Background Electroconvulsive therapy (ECT) is effective for schizophrenia but often impairs delayed memory, whereas magnetic seizure therapy (MST) typically spares cognition. We investigated whether these modalities differentially affect 40-Hz auditory steady-state responses (ASSR)—a marker of gamma synchrony critical for memory—and if these changes predict cognitive outcomes. Methods This study is a secondary analysis of a randomized clinical trial for schizophrenia comparing ECT (n = 16) and MST (n = 17). Clinical symptoms and cognition were assessed using Positive and Negative Syndrome Scale (PANSS) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline and after 10 treatment sessions. 40-Hz ASSR were recorded via EEG at baseline and after the first treatment session. Results Both treatments improved psychotic symptoms. However, ECT induced cognitive deficits (particularly delayed memory) and significant reductions in acute ASSR power and phase-locking. In contrast, MST preserved both cognitive function and ASSR integrity. Notably, within the ECT group, greater acute suppression of ASSR power predicted better preservation of delayed memory. Conclusion MST demonstrates a superior safety profile compared to ECT, preserving both gamma synchrony and memory. The association between acute gamma suppression and better memory retention in ECT suggests this reduction may be an adaptive physiological response. Thus, early ASSR changes may serve as a predictive biomarker for cognitive tolerability.

Background Frontotemporal neural synchronization and hemispheric lateralization imbalances are core features of major depressive disorder (MDD), but objective Functional near-infrared spectroscopy (fNIRS) - derived biomarkers capturing these abnormalities remain underdeveloped. Methods We recruited 236 MDD patients and 124 healthy controls (HCs) who completed a verbal fluency task (VFT) during 52-channel fNIRS scanning. Regional Homogeneity (ReHo) and hemispheric Laterality Index (LI) were computed to assess local neural synchronization and interhemispheric balance across four VFT phases (pre-task, task-period, post-task, whole-process). Interhemispheric functional connectivity (Spearman partial correlation) and a random forest classifier (5-fold stratified cross-validation) were further analyzed, with false discovery rate (FDR) correction for multiple comparisons. Results Compared to HCs, MDD patients showed reduced ReHo in left inferior frontal gyrus (LIFG) and left temporal lobe (LT) across all phases (FDR-corrected p < 0.05), a pathological rightward shift in LI (most pronounced during task-period: LI_T = 0.006, LI_IFG = 0.015, LI_F = 0.015), and impaired interhemispheric connectivity in LIFG-RIFG (task-period z = 2.39, p = 0.017). The random forest model integrating ReHo features achieved robust diagnostic performance, with the highest area under the curve (AUC) of 0.831 in the whole-process phase. Conclusions MDD is characterized by left-lateralized frontotemporal synchronization deficits, pathological rightward lateralization, and disrupted interhemispheric coordination during cognitive processing. fNIRS-derived ReHo features hold promise as non-invasive biomarkers for MDD diagnosis, advancing objective psychiatric assessment.

Serum cytokine alterations are associated with the usage of antipsychotic medications (AP). However, few studies have been designed to longitudinally measure cytokine changes during AP exposure in individuals at clinical high risk (CHR) for psychosis. This study aimed to assess changes in levels of cytokines after initiating AP in the prodromal phase. This longitudinal study involved individuals with CHR who completed the 1-year follow-up reassessment. Individuals with CHR were grouped into those treated with AP (AP + group) and those without (AP- group). Levels of vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, 2, 6, 8, and 10 were measured at baseline and 1 year after completion of the clinical assessment. This study included 88 CHR individuals (median age, 18 years and 40.9

BACKGROUND Impaired insight is a core feature of schizophrenia and an established predictor of psychosis in individuals at clinical high risk (CHR). However, the neurocognitive mechanisms underlying impaired insight in CHR populations remain unclear. AIM To investigate the role of neurocognitive deficits in impaired insight and examine their combined influence on psychosis risk over a six-year follow-up. METHODS A total of 312 CHR individuals were assessed for insight using the G12 item of the Positive and Negative Syndrome Scale. Participants were categorized into the low-impairment insight group (n = 151, G12 score < 3) and the high-impairment insight group (n = 161, G12 score >= 3). Neurocognition was evaluated using the MATRICS Consensus Cognitive Battery. RESULTS Performance on the Brief Visuospatial Memory Test-Revised (BVMT-R) was the only cognitive domain differentiating the insight groups after controlling for positive symptoms. The effect of BVMT-R on insight was most pronounced at moderate symptom levels. Moreover, risk-curve analyses indicated that higher BVMT-R scores were associated with a reduced conversion risk linked to impaired insight. CONCLUSION Incorporating visuospatial memory assessment may improve the identification of those at greatest risk and inform targeted interventions aimed at enhancing insight and reducing conversion to psychosis.

