A comparative study on dietary diversity and gut microbial diversity in children with autism spectrum disorder, attention-deficit hyperactivity disorder, their neurotypical siblings, and non-related neurotypical volunteers: a cross-sectional study.

BACKGROUND: Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. METHODS: Children aged 6-12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non-related neurotypical volunteers were recruited cross-sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule-2 (ADOS-2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha-diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non-related neurotypical controls. RESULTS: Ninety-eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non-related neurotypical controls). The alpha-diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed-effect model (F(4, 93) = 4.539, p = .02), (F(4, 93) = 3.185, p = .017), respectively. In a post-hoc pairwise comparison, patients with ASD had lower alpha-diversity compared with non-related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p = .211). CONCLUSIONS: Our study indicates disorder-specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co-occurrence, and strictly control for background information such as diet, to elucidate the gut-microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.

Reliability of Telepsychiatry Assessments Using the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV for Children With Neurodevelopmental Disorders and Their Caregivers: Randomized Feasibility Study.

BACKGROUND: Given the global shortage of child psychiatrists and barriers to specialized care, remote assessment is a promising alternative for diagnosing and managing attention-deficit/hyperactivity disorder (ADHD). However, only a few studies have validated the accuracy and acceptability of these remote methods. OBJECTIVE: This study aimed to test the agreement between remote and face-to-face assessments. METHODS: Patients aged between 6 and 17 years with confirmed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnoses of ADHD or autism spectrum disorder (ASD) were recruited from multiple institutions. In a randomized order, participants underwent 2 evaluations, face-to-face and remotely, with distinct evaluators administering the ADHD Rating Scale-IV (ADHD-RS-IV). Intraclass correlation coefficient (ICC) was used to assess the reliability of face-to-face and remote assessments. RESULTS: The participants included 74 Japanese children aged between 6 and 16 years who were primarily diagnosed with ADHD (43/74, 58%) or ASD (31/74, 42%). A total of 22 (30%) children were diagnosed with both conditions. The ADHD-RS-IV ICCs between face-to-face and remote assessments showed "substantial" agreement in the total ADHD-RS-IV score (ICC=0.769, 95% CI 0.654-0.849; P<.001) according to the Landis and Koch criteria. The ICC in patients with ADHD showed "almost perfect" agreement (ICC=0.816, 95% CI 0.683-0.897; P<.001), whereas in patients with ASD, it showed "substantial" agreement (ICC=0.674, 95% CI 0.420-0.831; P<.001), indicating the high reliability of both methods across both conditions. CONCLUSIONS: Our study validated the feasibility and reliability of remote ADHD testing, which has potential benefits such as reduced hospital visits and time-saving effects. Our results highlight the potential of telemedicine in resource-limited areas, clinical trials, and treatment evaluations, necessitating further studies to explore its broader application. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000039860; http://tinyurl.com/yp34x6kh.

Intestinal metabolites predict treatment resistance of patients with depression and anxiety.

BACKGROUND: The impact of the gut microbiota on neuropsychiatric disorders has gained much attention in recent years; however, comprehensive data on the relationship between the gut microbiome and its metabolites and resistance to treatment for depression and anxiety is lacking. Here, we investigated intestinal metabolites in patients with depression and anxiety disorders, and their possible roles in treatment resistance. RESULTS: We analyzed fecal metabolites and microbiomes in 34 participants with depression and anxiety disorders. Fecal samples were obtained three times for each participant during the treatment. Propensity score matching led us to analyze data from nine treatment responders and nine non-responders, and the results were validated in the residual sample sets. Using elastic net regression analysis, we identified several metabolites, including N-ε-acetyllysine; baseline levels of the former were low in responders (AUC = 0.86; 95% confidence interval, 0.69-1). In addition, fecal levels of N-ε-acetyllysine were negatively associated with the abundance of Odoribacter. N-ε-acetyllysine levels increased as symptoms improved with treatment. CONCLUSION: Fecal N-ε-acetyllysine levels before treatment may be a predictive biomarker of treatment-refractory depression and anxiety. Odoribacter may play a role in the homeostasis of intestinal L-lysine levels. More attention should be paid to the importance of L-lysine metabolism in those with depression and anxiety.

