Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

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.

Anomalous self-experiences and neurocognitive functioning in adolescents at risk for psychosis: Still no significant associations found between these two vulnerability markers.

BACKGROUND: Anomalous self-experiences (ASEs) and neurocognitive impairments are considered essential domains of vulnerability for developing psychotic disorders. However, little research exists of possible associations between ASEs and neurocognitive functions in individuals at-risk for psychosis. The interconnections between ASEs and neurocognitive impairments should therefore be clarified as much as possible, especially in young individuals at risk. No previous studies have investigated these two fundamental domains in non-help-seeking adolescents at risk for developing psychosis. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). Adolescents (N = 48, 94% females, mean age = 15.3) were invited to participate after completing a 14-year-old survey distributed by MoBA. At-risk adolescents were selected based on the 0.4% highest scores on 19 items assessing both psychotic-like experiences and ASEs. Five specifically selected and formulated items measuring ASEs were computed to an ASEs total score. Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery. RESULTS: Regression analyses revealed no significant relationships between ASEs and any neurocognitive domain. CONCLUSIONS: We did not find any significant associations between ASEs and neurocognitive functions in non-help-seeking adolescents at risk for psychotic disorders, which is in line with reports from other types of cohorts. Thus, ASEs and neurocognitive functions may be understood as two relatively separate domains that co-exist in at-risk states. These results underline the need for a wider scope when making predictions about future trajectories, e.g. the development of psychotic disorders. Including both ASEs and neurocognitive functioning in at-risk populations may increase the specificity of vulnerability criteria in this population and enhance our understanding of early psychosis psychopathology.

Basic self-disturbance trajectories in clinical high risk for psychosis: a one-year follow-up study.

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.

Disordered Selfhood in Schizophrenia and the Examination of Anomalous Self-Experience: Accumulated Evidence and Experience.

Disordered selfhood in schizophrenia was rediscovered at the turn of the millennium. In 2005, Psychopathology published the psychometric instrument, the Examination of Anomalous Self-Experience (EASE). In this article, we summarize the historical background of the creation of the EASE, explicate the notion of the disorder of basic or minimal self with the help of phenomenological philosophy, and provide a brief description of clinical manifestations targeted by the EASE. We also present our personal experience using and teaching the EASE and summarize the empirical evidence obtained so far. We conclude that the basic self-disorder represents a crucial phenotype of schizophrenia spectrum disorders and that this phenotype offers a potential avenue to empirical pathogenetic research and psychotherapeutic treatment.

Anomalous self-experiences are strongly associated with negative symptoms in a clinical high-risk for psychosis sample.

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.

Anomalous Self-Experiences: Markers of Schizophrenia Vulnerability or Symptoms of Depersonalization Disorder? A Phenomenological Investigation of Two Cases.

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.

Anomalous self-experience and childhood trauma in first-episode schizophrenia.

BACKGROUND: Anomalous self-experiences (ASEs) are viewed as core features of schizophrenia. Childhood trauma (CT) has been postulated as a risk factor for developing schizophrenia. AIM: The aim of this study is to investigate the relationships between CT, depression and ASEs in schizophrenia. METHOD: ASEs were assessed in 55 patients in the early treated phases of schizophrenia using the Examination of Anomalous Self-Experience (EASE) instrument. Data on CT were collected using the Childhood Trauma Questionnaire, short form (CTQ-SF). This consists of 5 subscales: physical abuse, sexual abuse, emotional abuse, emotional neglect, and physical neglect. Assessment of depression was based on the Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: We found significant associations between EASE total score and CTQ total score and between EASE total score and emotional neglect subscore in women, but not men. We also found significant associations between CDSS total score and CTQ total score and between CDSS total score and emotional abuse, emotional neglect, and physical neglect subscores in women, but not men. In men we did not find any significant associations between EASE total score, CDSS total score and any CTQ scores. CONCLUSION: CT was significantly associated with higher levels of ASEs in women in the early treated phases of schizophrenia, but not in men. This again associated with an increase in depressive symptoms.

The role of the antileukoprotease SLPI in smoking-induced human papillomavirus-independent head and neck squamous cell carcinomas.

