Clinical High-risk Group Research Articles

Exploration of Risk Factors for Pancreatic Cancer and Development of a Clinical High-Risk Group Rating Scale.

(1) Background: There are few studies on people at high risk for clinical pancreatic cancer (PC). We aimed to explore the risk factors of PC and establish a scale for identifying high-risk populations of clinical PC. (2) Methods: We conducted a matched case-control study, retrospectively collecting demographic data and common clinical indicators from all subjects. Logistic regression was used to explore the risk factors of PC. Based on these factors, we created a high-risk population rating scale, which showed a higher diagnostic value. (3) Results: 385 cases and 428 controls were finally enrolled in our study. Multivariate analysis showed that body mass index (BMI) below 18.5 kg/m2 (OR 5.944, 95%CI: 1.759~20.084), smoking (OR 2.745, 95%CI: 1.555~4.844), new-onset diabetes (OR 5.239, 95%CI: 2.091~13.125), low high-density lipoprotein cholesterol (HDL-C) levels (OR 1.790, 95%CI: 1.044~3.069), and carbohydrate antigen 19-9 (CA19-9) levels no less than 35 U/mL (OR 160.328, 95%CI: 83.392~308.243) were associated with an increased risk of PC, whereas high total cholesterol (TC) levels were related to a lower risk of PC (OR 0.392, 95%CI: 0.211~0.730). The high-risk population scale, whose area under the receiver operating curve reached 0.948 (p < 0.001), showed a greater clinical diagnostic value. (4) Conclusions: Smoking history, new-onset diabetes, BMI, TC, HDL-C, and CA19-9 levels were associated with the risk of PC. The high-risk population rating scale might be used for early clinical PC screening.

Patient-Reported Outcome Measures in Clinical High Risk for Psychosis: A Systematic Review.

A key issue in both research and clinical work with youth at clinical high risk (CHR) of psychosis is that there are clearly heterogenous clinical outcomes in addition to the development of psychosis. Thus, it is important to capture the psychopathologic outcomes of the CHR group and develop a core outcomes assessment set that may help in dissecting the heterogeneity and aid progress toward new treatments. In assessing psychopathology and often poor social and role functioning, we may be missing the important perspectives of the CHR individuals themselves. It is important to consider the perspectives of youth at CHR by using patient-reported outcome measures (PROMs). This systematic review of PROMs in CHR was conducted based on a comprehensive search of several databases and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Sixty-four publications were included in the review examining PROMs for symptoms, functioning, quality of life, self-perceptions, stress, and resilience. Typically, PROMs were not the primary focus of the studies reviewed. The PROMs summarized here fit with results published elsewhere in the literature based on interviewer measures. However, very few of the measures used were validated for CHR or for youth. There are several recommendations for determining a core set of PROMs for use with CHR.

Cerebellar correlates of social dysfunction among individuals at clinical high risk for psychosis.

Social deficits are a significant feature among both individuals with psychosis and those at clinical high-risk (CHR) for developing psychosis. Critically, the psychosis risk syndrome emerges in adolescence and young adulthood, when social skill development is being fine-tuned. Yet, the underlying pathophysiology of social deficits in individuals at CHR for psychosis remains unclear. Literature suggests the cerebellum plays a critical role in social functioning. Cerebellar dysfunction in psychosis and CHR individuals is well-established, yet limited research has examined links between the cerebellum and social functioning deficits in this critical population. In the current study, 68 individuals at CHR for developing psychosis and 66 healthy controls (HCs) completed social processing measures (examining social interaction, social cognition, and global social functioning) and resting-state MRI scans. Seed-to-voxel resting-state connectivity analyses were employed to examine the relationship between social deficits and lobular cerebellar network connectivity. Analyses indicated that within the CHR group, each social domain variable was linked to reduced connectivity between social cerebellar subregions (e.g., Crus II, lobules VIIIa and VIIIb) and cortical regions (e.g., frontal pole and frontal gyrus), but a control cerebellar subregion (e.g., lobule X) and was unrelated to these social variables. These results indicate an association between several cerebellar lobules and specific deficits in social processing. The cerebellum, therefore, may be particularly salient to the social domain and future research is need to examine the role of the cerebellum in psychosis.

