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BACKGROUND: Impaired gamma band oscillation, specifically 40-Hz auditory steady state response (ASSR) has been robustly found in schizophrenia, while there is relatively little evidence characterizing the ASSR before full-blown psychosis. OBJECTIVE: To characterize gamma-band ASSR in populations at clinical high-risk for psychosis (CHR). METHODS: One hundred and seven CHR subjects and sixty-five healthy control (HC) subjects were included and completed clinical assessments, the ASSR paradigm of electroencephalography (EEG) and cognitive assessments. Both indices of event-related spectrum perturbation (ERSP) and intertrial coherence (ITC) in response to 20-Hz, 30-Hz and 40-Hz click sounds were respectively qualified and compared between these two groups, as well as the relationship to clinical psychopathology and cognitive function was assessed. RESULTS: At 40-Hz click sounds, ERSP in HC group (1.042 ± 0.047) was statistical significantly increased than that in CHR group (0.873 ± 0.036) (p = 0.005)ï¼at 30-Hz, ERSP in HC group (0.536 ± 0.024) was increased than that in CHR group (0.483 ± 0.019), but the difference was trend statistical significance (p = 0.083)ï¼at 20-Hz, ERSP in HC group (0.452 ± 0.017) was not different significantly from CHR group (0.418 ± 0.013) (p = 0.104). ERSP of the HC group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of the three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001ï¼20-Hz vs. 30-Hz: p = 0.003). Similarly, ERSP of the CHR group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of these three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001ï¼20-Hz vs. 30-Hz: p = 0.002). A statistically significant small positive correlation of 40-Hz ERSP with signal processing speed score was observed in the HC group (ρ = 0.27, p = 0.029). A statistically significant small negative correlation of 40-Hz ERSP with visual learning score was observed in the CHR group (ρ = -0.22, p = 0.023). CONCLUSION: Impaired 40-Hz but undamaged hierarchical organization mode of auditory steady state presented in the CHR populations. Abnormal 40 Hz ASSR for CHR might be associated with cognitive functions, such as information processing speed and visual memory.
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BACKGROUND: Structural and functional neurobiological abnormalities have been observed in schizophrenia. Previous studies have concentrated on specific illness stages, obscuring relationships between functional/structural changes and disorder progression. The present study aimed to quantify structural and functional abnormalities across different clinical stages using functional near-infrared spectroscopy (fNIRS) and structural magnetic resonance imaging (sMRI). METHODS: Fifty-four participants with first-episode schizophrenia (FES), 120 with clinically high risk of psychosis (CHR), and 111 healthy controls (HCs) underwent functional near-infrared spectroscopy (fNIRS) to measure oxyhemoglobin (Oxy-Hb) during the verbal fluency task. Among them, 28FES, 64CHR and 55HC also finished sMRI. Oxy-Hb and gray matter volume (GMV) were compared among the three groups while controlling for covariates, including age, sex, years of education, and task performance. Mediation analysis was utilized to determine the mediating effect of GMV on Oxy-Hb and cognition. RESULTS: Compared with the HC group, CHR and FES groups showed significantly reduced brain activity. However, there were no significant differences between the FES and CHR. Pronounced GMV increase in the right frontal pole area (F = 4.234, p = 0.016) was identified in the CHR and FES groups. Mediation analysis showed a significant mediation effect of the right frontal pole GMV between Channel 31 Oxy-Hb and processing speed (z = 2.105, p = 0.035) and attention/vigilance (z = 1.992, p = 0.046). CONCLUSIONS: Brain activation and anatomical deficits were observed in different brain regions, suggesting that anatomical and functional abnormalities are dissociated in the early stages of psychosis. The relationship between neural activity and anatomy may reflect a specific pathophysiology related to cognitive deterioration in schizophrenia.