BACKGROUND:Abnormalities in event-related potential P300 have been reported in clinical high-risk (CHR) populations, reflecting deficits in cognitive processes. Studies suggest that task-induced changes in the exponent are associated with working memory capacity. The present study aimed to compare visual P300 amplitude and task-related exponent modulation during a visual oddball paradigm among CHR individuals, and to examine whether the exponent could serve as potential biomarker for clinical outcomes. METHODS:CHR and healthy controls (HC) were enrolled and completed a visual oddball task while EEG was recorded. CHR participants were divided into psychosis converters (CHRC) and non-converters (CHR-NC) group according to the clinical outcomes of two-year follow-up. P300 amplitude and the pre- to post-stimulus change in aperiodic exponent (Δ-exponent) were analyzed. Logistic regression modeling was performed to evaluate the predictive power of Δ-exponent. RESULTS:P300 amplitude at parietal region was significantly lower in the CHR-C group compared to the HC (p = 0.01) group. The Δ-exponent was significantly attenuated in CHR-C relative to HC (p < 0.01) and CHR-NC (p = 0.01). Logistic regression showed that Δ-exponent may have better predictive power than P300 amplitude (mean AUC difference 0.13, 95%CI: 0.002-0.38), and a reduction in Δ-exponent was associated with psychosis conversion (OR = 0.43(0.23-0.75), p < 0.01). CONCLUSION:Attenuation of the visual oddball task-induced change in aperiodic exponent is observed in CHR individuals who later convert to psychosis and may hold better predictive power compared to P300 amplitude. Δ-exponent may serve as a potential neurobiological biomarker in the CHR population.

BACKGROUND:Cognitive impairment in first-episode schizophrenia (FES) is a major contributor to functional decline, but antipsychotics provide limited cognitive improvement, and few repetitive transcranial magnetic stimulation (rTMS) studies have targeted the orbitofrontal cortex (OFC). This study investigated whether right OFC rTMS enhances specific cognitive functions in FES and its relationship with symptom reduction. METHODS:Ninety drug-naive FES patients were enrolled, with 48 receiving active right OFC rTMS and 42 sham stimulation for 20 sessions over 8 weeks, while all patients took olanzapine (10-20 mg/day). Cognitive function was assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) at baseline and week 4, and psychotic symptoms were rated with the Positive and Negative Syndrome Scale (PANSS). RESULTS:Repeated-measures analysis of variance (RMANOVA) demonstrated a significant Time×Group interaction for visuospatial memory (assessed via the Brief Visuospatial Memory Test-Revised, BVMT; F = 5.079, df = 1, 83, p = 0.027, η2 = 0.058). Post hoc tests revealed significant BVMT improvement in the active group (p < 0.001) but not in the sham group (p = 0.312). In the active group, improvements in BVMT and Neuropsychological Assessment Battery (NAB) scores were significantly correlated with lower PANSS total scores after Bonferroni correction. CONCLUSIONS:These findings indicate that right OFC rTMS improves specific cognitive functions in FES, with cognitive benefits associated with symptom alleviation, supporting the right OFC as a promising target for cognitive intervention in FES.