Recently, we showed that increased SLPI levels prevent human papillomavirus (HPV) infections and metastasis in smoking-induced, non-HPV-driven head and neck squamous cell carcinoma (HNSCC). Here, we focus on the role of SLPI in non-HPV-driven HNSCC, investigating tumor tissue and non-neoplastic mucosa from the same patients and from non-HNSCC patients. Gene and protein expression of SLPI and gene expression of annexin 2 (a SLPI receptor), nicotine receptor (α7AChR) and arylhydrocarbon receptor (AhR) were analyzed in HNSCC patients (20 smokers; 16 nonsmokers). SLPI-results were correlated with the patients' HPV status. Non-neoplastic mucosa of HNSCC patients and normal mucosa from non-HNSCC individuals (18 smokers; 20 nonsmokers) was analyzed for the same parameters. Tissue of the inferior turbinate (n = 10) was incubated with nicotine for analysis of the same genes. SLPI gene expression in tumor tissue was 109.26 ± 23.08 times higher in smokers versus nonsmokers. Non-neoplastic mucosa of smokers showed also higher SLPI gene expression (10.49 ± 1.89-fold non-HNSCC; 18.02 ± 3.93-fold HNSCC patients). Annexin 2 gene expression was also increased in smokers. SLPI data were corroborated by immunohistochemistry. A nicotine dependent correlation between SLPI and annexin 2 gene expression (r(2) = 0.15, p < 0.001) was shown ex vivo. Nicotine and smoking increased α7AChR and AhR gene expression. Five patients, showing no/low SLPI expression, were HPV16-positive. A significant correlation between smoking and SLPI expression in tumors and to our knowledge for the first time in mucosa of HNSCC and non-HNSCC patients was established. Together with the finding that all patients with HPV infection showed no/low SLPI expression, these data support our intriguing hypothesis that smoking induced upregulated SLPI prevents HPV infections.

Anomalous self-experiences contribute independently to social dysfunction in the early phases of schizophrenia and psychotic bipolar disorder.

BACKGROUND: Psychotic disorders are associated with significant social dysfunction. Anomalous self-experiences (ASE) present in psychotic disorders could contribute to social dysfunction. AIM: To investigate if ASE contribute to social dysfunction in the early phases of psychotic disorders after controlling for factors related to social functioning including diagnoses. METHODS: ASE were assessed by means of the EASE (Examination of Anomalous Self-Experience) in 76 patients referred to their first adequate treatment for schizophrenia or psychotic bipolar disorder. Diagnoses, symptom severity, and functioning were assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Premorbid Adjustment Scale, Global Assessment of Functioning--Split Version, and Social Functioning Scale. Neurocognitive assessments included measures of psychomotor speed, working memory, executive and memory functions. Duration of untreated psychosis was also assessed. RESULTS: High levels of ASE were significantly associated with poorer social functioning in the early phases of schizophrenia and psychotic bipolar disorder also after correcting for diagnosis. CONCLUSION: This study demonstrates the significance of ASE for social dysfunction in patients with psychotic disorders, and contributes to the understanding of the complexity of illness-related factors that affect social functioning.

Implementation of guidelines on Family Involvement for persons with Psychotic disorders: a pragmatic cluster randomized trial. Effect on relatives' outcomes and family interventions received.

Background: Family interventions (FI) are recommended as part of the treatment for psychotic disorders, but the implementation in mental health services is generally poor. Recently, The Implementation of guidelines on Family Involvement for persons with Psychotic disorders (IFIP) trial, demonstrated significant improvements in implementation outcomes at cluster-level. This sub-study aims to examine the effectiveness of the IFIP intervention on relatives' outcomes and received FI. Methods: A cluster randomized controlled trial, was conducted in 15 Norwegian Community Mental Health Center (CMHC) units that were randomized to either the IFIP intervention, including implementation interventions and clinical interventions, or treatment as usual (TAU). The clinical interventions consisted of FI: basic family involvement and support (BFIS) to all patients and family psychoeducation (FPE) to as many as possible. Patients with psychotic disorders and their closest relative were invited to fill in questionnaires at inclusion and 6 months and 12 months follow-up. Received FI was reported by both relatives and clinicians. The relatives' primary outcome was satisfaction with health service support, measured by the Carer well-being and support questionnaire part B (CWS-B). The relatives' secondary outcomes were caregiver experiences, expressed emotions and quality of life. Patients' outcomes will be reported elsewhere. Results: In total 231 patient/relative pairs from the CMHC units were included (135 intervention; 96 control).The relatives in the intervention arm received an increased level of BFIS (p=.007) and FPE (p < 0.05) compared to the relatives in the control arm, including involvement in crisis planning. The primary outcome for relatives' satisfaction with health service support, showed a non-significant improvement (Cohen's d = 0.22, p = 0.08). Relatives experienced a significant reduced level of patient dependency (Cohen's d = -0.23, p = 0.03). Conclusion: The increased support from clinicians throughout FI reduced the relatives' perceived level of patient dependency, and may have relieved the experience of responsibility and caregiver burden. The COVID-19 pandemic and the complex and pioneering study design have weakened the effectiveness of the IFIP intervention, underscoring possible potentials for further improvement in relatives' outcomes. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03869177.