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BACKGROUND: Restricted scan path mode is hypothesized to explain abnormal scanning patterns in patients with schizophrenia. Here, we calculated entropy scores (drawing upon gaze data to measure the statistical randomness of eye movements) to quantify how strategical and random participants were to process image stimuli. METHODS: Eighty-six patients with first-episode schizophrenia (FES), 124 individuals at clinical high risk (CHR) for psychosis, and 115 healthy controls (HCs) completed an eye-tracking examination for freely viewing 35 static images (each presented 10s) and cognitive assessments. We compared the group differences in overall entropy score, as well as entropy scores under various conditions. Furthermore, we also investigated the correlation between entropy scores and symptoms along with cognitive function. RESULTS: Increased overall entropy scores were noted in FES and CHR groups relative to HCs, and these differences were already apparent within 0â¼2.5s. In addition, the CHR group exhibited higher entropy when viewing low-meaning images compared to HCs. Moreover, the entropy within 0â¼2.5s showed significant correlations with negative symptoms in the FES group, Attention/Vigilance scores in the CHR group, as well as Speed of processing and Attention/Vigilance scores across all three groups. CONCLUSIONS: The results indicate that FES and CHR individuals scan pictures more randomly and less strategically than HCs. These patterns also correlate with clinical symptoms and neurocognition. The present study highlights the potential of the eye movement entropy measure as a neurophysiological marker for early psychosis.
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BACKGROUND AND HYPOTHESIS: Substantive inquiry into the predictive power of eye movement (EM) features for clinical high-risk (CHR) conversion and their longitudinal trajectories is currently sparse. This study aimed to investigate the efficiency of machine learning predictive models relying on EM indices and examine the longitudinal alterations of these indices across the temporal continuum. STUDY DESIGN: EM assessments (fixation stability, free-viewing, and smooth pursuit tasks) were performed on 140 CHR and 98 healthy control participants at baseline, followed by a 1-year longitudinal observational study. We adopted Cox regression analysis and constructed random forest prediction models. We also employed linear mixed-effects models (LMMs) to analyze longitudinal changes of indices while stratifying by group and time. STUDY RESULTS: Of the 123 CHR participants who underwent a 1-year clinical follow-up, 25 progressed to full-blown psychosis, while 98 remained non-converters. Compared with the non-converters, the converters exhibited prolonged fixation durations, decreased saccade amplitudes during the free-viewing task; larger saccades, and reduced velocity gain during the smooth pursuit task. Furthermore, based on 4 baseline EM measures, a random forest model classified converters and non-converters with an accuracy of 0.776 (95% CI: 0.633, 0.882). Finally, LMMs demonstrated no significant longitudinal alterations in the aforementioned indices among converters after 1 year. CONCLUSIONS: Aberrant EMs may precede psychosis onset and remain stable after 1 year, and applying eye-tracking technology combined with a modeling approach could potentially aid in predicting CHRs evolution into overt psychosis.
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Response inhibition deficits in schizophrenia (SZ) are accompanied by reduced neural activities using event-related potential (ERP) measurements. However, it remains unclear whether the reduction in inhibition-related ERPs in SZ is contingent upon prepotent motor tendencies. This study aimed to examine the relationship between ERP markers of prepotent motor activity (lateralised readiness potential, LRP) and response inhibition (P3) by collecting behavioural and EEG data from healthy control (HC) subjects and SZ patients during a modified Go/No-Go task. A trial-averaged analysis revealed that SZ patients made more commission errors in No-Go trials compared with HC subjects, although there was no significant difference in the inhibition-related P3 effect (i.e. larger P3 amplitudes in No-Go compared with Go trials) between the two groups. Subsequently, No-Go trials were sorted and median-split into bins of stronger and weaker motor tendencies. Both HC and SZ participants made more commission errors when faced with stronger motor tendencies. The LRP-sorted P3 data indicated that HC subjects exhibited larger P3 effects in response to stronger motor tendencies, whereas this trial-by-trial association between P3 and motor tendencies was absent in SZ patients. Furthermore, SZ patients displayed diminished P3 effects in No-Go trials with stronger motor tendencies but not in trials with weaker motor tendencies, relative to HC subjects. Taken together, these findings suggest that SZ patients are unable to dynamically adjust inhibition-related neural activities in response to changing inhibitory control demands and emphasise the importance of considering prepotent motor activity when investigating the neural mechanisms underlying response inhibition deficits in SZ.
