Clinical High Risk For Psychosis Research Articles

Neurocognition in adolescents and young adults at clinical high risk for psychosis: Predictive stability for social and role functioning

The prodromal phase of schizophrenia provides an optimal opportunity to mitigate the profound functional disability that is often associated with fully expressed psychosis. Considerable evidence supports the importance of neurocognition in the development of interpersonal (social) and academic (role) skills. Further findings from adolescents and young adults at clinical high risk for developing psychosis (CHRP) suggest that treatment for functioning might be most effective when targeting early and specific neurocognitive deficits. The current study addresses this critical intervention issue by examining the potential of neurocognitive deficits at intake for predicting social and role functioning over time in CHR-P youth. The study included 345 CHR-P participants from the second phase of the North American Prodrome Longitudinal Study (NAPLS2) with baseline neurocognition and 2-year follow-up data on social and role functioning. Slower baseline processing speed consistently predicted poor social functioning over time, while attention deficits predicted poor role functioning at baseline and follow-up. In addition, the impact of processing speed and attention impairments on social and role functioning, respectively, persisted even when adjusting the regression models for attenuated positive, negative, and disorganized symptoms, and transition status. The current study demonstrates for, arguably the first time, that processing speed and attention are strongly predictive of social and role functioning over time, respectively, above and beyond the impact of symptoms and those CHR-P individuals that develop psychosis over the course of the study. These findings imply that early neurocognition is a critical treatment target linked to the developmental trajectory of social and role functioning.

The influence of complex psychiatric comorbidities on treatment for clinical high-risk for psychosis: A preliminary study.

Despite increasingly refined tools for identifying individuals at clinical high-risk for psychosis (CHR-P), less is known about the effectiveness of CHR-P interventions. The significant clinical heterogeneity among CHR-P individuals suggests that interventions may need to be personalized during this emerging illness phase. We examined longitudinal trajectories within-persons during treatment to investigate whether baseline factors predict symptomatic and functional outcomes. A total of 36 CHR-P individuals were rated on attenuated positive symptoms and functioning at baseline and each week during CHR-P step-based treatment. Linear mixed-effects models revealed that attenuated positive symptoms decreased during the study period, while functioning did not significantly change. When examining baseline predictors, a significant group-by-time interaction emerged whereby CHR-P individuals with more psychiatric comorbidities at baseline (indicating greater clinical complexity) improved in functioning during the study period relative to CHR-P individuals with fewer comorbidities. Individual differences in clinical complexity may predict functional response during the early phases of CHR-P treatment.

Improving processing speed in adolescents at clinical high risk for psychosis with the Specific COgnitive REmediation plus Surround (SCORES) intervention: Study protocol.

Recent preventative approaches with young people at clinical high risk for psychosis (CHR-P) have focused on the remediation of the cognitive deficits that are readily apparent and predictive of future illness. However, the small number of trials using cognitive remediation with CHR-P individuals have reported mixed results. The proposed 2-phased study will test an innovative internet-based and remotely-delivered Specific COgnitive REmediation plus Surround (or SCORES) intervention that targets early processing speed deficits in CHR-P adolescents aged 14-20 years old. In the first R61 phase, a single-arm 2-year proof of concept study, 30 CHR-P individuals will receive SCORES for 10 weeks (4 h per week/40 h total) with a midpoint assessment at 20 h (5 weeks) to demonstrate target engagement and identify the optimal dose needed to engage the target. The Go/No-Go criteria to move to the R33 phase will be processing speed scores improving by a medium effect size (Cohen's d ≥ .6). The proposed package includes a set of complimentary support surround procedures to increase enjoyment and ensure that participants will complete the home-based training. In the second R33 phase, a 3-year pilot study, we will replicate target engagement in a new and larger sample of 54 CHR-P individuals randomized to SCORES (optimized dose) or to a video game playing control condition. In addition, the R33 phase will determine if changes in processing speed are associated with improved social functioning and decreasing attenuated positive symptoms. The support surround components of the intervention will remain constant across phases and conditions in the R33 phase to firmly establish the centrality of processing speed training for successful remediation. The SCORES study is a completely virtual intervention that targets a core cognitive mechanism, processing speed, which is a rate-limiting factor to higher order behaviours and clinical outcomes in CHR-P adolescents. The virtual nature of this study should increase feasibility as well improve the future scalability of the intervention with considerable potential for future dissemination as a complete treatment package.

