psychiatric clinical settings.

BACKGROUND: Depression and anxiety among general hospital patients are common and under-recognized in China. This study aimed toward developing a short questionnaire for screening depression and anxiety in non-psychiatric clinical settings, and to test its reliability and validity. METHODS: The item pool which included 35 questions about emotional distress was drafted through a comprehensive literature review. An expert panel review and the first clinical test with 288 general hospital patients were conducted for the primary item selection. The second clinical test was performed to select the final item in 637 non-psychiatric patients. The reliability and validity of the final questionnaire were tested in 763 non-psychiatric patients, in which 211 subjects were interviewed by psychiatrists using Mini International Neuropsychiatric Interview (MINI). Multiple data analysis methods including principal components analysis (PCA), item response theory (IRT), and receiver operating characteristic (ROC) curve were used to select items and validate the final questionnaire. RESULTS: The series selection of items resulted in a 9-item questionnaire, namely Huaxi Emotional-distress Index (HEI). The Cronbach's α coefficient of HEI was 0.90. The PCA results showed a unidimensional construct. The area under the ROC curve (AUC) was 0.88 when compared with MINI interview. Using the optimal cut-off score of HEI (≥11), the sensitivity and specificity were 0.880 and 0.766, respectively. CONCLUSIONS: The HEI is considered as a reliable and valid instrument for screening depression and anxiety, which may have substantial clinical value to detect patients' emotional disturbances especially in the busy non-psychiatric clinical settings in China.

[Role of HPA and HPT Axis in Anxiety Disorder Complicated with Diabetes Mellitus].

OBJECTIVE: To determine the mediating role of hypothalamic-pituitary-adrenal axis (HPA) and hypothalamic-pituitary-thyroid axis (HPT) axis in anxiety disorder in patients with diabetes mellitus. METHODS: A total of 562 hospitalized patients with anxiety disorder participate in the study. Serum thyroid-stimulating hormone (TSH),total triiodothyronine (TT3),free triiodothyronine (FT3),total tetraiodothyronine (TT4),free tetraiodothyronine (FT4) ,adrenocorticotropic hormone (ACTH) and cortisol (PTC) were measured. Glucose tolerance test (OGTT) was performed,estimating insulin resistance index (HOMA IR) and insulin sensitivity index (WBISI). RESULTS: Of the participants,83 (14.8%) had diabetes. In those who were younger than 40 yr.,the diabetic patients were more likely to have abnormal FT4 and HPT ( P<0.05). The patients with diabetes were more likely to be older (OR=1.067, 95%CI:1.041-1.094, P=0.000) and have higher FT4 (OR=1.104, 95%CI:1.022-1.193, P=0.012) and PTC (OR=1.001, 95%CI:1.000-1.003, P=0.025) . Insulin resistance index increased while insulin sensitivity index decreased ( P<0.05) with abnormal PTC and HPA axis. Insulin sensitivity index decreased ( P<0.05) when ACTH,HPT axis,FT4 and TT3 were abnormal. CONCLUSION: Abnormal HPA or HPT axis mediates diabetic complications in patients with anxiety disorder. Early interventions on neuroendocrine hormone abnormality may help prevent diabetes in patients with anxiety disorder.

Validation of the Chinese version of the PHQ-15 in a tertiary hospital.

BACKGROUND: This study aimed to investigate the reliability and validity of the Chinese version of the Patient Health Questionnaire (PHQ-15) in a tertiary hospital. METHODS: Using a cross-sectional study design, the Chinese version of the PHQ-15 was administered to a total of 1329 inpatients. To examine the discriminant validity of this questionnaire, we investigated the correlation of the PHQ-15 score with sociodemographic data and the PHQ-9 and GAD-7 scale scores. Exploratory factor analysis was performed to assess the internal consistency of the PHQ-15. To evaluate the consistency of this questionnaire with item response theory (IRT), IRT analysis was performed. RESULTS: The Chinese version of the PHQ-15 showed good reliability (Cronbach's alpha = 0.83). The correlations of the PHQ-15 scores with the PHQ-9 depression scale scores (r = 0.565) and the GAD-7 anxiety scale scores (r = 0.512) were moderate; these results suggested that the PHQ-15 had discriminant validity. We identified three factors, referred to as "cardiopulmonary," "gastrointestinal," and "pain/neurological," which explained 56 % of the total variance. A second-order factor analysis including these three factors produced an acceptable model. Several items (4, 8 and 11) displayed extreme floor effects. Additionally, item 4 displayed a very small variance of 0.35 and showed very small differences in its thresholds based on IRT analysis. CONCLUSIONS: The PHQ-15 scale had good reliability and high validity to detect patients with high somatic symptom severity in a Chinese tertiary hospital. Several of the current findings were consistent with previous research on the PHQ-15 in Western countries and in China. To improve the diagnostic quality of this questionnaire, items 4, 8 and 11 can be omitted.