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Esquizofrenia , Humanos , Potenciais Evocados/fisiologia , Inibição Psicológica , Atividade Motora , Eletroencefalografia , Tempo de Reação/fisiologiaRESUMO
Error monitoring plays a key role in people's adjustment to social life. This study aimed to examine the direct (DE) and indirect effects (IDE) of error monitoring, as indicated by error-related negativity (ERN), on social functioning in a clinical cohort from high-risk (APS) to first-episode psychosis (FEP). This study recruited 100 outpatients and 49 healthy controls (HC). ERN was recorded during a modified flanker task; social functioning was evaluated using the social scale of global functioning. The path analysis was executed using the "lavaan" package. When controlling for age and education, the clinical cohort had a smaller ERN than the HC group (F1, 145 = 19.58, p < 0.001, partial η2 = 0.12, 95%CI: 0.04-0.22). ERN demonstrated no substantial direct impact on current social functioning; however, it manifested indirect influences on social functioning via the disorganization factor of the Positive and Negative Syndrome Scale, both with (standardized IDE: -0.139, p = 0.009) and without (standardized IDE: -0.087, p = 0.018) accounting for the diagnosis, defined as a dummy variable (FEP = 1 and APS = 0) and included as a covariate. These findings suggest that error monitoring, as indicated by ERN, may serve as a potential prognostic indicator of social functioning in patients with psychosis.
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Transtornos Psicóticos , Interação Social , Humanos , Transtornos Psicóticos/diagnóstico , Ajustamento SocialRESUMO
We aimed to determine the relationship between electrophysiological signatures of error monitoring and clinical insight among outpatients with attenuated psychosis syndrome (APS) and first-episode psychosis (FEP). Error-related negativity (ERN), error positivity (Pe), and correct response negativity (CRN) were recorded during a modified flanker task for patients with FEP (n = 32), APS individuals (n = 58), and healthy controls (HC, n = 49). Clinical insight was measured using the Schedule of Assessment of Insight (SAI) and included awareness of illness (SAI-illness), relabeling of specific symptoms (SAI-symptoms), and treatment compliance (SAI-treatment). Compared with HC, patients with FEP showed smaller ERN (p < 0.001) and Pe (p = 0.011) amplitudes and individuals with APS showed smaller ERN amplitude (p = 0.009). No significant difference in CRN amplitude was observed among the groups. A smaller negative amplitude of ERN correlated with a lower score on SAI-symptoms (b = -0.032, 95% CI: 0.062 to -0.002, p = 0.035) and a decreased total score of SAI (b = -0.096, 95% CI: 0.182 to -0.010, p = 0.029). This links were adjusted for age, education, and diagnosis (a dummy variable with FEP = 1 and APS = 0), and was independent of positive symptoms. SAI-illness was predominantly influenced by diagnosis, whereas SAI-treatment was additionally affected by disorganized communications. Neither Pe nor CRN amplitude exhibited an association with clinical insight. Unconscious error detection, as indicated by ERN, may aid individuals at the preliminary stage of psychosis in recognizing the unusual symptoms.
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Potenciais Evocados , Transtornos Psicóticos , Humanos , Potenciais Evocados/fisiologia , Eletroencefalografia , Pacientes Ambulatoriais , Tempo de Reação/fisiologia , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnósticoRESUMO
INTRODUCTION: Transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (lDLPFC) has been widely used as a treatment for major depressive disorder (MDD) in the past two decades. Different methods for localising the lDLPFC target include the '5 cm' method, the F3 method and the neuro-navigational method. However, whether TMS efficacies differ between the three targeting methods remains unclear. We present a protocol for a systematic review and network meta-analysis (NMA) to compare the efficacies of TMS treatments using these three targeting methods in MDD. METHODS AND ANALYSIS: Relevant studies reported in English or Chinese and published up to May 2023 will be identified from searches of the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, China National Knowledge Infrastructure, Wan Fang Database, Chinese BioMedical Literature Database, and China Science and Technology Journal Database. We will include all randomised controlled trials assessing the efficacy of an active TMS treatment using any one of the three targeting methods compared with sham TMS treatment or comparing efficacies between active TMS treatments using different targeting methods. Interventions must include a minimum of 10 sessions of high-frequency TMS over the lDLPFC. The primary outcome is the reduction score of the 17-item Hamilton Depression Rating Scale, 24-item Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale. The dropout rate is a secondary outcome representing the TMS treatment's acceptability. Pairwise meta-analyses and a random-effects NMA will be conducted using Stata. We will use the surface under the cumulative ranking curve to rank the different targeting methods in terms of efficacy and acceptability. ETHICS AND DISSEMINATION: This systematic review and NMA does not require ethics approval. The results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023410273.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/terapia , Estimulação Magnética Transcraniana , Metanálise em Rede , Revisões Sistemáticas como Assunto , Projetos de Pesquisa , Metanálise como AssuntoRESUMO
OBJECTIVE: Intermittent theta burst stimulation (iTBS) is based on the phase-amplitude coupling (PAC) pattern. We aimed to investigate the effect of iTBS on PAC in resting electroencephalography (EEG), which may provide insight into the underlying mechanism. METHODS: Twenty-one healthy volunteers were recruited and received both active and sham neuroimaging-guided iTBS on two separate days, which was precisely delivered to the right superior temporal gyrus. On each experimental day, resting EEG was recorded before and after stimulation for each participant. PACs across electrodes and frequency bands were calculated and compared to investigate the effect of iTBS. RESULTS: Theta (4-6 Hz) -low gamma (45-55 Hz) PAC over the stimulation site had a significant interaction effect, which increased after the active iTBS but did not differ after the sham iTBS. No significant interaction effect occurred in other cross-frequency couplings such as delta-low gamma, alpha-low gamma, delta-high gamma, theta-high gamma, or alpha-high gamma PAC in the region of interest. CONCLUSION: iTBS selectively modulated theta-low gamma PAC at the stimulation area, which exhibited both region- and frequency- specificity. This suggests that PAC may be a bridge connecting external neuromodulation to internal neuroplasticity.
