Compensatory thickening of cortical thickness in early stage of schizophrenia.

Brain structural abnormality has been observed in the prodromal and early stages of schizophrenia, but the mechanism behind it is not clear. In this study, to explore the association between cortical abnormalities, metabolite levels, inflammation levels and clinical symptoms of schizophrenia, 51 drug-naive first-episode schizophrenia (FES) patients, 51 ultra-high risk for psychosis (UHR), and 51 healthy controls (HC) were recruited. We estimated gray matter volume (GMV), cortical thickness (CT), concentrations of different metabolites, and inflammatory marks among four groups (UHR converted to psychosis [UHR-C], UHR unconverted to psychosis [UHR-NC], FES, HC). UHR-C group had more CT in the right lateral occipital cortex and the right medial orbito-frontal cortex (rMOF), while a significant reduction in CT of the right fusiform cortex was observed in FES group. UHR-C group had significantly higher concentration of IL-6, while IL-17 could significantly predict CT of the right fusiform and IL-4 and IL-17 were significant predictors of CT in the rMOF. To conclude, it is reasonable to speculate that the increased CT in UHR-C group is related to the inflammatory response, and may participate in some compensatory mechanism, but might become exhaustive with the progress of the disease due to potential neurotoxic effects.

Models of mild cognitive deficits in risk assessment in early psychosis.

BACKGROUND: Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. METHODS: A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. RESULTS: Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. CONCLUSIONS: The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

Impacts of risk thresholds and age on clinical high risk for psychosis: a comparative network analysis.

One of the main goals for supporting people with a psychotic disorder is early detection and intervention, and the detection of Clinical High Risk (CHR) is a major challenge in this respect. This study sought to compare core symptoms of CHR for psychosis networks based on two CHR self-assessment tools, across different risk thresholds and age groups. This cross-sectional online investigation analyzed 936 individuals for CHR, in France and the UK, with the Prodromal Questionnaire-16 (PQ-16) and the Perceptual and Cognitive Aberrations (PCA). Twelve different symptom networks were constructed, assessing relationships, compactness, centrality, predictability, and comparisons between them, based on different thresholds and age groups. In the above-threshold PQ-16 network, the most central symptom was "Voices or whispers"; in the PCA network, the most central symptom was "Non-relevant thoughts distract or bother". They presented low overall predictability. No significant difference was found between them. This study makes three key contributions. First, this cross-network analyses highlight the relative importance of some central symptoms. Secondly, comparisons between networks demonstrate the unity of the CHR construct across scales, thresholds, and ages, affirming its phenotypic homogeneity, an essential issue for patient care pathways. Thirdly, the low average network predictability suggests the existence of unconsidered symptoms within these CHR networks. These results shed light on the organization of CHR symptoms using routine clinical questionnaires, offering insights for preventive targets in a logic of precision semiology.

Vocational functioning in young people accessing services for first-episode psychosis and ultra-high risk of psychosis: A longitudinal naturalistic cohort study.

AIMS: Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment. METHODS: This is a naturalistic sample of young people aged 12-25 with FEP (n = 1574) and UHR (n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time. RESULTS: On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment. CONCLUSION: While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care.

The full spectrum of clinical stages of psychosis at prison entry: prevalence and concurrent validity of symptom screening.

PURPOSE: Despite the high rates of psychotic disorders amongst people in prison, current prison mental health screening approaches have not included assessment of the full psychosis spectrum to capture those at-risk of an emerging psychosis as well as those with established illness nor assessed the concurrent validity of psychosis symptom screening. METHODS: Using a clinical staging approach to establish the prevalence of Ultra High Risk (UHR), first episode of psychosis (FEP) and established psychosis (EP) groups, 291 adults entering custody in two prison reception centres in NSW completed a two-stage (screening and validation) interview process. The Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to determine the clinical stages of psychosis and concurrent validity of symptom screening in identifying individuals on the psychosis spectrum was formally assessed. RESULTS: Amongst men and women entering prison, almost one quarter (24.1%) met UHR criteria, 5.1% met the FEP threshold and 10.6% had an established psychosis. Those on the psychosis spectrum reported greater disadvantage across sociodemographic and justice factors. The presence of perceptual disturbance and paranoid beliefs emerged as the two best screening items for identifying those with an underlying psychosis spectrum illness. CONCLUSION: The prevalence of psychosis spectrum illness, including the UHR state, amongst those entering prison is high. Current prison mental health approaches should include screening for the presence of perceptual disturbances and paranoid beliefs to improve the detection of psychosis spectrum illness.

Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

AIM: Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. METHODS: We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. RESULTS: The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. CONCLUSIONS: Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis.

INTRODUCTION: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). METHODS: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. RESULTS: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η2) = 0.051), a group effect related to IL-1ß (F = 4.590, p = 0.036, η2 = 0.062), and IL-2 (F = 7.521, p = 0.011, η2 = 0.212), but no time × group effect. DISCUSSION: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

Global reward processing deficits predict negative symptoms transdiagnostically and transphasically in a severe mental illness-spectrum sample.

Reward processing impairments are a key factor associated with negative symptoms in those with severe mental illnesses. However, past findings are inconsistent regarding which reward processing components are impaired and most strongly linked to negative symptoms. The current study examined the hypothesis that these mixed findings may be the result of multiple reward processing pathways (i.e., equifinality) to negative symptoms that cut across diagnostic boundaries and phases of illness. Participants included healthy controls (n = 100) who served as a reference sample and a severe mental illness-spectrum sample (n = 92) that included psychotic-like experiences, clinical high-risk for psychosis, bipolar disorder, and schizophrenia participants. All participants completed tasks measuring four RDoC Positive Valence System constructs: value representation, reinforcement learning, effort-cost computation, and hedonic reactivity. A k-means cluster analysis of the severe mental illness-spectrum samples identified three clusters with differential reward processing profiles that were characterized by: (1) global reward processing deficits (22.8%), (2) selective impairments in hedonic reactivity alone (40.2%), and (3) preserved reward processing (37%). Elevated negative symptoms were only observed in the global reward processing cluster. All clusters contained participants from each clinical group, and the distribution of these groups did not significantly differ among the clusters. Findings identified one pathway contributing to negative symptoms that was transdiagnostic and transphasic. Future work further characterizing divergent pathways to negative symptoms may help to improve symptom trajectories and personalized treatments.

Longitudinal evaluation on negative symptoms in young people at Ultra-High Risk (UHR) of psychosis: results from a 2-year follow-up study in a real-world care setting.

Negative Symptoms (NS) severely affect real-world functioning also in young people at UHR for developing psychosis. However, longitudinal research on beneficial effects of specialized treatments for NS in UHR people is still relatively scarce and inconclusive, especially in real-world care settings. The aims of the present research were: (1) to evaluate the longitudinal stability of NS levels in young UHR subjects treated within a specialized "Early Intervention in Psychosis" (EIP) program across a 2-year follow-up period, and (2) to investigate any relevant association of NS changes with the specific treatment components offered within the EIP program. One hundred UHR individuals (aged 12-25 years) completed the Positive And Negative Syndrome Scale (PANSS). A multiple linear regression analysis was conducted to examine significant associations between longitudinal changes in NS severity levels and the EIP treatment components. Across the follow-up, a significant decrease in NS clinical severity was observed. This reduction was associated with the intensity of individual psychotherapy sessions provided in the first year of treatment, a shorter duration of untreated illness at entry and the 2-year longitudinal decrease in positive symptom levels. In conclusion, NS are relevant in UHR people, but decrease over time together with the delivery of specialized EIP interventions. Specifically, our results showed that individual psychotherapy may reduce the clinical severity of NS at least during the first year of treatment.

Eye movement indices as predictors of conversion to psychosis in individuals at clinical high risk.

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.

Reinforcement learning profiles and negative symptoms across chronic and clinical high-risk phases of psychotic illness.