Aims:To investigate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) in improving cognitive function in older inpatients with schizophrenia. Design:Randomised controlled trial. Setting:Cognitive improvement in hospitalised older patients with schizophrenia in Shanghai. Participants:Fifty-one older inpatients with schizophrenia in Shanghai Mental Health Center. Intervention:The taVNS electrodes were placed on the skin with vagus nerve distribution in the taVNS group, whereas the electrodes were placed on the skin without vagus nerve distribution in the sham taVNS group. taVNS parameters included 25 Hz, the maximum tolerated current intensity (apparatus maximum load current ≤ 6 mA) and one 30-min session per day for 2 weeks, for a total of 10 interventions. Measurements:The primary outcome was a neurocognitive assessment. Safety was the secondary outcome measure. After each treatment session, adverse reactions were assessed using the self-administered Adverse Reaction Assessment Scale. Four subtests of the Cambridge Neuropsychological Test Automated Battery were further considered: reaction time (RTI), paired associate learning (PAL), multitasking test (MTT) and spatial working memory (SWM). Results:The time and interaction effects of between-group search errors were statistically significant (F = 9.51, p <  0.001). Compared to the sham taVNS, taVNS improved SWM performance in older patients with schizophrenia. Furthermore, the SWM performance after a single session of taVNS showed fewer errors in the taVNS group, whereas no such improvement was observed in the sham taVNS group. Unlike in SWM, there were no significant between-group differences in RTI, PAL or MTT after either a single stimulation or a session of 10 stimulations. Conclusions:taVNS may have the potential to improve SWM in older patients with schizophrenia.

BACKGROUND:Anxiety is highly prevalent and undertreated in first-episode schizophrenia(FES), but repetitive transcranial magnetic stimulation(rTMS) data for this comorbidity are scarce. The orbitofrontal cortex(OFC) is a key anxiety-regulating node, supporting its potential as a target. This study aimed to explore 1-Hz right OFC-rTMS's symptom-specific effects on FES mood. METHODS:This is a secondary analysis of a randomized controlled trial. Participants were drug-naive FES patients randomized to the active rTMS group(n = 51) or sham group(n = 45). All completed 20 intervention sessions, 20 sessions of active OFC-rTMS or sham, with 4-week follow-up, initiating oral olanzapine(10-20 mg/day) concurrently with the first rTMS session. Mood symptoms were assessed using the 24-item Hamilton Depression Rating Scale(HAMD) and the 14-item Hamilton Anxiety Rating Scale(HAMA). Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS). The main outcome was the changes in HAMD and HAMA scores from baseline to 2 weeks and 4 weeks. RESULTS:The active group showed greater PANSS total(t = -3.260, p = 0.002; Cohen's d = 0.672) and subscale improvements vs. the sham group. Repeated-measures ANOVA(controlling for covariates) revealed significant Time×Group interactions for HAMA total(F = 4.698, p = 0.010; partial η2 = 0.059) and psychic anxiety(F = 5.735, p = 0.004; partial η2 = 0.072), but not somatic anxiety. For HAMD, only anxiety/somatization(F = 8.397, p = 0.031; partial η2 = 0.099) and cognitive impairment(F = 6.240, p = 0.002; partial η2 = 0.076) showed interactions, with no specific effects on overall depressive symptoms. In the sham group, HAMD anxiety/somatization correlated with all PANSS subscales(r = 0.311-0.477, p < 0.05), but this correlation was absent in the active group(all p > 0.05). CONCLUSIONS:Right OFC-rTMS improves FES anxiety (not depression), supporting it as a targeted non-pharmacological option.

Background Schizophrenia (SCZ) exhibits considerable overlap with other psychiatric disorders in clinical symptoms and brain structural abnormalities, yet the relationship between these shared neuroanatomical patterns and individual clinical manifestations remains poorly understood. Methods We conducted a longitudinal study of 100 first-episode SCZ patients and 97 healthy controls (HCs), acquiring structural magnetic resonance imaging data at baseline and post antipsychotic treatment. Using normative modeling and summary statistics from eight psychiatric disorders, we computed a cross-disorder regional vulnerability index (RVI) that captures morphological similarity patterns across eight psychiatric disorders at the individual level. Results We found that SCZ patients demonstrated the highest RVI to bipolar disorder, major depressive disorder, and obsessive-compulsive disorder, with similarity levels increasing over the disease course. Cross-disorder RVI effectively discriminated SCZ patients from HCs, achieving classification accuracies of 0.83 at baseline and 0.87 at follow-up. Particularly, cross-disorder RVIs significantly correlated with symptom severity (p = 0.005), revealing divergent associations between positive and negative syndrome scales. Baseline cross-disorder RVI also predicted the improvement of negative syndrome following antipsychotic treatment (p = 0.021). Conclusions These findings highlight the potential of cross-disorder brain similarity profiling to improve personalized diagnosis and treatment in individuals with SCZ.