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis.

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 (ß = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (ß = 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.

Linguistic markers and basic self-disturbances among adolescents at risk of psychosis. A qualitative study.

Background: Language impairments are key features of schizophrenia spectrum disorders, and have also been suggested to signal enhanced psychosis risk. Incoherence, derailment, and monotonous speaking are however closely related to psychosis onset, and thus not very early markers. Recent phenomenologic-psychiatric studies claim that basic self-disturbance (BSD) may represent more useful early markers. Methods: We searched for distinctive irregular linguistics of 30 CHR outpatient adolescents, aged 12-18 years. Standard instruments established psychosis risk and BSD. Participants chose three personal and well manifested BSD phenomena. Ninety verbatim statements were analyzed and grouped into higher order clusters of linguistic irregularities. Findings: We identified five clusters of irregular language features: distinctive words, describing an atmosphere of unreality; irregular use of prepositions, indicating experiential detachment; shifts of personal pronouns, indicating identity confusion; near-literal use of metaphors and conjunctions indicating existential insecurity, and idiosyncratic use of adjectives indicating perceptual transcendence. Interpretation: The adolescents provided naturalistic descriptions of experiences that were markedly twisted and almost ineffable. This unique irregular "BSD -language" was highly meaningful in its proper context, expressing informative characteristics of first-personal experiential alterations, essential for early detection. The features may additionally represent precursors of psychosis transition, useful for clinical decision-making. Funding: Foundation Dam, Oslo, Norway (Grant Number 2017/FO143368).

A seven-year longitudinal study of the association between neurocognitive function and basic self-disorders in schizophrenia.

Introduction: Basic self-disorders (SDs) and neurocognitive impairments are fundamental trait-like aspects of schizophrenia spectrum disorders. There has been little research on the association between SDs and neurocognitive impairments in schizophrenia, and no longitudinal studies have investigated if they are related. The aim of this study was to investigate the association between SDs and neurocognitive function in a follow-up study of patients with schizophrenia. Methods: SDs and neurocognition were examined in 35 patients with schizophrenia during their first treatment and 7 years later (mean 7.1, SD 0.42). SDs were examined with the Examination of Anomalous Self-Experience (EASE) instrument. The neurocognitive examination included assessments of psychomotor speed, executive- and memory functions. Results: Poorer executive functions at baseline were significantly associated with more SDs 7 years later and smaller reductions in SDs over time. There were no significant associations between other neurocognitive functions and SDs. Discussion: Executive functions are important for self-regulation, and impairments in these functions in everyday life may have an impact on the development and/or persistence of SDs.

Normative modeling of brain morphometry in Clinical High-Risk for Psychosis.

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 ADSSA showed significant but weak associations (|ß|<0.09; PFDR<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.

The association between anomalous self-experience and suicidality in first-episode schizophrenia seems mediated by depression.

BACKGROUND: A recent hypothesis is that suicidality in schizophrenia may be linked to the patients' altered basic self-awareness or sense of self, termed self-disorders (SDs). AIM: The aim of the study was to investigate whether SDs in first-episode schizophrenia spectrum disorders are related to suicidality and whether this relationship is independent of or mediated by depression or other standard clinical measures. METHOD: Self-disorders were assessed in 49 patients with first-episode schizophrenia by means of the Examination of Anomalous Self-Experience (EASE) instrument. Symptoms severity and functioning were assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, and Global Assessment of Functioning-Split Version. Suicidality was measured by the Calgary Depression Scale for Schizophrenia item 8. RESULTS: Analyses detected a significant association between current suicidality, current depression, and SDs as measured by the EASE. The effect of SDs on suicidal ideation appeared to be mediated by depression. CONCLUSION: The interaction between anomalous self-experiences and depression could be a rational clinical target for the prevention of suicidality in the early phases of schizophrenia and supports the rationale for including assessment of SDs in early intervention efforts.