Large-Scale Thalamocortical Triple Network Dysconnectivities in Patients With First-Episode Psychosis and Individuals at Risk for Psychosis.

Aberrant thalamocortical connectivity and large-scale network interactions among the default mode network (DMN), salience network (SN), and executive control network (ECN) (ie, triple networks) have been regarded as critical in schizophrenia pathophysiology. Despite the importance of network properties and the role of the thalamus as an integrative hub, large-scale thalamocortical triple network functional connectivities (FCs) in different stages of the psychotic disorder have not yet been reported. Thirty-nine first-episode psychosis (FEP) patients, 75 individuals at clinical high risk (CHR) for psychosis, 46 unaffected relatives (URs) of schizophrenia patients with high genetic loading, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Modular community detection was used to identify cortical and thalamic resting-state networks, and thalamocortical network interactions were compared across the groups. Thalamic triple networks included higher-order thalamic nuclei. Thalamic SN-cortical ECN FC was greater in the FEP group than in the CHR, UR, and HC groups. Thalamic DMN-cortical DMN and thalamic SN-cortical DMN FCs were greater in FEP and CHR participants. Thalamic ECN-cortical DMN and thalamic ECN-cortical SN FCs were greater in FEP patients and URs. These results highlight critical modulatory functions of thalamic triple networks and the shared and distinct patterns of thalamocortical triple network dysconnectivities across different stages of psychotic disorders. The current study findings suggest that large-scale thalamocortical triple network dysconnectivities may be used as an integrative biomarker for extending our understanding of the psychosis pathophysiology and for targeting network-based neuromodulation therapeutics.

Sex- and Age-Specific Deviations in Cerebellar Structure and Their Link With Symptom Dimensions and Clinical Outcome in Individuals at Clinical High Risk for Psychosis.

The clinical high-risk (CHR) period offers a temporal window into neurobiological deviations preceding psychosis onset, but little attention has been given to regions outside the cerebrum in large-scale studies of CHR. Recently, the North American Prodrome Longitudinal Study (NAPLS)-2 revealed altered functional connectivity of the cerebello-thalamo-cortical circuitry among individuals at CHR; however, cerebellar morphology remains underinvestigated in this at-risk population, despite growing evidence of its involvement in psychosis. In this multisite study, we analyzed T1-weighted magnetic resonance imaging scans obtained from N = 469 CHR individuals (61% male, ages = 12-36 years) and N = 212 healthy controls (52% male, ages = 12-34 years) from NAPLS-2, with a focus on cerebellar cortex and white matter volumes separately. Symptoms were rated by the Structured Interview for Psychosis-Risk Syndromes (SIPS). The outcome by two-year follow-up was categorized as in-remission, symptomatic, prodromal-progression, or psychotic. General linear models were used for case-control comparisons and tests for volumetric associations with baseline SIPS ratings and clinical outcomes. Cerebellar cortex and white matter volumes differed between the CHR and healthy control groups at baseline, with sex moderating the difference in cortical volumes, and both sex and age moderating the difference in white matter volumes. Baseline ratings for major psychosis-risk dimensions as well as a clinical outcome at follow-up had tissue-specific associations with cerebellar volumes. These findings point to clinically relevant deviations in cerebellar cortex and white matter structures among CHR individuals and highlight the importance of considering the complex interplay between sex and age when studying the neuromaturational substrates of psychosis risk.

Alterations in facial expressions in individuals at risk for psychosis: a facial electromyography approach using emotionally evocative film clips.

Negative symptoms such as blunted facial expressivity are characteristic of schizophrenia. However, it is not well-understood if and what abnormalities are present in individuals at clinical high-risk (CHR) for psychosis. This experimental study employed facial electromyography (left zygomaticus major and left corrugator supercilia) in a sample of CHR individuals (N = 34) and healthy controls (N = 32) to detect alterations in facial expressions in response to emotionally evocative film clips and to determine links with symptoms. Findings revealed that the CHR group showed facial blunting manifested in reduced zygomatic activity in response to an excitement (but not amusement, fear, or sadness) film clip compared to controls. Reductions in zygomatic activity in the CHR group emerged in response to the emotionally evocative peak period of the excitement film clip. Lower zygomaticus activity during the excitement clip was related to anxiety while lower rates of change in zygomatic activity during the excitement video clip were related to higher psychosis risk conversion scores. Together, these findings inform vulnerability/disease driving mechanisms and biomarker and treatment development.