Clinical subtypes of individuals at clinical high risk for psychosis (CHR), classified by baseline symptoms and cognitive performance, may follow distinct trajectories of symptom progression and functional outcomes. Baseline symptom, cognitive and EEG data were collected from 204 CHR individuals aged 13-38 years, who subsequently completed clinical assessments at 2 months, 1 year, and 2 years. Although baseline positive symptom scores and highest past-year global functioning did not differ significantly, the subtypes demonstrated divergent progression patterns across follow-ups. Baseline cognitive performance exerted sustained influence over subsequent assessments, with visuospatial learning and working memory showing significant long-term effects on positive symptoms or global functioning, highlighting them as core cognitive domains with longitudinal, cross-subtype impact on CHR progression. Brain network features also contributed to long-term outcomes. The involvement of microstate D was sustained over time, with its occurrence linked to functional outcomes in the most impaired subtype and its coverage associated with positive symptom trajectories in the moderately impaired subtype. We further constructed a predictive model incorporating the interaction between microstate D and subtype that effectively identified individuals who converted to psychosis, underscoring its potential as a dynamic biomarker for more precise CHR clinical profiles.

Background and Hypothesis Antipsychotics (APs) are often used among individuals with clinical high risk (CHR) for psychosis and affect cortical thickness (CT). Whether clinical and CT changes after initial AP use correlate with long-term clinical outcomes remains largely unknown. Study Design One hundred and thirty-eight CHRs and 65 healthy controls accepted 2 MRI scans at an interval of 2 months. CHRs were categorized as responders (n = 53) and non-responders (n = 69) based on their response to APs after 2-month treatment. According to 2-year outcomes, they were also subdivided into converters (n = 26) and non-converters (n = 96). The relationships among short-term CT changes, AP effects, and long-term outcomes were explored. Study Results At baseline, CHRs had CT reduction in the right inferior temporal cortex with a correlation with clinical symptoms. At 2 month, CHRs showed steeper gray matter loss in bilateral frontotemporal regions than healthy controls. Cortical thickness change rates of the clusters located in bilateral middle temporal and right lateral orbitofrontal cortex were negatively correlated with the cumulative AP dose. Furthermore, 2-year psychosis conversion rate was significantly higher in non-responders than responders (33.3% vs 5.1%). A random forest model based on demographic, clinical, baseline, and longitudinal CT variables predicted 2-year conversion with an AUC of 0.90 (accuracy: 0.83, sensitivity: 0.78, and specificity: 0.89), with model predictive power driven primarily by symptom and CT variables. Conclusions These findings contribute valuable insights into the potential impact of early AP treatment on brain morphology and clinical trajectories and highlight the importance of monitoring the initial treatment responses.

The T Helper (Th)1-Th2 imbalance has been observed during the transition from the clinical high-risk (CHR) state to psychosis. However, it remains unclear whether the complement system influences this imbalance during psychosis onset. This study aimed to investigate the dynamic interplay between complement activation and the Th1-Th2 balance during the progression of psychosis. A prospective case-control study was conducted to evaluate the Th1-Th2 balance, as indicated by interleukin(IL)-1Beta and IL-6 levels, in 49 individuals at CHR for psychosis and 26 age- and sex-matched healthy controls(HC). Based on the Th1-Th2 balance, the samples were divided into two groups: Th1 > Th2 and Th1 < Th2. Additionally, the levels of thirteen complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H, and Mannose-Binding Lectin) were measured at baseline. Correlations between cytokines and complement factors were examined, and longitudinal changes were assessed through a 1-year follow-up period. At baseline, significant differences were observed in complement characteristics (C4, C4b, C5, and B) between Th1 > Th2 and Th1 < Th2 balance states, highlighting variations in complement factors between the CHR and HC groups. In the CHR group, a negative association was noted between Th1-Th2 balance and complement factors, with significant correlations observed for components C4b, C5, I, C3, C4, and B. However, no significant correlation was found in the HC group. At follow-up, the Th1 < Th2 group exhibited a higher proportion of CHR individuals who converted to psychosis compared to the Th1 > Th2 group, indicating a significant association between Th1-Th2 balance and the onset of psychosis (χ2 = 12.09, p = 0.001). This shift in balance was notably linked to baseline complement C4b and C4 levels. Our study reveals a complex interplay between complement and inflammatory factor balance in psychosis onset, highlighting the potential role of complement, particularly associated with baseline C4b and C4 levels, in modulating Th1-Th2 balance and contributing to the pathogenesis of psychosis.

