Restoring thalamocortical circuit dysfunction by correcting HCN channelopathy in Shank3 mutant mice.

Thalamocortical (TC) circuits are essential for sensory information processing. Clinical and preclinical studies of autism spectrum disorders (ASDs) have highlighted abnormal thalamic development and TC circuit dysfunction. However, mechanistic understanding of how TC dysfunction contributes to behavioral abnormalities in ASDs is limited. Here, our study on a Shank3 mouse model of ASD reveals TC neuron hyperexcitability with excessive burst firing and a temporal mismatch relationship with slow cortical rhythms during sleep. These TC electrophysiological alterations and the consequent sensory hypersensitivity and sleep fragmentation in Shank3 mutant mice are causally linked to HCN2 channelopathy. Restoring HCN2 function early in postnatal development via a viral approach or lamotrigine (LTG) ameliorates sensory and sleep problems. A retrospective case series also supports beneficial effects of LTG treatment on sensory behavior in ASD patients. Our study identifies a clinically relevant circuit mechanism and proposes a targeted molecular intervention for ASD-related behavioral impairments.

Development and validation of a risk score model for predicting autism based on pre- and perinatal factors.

Background: The use of pre- and perinatal risk factors as predictive factors may lower the age limit for reliable autism prediction. The objective of this study was to develop a clinical model based on these risk factors to predict autism. Methods: A stepwise logistic regression analysis was conducted to explore the relationships between 28 candidate risk factors and autism risk among 615 Han Chinese children with autism and 615 unrelated typically developing children. The significant factors were subsequently used to create a clinical risk score model. A chi-square automatic interaction detector (CHAID) decision tree was used to validate the selected predictors included in the model. The predictive performance of the model was evaluated by an independent cohort. Results: Five factors (pregnancy influenza-like illness, pregnancy stressors, maternal allergic/autoimmune disease, cesarean section, and hypoxia) were found to be significantly associated with autism risk. A receiver operating characteristic (ROC) curve indicated that the risk score model had good discrimination ability for autism, with an area under the curve (AUC) of 0.711 (95% CI=0.679-0.744); in the external validation cohort, the model showed slightly worse but overall similar predictive performance. Further subgroup analysis indicated that a higher risk score was associated with more behavioral problems. The risk score also exhibited robustness in a subgroup analysis of patients with mild autism. Conclusion: This risk score model could lower the age limit for autism prediction with good discrimination performance, and it has unique advantages in clinical application.

Incidence and correlates of suicide attempts in adolescents with major depressive versus bipolar disorders: A cross-sectional study.

BACKGROUND: Major depressive disorders (MDD) and bipolar disorders (BD) are the most common psychiatric diagnoses of suicide attempts (SA) in adolescents. However, little is known regarding the differences in incidence and clinical-related features of SA between these two disorders. The study aims to examine the SA incidence and related factors in adolescents with MDD versus BD. METHOD: A retrospective survey was conducted in outpatients. SA incidence, demographic characteristics and substance use history were collected. Symptom Checklist-90 was used to measure the severity of symptoms. The Revised Chinese internet addiction scale and Barratt Impulsiveness Scale-11 were utilized to assess the presence of internet addiction and impulsiveness. The Childhood Trauma Questionnaire was used to measure childhood maltreatment subtypes. RESULTS: 295 MDD and 205 BD adolescents were recruited. The incidence of SA for MDD and BD were 52.5 % and 56.4 %, respectively. BD adolescents who attempted suicide showed worse symptoms, higher rates of nicotine and alcohol use, higher motor and non-planning impulsivity, and a more childhood physical abuse proportion than MDD adolescents with SA. Physical abuse in childhood was found to be associated with SA in both disorders (OR = 1.998 for MDD; OR = 2.275 for BD), while higher anxiety (OR = 1.705), and alcohol use (OR = 2.094) were only associated with SA in MDD. LIMITATIONS: Retrospective, cross-sectional design cannot draw causality, and biases in self-report measurements cannot be ignored. CONCLUSIONS: The findings revealed some difference between BD and MDD for adolescents with SA, and it emphasize significance of prompt identification and exact distinction between BD and MDD in adolescents.