Improved risk stratification by PET-based intratumor heterogeneity in children with high-risk neuroblastoma.

The substratification of high-risk neuroblastoma is challenging, and new predictive imaging biomarkers are warranted for better patient selection. The aim of the study was to evaluate the prognostic role of PET-based intratumor heterogeneity and its potential ability to improve risk stratification in neuroblastoma. Pretreatment 18F-FDG PET/CT scans from 112 consecutive children with newly diagnosed neuroblastoma were retrospectively analyzed. The primary tumor was segmented in the PET images. SUVs, volumetric parameters including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and texture features were extracted. After the exclusion of imaging features with poor and moderate reproducibility, the relationships between the imaging indices and clinicopathological factors, as well as event-free survival (EFS), were assessed. The median follow-up duration was 33months. Multivariate analysis showed that PET-based intratumor heterogeneity outperformed clinicopathological features, including age, stage, and MYCN, and remained the most robust independent predictor for EFS [training set, hazard ratio (HR): 6.4, 95% CI: 3.1-13.2, p<0.001; test set, HR: 5.0, 95% CI: 1.8-13.6, p=0.002]. Within the clinical high-risk group, patients with a high metabolic heterogeneity showed significantly poorer outcomes (HR: 3.3, 95% CI: 1.6-6.8, p=0.002 in the training set; HR: 4.4, 95% CI: 1.5-12.9, p=0.008 in the test set) compared to those with relatively homogeneous tumors. Furthermore, intratumor heterogeneity outran the volumetric indices (MTVs and TLGs) and yielded the best performance of distinguishing high-risk patients with different outcomes with a 3-year EFS of 6% vs. 47% (p=0.001) in the training set and 9% vs. 51% (p=0.004) in the test set. PET-based intratumor heterogeneity was a strong independent prognostic factor in neuroblastoma. In the clinical high-risk group, intratumor heterogeneity further stratified patients with distinct outcomes.

Social network size in adolescents at clinical high risk for psychosis.

Adolescents and young adults at clinical high risk (CHR) for psychosis report few close friends. Social support has been linked to conversion to psychosis and psychosis relapse in CHR individuals. Expanding earlier research on loneliness and friendships at a single timepoint, this study described composition and changes in social network and its association with clinical and cognitive symptoms among CHR adolescents. Ninety five individuals (46 CHR individuals, 49 healthy volunteers) completed baseline and 1-year follow-up Social Network Index (SNI) evaluations and clinical interviews. Analyses first examined SNI size and composition across 10 categories (e.g., family, close friends, coworkers, classmates) between groups. Then, the relationship between SNI size and baseline social symptoms (i.e., paranoia, social anhedonia, social anxiety, social cognition), social function, and changes in symptoms and social networks over 1-year were examined within the CHR group. CHR individuals showed smaller social networks overall, driven by fewer friendships and family relationships. Social cognition and social anxiety significantly related to SNI size at baseline, but social anhedonia and paranoia did not. SNI size related to social function, but with a modest effect size (r's=.45 and .56). Surprisingly, an increase in positive symptom severity related to an increase in familial but a decrease in coworker social network size. The social support deficits in the CHR group were specific to relatives and friendships, with social anxiety and social cognition as implicated symptoms. Social relationships may serve as a promising early intervention target in individuals at CHR for psychosis.