Background and Hypothesis Given that fixation stability is closely linked to cognition, we investigated fixation stability in patients at different stages of schizophrenia, its relationship with cognitive impairments, and its predictive role for conversion to psychosis. Study Design Fixation stability was measured by bivariate contour ellipse area (BCEA), and cognition was assessed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery for 75 patients with first-episode schizophrenia (FES), 75 patients with clinical high-risk (CHR) syndrome, and 75 healthy controls (HCs). After a 1-year longitudinal study, CHR follow-up outcomes were classified as CHR-converters and CHR-nonconverters. Diagnostic model for clinical stages and prediction model for conversion were constructed using logistic regression and Cox regression, respectively. Study Results Patients exhibited fixation instability and cognition impairments compared to HC, with impairments increasing from CHR to FES. In CHR, BCEA negatively correlated with Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery scores, but this correlation was absent in FES. Diagnostic model effectively discriminated HC and FES, with an area under the receiver-operating characteristic curve of 0.914. Among 66 CHR followed up for 1 year, 13 have converted to schizophrenia, with a conversion rate of 19.70%. When divided into large and small BCEA groups (33 each), the conversion rate was 27.27% and 12.12%. Conversion prediction model achieved an area under the receiver-operating characteristic curve of 0.708. Conclusions Our results indicate that fixation instability worsens with schizophrenia progression, which is associated with cognitive impairments. Additionally, BCEA may serve as a biomarker for predicting conversion to psychosis.

BACKGROUND AND HYPOTHESIS:The time taken for an individual who is at the clinical high-risk (CHR) stage to transition to full-blown psychosis may vary from months to years. This temporal aspect, known as the timeframe for conversion to psychosis (TCP), is a crucial but relatively underexplored dimension of psychosis development. STUDY DESIGN:The sample consisted of 145 individuals with CHR who completed a 5-year follow-up with a confirmed transition to psychosis within this period. Clinical variables along with functional variables such as the Global Assessment of Function (GAF) score at baseline (GAF baseline) and GAF-drop from the highest score in the past year. The TCP was defined as the duration from CHR identification to psychosis conversion. Participants were categorized into 3 groups based on TCP: "short" (≤6 months, ≤33.3%), "median" (7-17 months, 33.3%-66.6%), and "long" (≥18 months, ≥66.6%). The quantile regression analysis was applied. STUDY RESULTS:The overall sample had a median TCP of 11 months. Significant differences among the three TCP groups were observed, particularly in GAF-drop (χ2 = 8.806, P = .012), disorganized symptoms (χ2 = 7.071, P = .029), and general symptoms (χ2 = 6.586, P = .037). Greater disorganized symptoms (odds ratio [OR] = 0.824, P = .009) and GAF-drop (OR = 0.867, P = .011) were significantly associated with a shorter TCP, whereas greater general symptoms (OR = 1.198, P = .012) predicted a longer TCP. Quantile regression analysis demonstrated a positive association between TCP and GAF baseline above the 0.7 quantile and a negative association between TCP rank and GAF drop below the 0.5 quantile. CONCLUSIONS:This study underscores the pivotal role of functional characteristics in shaping TCP among individuals with CHR, emphasizing the necessity for a comprehensive consideration of temporal aspects in early prevention efforts.

Background:Cognitive impairment is a core feature of first-episode psychosis (FEP), but its age-associated cognitive patterns remain unclear. Prior studies suggest FEP is associated with baseline cognitive deficits and accelerated decline, yet inconsistencies exist regarding whether cognitive aging in FEP mirrors or diverges from healthy aging. Methods:We compared 378 drug-naive FEP patients and 477 healthy controls (HC) using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Clinical symptoms were evaluated via the Positive and Negative Syndrome Scale (PANSS). Age-correlations with cognitive domains were analyzed via Pearson's coefficients and Fisher's z-transformation. Results:FEP patients showed significant deficits across all cognitive domains (all p < 0.001) and disrupted age-associated cognitive patterns. In HC, age was associated with gradual declines in memory (e.g., HVLT-R r = -0.304, p < 0.001), working memory (r = -0.168, p < 0.001), and learning functions, aligning with normative aging. FEP patients showed a complex pattern: while some executive functions (e.g., Trail Making A) mirrored HC's negative age correlations, social cognition (r = 0.174, p < 0.001), attention (r = 0.125, p = 0.015), and specific learning domains exhibited positive age associations. Group comparisons revealed significant differences in age-cognition relationships for verbal memory, working memory, and overall cognitive composites (all p < 0.0028 after Bonferroni correction), indicating disrupted cognitive aging in FEP. Conclusions:FEP disrupts normative cognitive aging patterns, characterized by atypical decline and compensatory improvements. These findings highlight the need for longitudinal studies to clarify mechanisms and inform age-adapted interventions.