Negative symptoms are prominent in individuals with schizophrenia (SZ) and youth at clinical high-risk for psychosis (CHR). In SZ, negative symptoms are linked to reinforcement learning (RL) dysfunction; however, previous research suggests implicit RL remains intact. It is unknown whether implicit RL is preserved in the CHR phase where negative symptom mechanisms are unclear, knowledge of which may assist in developing early identification and prevention methods. Participants from two studies completed an implicit RL task: Study 1 included 53 SZ individuals and 54 healthy controls (HC); Study 2 included 26 CHR youth and 23 HCs. Bias trajectories reflecting implicit RL were compared between groups and correlations with negative symptoms were examined. Cluster analysis investigated RL profiles across the combined samples. Implicit RL was comparable between HC and their corresponding SZ and CHR groups. However, cluster analysis was able to parse performance heterogeneity across diagnostic boundaries into two distinct RL profiles: a Positive/Early Learning cluster (65% of participants) with positive bias scores increasing from the first to second task block, and a Negative/Late Learning cluster (35% of participants) with negative bias scores increasing from the second to third block. Clusters did not differ in the proportion of CHR vs. SZ cases; however, the Negative/Late Learning cluster had more severe negative symptoms. Although implicit RL is intact in CHR similar to SZ, distinct implicit RL phenotypic profiles with elevated negative symptoms were identified trans-phasically, suggesting distinct reward-processing mechanisms can contribute to negative symptoms independent of phases of illness.

Development and validation of a nomogram based on common biochemical indicators for survival prediction of children with high-risk neuroblastoma: A valuable tool for resource-limited hospitals.

BACKGROUND: Despite multiple attempts have been made to develop risk stratification within high-risk neuroblastoma (NB) patients (age of diagnosis ≥ 18 month-old with metastatic NB), the definition of "ultra high-risk NB" is still lack of consensus, and indicators for identifying this subgroup are still unclear. This study aimed to develop a nomogram based on easy-to-obtain blood-derived biofactors for identifying ultra high-risk NB patients with highest risk of death within 3 or 5 years. METHODS: One hundred sixty-seven NB patients who treated at Sun Yat-sen University Cancer Center between 2015 and 2023 were recruited and clustered randomly into training and validation cohorts (116 and 51 cases, respectively). Univariate and multivariate Cox analysis were performed in training set to screen independent prognostic indicators for constructing nomogram model of predicting 1-, 3- and 5-year overall survival (OS). The discrimination power of the nomogram in training and validation sets were assessed by concordance index (C-index) and calibration plot. Based on the risk score obtained from nomogram model, the prognostic accuracy of 1-, 3- and 5-year OS rates in training and validation cohorts were further evaluated using the area under receiver operating characteristic (ROC) curves (AUC). RESULTS: Through univariate and multivariate Cox analysis, independent prognostic indicators, including serum lactate dehydrogenase (LDH) and albumin (ALB), were identified in training set, and used to establish a nomogram model. The model showed good discrimination power with C-index in training cohort being 0.706 (95%CI: 0.633-0.788). According to the cut-point calculated based on the established nomogram, patients with a nomogram score > 34 points could be stratified to ultra high-risk NB subgroup, and this subgroup had poorer OS than those in non-ultra one (p < 0.001). AUC values of ROC curves for 3- and 5-year OS rates in the training set were 0.758 and 0.756, respectively. Moreover, based on the cut-point score (34 points) developed in training set, The model also showed good discrimination power with C-index of 0.773 (95%CI: 0.664-0.897) and powerful prognostic accuracy of AUC for 3- and 5-year OS rates being 0.825 and 0.826, respectively, in validation cohort. CONCLUSIONS: We developed a simple-to-use nomogram based on common laboratory indicators to identify the subgroup of ultra high-risk NB before treatment, providing these children even from developing countries or regions access to intensified multimodal treatments earlier and thus improving their long-term outcome.

A principle-based framework for disclosing a psychosis risk diagnosis.

In recent decades, researchers have attempted to prospectively identify individuals at high risk of developing psychosis in the hope of delaying or preventing psychosis onset. These psychosis risk individuals are identified as being in an 'At-Risk Mental State' (ARMS) through a standardised psychometric interview. However, disclosure of ARMS status has attracted criticism due to concerns about the risk-benefit ratio of disclosure to patients. Only approximately one quarter of ARMS patients develop psychosis after three years, raising concerns about the unnecessary harm associated with such 'false-positive' results. These harms are especially pertinent when identifying psychosis risk individuals due to potential stigma and discrimination in a young clinical population. A dearth of high-quality evidence supporting interventions for ARMS patients raises further doubts about the benefit accompanying an ARMS disclosure. Despite ongoing discussion in the bioethical literature, these concerns over the ethical justification of disclosure to ARMS patients are not directly addressed in clinical guidelines. In this paper, we aim to provide a unified disclosure strategy grounded in principle-based analysis for ARMS clinicians. After considering the ethical values at stake in ARMS disclosure, and their normative significance, we argue that full disclosure of the ARMS label is favoured in the vast majority of clinical situations due to the strong normative significance of enhancing patients' understanding. We then compare our framework with other approaches to ARMS disclosure and outline its limitations.

