Fat loss and muscle gain: The possible role of striatal dopaminergic tone in determining the efficacy of physical exercise.

The effectiveness of exercise for obesity is contentious due to individual response variability. Owing to the roles of dopamine in motor functions, metabolism, and appetite, this study aimed to identify striatal dopamine as a predictor of variability in exercise response, specifically in terms of fat loss and muscle gain. Healthy non-exercising males completed an 8-week program, exercising 1 h, 4 days a week. Striatal dopaminergic tone was assessed by measuring dopamine transporter availability using technetium-99 m labelled tropane derivative, [99mTc]TRODAT-1 (TRODAT), single-photon emission computed tomography, and body composition (fat and muscles mass) was analysed using bioelectrical impedance. Lower baseline dopamine levels were associated with greater fat mass loss (r = 0.58, p = 0.006), percentage fat mass loss (r = 0.53, p = 0.013), and increase in muscle mass (ß = -0.53, p = 0.035, after taking age and smoking status as covariates). These findings enhance our understanding of obesity neurobiology and exercise response variability, necessitating further research for targeted interventions based on dopaminergic profiles.

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.

A Delphi consensus on clinical features, diagnosis and treatment of major depressive disorder patients with anhedonia amongst psychiatrists in the Asia-Pacific.

Background: Anhedonia, a core diagnostic feature for major depressive disorder (MDD), is defined as the loss of pleasure and interest in daily activities. Its prevalence in MDD patients vary from 35 to 70%. Anhedonia in MDD negatively impacts functioning and is associated with treatment resistance and poorer prognosis for various clinical outcomes. Owing to its complexity, there remains considerable heterogeneity in the conceptualization, diagnosis and clinical management of anhedonia in MDD. Methods: This modified Delphi panel was conducted to elicit expert opinion and establish consensus on concepts relating to clinical features, diagnosis and treatment of MDD with anhedonia (MDDwA) amongst psychiatrists in the Asia-Pacific region. Seven themes were covered. A three-stage process was adopted for consensus generation (two online survey rounds, followed by a moderated consensus meeting). Statements were developed based on a literature review and input from a steering committee of six regional experts. The panel included 12 psychiatrists practicing in Australia, China, Hong Kong, Japan, South Korea and Taiwan with ≥5 years of specialist clinical experience, including assessment or management of patients with MDDwA. Results: Overall, consensus was achieved (median ≥8) on 89/103 statements (86%). About half of the statements (55/103, 53%) achieved consensus in Round 1, and 29/36 modified statements achieved consensus in Round 2. At the moderated consensus meeting, five modified statements were discussed by the steering committee and consensus was achieved on all statements (5/5). The findings highlighted a lack of clear and practical methods in clinical practice for assessing anhedonia in MDD patients and limited physician awareness of anhedonia in Asia-Pacific. Conclusion: Insights from this Delphi consensus provide a reference point for psychiatrists in Asia-Pacific to optimize their strategies for personalized diagnosis and management of patients with MDDwA. Identification of distinct and clinically relevant subtypes in MDD may be valuable for guiding personalized diagnosis and management approaches, including type-specific therapies.

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.

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.

Which Severe Mental Illnesses Most Increase the Risk of Developing Dementia? Comparing the Risk of Dementia in Patients with Schizophrenia, Major Depressive Disorder and Bipolar Disorder.

