Posterior cingulate and medial prefrontal excitation-inhibition balance in euthymic bipolar disorder.

BACKGROUND: Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD). METHOD: Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test. RESULTS: euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068). CONCLUSIONS: Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

Fat loss and muscle gain: The possible role of cortical glutamate in determining the efficacy of physical exercise.

BACKGROUND: Physical exercise is widely acknowledged for its health benefits, but its effectiveness in treating obesity remains contentious due to variability in response. Owing to the roles of glutamate in appetite regulation, food addiction, and impulsivity, this observational cohort-study evaluated medial prefrontal cortex (mPFC) glutamate as a predictor of variability in exercise response, specifically in terms of fat loss and muscle gain. METHODS: Healthy non-exercising adult men (n = 21) underwent an 8-week supervised exercise program. Baseline glutamate levels in the mPFC were measured through magnetic resonance spectroscopy. For exercise-dependent changes in body composition (fat and muscle mass), basal metabolic rate (BMR), and blood metabolic biomarkers related to lipid and glucose metabolism, measurements were obtained through bioelectrical impedance and blood sample analyses, respectively. RESULTS: The exercise program resulted in significant improvements in body composition, including reductions in percentage body fat mass, body fat mass, and waist-to-hip ratio and an increase in mean muscle mass. Furthermore, BMR and metabolic indicators linked to glucose and lipids exhibited significant changes. Notably, lower baseline glutamate levels were associated with greater loss in percentage body fat mass (r = 0.482, p = 0.027), body fat mass (r = 0.441, p = 0.045), and increase in muscle mass (r = -0.409, p = 0.066, marginal) following the exercise program. CONCLUSION: These preliminary findings contribute to our understanding of the neurobiology of obesity and emphasize the significance of glutamate in regulating body composition. The results also highlight cortical glutamate as a potential predictor of exercise-induced fat loss and muscle gain.

Peripheral inflammation is associated with impaired sadness recognition in euthymic bipolar patients.

BACKGROUND: Inflammation impairs cognitive function in healthy individuals and people with psychiatric disorders, such as bipolar disorder (BD). This effect may also impact emotion recognition, a fundamental element of social cognition. Our study aimed to investigate the relationships between pro-inflammatory cytokines and emotion recognition in euthymic BD patients and healthy controls (HCs). METHODS: We recruited forty-four euthymic BD patients and forty healthy controls (HCs) and measured their inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and TNF-α. We applied validated cognitive tasks, the Wisconsin Card-Sorting Test (WCST) and Continuous Performance Test (CPT), and a social cognitive task for emotion recognition, Diagnostic Analyses of Nonverbal Accuracy, Taiwanese Version (DANVA-2-TW). We analyzed the relationships between cytokines and cognition and then explored possible predictive factors of sadness recognition accuracy. RESULTS: Regarding pro-inflammatory cytokines, TNF-α was elevated in euthymic BD patients relative to HCs. In euthymic BD patients only, higher TNF-α levels were associated with lower accuracy of sadness recognition. Regression analysis revealed that TNF-α was an independent predictive factor of sadness recognition in patients with euthymic BD when neurocognition was controlled for. CONCLUSIONS: We demonstrated that enhanced inflammation, indicated by increased TNF-α, was an independent predictive factor of impaired sadness recognition in BD patients but not in HCs. Our findings suggested a direct influence of TNF-α on sadness recognition and indicated vulnerability to depression in euthymic BD patients with chronic inflammation.

Machine learning for prediction of schizophrenia based on identifying the primary and interaction effects of minor physical anomalies.

In the neurodevelopmental model of schizophrenia, minor physical anomalies (MPAs) are considered neurodevelopmental markers of schizophrenia. To date, there has been no research to evaluate the interaction between MPAs. Our study built and used a machine learning model to predict the risk of schizophrenia based on measurements of MPA items and to investigate the potential primary and interaction effects of MPAs. The study included 470 patients with schizophrenia and 354 healthy controls. The models used are classical statistical model, Logistic Regression (LR), and machine leaning models, Decision Tree (DT) and Random Forest (RF). We also plotted two-dimensional scatter diagrams and three-dimensional linear/quadratic discriminant analysis (LDA/QDA) graphs for comparison with the DT dendritic structure. We found that RF had the highest predictive power for schizophrenia (Full-training AUC = 0.97 and 5-fold cross-validation AUC = 0.75). We identified several primary MPAs, such as the mouth region, high palate, furrowed tongue, skull height and mouth width. Quantitative MPA analysis indicated that the higher skull height and the narrower mouth width, the higher the risk of schizophrenia. In the interaction, we further identified that skull height and mouth width, furrowed tongue and skull height, high palate and skull height, and high palate and furrowed tongue, showed significant two-item interactions with schizophrenia. A weak three-item interaction was found between high palate, skull height, and mouth width. In conclusion, we found that the two machine learning methods showed good predictive ability in assessing the risk of schizophrenia using the primary and interaction effects of MPAs.