Identifying clinical risk factors correlated with addictive features of non-suicidal self-injury among a consecutive psychiatric outpatient sample of adolescents and young adults.

Non-suicidal self-injury (NSSI) is an issue primarily of concern in adolescents and young adults. Recent literature suggests that persistent, repetitive, and uncontrollable NSSI can be conceptualized as a behavioral addiction. The study aimed to examine the prevalence of NSSI with addictive features and the association of this prevalence with demographic and clinical variables using a cross-sectional and case-control design. A total of 548 outpatients (12 to 22 years old) meeting the criteria for NSSI disorder of DSM-5 were enrolled and completed clinical interviews by 4 psychiatrists. NSSI with addictive features were determined by using a single-factor structure of addictive features items in the Ottawa self-injury inventory (OSI). Current suicidality, psychiatric diagnosis, the OSI, the revised Chinese Internet Addiction Scale, the Childhood Trauma Questionnaire, and the 20-item Toronto Alexithymia Scale were collected. Binary logistic regression analyses were used to explore associations between risk factors and NSSI with addictive features. This study was conducted from April 2021 to May 2022. The mean age of participants was 15.93 (SD = 2.56) years with 418 females (76.3%), and the prevalence of addictive NSSI was 57.5% (n = 315). Subjects with addictive NSSI had a higher lifetime prevalence of nicotine and alcohol use, a higher prevalence of current internet addiction, suicidality, and alexithymia, and were more likely to have physical abuse/neglect, emotional abuse, and sexual abuse than NSSI subjects without addictive features. Among participants with NSSI, the strongest predictors of addictive features of NSSI were female (OR = 2.405, 95% CI 1.512-3.824, p < 0.0001), alcohol use (OR = 2.179, 95% CI 1.378-3.446, p = 0.001), current suicidality (OR = 3.790, 95% CI 2.351-6.109, p < 0.0001), and psysical abuse in childhood (OR = 2.470, 95% CI 1.653-3.690, p < 0.0001). Nearly 3 out of 5 patients (12-22 years old) with NSSI met the criteria of NSSI with addictive features in this psychiatric outpatients sample. Our study demonstrated the importance of the necessity to regularly assess suicide risk, and alcohol use, as well as focus more on females and subjects who had physical abuse in childhood to prevent addictive NSSI.

Non-suicidal self-injury in Chinese population: a scoping review of prevalence, method, risk factors and preventive interventions.

Non-suicidal self-injury behavior (NSSI) is a serious public health concern that requires immediate attention. Despite the high prevalence of NSSI among the Chinese population, there is a significant gap in research on the comprehensive picture of this field. Therefore, a scoping review was conducted to investigate the prevalence, methods, risk factors, and preventive intervention programs related to NSSI in China. The review found that the estimated lifetime prevalence of NSSI among Chinese youth population is alarmingly high at 24.7% (N = 1,088,433). Common methods of NSSI include scratching, hitting, and biting. Additionally, the review synthesized 249 risk factors based on the biopsychosocial-ecological framework, highlighting the urgent need for intervention. However, only 12 empirical studies focus on NSSI prevention or intervention programs were included. These findings underscore the necessity for more clinical practices and larger studies to identify effective interventions and ultimately alleviate the burden of NSSI on the Chinese population. Funding: This review was supported by Humanity and Social Science Youth foundation of Ministry of Education (22YJCZH018), Science and Technology Innovation 2030 (STI2030-Major Projects:2021ZD0200702), National Natural Science Foundation of China (81825009), and Shuimu Tsinghua Scholar. No funding agencies were involved in the data collection, data analysis, and writing of this paper.

A multicomponent digital intervention to promote help-seeking for mental health problems and suicide in sexual and gender diverse young adults: A randomized controlled trial.