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Ritmo Teta , Estimulação Magnética Transcraniana , Humanos , Ritmo Teta/fisiologia , Eletroencefalografia , Plasticidade Neuronal/fisiologia , Voluntários SaudáveisRESUMO
BACKGROUND: Antipsychotic treatment has been shown to yield hippocampal and amygdalar volumetric changes in first-episode schizophrenia (FES). However, whether antipsychotic induced volumetric changes interact with age remains unclear. METHODS: The current study includes data from 120 medication naïve FES patients and 110 matched healthy controls (HC). Patients underwent MRI scans before (T1) and after (T2) antipsychotic treatment. HCs underwent MRI scans at baseline only. The hippocampus and amygdala were segmented via Freesurfer 7. General linear models were conducted to investigate the effect of age by diagnosis interaction on baseline volume. Linear mixed models (LMM) were used to detect the effect of age on volumetric changes from pre to post treatment in FES. RESULTS: GLM revealed a trending effect (F = 3.758, p = 0.054) of age by diagnosis interaction on the baseline volume of the left (whole) hippocampus, with older FES patients showing smaller hippocampal volumes, relative to HC, when controlled sex, education years, and ICV. LMM showed a significant age by time-point interaction effect (F = 4.194, estimate effect = -1.964, p = 0.043) on left hippocampal volume in all FES and significant time effect(F = 6.608,T1-T2(estimate effect) = 62.486, p = 0.011), whereby younger patients showed greater hippocampal volumetric decreases following treatment. At the subfield level, a significant time effect emerged in left molecular_layer_HP (F = 4.509,T1-T2(estimate effect) = 12.424, p = 0.032, FDR corrected) and left cornu ammonis(CA)4 (F = 4.800,T1-T2(estimate effect) = 7.527, p = 0.046, FDR corrected), implying volumetric reduction after treatment in these subfields. CONCLUSIONS: Our findings suggest that age plays an important role in the neuroplastic mechanisms of initial antipsychotics on the hippocampus and amygdala of schizophrenia.
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Antipsicóticos , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Antipsicóticos/farmacologia , Hipocampo/diagnóstico por imagem , Modelos Lineares , Tonsila do Cerebelo/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: Left ventrolateral prefrontal cortex (VLPFC) has been demonstrated to be a crucial region involved in the down-regulation of negative affect by cognitive reappraisal. However, the neural evidence of causality is still lacking. The current study was to investigate the contribution of left VLPFC in cognitive reappraisal by using single-pulse transcranial magnetic stimulation (spTMS) and electroencephalogram (EEG). METHODS: Fifteen participants repeated the cognitive reappraisal task at different TMS settings: no stimulation, spTMS applied at 300 ms after image onset to the left VLPFC, and to the vertex as a control site. EEG and behavioral data were concurrently recorded. TMS-evoked potential (TEP) and late positive potential (LPP) were investigated. RESULTS: In cognitive reappraisal, left VLPFC stimulation elicited stronger TEPs than vertex stimulation at 180 ms after TMS onset. Increased source activation of TEPs was identified in the precentral gyrus. Emotion regulation by reappraisal enlarged the trough of TEP at stimulation site. The left VLPFC stimulation led to enhanced LPP in cognitive reappraisal, which was negatively correlated with self-reported arousal. CONCLUSIONS: The TMS stimulation over left VLPFC influences the cognitive reappraisal process by potentiating the neural responses. Accordingly, the cortical region responsible for the execution of cognitive reappraisal is activated. The modulated neural activity is related to the behavioral response. The present study provided neural signatures for the facilitated execution of emotion regulation by left VLPFC stimulation, potentially contributing to the therapeutic protocols for mood disorders.