The relationship between sleep, gut microbiota, and metabolome in patients with depression and anxiety: A secondary analysis of the observational study.

BACKGROUND: Growing attention is paid to the association between alterations in the gut microbiota and their metabolites in patients with psychiatric disorders. Our study aimed to determine how gut microbiota and metabolomes are related to the sleep quality among patients with depression and anxiety disorders by analyzing the datasets of our previous study. METHODS: Samples were collected from 40 patients (depression: 32 patients [80.0%]); anxiety disorders: 8 patients [20.0%]) in this study. Gut microbiomes were analyzed using 16S rRNA gene sequencing and gut metabolomes were analyzed by a mass spectrometry approach. Based on the Pittsburgh Sleep Quality Index (PSQI), patients were categorized into two groups: the insomnia group (PSQI score ≥ 9, n = 20) and the non-insomnia group (PSQI score < 9, n = 20). RESULTS: The insomnia group showed a lower alpha diversity in the Chao1 and Shannon indices than the non-insomnia group after the false discovery rate (FDR) correction. The relative abundance of genus Bacteroides showed a positive correlation with PSQI scores in the non-insomnia group. The concentrations of glucosamine and N-methylglutamate were significantly higher in the insomnia group than in the non-insomnia group. CONCLUSIONS: Our findings suggest that specific taxa could affect the sleep quality among patients with depression and anxiety disorders. Further studies are needed to elucidate the impact of sleep on specific gut microbiota and metabolomes in depression and anxiety disorders.

Telepsychiatry versus face-to-face treatment: systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The COVID-19 pandemic has transformed healthcare significantly and telepsychiatry is now the primary means of treatment in some countries. AIMS: To compare the efficacy of telepsychiatry and face-to-face treatment. METHOD: A comprehensive meta-analysis comparing telepsychiatry with face-to-face treatment for psychiatric disorders. The primary outcome was the mean change in the standard symptom scale scores used for each psychiatric disorder. Secondary outcomes included all meta-analysable outcomes, such as all-cause discontinuation and safety/tolerability. RESULTS: We identified 32 studies (n = 3592 participants) across 11 mental illnesses. Disease-specific analyses showed that telepsychiatry was superior to face-to-face treatment regarding symptom improvement for depressive disorders (k = 6 studies, n = 561; standardised mean difference s.m.d. = -0.325, 95% CI -0.640 to -0.011, P = 0.043), whereas face-to-face treatment was superior to telepsychiatry for eating disorder (k = 1, n = 128; s.m.d. = 0.368, 95% CI 0.018-0.717, P = 0.039). No significant difference was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 26, n = 2290; P = 0.248). Telepsychiatry had significantly fewer all-cause discontinuations than face-to-face treatment for mild cognitive impairment (k = 1, n = 61; risk ratio RR = 0.552, 95% CI 0.312-0.975, P = 0.040), whereas the opposite was seen for substance misuse (k = 1, n = 85; RR = 37.41, 95% CI 2.356-594.1, P = 0.010). No significant difference regarding all-cause discontinuation was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 27, n = 3341; P = 0.564). CONCLUSIONS: Telepsychiatry achieved a symptom improvement effect for various psychiatric disorders similar to that of face-to-face treatment. However, some superiorities/inferiorities were seen across a few specific psychiatric disorders, suggesting that its efficacy may vary according to disease type.

Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses.

The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.

Efficacy and safety/tolerability of antipsychotics in the treatment of adult patients with major depressive disorder: a systematic review and meta-analysis.