The Association between Default-mode Network Functional Connectivity and Childhood Trauma on the Symptom Load in Male Adults with Methamphetamine Use Disorder.

Objective: : The relationship between adverse childhood experiences and methamphetamine use disorder (MUD) has been shown in previous studies; nevertheless, the underlying neural mechanisms remain elusive. Childhood trauma is associated with aberrant functional connectivity (FC) within the default-mode network (DMN). Furthermore, within the DMN, FC may contribute to impaired self-awareness in addiction, while cross-network FC is critical for relapse. We aimed to investigate whether childhood trauma was associated with DMN-related resting-state FC among healthy controls and patients with MUD and to examine whether DMN-related FC affected the effect of childhood trauma on the symptom load of MUD diagnosis. Methods: : Twenty-seven male patients with MUD and 27 male healthy controls were enrolled and completed the Childhood Trauma Questionnaire. DMN-related resting-state FC was examined using functional magnetic resonance imaging. Results: : There were 47.1% healthy controls and 66.7% MUD patients in this study with adverse childhood experiences. Negative correlations between adverse childhood experiences and within-DMN FC were observed in both healthy controls and MUD patients, while within-DMN FC was significantly altered in MUD patients. The detrimental effects of adverse childhood experiences on MUD patients may be attenuated through DMN-executive control networks (ECN) FC. Conclusion: : Adverse childhood experiences were negatively associated with within-DMN FC in MUD patients and healthy controls. However, DMN-ECN FC may attenuate the effects of childhood trauma on symptoms load of MUD.

Are the sensorimotor control capabilities of the hands the factors influencing hand function in people with schizophrenia?

BACKGROUND: Previous works reported people with schizophrenia experienced inferior hand functions which influence their daily participation and work efficiency. Sensorimotor capability is one of indispensable elements acting in a well-executed feed-forward and feedback control loop to contribute to hand performances. However, rare studies investigated contribution of sensorimotor ability to hand functions for people with schizophrenia. This study aimed to explore hand function in people with schizophrenia based on the perspective of the sensorimotor control capabilities of the hands. METHODS: Twenty-seven people at the chronic stage of schizophrenia were enrolled. The following assessment tools were used: the Purdue Pegboard Test (PPT) and the VALPAR Component Work Sample-8 (VCWS 8) system for hand function; the Self-Reported Graphic version of the Personal and Social Performance (SRG-PSP) scale for functionality; and the Semmes-Weinstein Monofilaments (SWM), the pinch-holding-up-activity (PHUA) test and the Manual Tactile Test (MTT) for the sensory and sensorimotor parameters. The Clinical Global Impression-Severity (CGI-S) scale and the Extrapyramidal Symptom Rating Scale (ESRS) were used to grade the severity of the illness and the side-effects of the drugs. Spearman's rank correlation coefficient was used to analyze associations among hand function, functionality, and sensorimotor capabilities. A multiple linear regression analysis was used to identify the determinants of hand function. RESULTS: The results indicated that both hand function and sensorimotor capability were worse in people with schizophrenia than in healthy people, with the exception of the sensory threshold measured with the SWM. Moreover, the sensorimotor abilities of the hands were associated with hand function. The results of the regression analysis showed that the MTT measure of stereognosis was a determinant of the PPT measure of the dominant hand function and of the performance on the VCWS 8, and that the ESRS and the MTT measure of barognosis were determinants of the performance on the assembly task of the PPT. CONCLUSIONS: The findings suggested that sensorimotor capabilities, especially stereognosis and barognosis, are crucial determinants of hand function in people with schizophrenia. The results also revealed that the side effects of drugs and the duration of the illness directly affect hand function. CLINICAL TRAIL REGISTRATION: ClinicalTrials.gov , identifier NCT04941677, 28/06/2021.

Mentalizing in a movie for the assessment of social cognition (MASC): the validation in a taiwanese sample.