Staging's determinants in early intervention youth: a retrospective study.

OBJECTIVES: Since 2019 our early intervention unit has assessed help-seekers, mainly referred by psychiatric departments, and we have conducted a descriptive retrospective study. Our objective was to identify clinical determinants associated to staging at assessment for our three groups: "no psychosis", "ultra-high risk" and "first episode psychosis". METHODS: One hundred and thirteen participants (mean age 20.05±3.28) were enrolled, mainly referred by adult psychiatry (81.4%). We tested the association of each group with the following determinants: age, gender, family history of psychosis, referral (adolescent or adult psychiatry), cognitive, depressive complaint, cannabis active consumption, and current activity (scholar or employment). RESULTS: Multivariate analyses showed significant association with depressive symptoms (P=0.019) but an absence of family history of psychosis (P=0.002) or current activity (P=0.09) for "no psychosis" group. "Ultra-high risk" was significantly correlated with a family history of psychosis (P=0.001) and adolescent psychiatry referral (P=0.044) but an absence of depressive complaint (P=0.04). As for "first episode psychosis", we found significant cognitive complaint (P=0.026), family history (P=0.024) and current activity (0.026). CONCLUSIONS: As all our participants were seen in tertiary care, adolescent psychiatrists were more efficient in detecting a high-risk state. "No psychosis" help-seekers presented in fact mood issues, which have been confused with attenuated psychotic symptoms by their addressers, who have probably been misled by their absence of activity integration. High-risk and characterized psychotic episodes were logically correlated with family history. Surprisingly, "first episode psychosis" youth were currently integrated in scholarly or professional life despite an active cognitive complaint. Robust studies, especially prospective cohorts, are needed to test these associations.

The full spectrum of clinical stages of psychosis among mentally ill prisoners in New South Wales (NSW), Australia.

Research on the association between psychosis and criminal offending has typically focused on violent offenders with chronic psychotic illness. This stages of psychosis in prison (SOPP) study used a clinical staging approach to identify adult men referred to prison mental health services who had an at-risk mental state (ARMS), first episode of psychosis (FEP) or an established psychotic illness. Of the 105 participants included, 6% were determined to have FEP, 6% met ARMS criteria and the remainder had an established psychotic illness. Compared to a prison control sample, individuals on the psychosis spectrum were found to have higher levels of social disadvantage and other co-occurring mental health and substance use problems but were not more likely to have committed a violent offence. These findings support the notion that risk of criminal justice contact and complex illness burden exist across the full spectrum of psychotic illness.

Assessing the prevalence of psychotic symptoms in epileptic patients at a tertiary clinic.

Background: The International League against Epilepsy (ILAE) defines epilepsy as a brain disorder characterised by an enduring risk to generate seizures with neurobiological, cognitive, psychological and social consequences. Psychotic disorders in epilepsy are a serious psychiatric complication affecting the prognosis, morbidity and mortality of patients. There is a paucity in literature with regard to the prevalence of psychotic symptoms in epileptic patients in low- to middle-income countries. Aim: This study aimed to look at the prevalence of psychotic symptoms in epileptic patients at an outpatient clinic using the prodromal questionnaire 16 (PQ-16). Setting: The study was conducted at the epilepsy clinic at Charlotte Maxeke Academic Hospital (CMJAH), a tertiary hospital located in Johannesburg, South Africa. Method: The PQ-16 was distributed to patients at the epilepsy clinic at CMJAH. Results: The study consisted of 121 participants. The prevalence of patients found to be at high risk of psychosis (i.e., PQ-16 score > 6) was 61.2% (95% lower confidence interval (LCI): 0.53, upper confidence interval (UCI): 0.70). None of the demographic variables showed significant associations in the percentage of patients found to be at high risk. No association was found between any antiepileptic drug and high risk of psychosis. Conclusion: The high prevalence of psychotic like experiences found suggests it is imperative to screen for psychotic disorders in epileptic patients and if required to involve neuropsychiatrists in their management. Contribution: This study highlights the importance of assessing psychotic symptoms in epileptic patients and the importance of a multidisciplinary approach in managing these complex patients.