Childhood Maltreatment and Its Association with Cognitive Ability in Young People Suspected to Be at Clinical High Risk of Psychosis

Introduction: Childhood maltreatment is associated with both reduced cognitive functioning and the development of psychotic symptoms. However, the specific relationship between childhood maltreatment, cognitive abilities and (pre)psychotic symptoms remains unclear. Therefore, the aim of this study was to investigate the association between childhood maltreatment and tasks of verbal memory and processing speed in a help-seeking sample of an early detection of psychosis service. Methods: A total of 274 participants consisting of 177 clinical high risk (CHR) for psychosis subjects and 97 clinical controls (CC) with subthreshold CHR underwent a battery of neurocognitive assessments measuring the latent variables verbal memory and processing speed. Additionally, the Trauma and Distress Scale (TADS) was administered to assess varying childhood maltreatment subtypes. Structural equation modeling (SEM) was used to examine associations between verbal memory, processing speed, and maltreatment subtypes. Other factors in the model were age, gender, clinical group (CHR or CC), and the presence of different CHR criteria. Results: Physical abuse was associated with lower scores in verbal memory and processing speed. The explained variance in the SEM reached up to 9.5% for verbal memory and 24.9% for processing speed. Both latent variables were each associated with the presence of cognitive-perceptive basic symptoms. Lower verbal memory was additionally associated with the clinical high-risk group, and processing speed capacity was associated with higher age and female gender. Conclusion: Childhood physical abuse in particular was associated with poorer performance on verbal memory and processing speed across both groups of CHR and CC with subthreshold CHR symptoms. This adds to the current literature on reduced cognitive abilities when childhood maltreatment had occurred, albeit subtype dependent. Our findings, together with high prevalence rates of childhood maltreatment in patients with psychosis or CHR states, along with the presence of cognitive deficits in these patients, highlight the importance of not only assessing cognition but also childhood maltreatment in managing these patients. Future research should investigate the specific biological mechanisms of childhood maltreatment on verbal memory and processing speed in CHR subjects, as neurobiological alterations might explain the underlying mechanisms.

Dopaminergic alterations in populations at increased risk for psychosis: A systematic review of imaging findings.

Alterations of the dopaminergic system may be important neurobiological correlates of vulnerability and transition to psychosis. We systematically reviewed the evidence for dopaminergic alterations demonstrated by in-vivo imaging studies in humans at increased risk of developing psychosis, covering clinical, genetic, and environmental high-risk groups. All 63 included studies utilized Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), or neuromelanin-sensitive Magnetic Resonance Imaging (NM-MRI) methods to collect data concerning the dopaminergic system during rest and/or following pharmacological, behavioural, or cognitive challenges. The current evidence highlights that 1) striatal dopamine D2/3 receptor availability is unaltered in all three high-risk groups compared with healthy individuals; 2) striatal dopamine synthesis capacity (sDSC) is increased in some clinical and genetic high-risk individuals relative to controls (e.g. people that meet clinical criteria for being at ultra-high risk of developing psychosis and individuals with 22q11.2 deletion syndrome), while sDSC is decreased in cannabis-using environmental high-risk individuals. It seems likely that all three high-risk groups can be stratified into multiple subgroups, with varying risks to develop psychosis, transition rates, and underlying neurobiology. The present results support the hypothesis that dopaminergic abnormalities occur before high-risk individuals develop psychosis.

The Investigation of Cognitive Functions and Clinical High Risk Status for Psychosis in First-Degree Relatives of Patients with Substance Induced Psychotic Disorder

IntroductionThe etiology of substance-induced psychotic disorder (SIPD) is an important research area to study.ObjectivesIt is aimed to investigate clinical risk status for psychosis, schizotypal features and neurocognitive functions in siblings of the patients who have been diagnosed as SIPD and who have no family history of psychotic spectrum disorder.MethodsThis study included 41 healthy siblings of patients who have been diagnosed as SIPD according to DSM-V and 41 healthy controls without family history of psychiatric disorders (matched on age, gender, and years of education). The data collected with sociodemographic and clinical data form, Digid Span Test, Trail Making Test A, Trail Making Test B, Verbal Fluency Test and Stroop Test, Comprehensive Assesment of At-Risk Mental States (CAARMS) and Structured Interview for Schizotypy-Revised.ResultsIt is determined that %41.5 of siblings and %7.3 of healthy controls are in one of the clinical high risk groups for psychosis according to CAARMS. There is significant difference in Trail Making Test A error and Trail Making Test B error and correction, verbal fluency test- lexical fluency-perseveration mean scores between siblings of patients and healthy controls.ConclusionsSiblings of patients with SIPD have more schizotypal features than healthy control group and they take part more frequent in one of high risk group for psychosis. Schizotypal features are known as trait factor and show genetic predisposition. Siblings who are in high risk groups have more schizotypal features and it may point that predisposition to psychosis is more related to underlying genetic predisposition than environmental factors and social stressors.DisclosureNo significant relationships.