Objective: Previous studies have shown that certain severe mental illnesses (SMIs) increase the risk of dementia, but those that increase the risk to a greater degree in comparison with other SMIs are unknown. Furthermore, physical illnesses may alter the risk of developing dementia, but these cannot be well-controlled. Methods: Using the Taiwan National Health Insurance Research Database, patients with schizophrenia, bipolar disorder and major depressive disorder (MDD) were recruited. We also recruited normal healthy subjects as the control group. All subjects were aged over 60 years, and the duration of follow-up was from 2008 to 2015. Multiple confounders were adjusted, including physical illnesses and other variables. Use of medications, especially benzodiazepines, was analyzed in a sensitivity analysis. Results: 36,029 subjects (MDD: 23,371, bipolar disorder: 4,883, schizophrenia: 7,775) and 108,084 control subjects were recruited after matching according to age and sex. The results showed that bipolar disorder had the highest hazard ratio (HR) (HR: 2.14, 95% confidence interval [CI]: 1.99-2.30), followed by schizophrenia (HR: 2.06, 95% CI: 1.93-2.19) and MDD (HR: 1.60, 95% CI: 1.51-1.69). The results remained robust after adjusting for covariates, and sensitivity analysis showed similar results. Anxiolytics use did not increase the risk of dementia in any of the three groups of SMI patients. Conclusion: SMIs increase the risk of dementia, and among them, bipolar disorder confers the greatest risk of developing dementia. Anxiolytics may not increase the risk of developing dementia in patients with an SMI, but still need to be used with caution in clinical practices.

Treatment Retention Rates of 3-monthly Paliperidone Palmitate and Risk Factors Associated with Discontinuation: A Population-based Cohort Study.

Objective: Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. Methods: We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. Results: The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration > 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180-360 days (adjusted relative risk [aRR], 1.76) or < 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. Conclusion: Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

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.

Elevated C-Reactive Protein Levels Modify the Effect of Magnesium on Depressive Symptoms: A Population-Based Study.

Depression is a profound public health concern, yet its etiology remains unclear. A body's magnesium status and low-grade systemic inflammation are associated with depression. However, the interaction of magnesium status and inflammation on depression/depressive symptoms is unknown. We assessed the association between serum magnesium levels and depressive symptoms by analyzing data from the Nutrition and Health Survey in Taiwan 2005-2008. In total, 2196 participants aged ≥20 years were included. Depressive symptoms were assessed using the 5-item Brief-Symptom Rating Scale. We performed logistic regression and multiple linear regression analyses to examine the association. A dose-response analysis was performed using restricted cubic spline models, and stratification by chronic inflammation was also performed. We found that higher serum magnesium levels were associated with lower depression scores and a lower risk of depression. In the subgroup analysis, serum magnesium levels were inversely associated with depressive symptoms more prominently among people with higher CRP levels, with a threshold at 5 mg/L (≥5 vs. <5) showing a greater difference than at 3 mg/L (≥3 vs. <3). Conclusions: Serum magnesium levels were inversely associated with depressive symptoms. This inverse association was affected by inflammation level. A dose-response relationship was also observed.

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.

Effects of comorbid alcohol use disorder on bipolar disorder: Focusing on neurocognitive function and inflammatory markers.

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers. METHOD: We recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-ß1 (TGF-ß1), and brain-derived neurotrophic factor (BDNF)] were assessed. RESULTS: BD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05). CONCLUSION: Our results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.

Taiwan consensus on biological treatment of bipolar disorder during the acute, maintenance, and mixed phases: The 2022 update.

BACKGROUND: Bipolar disorder is a mood dysregulation characterized by recurrent symptoms and episodes of mania, hypomania, depression, and mixed mood. The complexity of treating patients with bipolar disorder prompted the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) to publish the first Taiwan consensus on pharmacological treatment of bipolar disorders in 2012. This paper presents the updated consensus, with changes in diagnostic criteria (i.e., mixed features) and emerging pharmacological evidence published up to April 2022. METHODS: Our working group systemically reviewed the clinical research evidence and international guidelines and determined the levels of evidence for each pharmacological treatment on the basis of the most recent World Federation of Societies of Biological Psychiatry grading system. Four clinical-specific issues were proposed. The current TSBPN Bipolar Taskforce then discussed research evidence and clinical experience related to each treatment option in terms of efficacy and acceptability and then appraised final recommendation grades through anonymous voting. RESULTS: In the updated consensus, we include the pharmacological recommendations for bipolar disorder with mixed features considering its high prevalence, the severe clinical prognosis, and the absence of approved medications. Cariprazine, lurasidone, repetitive transcranial magnetic stimulation, and ketamine are incorporated as treatment options. In the maintenance phase, the application of long-acting injectable antipsychotics is emphasized, and the hazards of using antidepressants and conventional antipsychotics are proposed. CONCLUSIONS: This updated Taiwan consensus on pharmacological treatment for bipolar disorder provides concise evidence-based and empirical recommendations for clinical psychiatric practice. It may facilitate treatment outcome improvement in patients with bipolar disorder.

