Clinical High-risk State For Psychosis Research Articles

Debate: Better use of existing services, not more new pathways, is required for psychosis prevention in young people - Commentary on Salazar de Pablo and Arango: 'Prevention of psychosis in adolescents: does CAMHS have a role?'

There has been much academic interest in 'the clinical high-risk state for psychosis' (CHR-P) concept. Whilst early intervention in psychosis (EIP) services have offered input to individuals meeting the CHR-P criteria the involvement of CAMHS clinicians in supporting young people with ideational and perceptual disturbance has been more inconsistent and uncertain. We bring together our relevant lived experience, empirical evidence and clinical and research expertise to write this commentary. We assert that the CHR-P paradigm needs to be revised. This should reflect the low transition rates to psychosis and the prevalent general, impairing psychopathology in individuals meeting these criteria. Nevertheless, it is clear that both CAMHS and EIP services have potential roles in meeting the needs of young people affected by distressing ideational and perceptual disturbance. We suggest that new care pathways and services are not required for young people affected by distressing psychosis-like experiences. Rather more effective joint working between CAMHS, EIP, crisis services and other agencies could meet the needs of these young people more comprehensively.

Analysis of polyunsaturated fatty acids in antipsychotic-free individuals with at-risk mental state and patients with first-episode schizophrenia.

Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES). This study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS). Eicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30). The findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.

Anatomical variations in the insular cortex in individuals at a clinical high-risk state for psychosis and patients with schizophrenia.

Since the number of insular gyri is higher in schizophrenia patients, it has potential as a marker of early neurodevelopmental deviations. However, it currently remains unknown whether the features of the insular gross anatomy are similar between schizophrenia patients and individuals at risk of psychosis. Furthermore, the relationship between anatomical variations in the insular cortex and cognitive function has not yet been clarified. The gross anatomical features (i.e., the number of gyri and development pattern of each gyrus) of the insular cortex were examined using magnetic resonance imaging, and their relationships with clinical characteristics were investigated in 57 subjects with an at-risk mental state (ARMS) and 63 schizophrenia patients in comparison with 61 healthy controls. The number of insular gyri bilaterally in the anterior subdivision was higher in the ARMS and schizophrenia groups than in the control group. The schizophrenia group was also characterized by a higher number of insular gyri in the left posterior subdivision. A well-developed right middle short insular gyrus was associated with symptom severity in first-episode schizophrenia patients, whereas chronic schizophrenia patients with a well-developed left accessory gyrus were characterized by less severe cognitive impairments in motor and executive functions. The features of the insular gross anatomy were not associated with clinical characteristics in the ARMS group. The features of the insular gross anatomy that were shared in the ARMS and schizophrenia groups may reflect a vulnerability to psychosis that may be attributed to anomalies in the early stages of neurodevelopment. However, the contribution of the insular gross anatomy to the clinical characteristics of schizophrenia may differ according to illness stages.

Resting state hyperconnectivity of the default mode network in schizophrenia and clinical high-risk state for psychosis.

Disrupted functional connectivity (FC) of the default mode network (DMN) may have a pathophysiological role in schizophrenia. However, functional magnetic resonance imaging (fMRI) of the DMN in schizophrenia patients has shown inconsistent results. It also remains unclear whether individuals with at-risk mental state (ARMS) have an altered DMN connectivity and whether it is related to clinical characteristics. This fMRI study examined resting-state FCs of the DMN and its relevance to clinical/cognitive variables in 41 schizophrenia patients, 31 ARMS individuals, and 65 healthy controls. Compared with controls, schizophrenia patients had significantly increased FCs within the DMN and between the DMN and diverse cortical areas, whereas ARMS patients had increased FCs only between the DMN and occipital cortex. FC of the lateral parietal cortex with superior temporal gyrus was positively correlated with negative symptoms in schizophrenia, whereas FC of that with interparietal sulcus was negatively correlated with general cognitive impairment in ARMS. Our findings suggest that increased FCs between the DMN and visual network commonly seen in schizophrenia and ARMS subjects may reflect a network-level disturbance representing a general vulnerability to psychosis. In addition, FC changes related to the lateral parietal cortex may underpin clinical characteristics of ARMS and schizophrenia subjects.

Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study.

The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p < 0.05. Whole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [F(3,143) = 1,41, p = 0.24], bilateral frontal cortex [F(3,143) = 1.01, p = 0.39], hippocampus [F(3,143) = 0.63, p = 0.60] or striatum [F(3,143) = 0.52, p = 0.57] rCBF. Similar null findings were observed in lateralized ROIs (p > 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.

Correlations of thought disorders with attenuated positive symptoms at clinical high-risk state for psychosis

IntroductionOne of the methods for early diagnosis in individuals at clinical high-risk state for psychosis could be the identifying specific symptoms, such as thought disorders. Thought disorders may be a separate symptom, unrelated to attenuated positive symptoms (APS) with an independent predictive value.ObjectivesCorrelation analysis of thought disorders and APS in patients at clinical high-risk state for psychosis.MethodsThe study included 30 young men (mean age 19.2±2.1 years) hospitalized at the clinic of the FSBSI “Mental Health Research Centre” with the APS in the first depressive episode (F32.1, F32.2, F32.28, F32.8) which is considered as clinical high-risk state for psychosis. The severity of thought impairment was assessed using the Thought, Language and Communication Scale (TLC). Subsequently was performed the search for correlations of scores on the TLC and the severity of “prodromal” symptoms, according to The Scale of Prodromal Symptoms (SOPS).ResultsThe median value of the total score on the TLC was 20 [17.25;23.5]. The most important finding is the discovery of only minor correlations of thought disorder with “prodromal” symptoms. Indeed, the total score on the TLC correlated only with the total score on the SOPS at admission (r=0.370, p&lt;0.05). Such symptoms of the TLC scale as «Derailment», «Incoherence», «Perseveration» did not find any correlation with prodromal symptoms (p&gt;0.05).ConclusionsThe obtained data indicates the independent nature of thought disorder in patients at clinical high-risk state for schizophrenia, which leads the need to determine its own prognostic value.Disclosure of InterestNone Declared

Unique contribution of neurotransmitter maps for predicting cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis

Unique contribution of neurotransmitter maps for predicting cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis

Visual disturbances in recent-onset psychosis and clinical high-risk state for psychosis

Visual disturbances in recent-onset psychosis and clinical high-risk state for psychosis

62.1 Epidemiology and Diagnosis of Clinical High-Risk State for Psychosis (CHR-P) Syndromes

The concept of clinical high risk for psychosis (CHR-P) has been present since the 1990s. However, it is only through more recent increases in worldwide research publications and increased specialty CHR-P clinics that the epidemiology of this patient population is being better understood. The prospective concept of CHR-P replaces the retrospective concept of the prodromal period of psychosis.

62.3 An Innovative Intensive Outpatient Program for Adolescents With Clinical High-Risk State for Psychosis (CHR-P) Syndromes

Participants will learn about the structure and efficacy of a novel treatment approach for adolescents at clinical high risk of developing psychosis (CHR-P) via a specialty intensive outpatient program (IOP).

62.4 Prevention and Therapy Approaches to Clinical High-Risk State for Psychosis (CHR-P) in an Intensive Outpatient Program

62.4 Prevention and Therapy Approaches to Clinical High-Risk State for Psychosis (CHR-P) in an Intensive Outpatient Program

62.2 Evidence-Based Treatment for Clinical High-Risk State for Psychosis (CHR-P) Syndromes

A number of early-intervention treatment approaches have been developed worldwide to treat individuals experiencing early psychosis. The objective of this talk is to describe evidence-based treatments of youth identified as having elevated risk for developing psychosis.

