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Background: Shared decision-making between clinicians and service users is crucial in mental health care. One significant barrier to achieving this goal is the lack of user-centered services. Integrating digital tools into mental health services holds promise for addressing some of these challenges. However, the implementation of digital tools, such as mobile apps, remains limited, and attrition rates for mental health apps are typically high. Design thinking can support the development of tools tailored to the needs of service users and clinicians., Objective: This study aims to develop and beta test a digital tool designed for individuals with severe mental disorders or substance use disorders to facilitate shared decision-making on treatment goals and strategies within mental health services., Methods: We used a user-centered design approach to develop iTandem, an app facilitating collaborative treatment between service users and clinicians. Through qualitative interviews and workshops, we engaged 6 service users with severe mental disorders or substance use disorders, 6 clinicians, and 1 relative to identify and design relevant app modules. A beta test of iTandem was conducted to refine the app and plan for a pilot trial in a clinical setting. After 6 weeks of app use, 5 clinicians and 4 service users were interviewed to provide feedback on the concept, implementation, and technical issues. Safety and ethical considerations were thoroughly discussed and addressed., Results: To avoid overload for the service users, we applied a pragmatic take on module content and size. Thus, iTandem includes the following 8 modules, primarily based on the needs of service users and clinicians: Sleep (sleep diary), Medication (intake and side effects), Recovery (measures, including well-being and personal recovery, and exercises, including good things and personal strengths), Mood (mood diary and report of daily feelings), Psychosis (level of positive symptoms and their consequences and level of negative symptoms), Activity (goal setting and progress), Substance use (weekly use, potential triggers or strategies used to abstain), and Feedback on therapy (of individual sessions and overall rating of the past week). For the beta testing, service users and clinicians collaborated in choosing 2-3 modules in iTandem to work with during treatment sessions. The testing showed that the app was well received by service users, and that facilitation for implementation is crucial., Conclusions: iTandem and similar apps have the potential to enhance treatment outcomes by facilitating shared decision-making and tailoring treatment to the needs of service users. However, successful implementation requires thorough testing, iterative development, and evaluations of both utility and treatment effects. There is a critical need to focus on how technology integrates into clinical settings-from development to implementation-and to conduct further research on early health technology assessments to guide these processes., (©Kristin Lie Romm, Mari Skoge, Elizabeth Ann Barrett, Lars-Christian Berentzen, Dagfinn Bergsager, Pål Fugelli, Thomas Bjella, Erlend Strand Gardsjord, Kristine Kling, Sindre Hembre Kruse, Kari Jorunn Kværner, Ingrid Melle, Erlend Mork, Henrik Myhre Ihler, Eline Borger Rognli, Carmen Simonsen, Tor Gunnar Værnes, Sofie Ragnhild Aminoff. Originally published in JMIR Formative Research (https://formative.jmir.org), 17.01.2025.)

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings., (© 2024. The Author(s).)

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals., Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder., Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022., Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores., Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (β = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (β = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate)., Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals., Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder., Design Setting and Participants: Clinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P individuals [47.09% female; mean age: 20.75 (4.74) years] and 1,237 healthy individuals [44.70% female; mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group., Main Outcomes and Measures: For each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of individuals with infranormal (z<-1.96) or supranormal (z>1.96) scores., Results: CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P individuals with infranormal or supranormal values in any metric was low (<12%) and similar to that of healthy individuals. CHR-P individuals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADS SA showed significant but weak associations (|β|<0.09; P FDR <0.05) with positive symptoms and IQ., Conclusions and Relevance: The study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk.

Basic self-disturbance (BSD) has been proposed as a driver of symptom development in schizophrenia spectrum disorders (SSDs). In a one-year follow-up of 32 patients (15-30 years) at putative risk for psychosis, we investigated trajectories of BSD levels from baseline to follow-up, and associations between clinical characteristics at baseline and follow-up, including follow-up levels of BSD (assessed with the EASE). Clinical high risk (CHR) for psychosis status and symptom severity were assessed with the SIPS/SOPS scales and also according to the cognitive basic symptoms high-risk criteria (COGDIS). DSM-IV diagnoses, functioning and other clinical characteristics were assessed with standard clinical instruments. Higher severity of negative symptoms and meeting COGDIS criteria at baseline were associated with higher BSD levels at follow-up. All measured at follow-up, higher BSD levels correlated with higher severity of positive, negative, disorganization and general symptoms, and with a lower level of global functioning. We found higher BSD levels at follow-up in subjects with schizotypal personality disorder (SPD) at baseline (n = 5) and in SSDs at follow-up (n = 12, including nine with SPD). Mean BSD levels decreased significantly from baseline to follow-up, but individual trajectories varied considerably. Increased BSD levels were associated with higher baseline BSD levels, non-remission of positive symptoms and functional decline. Overall, the current study indicates that subgroups in the CHR population with a higher risk of non-remission or deterioration may be identified by supplementing CHR criteria with assessment of BSD and negative symptoms., (© 2021. The Author(s).)

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation., (© 2022. The Author(s).)