Disorganization in individuals at clinical high risk for psychosis: psychopathology and treatment response.

Disorganization is a nuclear dimension of psychosis, especially in schizophrenia. Despite its relevant association with poor prognosis and negative outcomes, it is still under-investigated compared to positive and negative symptoms, in particular at the onset of illness. This study explored disorganization in youth at Clinical High Risk for Psychosis (CHR-P) over a 2-year period. A sample of 180 CHR-P participants (50% males; 51.1% with baseline second-generation antipsychotic medication) recruited within a specialized CHR-P service completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Across the follow-up, we examined key associations of disorganization with other domains of psychopathology, functioning, and treatment response using Spearman's rank correlation coefficients and linear regression analyses. Our results showed a significant longitudinal reduction in disorganization severity levels across the follow-up. This decrease was significantly associated with improvements in negative symptoms and daily functioning, with a shorter duration of untreated psychiatric symptoms, and with baseline equivalent dose of antipsychotic medication. No significant longitudinal associations with other treatment component of the PARMS program were found. Our findings suggest a longitudinal improvement in disorganization dimension in CHR-P individuals, especially in the context of early interventions targeting reduction in the duration of untreated psychiatric symptoms and favoring a prompt antipsychotic therapy.

Clinical utility of the at-risk for psychosis state beyond transition: A multidimensional network analysis.

To be relevant to healthcare systems, the clinical high risk for psychosis (CHR-P) concept should denote a specific (i.e., unique) clinical population and provide useful information to guide the choice of intervention. The current study applied network analyses to examine the clinical specificities of CHR-P youths compared to general help-seekers and non-CHR-P youth. 146 CHR-P (mean age = 14.32 years) and 103 non-CHR-P (mean age = 12.58 years) help-seeking youth were recruited from a neuropsychiatric unit and assessed using the Structured Interview for Psychosis-Risk Syndromes, Children's Depression Inventory, Multidimensional Anxiety Scale for Children, Global Functioning: Social, Global Functioning: Role, and Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale. The first network structure comprised the entire help-seeking sample (i.e., help-seekers network), the second only CHR-P patients (i.e., CHR-P network), and the third only non-CHR-P patients (i.e., non-CHR-P network). In the help-seekers network, each variable presented at least one edge. In the CHR-P network, two isolated "archipelagos of symptoms" were identified: (a) a subgraph including functioning, anxiety, depressive, negative, disorganization, and general symptoms; and (b) a subgraph including positive symptoms and the intelligence quotient. In the non-CHR-P network, positive symptoms were negatively connected to functioning, disorganization, and negative symptoms. Positive symptoms were less connected in the CHR-P network, indicating a need for specific interventions alongside those treating comorbid disorders. The findings suggest specific clinical characteristics of CHR-P youth to guide the development of tailored interventions, thereby supporting the clinical utility of the CHR-P concept.

Investigation of Siblings of Patients Diagnosed with Substance-Induced Psychotic Disorder in terms of Cognitive Functions and Clinical High-Risk State for Psychosis