Cognitive impairment plays a crucial role in the development from clinical high-risk(CHR) to schizophrenia-spectrum psychosis. Understanding its dynamic change trajectories has significant preventive value. This study aims to comprehensively explore the dynamic cognitive trajectories of clinical high-risk(CHR) individuals over a three-year period, compare the trajectories among CHR individuals who convert to psychosis(CHR-C), those who do not(CHR-NC), and healthy controls(HC). This prospective study was part of the Shanghai At Risk for Psychosis(SHARP)-extended program. CHR participants, from psychological counseling outpatient clinics and medication - naive, were followed up at baseline (T1), 2 months ± 1 week (T2), 1 year ± 1 month (T3), 2 years ± 1 month (T4), and 3 years ± 1 month (T5). All participants completed the Chinese version of the MATRICS Consensus Cognitive Battery(MCCB) at these five strictly fixed time points to assess neurocognitive function. Conversion to psychosis was determined as main outcome. A total of 43 CHR(median age, 16[IQR, 15–18] years; 14 men[32.6

BACKGROUND: Longitudinal changes in cognitive function may be crucial in predicting clinical outcomes in clinical high-risk (CHR) individuals. In this study, we aimed to investigate the predictive value of baseline cognitive impairment and short-term cognitive changes for nonremission and conversion to psychosis in individuals at CHR for psychosis compared with healthy control individuals (HCs). METHODS: This study used a multiple-group prospective design with a 3-year follow-up. CHR individuals and HCs were assessed at baseline and at a 2-month follow-up. Neuropsychological performance was evaluated using the Chinese version of the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery. RESULTS: The study included 310 CHR individuals and 93 HCs. Significant improvements in predicting nonremission in CHR individuals were observed when incorporating cognitive changes over 2 months (area under the receiver operating characteristic curve [AUC] for baseline cognition, 0.690; AUC for changes, 0.819; z = 3.365, p < .001). Key predictors included the Hopkins Verbal Learning Test-Revised ((3 = 0.083, p = .003), Wechsler Memory Scale-III spatial span ((3 = 0.330, p < .001), and Brief Visuospatial Memory Test-Revised ((3 = 0.127, p < .001). Conversely, predicting conversion to psychosis showed no significant difference between baseline and 2-month cognitive changes (AUC for baseline cognition, 0.667; AUC for changes, 0.666; z = 0.021, p = .242). CONCLUSIONS: The findings underscore the importance of dynamic cognitive monitoring in CHR individuals. Shortterm cognitive changes significantly enhanced the prediction of nonremission but did not add predictive value for conversion to psychosis beyond baseline assessments. Specific cognitive domains, such as verbal learning and working memory, were particularly valuable for predicting clinical outcomes.

The auditory steady-state response (ASSR) is a robust index for schizophrenia. Abnormal phase-amplitude coupling (PAC) in schizophrenia might be influenced by the confounding factors of illness stages and antipsychotic treatments. To exclude the effects of confounding factors, we examined abnormal PAC in antipsychotic-naïve patients with first-episode schizophrenia (FES) during the ASSR. 67 FES and 84 healthy controls (CON) were recruited and their EEG data were collected during the 20 Hz ASSR, 30 Hz ASSR, 40 Hz ASSR, and resting states. All the possible PAC patterns at Fz were compared between FES and CON, and the electrodes of abnormal PACs were explored. Results showed that FES had significantly higher beta-high gamma PAC at the prefrontal cortex and lower theta-low gamma PAC at the fronto-central cortex than CON during all the three ASSR blocks but not in the Resting block. FES showed lower correlations of PAC values between any two of the ASSR blocks than CON. Beta-high gamma PAC was negatively correlated with the cognitive scores of visual learning and attention, while theta-low gamma PAC was positively correlated with the score of symbol coding. Abnormal PAC of FES in specific brain regions may provide electrophysiological biomarkers for abnormal circuits.