SLC17A7 gene may be the indicator of selective serotonin reuptake inhibitor treatment response in the Chinese Han population.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for major depressive disorder (MDD), although the treatment outcomes vary in different people. The vesicular glutamate transporter 1 coded by SLC17A7 gene has been reported associated with MDD. According to its role in glutamate transmission, it is reasonable to consider it as a potential pharmacogenetic candidate in SSRI treatment. A total of 290 MDD patients who had been taking SSRIs for 6 weeks were recruited. Their genotypes were assessed for the presence of 4 single-nucleotide polymorphisms, which were selected from either the HapMap Chinese ethnic group or the literature report. Treatment effects were evaluated by the change rate of Hamilton Rating Scale for Depression. After the adjustment for the false discovery rate, 1 single-nucleotide polymorphism (rs74174284, false discovery rate; P = 0.032) demonstrated significant association with SSRI treatment response at week 6. Our results suggest that genetic variants in the SLC17A7 gene may be indicators of treatment response in MDD patients treated by SSRIs.

Relationship between human oral microbiome dysbiosis and neuropsychiatric diseases: An updated overview.

The role of the gut-brain axis in mental health disorders has been extensively studied. As the oral cavity is the starting point of the digestive tract, the role that the oral microbiota plays in mental health disorders has gained recent attention. Oral microbiota can enter the bloodstream and trigger inflammatory responses or translocate to the brain through the trigeminal nerve or olfactory system. Hence, the concept of the oral microbiota-brain axis has emerged. Several hypotheses have been suggested that the oral microbiota can enter the gastrointestinal tract and affect the gut-brain axis; however, literature describing oral-brain communication remains limited. This review summarizes the characteristics of oral microbiota and its mechanisms associated with mental health disorders. Through a comprehensive examination of the relationship between oral microbiota and various neuropsychiatric diseases, such as anxiety, depression, schizophrenia, autism spectrum disorder, epilepsy, Parkinson's disease, and dementia, this review seeks to identify promising avenues of future research.

The digestion and dietary carbohydrate pathway contains 100% gene mutations enrichment among 117 patients with major depressive disorder.

Introduction: Major depressive disorder (MDD) is partially inheritable while its mechanism is still uncertain. Methods: This cross-sectional study focused on gene pathways as a whole rather than polymorphisms of single genes. Deep sequencing and gene enrichment analysis based on pathways in Reactome database were obtained to reveal gene mutations. Results: A total of 117 patients with MDD and 78 healthy controls were enrolled. The Digestion and Dietary Carbohydrate pathway (Carbohydrate pathway) was determined to contain 100% mutations in patients with MDD and 0 mutation in matched healthy controls. Discussion: Findings revealed in the current study enable a better understanding of gene pathways mutations status in MDD patients, indicating a possible genetic mechanism of MDD development and a potential diagnostic or therapeutic target.

Abnormal functional connectivity within the prefrontal cortex is associated with multiple plasma lipid species in major depressive disorder.

BACKGROUND: Abnormalities in functional connectivity (FC) in major depressive disorder (MDD) have been widely reported. Analysis of the relationship between FC and plasma lipid profiles would be meaningful in the exploration of pathophysiological mechanisms and helpful for the identification of biomarkers for MDD. METHODS: Patients with MDD (n = 49) and healthy controls (HC, n = 87) were recruited. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected for FC construction. The plasma lipid profiles were acquired using ultra-performance liquid chromatography (UPLC) and mass spectrometry (MS) analysis and clustered as co-expression modules. The differential FC and lipid modules between HCs and patients with MDD were identified, and then the association between FC and lipid co-expression modules was analyzed using correlation analysis. The modules associated molecular function was explored using metabolite set enrichment analysis (MSEA). RESULTS: MDD-associated FC and lipid co-expression modules were identified. One module was associated with FC values between the right orbital part of the middle frontal gyrus and the opercular part of the left inferior frontal gyrus, which was enriched in lipid sets of diacylglycerols and fatty alcohols; another module was associated with FC values between the right middle frontal gyrus and the right anterior cingulate and paracingulate gyri, which was enriched in lipid sets of glycerophosphocholines and glycerophosphoethanolamines. CONCLUSION: Our results indicated that abnormal FC in the prefrontal cortex is associated with multiple plasma lipid species, which may provide novel clues for exploring the pathophysiology of MDD.