BACKGROUND: Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy. METHODS: A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events. RESULTS: Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, n = 4375), amisulpride [1.99 (1.55-2.55)], sulpiride [1.50 (1.03-2.17)], and quetiapine [1.48 (1.23-1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, n = 8349), ziprasidone [1.80 (1.07-3.04)], risperidone [1.59 (1.19-2.14)], aripiprazole [1.54 (1.35-1.76)], brexpiprazole [1.41 (1.21-1.66)], cariprazine [1.27 (1.07-1.52)], and quetiapine [1.23 (1.08-1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior. CONCLUSION: Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.

The Potential Impact of Age on Gut Microbiota in Patients with Major Depressive Disorder: A Secondary Analysis of the Prospective Observational Study.

We aimed to investigate the impact of aging on the relationship among the composition of gut microbiota, gastrointestinal (GI) symptoms, and the course of treatment for major depressive disorder (MDD) by analyzing the datasets from our previous study. Patients with MDD were recruited, and their stools were collected at three time points (baseline, midterm, and endpoint) following the usual antidepressant treatment. Gut microbiota were analyzed using 16S rRNA gene sequencing. Patients were categorized into two groups based on their age: the late-life group over 60 years and the middle-aged group under 60 years. GI symptoms were assessed with scores of item 11 of the Hamilton Anxiety Rating Scale. One hundred and ninety samples were collected from 32 patients with MDD. Several gut microbes had higher relative abundances in the late-life group than in the middle-aged group. In addition, the late-life group showed significantly higher diversity in the Chao1 index at baseline compared with the middle-aged group. We further found possible microbial taxa related to GI symptoms in patients with late-life depression. The abundance of several bacterial taxa may contribute to GI symptoms in the late-life depression, and our findings suggest that the therapeutic targets for the application of gut microbiota may differ depending on the age group of patients with depression.

Association of work environment with stress and depression among Japanese workers.

BACKGROUND: There is a lack of studies that investigated the effect of a wide range of work environmental factors on stress and depression in Japan. OBJECTIVES: To examine the association of work environment factors with stress and depression among workers in Japan. METHODS: We conducted questionnaire surveys of workers that mainly engage in desk work in Japan. Stress was assessed through the Perceived Stress Scale (PSS), depression through the Patient Health Questionnaire-9 (PHQ-9), and work environment through physical and psychological workplace environment questionnaires. Workers were divided into low and high stress groups based on PSS score (median split), and divided into non-depressed and depressed groups based on their PHQ-9 score (< 5, and ≥5); these groups were then compared with their working environment. In addition, a multiple regression analysis was performed. RESULTS: Responses were obtained from 210 subjects. Multiple regression analysis showed that "Ability to work at one's own pace" and "Ability to apply personal viewpoint to work," etc., had effect on stress, while "Workplace harassment" and "Support from colleagues," etc., had effect on depression. CONCLUSIONS: The results suggest that stress and depression in Japanese workers are related to factors such as job demands, control of work, workplace harassment, and psychological safety.

Subjective well-being and month-long LF/HF ratio among deskworkers.

The importance of workers' well-being has been recognized in recent years. The assessment of well-being has been subjective, and few studies have sought potential biomarkers of well-being to date. This study examined the relationship between well-being and the LF/HF ratio, an index of heart rate variability that reflects sympathetic and parasympathetic nerve activity. Pulse waves were measured using photoplethysmography through a web camera attached to the computer used by each participant. The participants were asked to measure their pulse waves while working for 4 weeks, and well-being was assessed using self-reported measures such as the Satisfaction With Life Scale (SWLS), the Positive and Negative Affect Schedule (PANAS), and the Flourishing Scale (FS). Each of the well-being scores were split into two groups according to the median value, and the LF/HF ratio during work, as well as the number of times an LF/HF ratio threshold was either exceeded or subceeded, were compared between the high and low SWLS, positive emotion, negative emotion, and FS groups. Furthermore, to examine the effects of the LF/HF ratio and demographic characteristics on well-being, a multiple regression analysis was conducted. Data were obtained from 169 participants. The results showed that the low FS group had a higher mean LF/HF ratio during work than the high FS group. No significant differences were seen between the high and low SWLS groups, the high and low positive emotion groups, or the high and low negative emotion groups. The multiple regression analysis showed that the mean LF/HF ratio during work affected the FS and SWLS scores, and the number of times the mean LF/HF ratio exceeded +3 SD had an effect on the positive emotion. No effect of the LF/HF ratio on negative emotions was shown. The LF/HF ratio might be applicable as an objective measure of well-being.