Objective: This study aimed to investigate the influence of familial predisposition on substance-induced psychosis among healthy siblings of patients diagnosed with substance-induced psychotic disorder, who themselves lack any family history of psychotic disorders. Additionally, the study aimed to explore clinical high-risk states for psychosis, schizotypal features, and neurocognitive functions in comparison to a healthy control group. Method: The study compared healthy siblings of 41 patients diagnosed with substance-induced psychotic disorder with 41 healthy volunteers without a family history of psychotic disorders, matching age, gender, and education. Sociodemographic and clinical characteristics of participants were obtained using data collection forms. The Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Structured Interview for Schizotypy-Revised Form (SIS-R) scales were utilized to assess clinical high risk for psychosis. Neurocognitive functions were evaluated with digit span test (DST), trail making test part A-B (TMT), verbal fluency test (VFT), and Stroop test (ST). Results: Analysis using the CAARMS scale revealed that 39% of siblings and 7.3% of the control group were at clinically high risk for psychosis, indicating a significant difference in rates of psychotic vulnerability. Comparison between siblings and the control group showed significant differences in mean SIS-R subscale scores, including social behavior, hypersensitivity, referential thinking, suspiciousness, illusions, and overall oddness, as well as in mean neurocognitive function scores, including errors in TMT-A, TMT-B, and VFT out-of-category errors, with siblings exhibiting poorer performance. Conclusion: Our study suggests that healthy siblings of patients with substance-induced psychosis exhibit more schizotypal features and have a higher risk of developing psychosis compared to healthy controls. Additionally, siblings demonstrate greater impairment in attention, response inhibition, and executive functions compared to healthy controls, indicating the potential role of genetic predisposition in the development of substance-induced psychotic disorder.

Supplemental Material for Disrupted Coherence Between Autonomic Activation and Emotional Expression in Individuals at Clinical High Risk for Psychosis

Supplemental Material for Disrupted Coherence Between Autonomic Activation and Emotional Expression in Individuals at Clinical High Risk for Psychosis

Environmental and psychopathological predictors of clinical high-risk of psychosis in adolescence.

Clinical high-risk of psychosis (CHRp) samples can be heterogeneous, consisting essentially of people with not only psychotic-like experiences but also nonspecific symptoms that may reflect common mental disorders such as depression, anxiety, or substance abuse pathologies. Few studies have attempted to analyze and understand psychosis risk in relation to both environmental (ER) and psychopathological risk (PsR) factors. This study aimed to determine the clinical risk of psychosis in adolescents. A representative sample of 1824 Spanish adolescents from the general population was evaluated using different scales to thoroughly examine the possible interaction of CHRp with various ER and PsR factors. Partial correlations were calculated to assess the relationships between the variables. A series of hierarchical linear regression models were then used to obtain a CHRp predictor model. The CHRp predictor model indicated that PsR was the most significant determining factor, explaining 22% of the total associated variance of CHRp. However, the ER factor also emerged as a significant predictor of high-risk psychosis (accounting for 9% of the variance). A predictive model for CHRp in adolescents was found, in which common psychological problems were presented as more determinant risk factors than ER disruptors. Furthermore, certain transdiagnostic processes, such as psychological inflexibility, may play a central role in the development of mental health problems, including psychosis. Specifying the mechanisms underlying the emergence of CHRp in adolescence is the key to optimizing the focus of preventive therapeutic interventions in these early stages.

Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis.

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

Adjustment of Regional Cortical Thickness Measures for Global Cortical Thickness Obscures Deficits Across the Schizophrenia Spectrum: A Cautionary Note About Normative Modeling of Brain Imaging Data

Recent neuroimaging studies and publicly disseminated analytic tools suggest that regional morphometric analyses covary for global thickness. We empirically demonstrated that this statistical approach severely underestimates regional thickness dysmorphology in psychiatric disorders. Study 1 included 90 healthy control participants, 51 participants at clinical high risk for psychosis, and 78 participants with early-illness schizophrenia. Study 2 included 56 healthy control participants, 83 participants with nonaffective psychosis, and 30 participants with affective psychosis. We examined global and regional thickness correlations, global thickness group differences, and regional thickness group differences with and without global thickness covariation. Global and regional thickness were strongly correlated across groups. Global thickness was lower in the schizophrenia spectrum groups than the other groups. Regional thickness deficits in schizophrenia spectrum groups were attenuated or eliminated with global thickness covariation. Eliminating the variation that regional thickness shares with global thickness eliminated disease-related effects. This statistical approach results in erroneous conclusions that regional thickness is normal in disorders like schizophrenia or clinical high risk syndrome.

Identification of youth at clinical high-risk for psychosis: A community-based study from India.