BACKGROUND: LGBTQ+ community's higher susceptibility to worse mental health outcomes and more help-seeking barriers compared to the cis-heterosexual population. Despite the LGBTQ+ population facing higher mental health risks, there has been a dearth of research focusing on developing tailored interventions targeting them. This study aimed to assess the effectiveness of a digital multicomponent intervention in promoting help-seeking for mental health issues in LGBTQ+ young adults. METHODS AND FINDINGS: We recruited LGBTQ+ young adults aged between 18 and 29 who scored moderate or above on at least 1 dimension of the Depression Anxiety Stress Scale 21 and did not have help-seeking experiences in the past 12 months. Participants (n = 144) were stratified by gender assigned at birth (male/female) and randomly allocated (1:1 ratio) to the intervention or active control parallel condition by generating a random number table, so they were blinded to the intervention condition. All participants received online psychoeducational videos, online facilitator-led group discussions, and electronic brochures in December 2021 and January 2022, with the final follow-up in April 2022. The contents of the video, discussion, and brochure are help-seeking for the intervention group and general mental health knowledge for the control group. The primary outcomes were help-seeking intentions for emotional problems and suicidal ideation and attitudes toward seeking help from mental health professionals at the 1-month follow-up. The analysis was performed by including all participants based on their randomized group regardless of adherence to the protocol. A linear mixed model (LMM) was used for analysis. All models were adjusted for baseline scores. Chinese Clinical Trial Registry: ChiCTR2100053248. A total of 137 (95.1%) participants completed a 3-month follow-up, and 4 participants from the intervention condition and 3 from the control condition did not complete the final survey. Compared with the control group (n = 72), a significant improvement was found in help-seeking intentions for suicidal ideation in the intervention group (n = 70) at post-discussion (mean difference = 0.22, 95% CI [0.09, 0.36], p = 0.005), 1-month (mean difference = 0.19, 95% CI [0.06, 0.33], p = 0.018), and 3-month follow-ups (mean difference = 0.25, 95% CI [0.11, 0.38], p = 0.001). There was also a significant improvement in the intervention condition on the help-seeking intention for emotional problems at 1-month (mean difference = 0.17, 95% CI [0.05, 0.28], p = 0.013) and 3-month follow-ups (mean difference = 0.16, 95% CI [0.04, 0.27], p = 0.022) compared with the control group. Participants' depression and anxiety literacy and help-seeking encouragement related knowledge in intervention conditions showed significant improvements. There were no significant improvements in actual help-seeking behaviors, self-stigma toward seeking professional assistance, depression, and anxiety symptoms. No adverse events or side effects were observed. However, the follow-up time point was limited to 3 months which might not be long enough for drastic mindset and behavioral changes in help-seeking to occur. CONCLUSIONS: The current intervention was an effective approach in promoting help-seeking intentions, mental health literacy, and help-seeking encouragement-related knowledge. Its brief yet integrated intervention format could also be utilized in treating other imminent concerns confronted by LGBTQ+ young adults. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100053248.

The clinical application of Chinese herbal medication to depression: A narrative review.

Depression severely impairs psychosocial functioning and quality of life, which places a huge burden on patients and their families. However, the physiological mechanism of depression remains unknown. Treatment with existing antidepressant medications is effective in around 50% of patients according to various studies, but is associated with severe side effects including nausea and headaches. Chinese herbal medicine (CHM) has been approved and widely used for depression as an alternative medicine in Chinese culture for decades. It has certain advantages and potential in the prevention and treatment of depression. In this review, we summarize the currently available evidence for the efficacy of CHM for the treatment of depression and physiological diseases comorbid with depression. We further discuss the possible mechanisms of action of CHM and the relationships to our current understanding of depression. The majority of current evidence has suggested that the combined treatment with CHM and mainstream antidepressants improves the response rate and reduces the side effects, while CHM alone could be more effective than placebo. However, the results should be carefully interpreted due to the shortcomings of existing clinical trials and a high risk of bias in meta-analyses. Our review provides a summary of the current applications and understanding of widely used CHMs for depression.

Relapse in patients with schizophrenia and amisulpride-induced hyperprolactinemia or olanzapine-induced metabolic disturbance after switching to other antipsychotics.

Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.

Purine signaling pathway dysfunction in autism spectrum disorders: Evidence from multiple omics data.

Introduction: Previous studies have suggested that the dysregulation of purine metabolism may be associated with autism spectrum disorder (ASD). Here, we adopted metabolomics and transcriptomics to verify and explore the underlying molecular mechanism of purine metabolism dysfunction in ASD and identify potential biomarkers within the purine metabolism pathway. Methods: Ultra-high-performance liquid chromatography-mass spectrometry was used to obtain the plasma metabolic profiles of 12 patients with ASD and 12 typically developing (TD) children. RNA sequencing was used to screen differentially expressed genes related to the purine metabolic pathway and purine receptor-coding genes in 24 children with ASD and 21 healthy controls. Finally, serum uric acid levels were compared in 80 patients with ASD and 174 TD children to validate the omics results. Results: A total of 66 identified metabolites showed significant between-group differences. Network analysis showed that purine metabolism was the most strongly enriched. Uric acid was one of the most highlighted nodes within the network. The transcriptomic study revealed significant differential expression of three purine metabolism-related genes (adenosine deaminase, adenylosuccinate lyase, and bifunctional enzyme neoformans 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase) (p < 0.01) and five purinergic receptor genes (P2X7, P2Y2, P2Y6, P2Y8, and P2Y10) (p < 0.05). In the validation sample, there was a significant difference in serum uric acid levels between the two groups (p < 0.001), and the area under the curve for uric acid was 0.812 (sensitivity, 82.5%; specificity, 63.8%). Discussion: Patients with ASD had dysfunctional purine metabolic pathways, and blood uric acid may be a potential biomarker for ASD.

Investigating and comparing the psychometric properties of the Chinese Mandarin version of social responsiveness scale-2 and its shortened version in preschool-age children with autism spectrum disorder.

We aimed to investigate and compare the psychometric properties of the Chinese Mandarin Social Responsiveness Scale-2 (SRS-2) and its shortened version. The study assessed 670 children with autism spectrum disorder (ASD) aged 30-54 months and 138 typical developmental (TD) children of the same age in mainland China. Our item reliability test revealed that only 36 items of the 65 items in the Chinese Mandarin SRS-2 (Preschool) met the reliability criteria. Moreover, the shortened version of SRS-2 (Preschool) with four subscales and 30 items maintained strong correlations (r = 0.961) with the Chinese Mandarin SRS-2 (Preschool), and demonstrated improved psychometric performance on the 4-week test-retest reliability (intraclass correlations was 0.70), internal consistency (Cronbach's alpha 0.71-0.91), construct validity, and convergent validity with the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, and Child Behavior Checklist. Receiver operating characteristics (ROC) analyses showed excellent and comparable discriminant validity of the shortened version with an area under the curve of 0.992. Our data suggested a cutoff ≥ 22.5 for the shortened version, with good accuracy in screening autism symptoms (sensitivity=96.9 %, specificity=94.2 %). Our findings demonstrated that the shortened version of SRS-2 (Preschool) was a reliable and valid instrument for identifying preschoolers with ASD in mainland China.

Association between history of miscarriage and autism spectrum disorder.

This case-control study was designed to examine the association between different types of miscarriage history and autism spectrum disorder (ASD), and determine whether the number of miscarriage history affects the risk of ASD. All of 2274 children with ASD and 1086 healthy controls were recruited. Sociodemographic and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Multivariable logistic regression analyses were applied to investigate association between miscarriage history and ASD. Stratified analyses based on sex and types of miscarriages were similarly performed. History of miscarriage was potential risk factors for ASD ([aOR] = 2.919; 95% [CI] = 2.327-3.517). Stratified analyses revealed that induced ([aOR] = 2.763, 95% [CI] = 2.259-3.379) and spontaneous miscarriage history ([aOR] = 3.341, 95% [CI] = 1.939-4.820) were associated with high risk of ASD, respectively. A sex-biased ratio in the risk of ASD was observed between females ([aOR] = 3.049, 95% [CI] = 2.153-4.137) and males ([aOR] = 2.538, 95% [CI] = 1.978-3.251). Stratified analysis of induced miscarriage history revealed that only iatrogenic miscarriage history was associated with an increased risk ASD ([aOR] = 2.843, 95% [CI] = 1.534-4.268). Also, multiple spontaneous miscarriage histories ([aOR] = 1.836, 95% [CI] = 1.252-2.693) were associated with higher autism risk than one spontaneous miscarriages history ([aOR] = 3.016, 95% [CI] = 1.894-4.174). In conclusion, miscarriage history is related to an increased risk for ASD in offspring, which is affected by the types of miscarriage and sex of the fetus.