BACKGROUND: The present study evaluated the psychometrics properties of a sensitive video-based test used in the evaluation of mentalizing skills, that is, the Movie for the Assessment of Social Cognition-Taiwanese version (MASC-TW). METHODS: We recruited two independent samples of nonclinical participants (N = 167) and adult patients with schizophrenia (N = 41). The MASC-TW and two other social cognition measures, namely the Chinese version of Theory of Mind task (ToM) and the Taiwanese version of the Diagnostic Analysis of Nonverbal Accuracy-2 (DANAV-TW-2), and an executive function measure of the Wisconsin Card Sorting Test (WCST), were administered to both groups. RESULTS: The MASC proved to be a reliable measure of mentalizing capacity, high Cronbach's α value of 0.87. The intraclass correlation coefficient for the MASC-TW total correct scores was 0.85 across three waves of data collection. Across the entire sample, the scores on the MASC-TW were significantly correlated with verbal and nonverbal scores for the ToM task and recognition of facial and prosodic emotion on the DANAV-TW-2. Both executive function and emotion recognition emerged as noteworthy predictors of mentalizing, indicating that these two variables might play crucial roles in the development of mentalizing capacities. Finally, a receiver operating characteristic analysis revealed that in patients with schizophrenia, the MASC was the most accurate discriminator of diagnostic groups, highlighting the validity of the MASC. CONCLUSIONS: Overall, the MASC-TW is an ecologically valid and useful tool for assessing mentalizing abilities in a Taiwanese population.

The relationship between peripheral insulin resistance and social cognitive deficits among euthymic patients with bipolar disorder.

BACKGROUND: Despite extensive literature documenting emotion-related social-cognitive deficits in euthymic patients with bipolar disorder (BD), the factors contributing to these deficits have not been definitively established. To address this gap, the present study aimed to examine the association between peripheral insulin resistance (IR) and emotion-related social-cognitive abilities in BD patients and controls. METHOD: Sixty-five BD patients and 38 non-psychiatric controls were recruited, and their social cognitive ability and IR were measured using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the homeostasis model assessment of insulin resistance (HOMA-IR), respectively. RESULTS: The study found that the BD patients scored significantly lower than the non-psychiatric controls in the task of emotional management. The BD patients had a higher mean HOMA-IR value as compared with the controls but this result was not statistically significant (p = 0.051). The interaction between BD diagnosis and HOMA-IR value was significant on the MSCEIT Facilitating emotions branch and Facilitation subscale (p = 0.024, p = 0.010), and post-hoc analyses revealed that the BD patients in the higher HOMA-IR group had significantly lower scores than BD patients in the lower HOMA-IR group and the non-psychiatric controls in the higher HOMA-IR group on both the MSCEIT Facilitating emotion branch and Facilitation subscale. LIMITATIONS: Due to the cross-sectional nature of the study, causality could not be inferred. The study did not examine potential mediators or moderators between IR and social cognition. CONCLUSIONS: The results suggested that BD patients with IR experience additional impairment in specific domains of social cognition.

Social cognitive deficit is associated with visuomotor coordination impairment and dopamine transporter availability in euthymic bipolar disorder.

BACKGROUND: Extensive evidence has suggested functional connections between co-occurring visuomotor and social cognitive deficits in neuropsychiatric disorders; however, such association has not been studied in bipolar disorder (BD). We aimed to investigate the relationship between visuomotor coordination and social cognition in the euthymic stage of BD (euBD). Given the shared neurobiological underpinnings involving the dopaminergic system and corticostriatal circuitry, we hypothesized a positive correlation between social cognition and visuomotor coordination in euBD patients. METHODS: 40 euBD patients and 59 healthy control (HC) participants underwent evaluation of social (Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW)), non-social cognitive function and visuomotor coordination. A subgroup of participants completed single-photon emission computed tomography for striatal dopamine transporter (DAT) availability assessment. RESULTS: EuBD patients showed impaired nonverbal emotion recognition (ps ≤ 0.033) and poorer visuomotor coordination (ps < 0.003) compared to HC, with a positive correlation between these two abilities (r = 0.55, p < 0.01). However, after considering potential confounding factors, instead of visuomotor coordination, striatal DAT availability was a unique predictor of emotion recognition accuracy in euBD (beta = 0.33, p = 0.001). CONCLUSION: Our study result supported a functional association between social cognition and visuomotor coordination in euBD, with striatal dopaminergic dysfunction emerged as a crucial contributing factor in their interrelation.

Disrupted white matter network of brain structural connectomes in bipolar disorder patients revealed by q-ball imaging.