Plasmatic endocannabinoids are decreased in subjects with ultra-high risk of psychosis.

The onset of frank psychosis is usually preceded by a prodromal phase characterized by attenuated psychotic symptoms. Currently, research on schizophrenia prodromal phase (ultra-high risk for psychosis [UHR]) has focused on the risk of developing psychosis, on the transition to full blown psychosis and on its prediction. Neurobiological differences between UHR individuals who fully recover (remitters) versus those who show persistent/progressive prodromal symptoms (nonremitters) have been little explored. The endocannabinoid system constitutes a neuromodulatory system that plays a major role in brain development, synaptic plasticity, emotional behaviours and cognition. It comprises two cannabinoid receptors (CB1/CB2), two endocannabinoid ligands, arachidonylethanolamide (AEA) and 2-arachidonoylglycerol (2AG) along with their inactivation enzymes. Despite much evidence that the endocannabinoid system is imbalanced during psychosis, very little is known about it in UHR. Therefore, we aimed to quantify the plasma endocannabinoid levels in UHR and healthy controls (HC) and verify if these metabolites could differentiate between remitters and nonremitters. Circulating concentrations of AEA (p = .003) and 2AG (p < .001) were lower in UHR when compared with HC, with no difference between remitters and nonremitters. Regarding clinical evolution, it was observed that out of 91 UHRs initially considered, 16 had psychiatric complaints (3 years of follow-up). Considering those subjects, there were weak correlations between clinical parameters and plasma concentrations of endocannabinoids. Our results suggest that the endocannabinoids are imbalanced before frank psychosis and that changes can be seen in plasma of UHR individuals. These molecules proved to be potential biomarkers to identify individuals in the prodromal phase of psychosis.

Automatic auditory processing features in distinct subtypes of patients at clinical high risk for psychosis: Forecasting remission with mismatch negativity.

Individuals at clinical high risk (CHR) for psychosis exhibit a compromised mismatch negativity (MMN) response, which indicates dysfunction of pre-attentive deviance processing. Event-related potential and time-frequency (TF) information, in combination with clinical and cognitive profiles, may provide insight into the pathophysiology and psychopathology of the CHR stage and predict the prognosis of CHR individuals. A total of 92 individuals with CHR were recruited and followed up regularly for up to 3 years. Individuals with CHR were classified into three clinical subtypes demonstrated previously, specifically 28 from Cluster 1 (characterized by extensive negative symptoms and cognitive deficits), 31 from Cluster 2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 33 from Cluster 3 (characterized by the mildest symptoms and cognitive deficits). Auditory MMN to frequency and duration deviants was assessed. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired using TF analysis. Predictive indices for remission were identified using logistic regression analyses. As expected, reduced frequency MMN (fMMN) and duration MMN (dMMN) responses were noted in Cluster 1 relative to the other two clusters. In the TF analysis, Cluster 1 showed decreased theta and alpha ITC in response to deviant stimuli. The regression analyses revealed that dMMN latency and alpha ERSP to duration deviants, theta ITC to frequency deviants and alpha ERSP to frequency deviants, and fMMN latency were significant MMN predictors of remission for the three clusters. MMN variables outperformed behavioral variables in predicting remission of Clusters 1 and 2. Our findings indicate relatively disrupted automatic auditory processing in a certain CHR subtype and a close affinity between these electrophysiological indexes and clinical profiles within different clusters. Furthermore, MMN indexes may serve as predictors of subsequent remission from the CHR state. These findings suggest that the auditory MMN response is a potential neurophysiological marker for distinct clinical subtypes of CHR.

Thalamic dysconnectivity in the psychosis risk syndrome and early illness schizophrenia.

BACKGROUND: Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset. METHODS: Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups. RESULTS: Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups. CONCLUSIONS: PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages.

Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis.

BACKGROUND: Psychosis is associated with a reasoning bias, which manifests as a tendency to 'jump to conclusions'. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes. METHODS: In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A 'beads' task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point. RESULTS: There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ. CONCLUSIONS: In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.