Correlation Between Schizophrenia and Coronavirus Disease in North Sumatera, Indonesia: A Correlative Analytical Study.

BackgroundIn the first quarter of 2020, two cases of coronavirus disease (COVID-19) were reported in Indonesia, approximately 4 months after the first case was reported in China. The numbers continued to increase following the introduction of many variants of the virus. The pandemic may have an impact on the community's mental health, particularly on those with mental illnesses. Therefore, this study aimed to determine the correlation between schizophrenia and COVID-19 based on demographic characteristics.MethodsThis nominal-nominal and numerical-nominal correlative analytical study used a cross-sectional approach and was conducted at a psychiatric hospital in North Sumatra. The sample population consisted of 48 patients and 48 healthy controls, who were selected using a non-probability consecutive sampling method.ResultsThe analysis showed that there were correlations between schizophrenia and COVID-19 (r = 0.417, p < 0.001) and between the age of patients with schizophrenia and COVID-19 with (r = 0.544).ConclusionsCOVID-19 is correlated with schizophrenia and the age of patients with schizophrenia. We recommend that patients with schizophrenia follow the same health guidelines as the clinical high-risk group for COVID-19 and receive the same treatment. Physicians that treat patients with COVID-19 should pay close attention to those with schizophrenia because they may underestimate their condition.

The impact of COVID-19 pandemic on individuals at clinical high-risk for psychosis: Evidence from eye-tracking measures

Emerging evidence suggested that people with severe mental disorders were more vulnerable to the negative effects of the COVID-19 pandemic. However, few researches investigated the influence of global pandemics on people at clinical high risk (CHR) for psychosis. This study aimed to investigate the impact of the COVID-19 pandemic on clinical symptoms, psychological distress, and eye-tracking characteristics in CHR individuals and healthy participants. Forty-nine CHR individuals and 50 healthy controls (HC) were assessed by PTSD Checklist for DSM-5 (PCL-5), Perceived Stress Scale, 10-item version (PSS-10), and Coronavirus Impact Scale (CIS). Eye movement performances were measured by the tests of fixation stability, free-viewing, and anti-saccade. According to the mean score of CIS, participants were stratified into high-impact (n = 35) and low-impact (n = 64) subgroups. Compared with the HC group, CHR participants reported significantly higher levels of post-traumatic symptoms caused by the COVID-19 pandemic and showed abnormalities in most of the eye movement indexes. Among the altered indexes, the saccade amplitude of fixation stability test (far distractor), the scan path length of free-viewing test, and the accuracy of anti-saccade test were negatively affected by the severity of impact level in the CHR group. Moreover, the altered eye movement indexes were significantly associated with the total scores of CIS, PCL-5, and subscales of the Scale of Prodromal Syndromes (SOPS) among CHR individuals. Overall, our findings suggested the negative impact of the COVID-19 pandemic on the eye movement characteristics of CHR individuals. The present study provides valuable information on physiological distress related to the COVID-19 pandemic and sensitive neuropsychological biomarkers that interacted with social and environment stress in the CHR population.

Pineal morphology of the clinical high-risk state for psychosis and different psychotic disorders

BackgroundPineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders. MethodsThis magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups. ResultsPineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups. ConclusionThese results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis.

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

BackgroundDisrupted white matter (WM) microstructure has been commonly identified in youth at clinical high risk (CHR) for psychosis. Several lines of evidence suggest that fatty acids, especially unsaturated fatty acids...

Altered attentive bias towards interpersonal communication information across phases of schizophrenia: an eye-tracking study

BackgroundEye movement abnormality in schizophrenia has been studied for several decades. However, patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented.AimsThis pilot...

Attenuated niacin-induced skin flush response in individuals with clinical high risk for psychosis

BackgroundImpaired sensitivity of the skin flush response to niacin is one of the most replicated findings in patients with schizophrenia. However, prior studies have usually focused on postonset psychosis, and...