BACKGROUND: Structural and functional brain changes have been found to be associated with altered emotion and cognition in patients with bipolar disorder (BD). Widespread microstructural white matter abnormalities have been observed using traditional structural imaging in BD. q-Ball imaging (QBI) and graph theoretical analysis (GTA) improve the specificity and sensitivity and high accuracy of fiber tracking. We applied QBI and GTA to investigate and compare the structural connectivity alterations and network alterations in patients with and without BD. METHODS: Sixty-two patients with BD and 62 healthy controls (HCs) completed a MR scan. We evaluated the group differences in generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA) values by voxel-based statistical analysis with QBI. We also evaluated the group differences in topological parameters of GTA and subnetwork interconnections in network-based statistical analysis (NBS). RESULTS: The QBI indices in the BD group were significantly lower than those in the HC group in the corpus callosum, cingulate gyrus, and caudate. The GTA indices indicated that the BD group demonstrated less global integration and higher local segregation than the HC group, but they retained small-world properties. NBS evaluation showed that the majority of the more connected subnetworks in BD occurred in thalamo-temporal/parietal connectivity. CONCLUSION: Our findings supported white matter integrity with network alterations in BD.

Altered glutamate level and its association with working memory among patients with treatment-resistant schizophrenia (TRS): a proton magnetic resonance spectroscopy study.

BACKGROUND: Treatment-resistant schizophrenia (TRS) and non-TRS may be associated with different dopaminergic and glutamatergic regulations. The concept of dysregulated glutamatergic concentrations in specific brain regions remains controversial. Herein, we aimed to assess (i) the distribution of the glutamatergic concentration in the brain, (ii) the association between working memory (WM) differences in TRS and non-TRS patients, and (iii) whether an alteration in the glutamate (Glu) level is associated with WM. METHODS: The participants included 38 TRS patients, 35 non-TRS patients, and 19 healthy controls (HCs), all of whom underwent 1.5-Tesla proton magnetic resonance spectroscopy of anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC). The ratios of glutamatergic neurometabolites to N-acetylaspartate + N-acetyl aspartylglutamate (NAAx) were calculated. Cognitive function was assessed using the Wechsler Adult Intelligence Scales, 4th Edition, which included the working memory index (WMI). RESULT: The TRS patients had a higher glutamate + glutamine (Glx)/NAAx ratio compared to the non-TRS patients and HCs in the ACC, but this was not significantly different in the MPFC. WM was negatively correlated with Glx/NAAx in the ACC among the non-TRS patients, but not in the TRS patients or HCs. CONCLUSIONS: Our findings were consistent with most studies indicating that the glutamatergic concentration in the ACC plays important roles in the classification of TRS and cognition. Our results may provide potential evidence for predictors and treatment response biomarkers in TRS patients. Further research is needed to probe the value using the relationship between Glu and WM as a potential prognostic predictor of schizophrenia.

DNA methylation signature aberration as potential biomarkers in treatment-resistant schizophrenia: Constructing a methylation risk score using a machine learning method.

Treatment-resistant schizophrenia (TRS) is defined as a non-response to at least two trials of antipsychotic medication with an adequate dose and duration. We aimed to evaluate the discriminant abilities of DNA methylation probes and methylation risk score between treatment-resistant schizophrenia and non-treatment-resistant schizophrenia. This study recruited 96 schizophrenia patients (TRS and non-TRS) and 56 healthy controls (HC). Participants were divided into a discovery set and a validation set. In the discovery set, we conducted genome-wide methylation analysis (human MethylationEPIC 850K BeadChip) on the subject's blood DNA and discriminated significant methylation signatures, then verified these methylation signatures in the validation set. Based on genome-wide scans of TRS versus non-TRS, thirteen differentially methylated probes were identified at FDR <0.05 and >20% differences in DNA methylation ß-values. Next, we selected six probes within gene coding regions (LOC404266, LOXL2, CERK, CHMP7, and SLC17A9) to conduct verification in the validation set using quantitative methylation-specific PCR (qMSP). These six methylation probes showed satisfactory discrimination between TRS patients and non-TRS patients, with an AUC ranging from 0.83 to 0.92, accuracy ranging from 77.8% to 87.3%, sensitivity ranging from 80% to 90%, and specificity ranging from 65.6% to 85%. This methylation risk score model showed satisfactory discrimination between TRS patients and non-TRS patients, with an accuracy of 88.3%. These findings support that methylation signatures may be used as an indicator of TRS vulnerability and provide a model for the clinical use of methylation to identify TRS.