The impact of visual dysfunctions in recent-onset psychosis and clinical high-risk state for psychosis

Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive interventions. We systematically investigated the relationship between VisDys and core clinical measures across three early phase psychiatric conditions. Second, we used a novel multivariate pattern analysis approach to predict VisDys by resting-state functional connectivity within relevant brain systems. VisDys assessed with the Schizophrenia Proneness Instrument (SPI-A), clinical measures, and resting-state fMRI data were examined in recent-onset psychosis (ROP, n = 147), clinical high-risk states of psychosis (CHR, n = 143), recent-onset depression (ROD, n = 151), and healthy controls (HC, n = 280). Our multivariate pattern analysis approach used pairwise functional connectivity within occipital (ON) and frontoparietal (FPN) networks implicated in visual information processing to predict VisDys. VisDys were reported more often in ROP (50.34%), and CHR (55.94%) than in ROD (16.56%), and HC (4.28%). Higher severity of VisDys was associated with less functional remission in both CHR and ROP, and, in CHR specifically, lower quality of life (Qol), higher depressiveness, and more severe impairment of visuospatial constructability. ON functional connectivity predicted presence of VisDys in ROP (balanced accuracy 60.17%, p = 0.0001) and CHR (67.38%, p = 0.029), while in the combined ROP + CHR sample VisDys were predicted by FPN (61.11%, p = 0.006). These large-sample study findings suggest that VisDys are clinically highly relevant not only in ROP but especially in CHR, being closely related to aspects of functional outcome, depressiveness, and Qol. Findings from multivariate pattern analysis support a model of functional integrity within ON and FPN driving the VisDys phenomenon and being implicated in core disease mechanisms of early psychosis states.

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.

Evidence of discontinuity between psychosis-risk and non-clinical samples in the neuroanatomical correlates of social function

ObjectiveSocial dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the lower end of the normal distribution of individual differences in social functioning. MethodsWe used a machine learning classifier to test for the presence of a previously validated brain structural pattern associated with impaired social outcome in CHR-P (CHR-outcome-neurosignature) in the neuroimaging profiles of individuals from two non-clinical samples (total n = 1763) and examined its association with social function, psychopathology and cognition. ResultsAlthough the CHR-outcome-neurosignature could be detected in a subset of the non-clinical samples, it was not associated was adverse social outcomes or higher psychopathology levels. However, participants whose neuroanatomical profiles were highly aligned with the CHR-outcome-neurosignature manifested subtle disadvantage in fluid (PFDR = 0.004) and crystallized intelligence (PFDR = 0.01), cognitive flexibility (PFDR = 0.02), inhibitory control (PFDR = 0.01), working memory (PFDR = 0.0005), and processing speed (PFDR = 0.04). ConclusionsWe provide evidence of divergence in brain structural underpinnings of social dysfunction derived from a psychosis-risk enriched population when applied to non-clinical samples. This approach appears promising in identifying brain mechanisms bound to psychosis through comparisons of patient populations to non-clinical samples with the same neuroanatomical profiles.

Using combined environmental-clinical classification models to predict role functioning outcome in clinical high-risk states for psychosis and recent-onset depression.

Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning. We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample. Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD). Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD. Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.

Anomalous self-experiences (ASE) in relation to clinical high risk for psychosis (CHR[sbnd]P), childhood trauma and general psychopathology among adolescent and young adult help seekers

BackgroundAnomalous self-experiences (ASE) are suggested as a phenotypic core feature of schizophrenia spectrum disorders and present in at risk samples as well. In our study, we investigated the relation between ASE and clinical high risk state for psychosis (CHRP) against the background of further influencing factors like childhood trauma and general psychopathology. Methods126 help-seeking adolescents were included. CHR-P patients were identified using the Structured Interview for Psychosis-Risk Syndromes (SIPS). ASE were assessed with the Inventory of Psychotic-like Anomalous Self-Experiences (IPASE). Childhood trauma, depression and anxiety were assessed with well-established questionnaires (CTQ; PHQ-9; GAD-7). ResultsCHR-P subgroup (n = 50, 39.7%) show significantly higher scores in IPASE total (t (81.07) = -5.150, p = .000) and CTQ total (t (85.95) = -2.75, p = .007) in comparison with the non CHR-P subgroup. Logistic regression analysis confirmed that IPASE total could predict CHR-P status (OR 1.03, 95% CI 1.01-1.04, p = .000). Furthermore, CTQ total and IPASE total show moderate to strong positive correlation (r = 0.44, p < .001) as well as CTQ total with both IPASE subdomains Cognition (r = 0.404, p < .001) and Self- Awareness (r = 0.443, p < .001). ConclusionThe CHR-P subgroup shows significantly more ASE than the non CHR-P subgroup. Further, ASE predicted CHR-P status. Our results indicated that ASE could play a considerable role in the identification of high risk for developing schizophrenia spectrum disorder and could complement CHR-P testing. Importantly, it seems that ASE may be related to exposure to childhood trauma.