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Regulação Emocional , Humanos , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Estimulação Magnética Transcraniana/métodos , Córtex Pré-Frontal/fisiologia , CogniçãoRESUMO
BACKGROUND AND HYPOTHESIS: Cognitive deficits in visuospatial learning (VSL) are highly associated with an increased risk of developing psychosis among populations with clinical high risk (CHR) for psychosis. Early interventions targeting VSL enhancement are warranted in CHR but remain rudimentary. We investigated whether personalized transcranial magnetic stimulation (TMS) over the left parieto-hippocampal network could improve VSL performance in CHR patients and if it could reduce the risk of psychosis conversion within 1 year. STUDY DESIGN: Sixty-five CHR patients were randomized to receive active or sham TMS treatments using an accelerated TMS protocol, consisting of 10 sessions of 20 Hz TMS treatments within 2 days. TMS target was defined by individual parieto-hippocampal functional connectivity and precisely localized by individual structural magnetic resonance imaging. VSL performance was measured using Brief Visuospatial Memory Test-Revised included in measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery (MCCB). Fifty-eight CHR patients completed the TMS treatments and MCCB assessments and were included in the data analysis. STUDY RESULTS: We observed significant VSL improvements in the active TMS subgroup (Cohen's d = 0.71, P < .001) but not in the sham TMS subgroup (Cohen's d = 0.07, P = .70). In addition, active TMS improved the precision of VSL performance. At a 1-year follow-up, CHR patients who received active TMS showed a lower psychosis conversion rate than those who received sham TMS (6.7% vs 28.0%, χ2 = 4.45, P = .03). CONCLUSIONS: Our findings demonstrate that personalized TMS in the left parieto-hippocampal network may be a promising preventive intervention that improves VSL in CHR patients and reduces the risk of psychosis conversion at follow-up.
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Transtornos Cognitivos , Disfunção Cognitiva , Transtornos Psicóticos , Esquizofrenia , Humanos , Estimulação Magnética Transcraniana/métodos , Esquizofrenia/complicações , Esquizofrenia/terapia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controleRESUMO
BACKGROUND: Clinical high risk (CHR) of psychosis is characterized by cognitive impairment in social interaction. However, research investigating the neurobiological underpinnings of social interactions and interpersonal relationships in CHR participants is sparse. METHODS: 21 CHR and 54 healthy controls (HCs) participated in the study. Dyads were formed between one CHR, one sex-matched HC, and two sex-matched HCs comprising 19 CHR-HC dyads and 19 HC-HC dyads. The concentration changes of oxyhemoglobin and deoxyhemoglobin were examined during a two-block button-press "cooperation" and "competition" task using functional near-infrared spectroscopy(fNIRS) hyperscanning technology. CHR diagnosis and psychopathological assessments were performed by Structured Interview for Prodromal Syndromes (SIPS) and Scale of Prodromal Symptoms (SOPS). Neural synchronizations were compared between CHR-HC dyads and HC-HC dyads. Correlation analyses were performed to identify the relationship between neural synchronization, clinical syndrome and cognition. RESULTS: During the cooperation, but not the competition task, the CHR-HC dyads showed reduced inter-brain neural synchronization (INS) in the right inferior frontal gyrus (IFG) compared to the HC-HC dyads. INS also showed a positive correlation with the average cooperation rate. Moreover, the reduced INS in the CHR-HC group was significantly correlated with symptoms score of suspiciousness/persecutory ideas and movement disorders. CONCLUSIONS: The decreased INS in right IFG during cooperation could account for CHR's cognitive impairment of social interaction. Our findings provide evidence that inter-brain neural synchronization potentially represents a biomarker of social interaction deficits of CHR.