Association Between Inflammatory Cytokines, Executive Function, and Substance Use in Patients With Opioid Use Disorder and Amphetamine-Type Stimulants Use Disorder.

BACKGROUND: Long-term opioid and amphetamine-type stimulants (ATS) abuse may affect immunological function and impair executive function. We aimed to determine whether biomarkers of inflammation and executive function were associated with substance use in individuals with opioid use disorder (OUD) and ATS use disorder (ATSUD). The interactions between these biomarkers were also explored. METHODS: We assessed plasma cytokines [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-8, IL-6, transforming growth factor (TGF)-ß1, brain-derived neurotrophic factor (BDNF), and executive function in terms of the Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) in OUD and ATSUD patients and healthy controls (HC). OUD and ATSUD patients were followed for 12 weeks, and their urine morphine and amphetamine tests, cytokine levels, and executive function were repeatedly measured. RESULTS: We enrolled 483 patients and 145 HC. Plasma TNF-α, CRP, IL-8, IL-6, and BDNF levels and most subscale scores on the WCST and CPT significantly differed between OUD and ATSUD patients and HC. Increased TNF-α levels and more perseveration error on the WCST were significantly associated with more urine drug-positive results and less abstinence. Plasma IL-6 and CRP levels were significantly negatively correlated with WCST and CPT performance. CONCLUSION: OUD and ATSUD patients had more inflammation and worse executive function than HC. Inflammatory markers and WCST performance were associated with their urinary drug results, and higher inflammation was associated with poor executive function. Studies on regulating the inflammatory process and enhancing executive function in OUD and ATSUD are warranted.

Associations of leptin and corticostriatal connectivity in bipolar disorder.

Bipolar disorder (BD) and metabolic disturbance represent a chronic state of low-grade inflammation and corticostriatal circuitry alterations. Herein, we aimed to investigate whether plasma leptin, an adipokine that plays a key role in the interplay of metabolism and inflammation, is associated with corticostriatal connectivity in patients with BD. Twenty-eight BD I patients, 36 BD II patients and 66 healthy controls were enrolled and completed the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Recent Life Change Questionnaire. Fasting plasma leptin and C-reactive protein (CRP) levels were measured, and corticostriatal connectivity was examined using functional magnetic resonance imaging (fMRI). The relationships between leptin, CRP and body mass index (BMI) identified in the controls and BD II patients were absent in the BD I patients. We did not find a significant group difference in the leptin level; nevertheless, the negative correlation between leptin level and corticostriatal connectivity (ventrolateral prefrontal cortex and inferior temporal gyrus) observed in the healthy controls was absent in the BD patients. The disproportionate increase in leptin level with increasing BMI in BD indicated a potential inflammatory role of white adipose tissue in BD. Furthermore, higher CRP levels in BD I patients might induce leptin resistance. Collectively, our results implied vulnerability to inflammatory and metabolic diseases in patients with BD, especially BD I.

Striatal Dopamine Transporter Availability is Associated with Sleep Disturbance among Patients with Bipolar I Disorder: A Single-photon Emission Computed Tomography Study Using [99mTc] TRODAT-1.

Objective: Bipolar disorder (BD) is characterized by the poor sleep quality. Whether the striatal dopamine transporter (DAT) availability is related to sleep quality among patients with BD is unclear. Methods: Fifty-three euthymic patients with BD (24 BD-I and 29 BD-II) and sixty-eight healthy controls were enrolled. The Chinese Version of the Pittsburgh Sleep Quality Index (PSQI) was used, and the availability of DAT was assessed by single-photon emission computed tomography (SPECT) using [99mTc] TRODAT-1. Results: The sleep disturbance component of the PSQI was significantly associated with the level of DAT availability among patients with BD. Conclusion: The striatal dopaminergic activity that contributes to resilience to adversity was associated with sleep pattern among patients with BD.

A Longitudinal Study of the Association between the LEPR Polymorphism and Treatment Response in Patients with Bipolar Disorder.

Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether LEPR polymorphisms are associated with treatment response is still unknown. This longitudinal study aimed to investigate the associations between LEPR polymorphisms and VPA treatment response in BD patients who were drug naïve at their first diagnosis of BD. The single-nucleotide polymorphisms (SNPs) of LEPR (rs1137101, rs1137100, rs8179183, and rs12145690) were assayed, and the LEPR polymorphism frequencies of alleles and genotypes were not significantly different between the controls (n = 77) and BD patients (n = 130). In addition, after the 12-week course of VPA treatment in BD patients, the LEPR polymorphisms showed significant effects on changes in disease severity. Moreover, considering the effect of the LEPR haplotype, the frequency of the CAGG haplotype in BD patients was higher than that in the controls (9.3 vs. 2.9%, p = 0.016), and the LEPR CAGG haplotype was associated with a better treatment response than the other haplotypes in BD patients receiving VPA treatment. Therefore, LEPR polymorphisms might serve as mediators involved in the therapeutic action of VPA treatment.

Profiling antibody signature of schizophrenia by Escherichia coli proteome microarrays.

Schizophrenia (SZ) is influenced by genetic and environmental factors, and associated with chronic neuroinflammation. If the symptoms express after adolescence, environmental impacts are more substantial, and the disease is defined as adult-onset schizophrenia (AOS). Effects of environmental factors on antibody responses such as Escherichia coli (E. coli) to immunoglobulin G (IgG) and immunoglobulin M (IgM) might increase the severity of symptoms in SZ via the gut-brain axis. The purpose of this study is to reveal antibody profiles of SZ against bacterial protein antigens. We analyzed the IgG and IgM antibodies using E. coli proteome microarrays from 80 SZ patients and 40 healthy controls (HC). Using support vector machine to select panels of proteins differentiating between groups and conducted enrichment analysis for those proteins. We identified that the groL, pldA, yjjU, livG, and ftsE can classify IgGs in AOS vs HC achieved accuracy of 0.7. The protein yjjU, livG and ftsE can form the best combination panel to classify IgG in AOS vs HC with accuracy of 0.8. The enrichment results are highly related to ABC (ATP binding cassette) transporter in the protein domain and cellular component. We further found that the human ATP binding cassette subfamily b member 1 (ABCB1) autoantibody level in AOS is significantly higher than in HC. The findings suggest that AOS had different immunoglobulin production compared to early-onset schizophrenia (EOS) and HC. We also identified potential antibody biomarkers of AOS and found their antigens are enriched in ABC transporter related domains, including human ABCB1 protein.

Correlation between loneliness, personality traits, and treatment outcomes in patients with methamphetamine use disorder.

The aim of this study was to investigate whether loneliness and personality traits correlate with the treatment outcome of methamphetamine use disorder. In this 1-year longitudinal study, a total 106 participants (98 males, 8 females), with a mean age 36.3 ± 9.6 years were enrolled. We measured UCLA Loneliness Scale and Tridimensional Personality Questionnaire at baseline, while craving level at baseline, week 12, 24, 36, and 48. Urinary methamphetamine tests were given 17 times. For the evaluation of the data, multiple linear regression and generalized linear mixed models were used. The baseline results showed lower levels of the harm avoidance trait and higher levels of loneliness were significantly associated with higher craving levels (p=0.04 and 0.04). Moreover, loneliness was not only positively associated with craving levels (B=0.05, p<0.01) but with urinary methamphetamine positive results (B= 0.08, p=0.03) during one-year treatment. The findings suggested that loneliness was associated with poor methamphetamine treatment outcome (greater craving levels and higher proportion of positive methamphetamine urine tests) and lower harm avoidance traits are associated with higher craving levels.

Serotonin Modulates the Correlations between Obsessive-compulsive Trait and Heart Rate Variability in Normal Healthy Subjects: A SPECT Study with [123I]ADAM and Heart Rate Variability Measurement.

Objective: The impact of serotonergic system on obsessive-compulsive disorder (OCD) is well studied. However, the correlation between OC presentations and autonomic nervous system (ANS) is still unclear. Furthermore, whether the correlation might be modulated by serotonin is also uncertain. Methods: We recruited eighty-nine healthy subjects. Serotonin transporter (SERT) availability by [123I]ADAM and heart rate variability (HRV) tests were measured. Symptoms checklist-90 was measured for the OC presentations. The interaction between HRV and SERT availability were calculated and the correlation between HRV and OC symptoms were analyzed after stratified SERT level into two groups, split at medium. Results: The interactions were significant in the factors of low frequency (LF), high frequency (HF), and root mean square of successive differences (RMSSD). Furthermore, the significantly negative correlations between OC symptoms and the above HRV indexes existed only in subjects with higher SERT availability. Conclusion: OC symptoms might be correlated with ANS regulations in subjects with higher SERT availability.