[The Link Between Gut Microbiota and Cerebral Functions: An Update on the Pathogenesis and Treatment of Functional Gastrointestinal Disorders].

Recent studies have focused on the mechanism of brain effects on functional gastrointestinal disorders, through dysbiosis of the gut microbiota. Herein, we summarize the known pathogeneses of various functional gastrointestinal disorders relative to the gut microbiota, and discuss future gut microbiota-focused interventions for restoring dysbiosis, including probiotics and fecal microbiota transplantation.

Gastrointestinal symptoms and sensory abnormalities associated with behavioral problems in children with neurodevelopmental disorders.

Behavioral problems directly affect the quality of life of caregivers and children with autism spectrum disorder (ASD) and/or attention-deficit/hyperactivity disorder (ADHD), and is known to be associated with clinical factors such as gastrointestinal (GI) symptoms, sensory abnormalities, intellectual abilities, and use of medication. However, previous studies have not considered these relationships comprehensively. We conducted a cross-sectional study of 6-12-year-old children with diagnoses of ASD and/or ADHD at two hospitals in Japan. Scores for the aberrant behavior checklist (ABC), autism-spectrum quotient (AQ), and Conners 3, as well as information on daily sleep and exercise, GI symptoms, and Short Sensory Profile, were collected. Each factor was subjected to a correlation analysis to investigate its effect on ABC scores. A stepwise multiple linear regression analysis for the factors with p < 0.05 was performed. Data were obtained from 60 patients with a mean age of 8.3 years; 21 had ASD alone, 18 had ADHD alone, and 21 had ASD + ADHD. The correlation analyses identified six factors associated with ABC severity: (a) methylphenidate use, (b) Conners hyperactivity score, (c) Conners inattention score, (d) AQ score, (e) SSP score, and (f) GI symptom score. The multiple regression showed that "GI symptoms" and "sensory abnormalities" were independently associated with ABC severity. Although further studies are needed to show a causal relationship, appropriate assessment of GI symptoms and sensory abnormalities may help alleviate some problematic behaviors and improve the quality of life of children with neurodevelopmental disorders and their families. LAY SUMMARY: Behavioral problems in children with neurodevelopmental disorders are known to be associated with many factors. This study aimed to comprehensively investigate the known factors. We have discovered that "gastrointestinal symptoms" and "sensory abnormalities" were independently associated with Behavioral problems. Our results suggest that it is important for clinicians and caregivers to pay more attention to children's GI symptoms and sensory abnormalities that may not present as obvious symptoms or complaints.

Fecal Microbial and Metabolomic Change during treatment course for depression: An Observational Study.

BACKGROUND: There is growing evidence regarding the connection between alterations in gut microbiota and their metabolites in patients with depressive disorders, suggesting a potential role in pathophysiology. Our study aimed to investigate the relationship between microbial, metabolomic features and the course of treatment for depression in a real-world clinical setting. METHODS: Patients diagnosed with depressive disorders were recruited, and their stool was collected at three time points during their depression treatments. Patients were divided into three groups: non-responders, responders, and stable remitters. Gut microbiomes were analyzed using 16S rRNA gene sequencing, and gut metabolomes were analyzed by a mass spectrometry approach. Microbiomes/metabolomes were compared between groups cross-sectionally and longitudinally. RESULTS: A total of 33 patients were recruited and divided into non-responders (n = 16), responders (n = 11), and stable remitters (n = 6). Non-responders presented lower alpha diversity in the Phylogenic Diversity index compared to responders during the treatment course (p = 0.003). Non-responders presented increased estimated glutamate synthesis functions by the microbiota compared to responders and stable remitters (p = 0.035). There were no specific microbiota or metabolome that differentiated the three groups. LIMITATIONS: Small sample size with no healthy controls. CONCLUSIONS: Our results indicate that both cross-sectional microbial features and longitudinal microbial transitions are different depending on the treatment course of depression. Controlled studies, as well as animal studies, are needed in the future to elucidate the causal relationship between microbiota and depression.

Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies.

BACKGROUND: Evidence of comparative benefits of long-acting injectable antipsychotics (LAIs) versus oral antipsychotics for schizophrenia has been inconsistent across study designs. The aim of this study was to evaluate the comparative benefits of LAIs versus oral antipsychotics in three study designs to inform clinical decision making. METHODS: We did a comprehensive systematic review and meta-analysis comparing LAIs versus oral antipsychotics for schizophrenia covering three study designs: randomised controlled trials (RCTs), cohort studies, and pre-post studies. Our literature search was without language restrictions, in MEDLINE and PubMed, the Cochrane Library, Scopus, and Embase, for studies published from database inception up to a last search on March 13, 2020. We also searched for unpublished studies and ClinicalTrials.gov. We included studies lasting at least 6 months that targeted adults with schizophrenia and related disorders (>80% of participants). Studies on penfluridol (neither an LAI or daily oral antipsychotic), case reports, and case series with fewer than 20 patients were excluded. Two investigators independently extracted study-level data and resolved disagreement by consensus, or via a third investigator. Study authors were contacted to obtain additional information as needed. For our primary outcome we meta-analysed the risk ratio (RR) for hospitalisation or relapse with LAIs versus oral antipsychotics by a random-effects model, with hospitalisation used preferentially over relapse. As secondary analyses, we reversed the preferential order to relapse over hospitalisation, and assessed hospitalisation risk and relapse risk individually. Other secondary outcomes included all meta-analysable data, classed by relevance to effectiveness, efficacy, safety, quality of life, cognitive function, and other outcomes, and analysed by study design. Dichotomous outcomes were expressed as pooled RR and continuous outcomes as standardised mean difference (SMD). The protocol is registered with PROSPERO (CRD42019142094). FINDINGS: We identified 14 687 records, of which 137 studies (397 319 patients) met the inclusion criteria (32 RCTs [23·4%; 8577 patients], 65 cohort studies [47·4%; 377 447 patients], and 40 pre-post studies [29·2%; 11 295 patients]) and were analysed. The quality of studies in terms of risk of bias varied across study designs and within each study design from low to high. LAIs were associated with a lower risk of hospitalisation or relapse than oral antipsychotics in each of the three study designs (RCTs: 29 studies, 7833 patients, RR 0·88 [95% CI 0·79-0·99], p=0·033; cohort studies: 44 studies, 106 136 patients, RR 0·92 [0·88-0·98], p=0·0044; pre-post studies: 28 studies, 17 876 patients, RR 0·44 [0·39-0·51], p<0·0001). This association was maintained across the study designs when we reversed the preferential order to risk of relapse over hospitalisation, and in individual analysis of hospitalisation risk. The association was maintained only in pre-post studies for relapse risk alone. In all other outcomes related to effectiveness, efficacy, safety, quality of life, cognitive function, and other outcomes, LAIs were more beneficial than oral antipsychotics in 60 (18·3%) of 328 comparisons, not different in 252 (76·8%) comparisons, and less beneficial in 16 (4·9%) comparisons when analysed by study design. Significant heterogeneity was observed across all three study designs. Publication biases were apparent in cohort and pre-post studies, but effect sizes were similar after trim-and-fill analyses. INTERPRETATION: Although study designs have strengths and weaknesses, including potential low quality of observational studies, we consistently identified significant benefit with LAIs versus oral antipsychotics in preventing hospitalisation or relapse, in settings ranging from restricted research (RCTs) to real-word application (cohort and pre-post studies). Our findings suggest that increased clinical use of LAIs could improve outcomes in schizophrenia. FUNDING: None. TRANSLATIONS: For the Chinese, French, German, Italian, Japanese, Portugese and Spanish translations of the abstract see Supplementary Materials section.

Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting.

BACKGROUND: The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. METHOD: We longitudinally investigated the relationship between patients' prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. RESULTS: We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = -0.00254, SE = 0.000595, P < .0001; estimate = -0.02644, SE = 0.00833, P = .002, respectively). CONCLUSION: Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients' types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

Neuronal network mechanisms associated with depressive symptom improvement following electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective antidepressant treatment for severe depression. Although recent structural magnetic resonance imaging (MRI) studies have consistently reported ECT-induced hippocampal volume increases, most studies did not find the association of the hippocampal volume changes with clinical improvement. To understand the underlying mechanisms of ECT action, we aimed to identify the longitudinal effects of ECT on hippocampal functional connectivity (FC) and their associations with clinical improvement. METHODS: Resting-state functional MRI was acquired before and after bilateral ECT in 27 depressed individuals. A priori hippocampal seed-based FC analysis and a data-driven multivoxel pattern analysis (MVPA) were conducted to investigate FC changes associated with clinical improvement. The statistical threshold was set at cluster-level false discovery rate-corrected p < 0.05. RESULTS: Depressive symptom improvement after ECT was positively associated with the change in the right hippocampus-ventromedial prefrontal cortex FC, and negatively associated with the right hippocampus-superior frontal gyrus FC. MVPA confirmed the results of hippocampal seed-based analyses and identified the following additional clusters associated with clinical improvement following ECT: the thalamus, the sensorimotor cortex, and the precuneus. CONCLUSIONS: ECT-induced change in the right frontotemporal connectivity and thalamocortical connectivity, and changes in the nodes of the default mode network were associated with clinical improvement. Modulation of these networks may explain the underlying mechanisms by which ECT exert its potent and rapid antidepressant effect.

Virtual reality exposure therapy for social anxiety disorder: a systematic review and meta-analysis.

BACKGROUND: Virtual reality exposure therapy (VRET) is currently being used to treat social anxiety disorder (SAD); however, VRET's magnitude of efficacy, duration of efficacy, and impact on treatment discontinuation are still unclear. METHODS: We conducted a meta-analysis of studies that investigated the efficacy of VRET for SAD. The search strategy and analysis method are registered at PROSPERO (#CRD42019121097). Inclusion criteria were: (1) studies that targeted patients with SAD or related phobias; (2) studies where VRET was conducted for at least three sessions; (3) studies that included at least 10 participants. The primary outcome was social anxiety evaluation score change. Hedges' g and its 95% confidence intervals were calculated using random-effect models. The secondary outcome was the risk ratio for treatment discontinuation. RESULTS: Twenty-two studies (n = 703) met the inclusion criteria and were analyzed. The efficacy of VRET for SAD was significant and continued over a long-term follow-up period: Hedges' g for effect size at post-intervention, -0.86 (-1.04 to -0.68); three months post-intervention, -1.03 (-1.35 to -0.72); 6 months post-intervention, -1.14 (-1.39 to -0.89); and 12 months post-intervention, -0.74 (-1.05 to -0.43). When compared to in vivo exposure, the efficacy of VRET was similar at post-intervention but became inferior at later follow-up points. Participant dropout rates showed no significant difference compared to in vivo exposure. CONCLUSION: VRET is an acceptable treatment for SAD patients that has significant, long-lasting efficacy, although it is possible that during long-term follow-up, VRET efficacy lessens as compared to in vivo exposure.