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Mapeamento Encefálico , Transtornos Psicóticos , Humanos , Espectroscopia de Luz Próxima ao Infravermelho , Interação Social , Oxiemoglobinas , Córtex Pré-Frontal/diagnóstico por imagem , Encéfalo , Transtornos Psicóticos/diagnóstico por imagem , Relações InterpessoaisRESUMO
Eye movement abnormalities have been established as an "endophenotype" of schizophrenia. However, less is known about the possibility of these abnormalities as biomarkers for psychosis conversion among clinical high risk (CHR) populations. In the present study, 108 CHR individuals and 70 healthy controls (HC) underwent clinical assessments and eye-tracking tests, comprising fixation stability and free-viewing tasks. According to three-year follow-up outcomes, CHR participants were further stratified into CHR-converter (CHR-C; n = 21) and CHR-nonconverter (CHR-NC; n = 87) subgroups. Prediction models were constructed using Cox regression and logistic regression. The CHR-C group showed more saccades of the fixation stability test (no distractor) and a reduced saccade amplitude of the free-viewing test than HC. Moreover, the CHR-NC group exhibited excessive saccades and an increased saccade amplitude of the fixation stability test (no distractor; with distractor) compared with HC. Furthermore, two indices could effectively discriminate CHR-C from CHR-NC with an area under the receiver-operating characteristic (ROC) curve of 0.80, including the saccade number of the fixation stability test (no distractor) and the saccade amplitude of the free-viewing test. Combined with negative symptom scores of the Scale of Prodromal Symptoms, the area was 0.81. These findings support that eye movement alterations might emerge before the onset of clinically overt psychosis and could assist in predicting psychosis transition among CHR populations.
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Transtornos Psicóticos , Esquizofrenia , Humanos , Movimentos Oculares , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Fatores de Risco , Movimentos Sacádicos , Sintomas ProdrômicosRESUMO
BACKGROUND: Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. METHODS: Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. RESULTS: Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)-left inferior temporal gyrus (ITG), right IFG-left ITG, right IFG-left middle frontal gyrus (MFG), and right IFG-right MFG in the FES group. CONCLUSION: Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.
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Esquizofrenia , Substância Branca , Humanos , Substância Branca/patologia , Corpo Caloso/patologia , Imagem de Tensor de Difusão , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Esquizofrenia/patologia , Herança Multifatorial , Anisotropia , EncéfaloRESUMO
Background: Self-reflectiveness, one dimension of cognitive insight, plays a protective role in an individual's mental state. Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness. Aims: This study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis. Methods: A total of 181 subjects, including individuals with attenuated positive symptoms (APS, n=122) and patients with first-episode psychosis (FEP, n=59), completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale. All subjects were classified into three groups according to their level of self-reflectiveness: low level (LSR, n=59), medium level (MSR, n=67) and high level (HSR, n=55). Both linear and non-linear relationships between self-reflectiveness and clinical symptoms were explored. Results: More individuals with APS were classified into the MSR group, while more patients with FEP were classified into the LSR group. The LSR group demonstrated less awareness of illness than the MSR and HSR groups, more stereotyped thinking and poorer impulse control but less anxiety than the MSR group, and lower levels of blunted affect and guilt feelings than the HSR group. The MSR group demonstrated lower stereotyped thinking than the HSR group. Compared to the LSR group, the MSR group had increased self-reflectiveness, improved awareness of illness, decreased stereotyped thinking, and better impulse control, but increased feelings of guilt. The HSR group showed increased stereotyped thinking when compared to the MSR group, but the other variables did not change significantly between these two groups. Overall, self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness, a U-shaped relationship with stereotyped thinking and poor impulse control, and an almost linear relationship with anxiety and guilt feelings. Conclusions: Self-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.
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Background: Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks. Abnormal neural oscillations have been discovered in patients with schizophrenia. However, there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis (CHR-P). The brain signals recorded by the magnetoencephalography (MEG) technique are not to be disrupted by the skull and scalp. Methods: In this study, we applied the MEG technique to record the resting-state neural activities in CHR-P. This was followed by a detailed MEG analysis method including three steps: (1) preprocessing, which was band-pass filtering based on the 0.5-60 Hz frequency range, removal of 50 Hz power frequency interference, and removal of electrocardiography (ECG) and electrooculography (EOG) artefacts by independent component analysis; (2) time-frequency analysis, a multitaper time-frequency transformation based on the Hanning window, and (3) source localisation, an exact low-resolution brain electromagnetic tomography. The method was verified by comparing a participant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state. Results: Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band (4-7 Hz) and the delta frequency band (1-3 Hz). Also, relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band. Conclusions: Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups. Further work will validate these characteristics in CHR-P cohorts.