A qualitative study on identity in individuals at clinical high risk for psychosis: " … Why does it have to be one thing?".

Qualitative research can shed light on the subjective experiences of individuals at clinical high risk (CHR) for psychosis, complement quantitative research, broaden our understanding of experiencing CHR, and inform intervention development. The aim of this study was to explore life experiences of individuals at CHR through qualitative research. Participants were 37 individuals at CHR (20 male, 17 female) aged 16-34 (Mage = 23.32 ± 5.26), and 16 healthy controls (HCs; 7 male, 9 female) aged 18-34 (Mage = 25.37 ± 4.05). Qualitative data were obtained through open-ended interviews (30-45 min). No a priori hypotheses were made, and thematic analyses were used to develop themes. Four major themes and one subtheme related to identity were identified through the iterative thematic analysis: defining a self-concept (with a subtheme of creativity), identity development/formation, feeling different from others, and change from a former self. Over 80% of the CHR cohort spontaneously discussed topics related to their identity, compared to 38% of HCs. HCs only reported content within the defining a self-concept theme, while the CHR group reported content within all themes. The present study demonstrates that identity formation is a major process for youth in general and that psychosis experiences can make this process more challenging. CHR participants spontaneously brought up multiple themes related to identity in open-ended interviews, suggesting the relevance of this topic in this population. Clinicians should continue to probe identity-related concerns on an individual basis and research should focus on integrating this framework into the conceptualization and treatment of CHR. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Bullying in clinical high risk for psychosis participants from the NAPLS-3 cohort.

Bullying is associated with a heightened risk for poor outcomes, including psychosis. This study aimed to replicate previous findings on bullying prevalence in clinical high-risk (CHR) individuals, to assess the longitudinal course of clinical and functional variables between bullied and non-bullied CHR and the association of bullying with premorbid functioning, clinical outcome, transition to psychosis and risk of violence. The sample consisted of 691 CHR participants and 96 healthy controls. Participants reported whether they had experienced bullying and how long it had lasted. Assessments included DSM-5 diagnoses, attenuated psychotic symptoms, negative symptoms, social and role functioning, depression, stress, premorbid functioning, and risk of violence. The bullied and non-bullied CHR groups were compared at baseline and further longitudinally on clinical and functioning variables and transition to psychosis. Bullying was more prevalent among CHR individuals than healthy controls. Bullied CHR had a higher prevalence of PTSD and more severe depression and stress at baseline than non-bullied CHR. There was no impact of bullying on clinical and functional variables over time. Bullying was not related to final clinical status or transition to psychosis. However, bullied participants had poorer premorbid functioning and a greater risk of violence. While bullying may not impact the likelihood of CHR individuals to transition to psychosis, it may be a risk factor for development of the at-risk state and may be related to a greater risk of violence. Future studies should consider bullying perpetration among CHR individuals.

Cerebello-limbic functional connectivity patterns in youth at clinical high risk for psychosis

Youth at clinical high risk (CHR) for psychosis can present not only with characteristic attenuated psychotic symptoms but also may have other comorbid conditions, including anxiety and depression. These undifferentiated mood symptoms can overlap with the clinical presentation of youth with Distress syndromes. Increased resting-state functional connectivity within cerebello-thalamo-cortical (CTC) pathways has been proposed as a trait-specific biomarker for CHR. However, it is unclear whether this functional neural signature remains specific when compared to a different risk group: youth with Distress syndromes. The purpose of the present work was to describe CTC alterations that distinguish between CHR and Distressed individuals.Using machine learning algorithms, we analyzed CTC connectivity features of CHR (n = 51), Distressed (n = 41), and healthy control (n = 36) participants. We found four cerebellar (lobes VII and left Crus II anterior/posterior) and two basal ganglia (right putamen and right thalamus) nodes containing a set of specific connectivity features that distinguished between CHR, Distressed and healthy control groups. Hyperconnectivity between medial lobule VIIb, somatomotor network and middle temporal gyrus was associated with CHR status and more severe symptoms. Detailed atlas parcellation suggested that CHR individuals may have dysfunction mainly within the associative (cognitive) pathways, particularly, between those brain areas responsible for the multi-sensory signal integration.