A two-stage process, wherein self-report screening precedes the structured interview, is suggested for identifying individuals at clinical high-risk for psychosis (CHR-P) in community samples. Aim of this study was to screen a community youth sample from India for CHR-P using the two-stage method. Specific objectives were to assess concordant validity of the self-report measure and predictive validity of the two-stage method. Based on probability sampling, 2025 youth aged 15-24 years were recruited from one rural and one urban area of Telangana, a Telugu-speaking state in India. Telugu version of the PRIME Screen-Revised (PS-R) and structured interview for psychosis-risk syndromes (SIPS) were used. CHR-P positive and negative cohorts were followed-up for transition to psychosis at 3-monthly intervals. One hundred ten individuals screened positive on PS-R. SIPS conducted on 67 out of 110 individuals confirmed 62 (92.54%) to be CHR-P positive. PS-R showed 98.41% sensitivity and 90.74% specificity. Among CHR-P positive, three participants transitioned to psychosis in 15 months. The hazard ratio for psychosis transition was 11.4. Screening accuracy of PS-R in the community youth sample in Telangana is optimum. The hazard ratio for psychosis transition in the community identified CHR-P indicates good predictive validity for the two-stage method.

Advancements and Future Directions in Prevention Based on Evaluation for Individuals With Clinical High Risk of Psychosis: Insights From the SHARP Study.

This review examines the evolution and future prospects of prevention based on evaluation (PBE) for individuals at clinical high risk (CHR) of psychosis, drawing insights from the SHARP (Shanghai At Risk for Psychosis) study. It aims to assess the effectiveness of non-pharmacological interventions in preventing psychosis onset among CHR individuals. The review provides an overview of the developmental history of the SHARP study and its contributions to understanding the needs of CHR individuals. It explores the limitations of traditional antipsychotic approaches and introduces PBE as a promising framework for intervention. Three key interventions implemented by the SHARP team are discussed: nutritional supplementation based on niacin skin response blunting, precision transcranial magnetic stimulation targeting cognitive and brain functional abnormalities, and cognitive behavioral therapy for psychotic symptoms addressing symptomatology and impaired insight characteristics. Each intervention is evaluated within the context of PBE, emphasizing the potential for tailored approaches to CHR individuals. The review highlights the strengths and clinical applications of the discussed interventions, underscoring their potential to revolutionize preventive care for CHR individuals. It also provides insights into future directions for PBE in CHR populations, including efforts to expand evaluation techniques and enhance precision in interventions.

Emotional tone in clinical high risk for psychosis: novel insights from a natural language analysis approach.

Individuals at clinical high risk (CHR) for psychosis experience subtle emotional disturbances that are traditionally difficult to assess, but natural language processing (NLP) methods may provide novel insight into these symptoms. We predicted that CHR individuals would express more negative emotionality and less emotional language when compared to controls. We also examined associations with symptomatology. Participants included 49 CHR individuals and 42 healthy controls who completed a semi-structured narrative interview. Interview transcripts were analyzed using Linguistic Inquiry and Word Count (LIWC) to assess the emotional tone of the language (tone -the ratio of negative to positive language) and count positive/negative words used. Participants also completed clinical symptom assessments to determine CHR status and characterize symptoms (i.e., positive and negative symptom domains). The CHR group had more negative emotional tone compared to healthy controls (t=2.676, p=.009), which related to more severe positive symptoms (r2=.323, p=.013). The percentages of positive and negative words did not differ between groups (p's>.05). Language analyses provided accessible, ecologically valid insight into affective dysfunction and psychosis risk symptoms. Natural language processing analyses unmasked differences in language for CHR that captured language tendencies that were more nuanced than the words that are chosen.

The Complex Latent Structure of Attenuated Psychotic Symptoms: Hierarchical and Bifactor Models of SIPS Symptoms Replicated in Two Large Samples at Clinical High Risk for Psychosis.