Therapeutic efficacy of sulforaphane in autism spectrum disorders and its association with gut microbiota: animal model and human longitudinal studies.

Introduction: Sulforaphane (SFN) has been found to alleviate complications linked with several diseases by regulating gut microbiota (GM), while the effect of GM on SFN for autism spectrum disorders (ASD) has not been studied. Therefore, this study aimed to investigate the relationship between the effects of SFN on childhood ASD and GM through animal model and human studies. Methods: We evaluated the therapeutic effects of SFN on maternal immune activation (MIA) induced ASD-like rat model and pediatric autism patients using three-chamber social test and OSU Autism Rating Scale-DSM-IV (OARS-4), respectively, with parallel GM analysis using 16SrRNA sequencing. Results: SFN significantly improved the sniffing times of ASD-like rats in the three-chamber test. For human participants, the average verbal or non-verbal communication (OSU-CO) scores of SFN group had changed significantly at the 12-wk endpoint. SFN was safe and no serious side effects after taking. GM changes were similar for both ASD-like rats and ASD patients, such as consistent changes in order Bacillales, family Staphylococcaceae and genus Staphylococcus. Although the gut microbiota composition was significantly altered in SFN-treated ASD-like rats, the alteration of GM was not evident in ASD patients after 12 weeks of SFN treatment. However, in the network analysis, we found 25 taxa correlated with rats' social behavior, 8 of which were associated with SFN treatment in ASD-like rats, For ASD patients, we found 35 GM abundance alterations correlated with improvements in ASD symptoms after SFN treatment. Moreover, family Pasteurellaceae and genus Haemophilus were found to be associated with SFN administration in the network analyses in both ASD-like rats and ASD patients. Discussion: These findings suggest that SFN could provide a novel avenue for preventing and treating ASD, and its therapeutic effects might be related to gut microbiota.

Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial.

Sulforaphane has been reported to possibly improve core symptoms associated with autism spectrum disorders from mostly small size studies. Here we present results of a larger randomized clinical trial (N = 108) in China. There were no significant changes in caregiver rated scales between sulforaphane and placebo groups. However, clinician rated scales showed a significant improvement in the sulforaphane group, and one third of participants showed at least a 30% decrease in score by 12 weeks treatment. The effects of sulforaphane were seen across the full range of intelligence and greater in participants over 10 years. Sulforaphane was safe and well-tolerated even for young children. The inconsistent results between caregiver and clinician rated scales suggest more clinical trials are needed to confirm our findings.

Relationship between RELN signaling pathway genes and language development of autism based on a cluster model. / RELNä¿¡å·é€šè·¯åŸºå› ä¸ŽåŸºäºŽèšç±»åˆ†æžæ¨¡åž‹çš„å­¤ç‹¬ç—‡è¯­è¨€å‘è‚²çš„å ³ç³».