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk., Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-)., Design, Setting, and Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020., Main Outcomes and Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group)., Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001)., Conclusions and Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.

Basic self-disturbance (BSD) is assumed to drive symptom development in schizophrenia spectrum disorders and in clinical high-risk (CHR) for psychosis. We investigated the relationship between BSD at baseline, assessed with the Examination of Anomalous Self-Experience (EASE), and symptoms and functional outcome after one year in 32 patients, including 26 CHR and six with non-progressive attenuated psychotic symptoms. Correlations between baseline BSD levels and positive, negative and disorganization symptoms, and global functioning level at follow-up were significant. Hierarchical regression analyses revealed that higher levels of baseline BSD predicted more severe positive symptoms and lower global functioning at follow-up, after adjusting for baseline positive symptoms and functioning. Subjects who were not in symptomatic and functional remission after one year had higher levels of BSD and negative symptoms, and lower functioning level, at baseline. Baseline BSD in participants with schizophrenia spectrum diagnoses at follow-up (9 of 12 were schizotypal personality disorder) were at the levels seen in schizotypal disorders in previous studies, but not significantly different from the other participants. Early identification and assessment of BSD may constitute a useful prognostic tool and a signal for therapeutic targets in CHR conditions. Further CHR studies investigating these relationships with larger samples are recommended., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Anomalous self-experiences (ASE) are considered as central features of the schizophrenia spectrum disorders and prodromal schizophrenia. We investigated total and single-item prevalence of these phenomena in a clinical high-risk (CHR) for psychosis sample, and associations with conventional psychosis-risk symptoms, present and childhood global/psychosocial functioning, and childhood trauma., Methods: The sample (n = 38) included 31 CHR, according to ultra-high risk or cognitive basic symptoms (COGDIS) criteria, and seven with non-progressive attenuated positive symptoms. Psychopathological evaluations included the Examination of Anomalous Self-Experience (EASE), Structured Clinical Interview for Prodromal Syndromes (SIPS), Schizophrenia Proneness Instrument - Adult (SPI-A) (only the COGDIS-criteria), a diagnostic interview (SCID-I), Global Assessment of Functioning - Split version (S-GAF), Premorbid Adjustment Scale (PAS) and Childhood Trauma Questionnaire (CTQ)., Results: The mean total EASE score was in line with reports from other CHR samples, and was particularly enhanced in schizotypal personality disorder and in subjects fulfilling COGDIS-criteria. The four most frequent EASE-items were present in two-thirds or more of the participants. EASE total was significantly associated with negative and disorganization symptoms. A multiple regression analysis revealed that the level of negative symptoms explained most of the variance in EASE total., Conclusions: These results corroborates other findings that anomalous self-experiences are frequent and important features in CHR conditions and in the schizophrenia spectrum. The strong associations with negative symptoms and cognitive disturbances (COGDIS) should be investigated in longitudinal studies to address causality, psychopathological pathways and schizophrenia spectrum specificity. The weaker correlation between EASE total and positive symptoms may partly be related to a restricted range of positive symptoms., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Basic self-disturbance (BSD) is proposed to constitute the clinical core of schizophrenia spectrum disorders, including prodromal states and schizotypy. Anomalous self-experiences (ASEs) are suggested as phenotypic variants of BSD, representing markers of schizophrenia vulnerability. However, ASEs are not restricted to the schizophrenia spectrum, but may also occur in non-psychotic states like depersonalization disorder (DPD). It is unclear to what extent the prevalence and nature of ASEs are differing between the two conditions. The main aim of this paper is to assess and compare ASEs in both conditions, based on literature and two illustrating cases. This might expand the understanding of these phenomena, and strengthen the basis for clinical differentiation., Methods: One patient with schizotypal personality disorder (SPD) and one with DPD were selected from an ongoing clinical high-risk (CHR) for psychosis study. ASEs were assessed with the Examination of Anomalous Self-Experience (EASE) and analyzed according to the two central dimensions of BSD: diminished self-affection and hyperreflexivity, as well as according to prototypical aspects of depersonalization. The cases were also analyzed and compared with respect to chronology, other symptomatology, and psychopathological pathways., Results: Both cases revealed ASEs reflecting the central dimensions of BSD as well as prototypical aspects of depersonalization. Only the SPD case however, linked ASEs to psychotic-like ideas of external influence and control. The symptoms had an insidious early childhood onset with no obvious triggers in the SPD case, and an abrupt adolescence onset triggered by second-time cannabis use and panic anxiety in the DPD case., Conclusions: The similarities and differences in ASEs, symptomatology and developmental pathways of the two cases might be accounted for by an updated model of self-disorders. The model proposes that schizophrenia manifests as a result of a combination of early "primary"-onset ASEs, reflecting dis-turbances in early neurodevelopment, and later occurring, "secondary" ASEs of a more defensive-protective character. In line with this, the DPD case may be characterized only by secondary ASEs and thus better protected against psychotic decompensation than the SPD case, tentatively affected by a combination of primary and secondary ASEs., (© 2018 S. Karger AG, Basel.)