Selective aggregation of self-disorders in first-treatment DSM-IV schizophrenia spectrum disorders.

Converging evidence indicates that self-disorders (SDs) selectively aggregate in schizophrenia spectrum conditions. The aim of this study was to test the discriminatory power of SDs with respect to schizophrenia and nonschizophrenia spectrum psychosis at first treatment contact. SDs were assessed in 91 patients referred for first treatment through the Examination of Anomalous Self-experience (EASE) instrument. Diagnoses, symptoms severity, and function were assessed using the Structural Clinical Interview for the DSM-IV, Structured Clinical Interview for the Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Young Mania Rating Scale, and Global Assessment of Functioning-Split Version. Most patients found it highly relevant to talk about SDs. EASE total score critically discriminated between schizophrenia, bipolar psychosis, and other psychoses. The EASE total score was the only clinical measure that showed a significant and robust association with the diagnosis of schizophrenia. Systematic exploration of anomalous self-experiences could improve differential diagnosis in first-treatment patients.

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

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.

Examination of anomalous self-experience in first-episode psychosis: interrater reliability.

BACKGROUND: The growing research focus on early detection of schizophrenia has fostered an increasing interest in the nonpsychotic experiential anomalies that may antedate schizophrenia spectrum disorders and assist early differential diagnosis. The Examination of Anomalous Self-Experience (EASE) is a phenomenologically inspired checklist, specifically designed to support the comprehensive assessment of these characteristic subjective experiences. AIM: To assess the interrater reliability of the EASE. SAMPLING AND METHODS: Twenty-five first-episode psychosis (FEP) patients were interviewed with the EASE. Videotaped interviews were blindly reevaluated. Internal consistency, overall interrater correlation and item interrater agreement (Cohen's kappa) were estimated. RESULTS: The EASE showed good to excellent internal consistency across the two raters (Cronbach's alpha above 0.87) and an overall inter-rater correlation above 0.80 (Spearman's rho, p < 0.001). The average kappa of the EASE was 0.65, ranging from 0.51 to 0.73 over the 5 domains; kappa values at an item level were very good in 9 items, good in 20 items, moderate in 11 items and fair in 4 items. CONCLUSION: The EASE provides a reliable and internally consistent clinical tool for the assessment of subjective experience in FEP patients, suggesting that this instrument could usefully supplement standard clinical assessments during the onset phase of psychosis.

Basic self-disturbance in subjects at clinical high risk for psychosis: Relationship with clinical and functional outcomes at one year follow-up.

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.

Basic self-disturbances are associated with Sense of Coherence in patients with psychotic disorders.

BACKGROUND: The Sense of Coherence (SOC) theory gives a possible explanation of how people can experience subjective good health despite severe illness. Basic self-disturbances (BSDs) are subtle non-psychotic disturbances that may destabilize the person's sense of self, identity, corporeality, and the overall 'grip' of the world. AIM: Our objective was to investigate associations between BSDs and SOC in patients with psychotic disorders. DESIGN: This is a cross-sectional study of 56 patients diagnosed with psychotic disorders inside and outside the schizophrenia spectrum (35 schizophrenia, 13 bipolar, and eight other psychoses). SOC was measured using Antonovsky's 13-item SOC questionnaire, and BSDs were assessed using the Examination of Anomalous Self-Experience (EASE) manual. Diagnosis, symptoms, and social and occupational performance were assessed using standardized clinical instruments. RESULTS: We found a statistically significant correlation (r = ) between high levels of BSDs and low levels of SOC (r = -0.64/p<0.001). This association was not influenced by diagnostics, clinical symptoms or level of functioning in follow-up multivariate analyses. CONCLUSION: A statistically significant association between BSDs and SOC indicates that the presence and level of self-disturbances may influence the person's ability to experience life as comprehensive, manageable and meaningful. However, the cross-sectional nature of the study precludes conclusions regarding the direction of this association.