OBJECTIVES: Autism is a neurodevelopment disorder with unclear etiology. High heterogeneity is one of the main issues in the etiological studies. This study explores the relationship between RELN signaling pathway related genes (RELN, VLDLR, LRP8, DAB1, CDK5, FYN) and language development of autism patients based on a cluster analysis model which is established to reduce the heterogeneity. METHODS: Autism children were recruited from 5 different medical/autism training institutes from Hunan, Shandong, and Henan provinces, and were divided into 2 parts according to the recruitment time: The first part was the training sample, which was recruited from October 2006 to May 2011, and the second part was the validation sample, which was recruited from July 2011 to May 2012. A two-step cluster analysis was performed to cluster 374 Chinese Han autism patients into different subgroups based on 2 parameters: Onset age of the first word and interval from the first word to the first phase. A Bayes discriminatory equation was established followed the cluster results. Then we used this equation to divide another 310 autism children into prior defined subgroups. After the genotyping data was screened, a single marker case-control association study was conducted. RESULTS: The cluster analysis clustered 374 samples into 3 subgroups. Onset ages of the first word in the Group A were (11.83±4.37) months and intervals from the first word to the first phase were (24.55±8.67) months; onset ages of the first word in the Group B were (12.17±3.46) months, intervals from the first word to the first phase were (7.07±3.79) months; onset ages of the first word of Group C were (30.94±7.60) months, intervals from the first word to the first phase were (4.73±4.80) months. The established equations based on the cluster analysis were YA=-14.442+0.525X1+0.810X2, YB=-4.964+0.477X1+0.264X2, YC=-19.843+1.175X1+0.241X2. Cross validated analysis showed that the false rate of the equation was 3.8%. A total of 341 single nucleotide polymorphism (SNP) in 6 genes passed the quality control. Before divided subgroups, none of these SNPs reached the significant P value (P>2.44×10-5, Bonferroni adjustment). However the result showed that rs1288502 of LRP8 in Group B was significantly different from the control group (P=6.45×10-6). CONCLUSIONS: Based on the cluster analysis of language development, we could establish a discriminatory equation to reduce heterogeneity of autism sample. The association test indicates that LRP8 genein RELN signaling pathway is related to a particular type of language development of autism patients.

Evaluating the Risk of Suicide and Violence in Severe Mental Illness: A Feasibility Study of Two Risk Assessment Tools (OxMIS and OxMIV) in General Psychiatric Settings.

Background: Two OxRisk risk assessment tools, the Oxford Mental Illness and Suicide (OxMIS) and the Oxford Mental Illness and Violence (OxMIV), were developed and validated using national linked registries in Sweden, to assess suicide and violence risk in individuals with severe mental illness (schizophrenia-spectrum disorders and bipolar disorders). In this study, we aim to examine the feasibility and acceptability of the tools in three different clinical services. Method: We employed a two-step mixed-methods approach, by combining quantitative analyses of risk scores of 147 individual patients, and thematic analyses of qualitative data. First, 38 clinicians were asked to use OxMIS and OxMIV when conducting their routine risk assessments in patients with severe mental illness. The risk scores for each patient (which provide a probability of the outcome over 12 months) were then compared to the unstructured clinical risk assessment made by the treating clinician. Second, we carried out semi-structured interviews with the clinicians on the acceptability and utility of the tools. Thematic analysis was conducted on the qualitative data to identify common themes, in terms of the utility, accuracy, and acceptability of the tools. The investigations were undertaken in three general adult psychiatric clinics located in the cities of Barcelona and Sevilla (Spain), and Changsha (China). Results: Median risk probabilities over 12 months for OxMIS were 1.0% in the Spanish patient sample and 1.9% in the Chinese sample. For OxMIV, they were 0.7% (Spanish) and 0.8% (Chinese). In the thematic analysis, clinicians described the tools as easy to use, and thought that the risk score improved risk management. Potential additions to predictors were suggested, including family history and the patient's support network. Concordance rates of risk estimates between the tools and clinicians was high for violence (94.4%; 68/72) and moderate for suicide (50.0%; 36/72). Conclusion: Both OxMIS and OxMIV are feasible and practical in different general adult psychiatric settings. Clinicians interviewed found that both tools provide a useful structured approach to estimate the risk of suicide and violence. Risk scores from OxMIS and OxMIV can also be used to assist clinical decision-making for future management.

Odor identification impairment in autism spectrum disorder might be associated with mitochondrial dysfunction.