The Association of Serum and Dietary Magnesium with Depressive Symptoms.

Depression is a leading cause of the global burden of disease and has a multifactorial etiology that includes nutrients. Magnesium status has been associated with depression with inconclusive results. The impact of chronic latent magnesium deficiency (CLMD, 0.75 ≤ serum magnesium < 0.85 mmol/L) on depression has not yet been investigated. We assessed the association between serum magnesium levels/dietary magnesium intake and depressive symptoms by analyzing nationally representative data from Taiwan (Nutrition and Health Survey in Taiwan, NAHSIT). We used the 5-item Brief Symptom Rating Scale to measure depressive symptoms. Subgroup analysis by sex was also performed. Serum magnesium levels had a low correlation with dietary magnesium intake. Higher serum magnesium levels were associated with lower depressive scores and a lower risk of depressive symptoms, but dietary magnesium intake showed no association. Sex differences were found. Compared with subjects with serum magnesium <0.75 mmol/L, those with ≥0.85 mmol/L had lower depressive scores. In conclusion, serum magnesium was inversely associated with depressive symptoms, but dietary magnesium intake was not. Subjects with CLMD showed similar depressive scores and were at a similar risk of depressive symptoms to those with serum magnesium < 0.75 mmol/L. CLMD should be considered while assessing the association between magnesium status and depressive symptoms.

Occupational evaluation of community-based psychiatric rehabilitation outcomes in individuals with severe mental illnesses: A ten-year retrospective study.

BACKGROUND: There is a lack of research on the effect of community-based psychiatric rehabilitation programs (CBPRs) in individuals with severe mental illness. This research used data from a retrospective study to examine the effect of a CBPR in a community rehabilitation center. MATERIALS AND METHODS: Clinical outcomes measures from a retrospective study were collected. Outcome measures were the Allen Cognitive Level Screen assessment, Purdue Pegboard Test, Chu's Attention Test, and Activities of Daily Living Rating Scale-III (ADLRS-III) before and immediately after 12 months of intervention. RESULTS: The 141 participants with mental illness were an average age of 35.29 years (SD = 8.75). The retrospective review of medical records showed 46 people dropped out within 12 months, and 95 people continued to participate in the rehabilitation program for 1 year. After 1 year of community rehabilitation, there was a trend for the participants who completed the intervention to improve on the ADLRS-III, Purdue Pegboard Test, and Chu's Attention Test. Participants who performed better on the occupational assessment were more likely to transit to the employment status. CONCLUSION: This study found the benefits of CBPR in work-related intervention for people with mental illness. Occupational assessments are relevant for studying changes in functional outcomes in people with mental illness receiving community-based rehabilitation.

Harm Avoidance is Correlated with the Reward System in Adult Patients with Attention Deficit Hyperactivity Disorder: A Functional Magnetic Resonance Imaging Study.

Objective: Hypoactivity in the reward system among patients with attention deficit hyperactivity disorder (ADHD) is a well-known phenomenon. Whether the activity in the reward pathway is related to harm avoidance, such as in sensitivity to punishment, is unclear. Evidence regarding the potential difference between ADHD patients and controls in terms of this association is scarce. Methods: Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa gambling test. Fourteen adults with ADHD and 14 controls were enrolled in the study. Results: Harm avoidance was found to be positively correlated with the activities of the bilateral orbitofrontal cortex and right insula in individuals with ADHD. A group difference was also confirmed. Conclusion: Understanding the roles of harm avoidance and brain activation during risk tasks is important.

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.