The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic symptoms. Hierarchical and bifactor models were developed for the SIPS in a large CHR sample (NAPLS-3, N = 787) and confirmed through preregistered replication in an independent sample (NAPLS-2, N = 1043). Criterion validity was tested through relationships with CHR status, comorbid symptoms/diagnoses, functional impairment, demographics, neurocognition, and conversion to psychotic disorders. Most variance in SIPS items (75%-77%) was attributable to a general factor. Hierarchical and bifactor models included a general factor and five specific/lower-order factors (positive symptoms, eccentricity, avolition, lack of emotion, and deteriorated thought process). CHR participants were elevated on the general factor and the positive symptoms factor. The general factor was associated with depressive symptoms; functional impairment; and mood, anxiety, and schizotypal personality diagnoses. The general factor was the best predictor of psychotic disorders (d ≥ 0.50). Positive symptoms and eccentricity had specific effects on conversion outcomes. The deteriorated thought process was least meaningful/replicable. Attenuated psychotic symptoms, measured by the SIPS, have a complex hierarchical structure with a strong general factor. The general factor relates to internalizing symptoms and functional impairment, emphasizing the roles of general psychopathological distress/impairment in psychosis risk. Shared symptom variance complicates the interpretation of raw symptom scores. Broad transdiagnostic assessment is warranted to model psychosis risk accurately.

Longitudinal Trajectories of Premorbid Social and Academic Adjustment in Youth at Clinical High Risk for Psychosis: Implications for Conversion.

Social and academic adjustment deteriorate in the years preceding a psychotic disorder diagnosis. Analyses of premorbid adjustment have recently been extended into the clinical high risk for psychosis (CHR) syndrome to identify risk factors and developmental pathways toward psychotic disorders. Work so far has been at the between-person level, which has constrained analyses of premorbid adjustment, clinical covariates, and conversion to psychosis. Growth-curve models examined longitudinal trajectories in retrospective reports of premorbid social and academic adjustment from youth at CHR (n = 498). Interaction models tested whether known covariates of premorbid adjustment problems (attenuated negative symptoms, cognition, and childhood trauma) were associated with different premorbid adjustment trajectories in converters vs non-converters (ie, participants who did/did not develop psychotic disorders within 2-year follow-up). Converters reported poorer social adjustment throughout the premorbid period. Converters who developed psychosis with an affective component reported poorer academic adjustment throughout the premorbid period than those who developed non-affective psychosis. Tentatively, baseline attenuated negative symptoms may have been associated with worsening social adjustment in the premorbid period for non-converters only. Childhood trauma impact was associated with fewer academic functioning problems among converters. Cognition effects did not differ based on conversion status. Premorbid social function is an important factor in risk for conversion to psychosis. Negative symptoms and childhood trauma had different relationships to premorbid functioning in converters vs non-converters. Mechanisms linking symptoms and trauma to functional impairment may be different in converters vs non-converters, suggesting possible new avenues for risk assessment.

Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery

BackgroundThe effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults.MethodsA total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP−). Therefore, the four groups were defined as Adolescent-AP−, Adolescent-AP+, Adult-AP−, and Adult-AP+.ResultsDuring the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP− group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP− group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP− group. The Adolescent-AP− group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults.ConclusionsEarly use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.

EEG-Based Event-Related Potential Biomarkers as Predictors of Clinical Outcomes in Youth at Clinical High Risk for Psychosis

EEG-Based Event-Related Potential Biomarkers as Predictors of Clinical Outcomes in Youth at Clinical High Risk for Psychosis

Social Engagement Moderates Relations Between Hippocampal-Temporoparietal Junction Connectivity and Neighborhood Social Fragmentation in Youth at Clinical High Risk for Psychosis

Social Engagement Moderates Relations Between Hippocampal-Temporoparietal Junction Connectivity and Neighborhood Social Fragmentation in Youth at Clinical High Risk for Psychosis

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

443. Ventral Tegmental Area Dysregulation During Goal-Relevant Behavior in Clinical High-Risk Psychosis

443. Ventral Tegmental Area Dysregulation During Goal-Relevant Behavior in Clinical High-Risk Psychosis