Deficits in olfactory function in autism spectrum disorder (ASD) have already been reported. However, the results of previous studies are not consistent, and the pathophysiological mechanisms of olfactory dysfunction in ASD are not clear. Fifty-three male ASD children or teenagers aged 9-16 years were recruited for the study. The identification and discrimination portion of the Sniffin' Sticks test (SST) was used to assess the olfactory function of the enrolled subjects. The severity of ASD core symptoms and the intelligence quotient (IQ) of participants were assessed. In addition, to explore the potential mechanism underlying olfactory dysfunction, a series of plasma biochemical indicators of oxidative stress, mitochondrial function and inflammation were measured. The mean raw scores on the SST identification and discrimination test of the study subjects were significantly lower than those of typically developing subjects reported in normative data studies. After adjusting for IQ, the odor identification score was not significantly associated with any ASD symptoms. Odor identification was found to be significantly associated with the ratio of L-lactate (L)/pyruvate (P) but not with other measured indicators. The current study validates the impairment of odor identification and discrimination in Chinese ASD children. Odor identification dysfunction may be an independent clinical symptom of ASD. The plasma L/P ratio was found to be significantly associated with odor identification performance, which suggests that mitochondrial dysfunction may be a potential mechanism underlying odor identification impairment in ASD.

Internet-based interventions to promote help-seeking for mental health in LGBTQ+ young adults: Protocol for a randomized controlled trial.

Background: Compared to its cis-heterosexual counterpart, the sexual and gender minority (SGM) population is disproportionately susceptible to mental health problems, including depression, anxiety, and minority stress. They are also facing unique help-seeking barriers when in need of support. Past research has shown promising results in using interventions to promote help-seeking intentions and attitudes of the cis-heterosexual population. However, there were no known help-seeking interventions targeting the SGM population. This protocol illustrates a study design to test the efficacy of a newly-developed internet-based program aimed to promote help-seeking for mental health in LGBTQ+ young adults. Methods: This study is a randomized controlled trial that aims to promote and improve the SGM young adults' help-seeking by integrating animated psychoeducational videos, group discussion, and the SGM youth help-seeking brochure. Primary outcomes, including help-seeking intentions and attitudes, will be measured at baseline, post-intervention, one-month post-intervention, and three-month post-intervention. The secondary outcomes, including help-seeking stigma, help-seeking literacy, mental health literacy, and help-seeking behaviors, will be measured at the same time points. Discussion: This is an internet-based, multi-dimensional, and integrative intervention tailored to the needs of the SGM population. It addresses an important gap in the current landscape of mental health promotion for the SGM population. The findings from this trial will provide new knowledge on promoting help-seeking among the SGM population, paving the road for future research that focuses on addressing mental health issues faced by the SGM population. Trial registration: Chictr.org.cn: ChiCTR2100053248.

Associations Between Academic Stress and Depressive Symptoms Mediated by Anxiety Symptoms and Hopelessness Among Chinese College Students.

Purpose: Explore the potential mediating effects of anxiety symptoms and hopelessness on the relationship between academic stress and depressive symptoms among Chinese college students. Patients and Methods: A total of 1309 college students with informed consent were recruited from a local university in China. Academic stress, anxiety symptoms, hopelessness, and depressive symptoms were assessed by self-report scales. Haye's PROCESS macro for SPSS was used to test the hypothesized mediation effect of anxiety symptoms and hopelessness in the relationship between academic stress and depressive symptoms. Results: Anxiety symptoms, hopelessness, and depressive symptoms were common among college students and were all significantly positively associated with academic stress levels. Academic stress could indirectly affect depressive symptoms by anxiety symptoms, hopelessness, and both anxiety symptoms and hopelessness. The total effect of academic stress on depressive symptoms was 0.063. The total effect of three indirect pathway was 0.039 which account for 62% of the total effect. Conclusion: The study detailed the specific process of depressive symptoms caused by academic stress in college students. Anxiety symptoms and hopelessness could mediate the relationship between academic stress and depressive symptoms. Paying attention to the anxiety levels and hopelessness levels of college students with high academic pressure is suggested as a means of preventing depression and promoting mental health.