5-years follow-up of patients with the clinical high-risk state for psychosi

IntroductionThe identification of the psychosis high-risk state in help-seeking patients with depressive symptoms offers the possibility of detection and intervention at the early stages of schizophrenia.ObjectivesEstimating the 5-year follow-up rate of the manifestation of psychosis and levels of functioning in patients with the clinical high-risk state and depressive symptoms.Methods81 inpatients (average age 19.6 years) with depressive symptoms and attenuated psychosis (60 patients with APS and 21 patients with BLIPS). Average duration of inpatient treatment was 56.3 days, antidepressant therapy (mean dosage equivalent to fluoxetine 43.1 mg/day) and antipsychotic therapy (mean dosage equivalent to chlorpromazine 408.9 mg/day) were conducted. All patients were followed up after discharge at least during 5 years (average follow-up 7.1 years). Levels of functioning were assessed on the PSP scale.ResultsThe manifestation of psychosis was identified in 21.0% (17 patients) (on average in the third year of follow-up), complete symptomatic and functional remission was established in 11.1% (9 patients) (PSP 100-81), complete symptomatic and incomplete functional remission was established in 27.2% (22 patients) (PSP 80-61). Incomplete symptomatic and incomplete functional remission – in 24.7% (20 patients) (PSP 60-41) and 13.5% (11 patients) (PSP&lt;40).ConclusionsThe combination of antidepressants and antipsychotics therapy in patients with the clinical high-risk state for psychosis reduced the risk of psychosis manifestation but did not significantly affect the level of outcome compared to other studies.DisclosureNo significant relationships.

Reduced Hippocampal Subfield Volume in Schizophrenia and Clinical High-Risk State for Psychosis.

Magnetic resonance imaging (MRI) studies in schizophrenia demonstrated volume reduction in hippocampal subfields divided on the basis of specific cytoarchitecture and function. However, it remains unclear whether this abnormality exists prior to the onset of psychosis and differs across illness stages. MRI (3 T) scans were obtained from 77 patients with schizophrenia, including 24 recent-onset and 40 chronic patients, 51 individuals with an at-risk mental state (ARMS) (of whom 5 subsequently developed psychosis within the follow-up period), and 87 healthy controls. Using FreeSurfer software, hippocampal subfield volumes were measured and compared across the groups. Both schizophrenia and ARMS groups exhibited significantly smaller volumes for the bilateral Cornu Ammonis 1 area, left hippocampal tail, and right molecular layer of the hippocampus than the healthy control group. Within the schizophrenia group, chronic patients exhibited a significantly smaller volume for the left hippocampal tail than recent-onset patients. The left hippocampal tail volume was positively correlated with onset age, and negatively correlated with duration of psychosis and duration of medication in the schizophrenia group. Reduced hippocampal subfield volumes observed in both schizophrenia and ARMS groups may represent a common biotype associated with psychosis vulnerability. Volumetric changes of the left hippocampal tail may also suggest ongoing atrophy after the onset of schizophrenia.

Mental Health Services Research Targeting the Clinical High-Risk State for Psychosis: Lessons, Future Directions and Integration with Patient Perspectives.

We summarize the history of the clinical high-risk stage of psychosis (CHR), current research on this stage and recent critiques of the field, and evaluate current CHR guidelines and frameworks. Following its identification and characterization, CHR services have successfully been developed in North America, Europe, Australia and elsewhere. As reflected in guidelines, these services and their orientation largely emerged as an outgrowth of the framework pioneered by early intervention services for first-episode psychosis. We critically discuss what is known so far about the subjective experience of the CHR syndrome, the meaning of this "unofficial" diagnosis as well as what is known and unknown about the service-related needs. While a range of outstanding questions remain in the field, there is a particular need for patient-oriented work and to investigate the service-related needs of young people at CHR.