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Background: Clinical high risk (CHR) of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a psychotic episode. CHR exhibits cognitive deficits; however, the underlying neurobiological mechanisms remain unclear. This study aimed to investigate whether brain activation measured by the levels of oxygenated hemoglobin (oxy-Hb) in CHR subjects could be correlated with cognitive deficits. Methods: Fifty-eight CHR individuals who fulfilled the criteria for attenuated positive syndrome as specified in the Structured Interview for Prodromal Syndrome (SIPS) and the Scale of Prodromal Syndrome (SOPS) and 58 age- and sex-matched healthy participants were included in the study. All subjects completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) that includes tests measuring attention, verbal memory, verbal fluency, executive function, and general intelligence. Functional near-infrared spectroscopy (fNIRS) was used to measure the level of oxy-Hb in the dorsolateral prefrontal and frontotemporal cortices. Results: We observed significantly decreased oxy-Hb levels in channel 32 (located in the right superior temporal gyrus, rSTG)) within the CHR individuals compared with that in the healthy controls (HCs) (t=-3.44, Bonferroni-corrected p=0.002), indicating lower brain activity. A significant positive correlation was observed between task-related ß values and working memory in the CHR group (r=0.35, p=0.008). Conclusions: The brain activation of rSTG is abnormal among subjects at clinicial high risk for psychosis. This abnormality is probably associated with the neural mechanisms of deficits in the working memory during the early stage of psychosis.
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Poor cognitive insight, including low self-reflectiveness and high self-certainty, contributes to poor clinical insight, which includes awareness of illness, relabelling of specific symptoms, and treatment compliance. However, inconsistent results regarding cognitive insight among individuals at clinical high risk of psychosis (CHR) have been reported. This study investigated the difference in cognitive insight among groups with different severity of positive symptoms and analysed the effect of cognitive insight on clinical insight in each group. All participants, including CHR individuals with 3 or 4 points (L-Pitem, n = 85) and 5 points (H-Pitem, n = 37) on any positive-symptom item of the Scale of Prodromal Syndromes, and patients with first-episode psychosis (FEP, n = 59), were measured cognitive and clinical insight using the Beck Cognitive Insight Scale and the Schedule of Assessment of Insight, respectively. The self-reflectiveness of cognitive insight was highest in the L-Pitem group and lowest in the FEP group. Self-reflectiveness was positively associated with awareness of illness in the L-Pitem and FEP groups; both self-reflectiveness and self-certainty was positively associated with treatment compliance in the L-Pitem group. Improving self-reflectiveness of cognitive insight may conduce to good clinical insight. Self-certainty may have different implication to individuals with mild prodromal symptoms.
Assuntos
Transtornos Psicóticos , Cognição , Humanos , Sintomas Prodrômicos , Transtornos Psicóticos/psicologiaRESUMO
BACKGROUND: Depression is a common debilitating mental disorder caused by various factors. Identifying and diagnosing depression are challenging because the clinical evaluation of depression is mainly subjective, lacking objective and quantitative indicators. The present study investigated the value and significance of eye movement measurements in distinguishing depressed patients from controls. METHODS: Ninety-five depressed patients and sixty-nine healthy controls performed three eye movement tests, including fixation stability, free-viewing, and anti-saccade tests, and eleven eye movement indexes were obtained from these tests. The independent t-test was adopted for group comparisons, and multiple logistic regression analysis was employed to identify diagnostic biomarkers. Support vector machine (SVM), quadratic discriminant analysis (QDA), and Bayesian (BYS) algorithms were applied to build the classification models. RESULTS: Depressed patients exhibited eye movement anomalies, characterized by increased saccade amplitude in the fixation stability test; diminished saccade velocity in the anti-saccade test; and reduced saccade amplitude, shorter scan path length, lower saccade velocity, decreased dynamic range of pupil size, and lower pupil size ratio in the free-viewing test. Four features mentioned above entered the logistic regression equation. The classification accuracies of SVM, QDA, and BYS models reached 86.0%, 81.1%, and 83.5%, respectively. CONCLUSIONS: Depressed patients exhibited abnormalities across multiple tests of eye movements, assisting in differentiating depressed patients from healthy controls in a cost-effective and non-invasive manner.