Characteristics Analysis, Clinical Outcome and Risk Factors for Fungal Peritonitis in Peritoneal Dialysis Patients: A 10-Year Case-Control Study.

Background: Fungal peritonitis (FP) is a rare but severe complication that can appear in patients receiving peritoneal dialysis (PD). This study aimed to investigate the incidence rate and clinical characteristics of FP, evaluate clinical outcomes between FP and bacterial peritonitis (BP) patients on PD, and especially estimate the risk factors for FP outbreak. Methods: All episodes of FP diagnosed in our hospital from January 1, 2011, to December 31, 2020, were reviewed in this single-center study. FP cases were analyzed and compared with patients diagnosed with BP in a 1:6 ratio matching for case-control study. Patient information, including clinical information, biochemical analysis, and outcomes, was recorded. Univariate and multivariate logistic regression model were used to analyze the risk factors for FP. Results: A total of 15 FP episodes were observed in 15 PD patients, with an FP rate of 0.0071 episodes per patient-year. Seventeen strains of fungi were isolated and identified. Candida was the most common pathogen (15 strains, 88.2%), followed by Aspergillus fumigatus (2 strains, 11.8%). Between the groups, FP group showed a higher rate of HD transfer and catheter removal, and a lower rate of PD resumption in the short-term outcome (all P < 0.01), while no significant difference in the mortality was noted during the whole study period. The multivariate logistic regression analysis showed that longer PD duration (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.012-1.073, P < 0.01), higher serum potassium (OR 3.373, 95% CI 1.068-10.649, P < 0.05), elevated estimated glomerular filtration rate (eGFR) (OR 1.845, 95% CI 1.151-2.955, P < 0.05), reduced serum albumin level (OR 0.820, 95% CI 0.695-0.968, P < 0.05) and peritoneal effluent polymorphonuclear (PMN) count (OR 0.940, 95%CI 0.900-0.981, P < 0.01) were significantly increased the risk for FP. Conclusion: These results suggested that FP leads to higher rate of catheter removal and HD transfer, and a lower rate of PD resumption than BP, and that additional attention should be paid to hypoalbuminemia, increased serum potassium, long PD duration, and low peritoneal effluent PMN in PD patients.

Associations Between Attention Deficit/Hyperactivity Disorder and Internet Gaming Disorder Symptoms Mediated by Depressive Symptoms and Hopelessness Among College Students.

PURPOSE: The mediating role of depressive symptoms and hopelessness on the relationship between attention deficit/hyperactivity disorder (ADHD) and internet gaming disorder (IGD) symptoms has not yet been elucidated. This study assessed this mediating effect in college students. PARTICIPANTS AND METHODS: Participants consisted of 1236 freshmen recruited at a local university. Symptoms of ADHD, IGD, depression and hopelessness were measured using self-report scales. The effect of ADHD on IGD mediated by depression and hopelessness was analyzed by Haye's PROCESS macro for SPSS (Model 6) using the bias-corrected percentile bootstrap method with 5000 bootstrapped samples. RESULTS: Symptoms of ADHD, depression and hopelessness were common in college students and were strongly associated with the appearance of IGD symptoms. ADHD symptoms of college students impacted their IGD symptoms directly and indirectly via depressive symptoms and hopelessness. The total effect of ADHD symptoms on IGD symptoms was 0.075 (standard error [SE]: 0.009, 95% confidence interval [CI] 0.057, 0.093), with a direct effect of 0.037 (SE: 0.010, 95% CI 0.018, 0.056, effect ratio: 49.3%), and total indirect effect was 0.038 (SE: 0.005, 95% CI 0.029, 0.050, effect ratio: 50.7%). CONCLUSION: Depressive symptoms and hopelessness can mediate the relationship between ADHD and IGD symptoms among college students. These findings point to the importance of evaluating ADHD, depressive and hopelessness symptoms for the prevention and treatment of adult IGD.