Clinical High Risk For Psychosis Individuals Research Articles

The 'Parma At-Risk mental states' (PARMS) program: General description and process analysis after 5 years of clinical activity.

From January 2016, the Parma Department of Mental Health developed a specialized care protocol - the 'Parma At-Risk Mental States' (PARMS) program - as a diffused service for early intervention in individuals at Clinical High Risk for Psychosis (CHR-P). The aims of this investigation were (1) to describe the PARMS structural organization and (2) to examine specific process indicators during the first 5 years of its clinical activity. All participants were adolescent and young adult help-seekers (aged 12-25 years) at CHR-P in accordance with well-defined psychometric criteria. At entry, 52 subjects were provided with a dedicated protocol of care and only 14 dropped out during the first year of treatment. The Duration of Untreated Illness (DUI) overall decreased over time. Most of CHR-P participants suffered from 'Attenuated Psychotic Symptoms' and 'Brief, Limited, Intermittent Psychotic Symptoms' in the same percentage (48.1% [n= 25]). The most common DSM-IV-TR diagnosis was schizotypal personality disorder, followed by borderline personality disorder and brief psychotic disorder. A specialized, evidence-based care protocol for CHR-P individuals within Italian adult and child/adolescent psychiatric services is feasible, also in adolescents, who have a high risk of falling through the child/adult service gap.

Physical Health in Clinical High Risk for Psychosis Individuals: A Cross-Sectional Study.

The clinical high risk for psychosis (CHR-P) phase represents an opportunity for prevention and early intervention in young adults, which also could focus on improving physical health trajectories. We conducted a RECORD-compliant clinical register-based cohort study. The primary outcome was to describe the physical health of assessed CHR-P individuals, obtained via Electronic Health Records at the South London and Maudsley (SLaM) NHS Foundation Trust, UK (January 2013-October 2020). The final database included 194 CHR-P subjects (46% female). Mean age was 23.70 ± 5.12 years. Percentage of tobacco smokers was 41% (significantly higher than in the age-matched general population [24%]). We found that 49% of subjects who consumed alcohol had an AUDIT-C (Alcohol Use Disorder Identification Test) score above 5 (hazardous drinking), with an average score of 4.94 (significantly higher than in the general population [2.75]). Investigating diet revealed low fiber intake in most subjects and high saturated fat intake in 10% of the individuals. We found that 47% of CHR-P subjects met the UK recommended physical activity guidelines (significantly lower than in the general population [66%]). Physical parameters (e.g., weight, heart rate, blood pressure) were not significantly different from the general population. This evidence corroborates the need for monitoring physical health parameters in CHR-P subjects, to implement tailored interventions that target daily habits.

Mapping the implementation and challenges of clinical services for psychosis prevention in England.

Indicated primary prevention of psychosis is recommended by NICE clinical guidelines, but implementation research on Clinical High Risk for Psychosis (CHR-P) services is limited. Electronic audit of CHR-P services in England, conducted between June and September 2021, addressing core implementation domains: service configuration, detection of at-risk individuals, prognostic assessment, clinical care, clinical research, and implementation challenges, complemented by comparative analyses across service model. Descriptive statistics, Fisher's exact test and Mann-Whitney U-tests were employed. Twenty-four CHR-P clinical services (19 cities) were included. Most (83.3%) services were integrated within other mental health services; only 16.7% were standalone. Across 21 services, total yearly caseload of CHR-P individuals was 693 (average: 33; range: 4-115). Most services (56.5%) accepted individuals aged 14-35; the majority (95.7%) utilized the Comprehensive Assessment of At Risk Mental States (CAARMS). About 65% of services reported some provision of NICE-compliant interventions encompassing monitoring of mental state, cognitive-behavioral therapy (CBT), and family interventions. However, only 66.5 and 4.9% of CHR-P individuals actually received CBT and family interventions, respectively. Core implementation challenges included: recruitment of specialized professionals, lack of dedicated budget, and unmet training needs. Standalone services reported fewer implementation challenges, had larger caseloads (p = 0.047) and were more likely to engage with clinical research (p = 0.037) than integrated services. While implementation of CHR-P services is observed in several parts of England, only standalone teams appear successful at detection of at-risk individuals. Compliance with NICE-prescribed interventions is limited across CHR-P services and unmet needs emerge for national training and investments.

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.

P535. Neighborhood Poverty and Hippocampal Volume Among Individuals at Clinical High Risk for Psychosis: The Moderating Role of Social Engagement

While hippocampal volume (HV) reduction has been shown in psychotic disorders, the relation of neighborhood poverty (NP) and HVs in clinical high risk for psychosis (CHR-P) individuals is unknown. In this study, we explore the associations between NP and HV, and whether social engagement (SE) moderated this relationship in CHR-P individuals.

MR-Spectroscopy of GABA and Glutamate/Glutamine Concentrations in Auditory Cortex in Clinical High-Risk for Psychosis Individuals.

Psychosis involves changes in GABAergic and glutamatergic neurotransmission in auditory cortex that could be important for understanding sensory deficits and symptoms of psychosis. However, it is currently unclear whether such deficits are present in participants at clinical high-risk for psychosis (CHR-P) and whether they are associated with clinical outcomes. Magnetic Resonance Spectroscopy (MEGAPRESS, 1H-MRS at 3 Tesla) was used to estimate GABA, glutamate, and glutamate-plus-glutamine (Glx) levels in auditory cortex in a large sample of CHR-P (n = 99), CHR-N (clinical high-risk negative, n = 32), and 45 healthy controls. Examined were group differences in metabolite concentrations as well as relationships with clinical symptoms, general cognition, and 1-year follow-up clinical and general functioning in the CHR-P group. Results showed a marginal (p = 0.039) main group effect only for Glx, but not for GABA and glutamate concentrations, and only in left, not right, auditory cortex. This effect did not survive multiple comparison correction, however. Exploratory post-hoc tests revealed that there were significantly lower Glx levels (p = 0.029, uncorrected) in the CHR-P compared to the CHR-N group, but not relative to healthy controls (p = 0.058, uncorrected). Glx levels correlated with the severity of perceptual abnormalities and disorganized speech scores. However, in the CHR-P group, Glx levels did not predict clinical or functional outcomes. Accordingly, the findings from the present study suggest that MRS-measured GABA, glutamate and Glx levels in auditory cortex of CHR-P individuals are largely intact.

Identifying Electroencephalography Biomarkers in Individuals at Clinical High Risk for Psychosis in an International Multi-Site Study.

BackgroundThe clinical high-risk for psychosis (CHR-P) paradigm was introduced to detect individuals at risk of developing psychosis and to establish preventive strategies. While current prediction of outcomes in the CHR-P state is based mostly on the clinical assessment of presenting features, several emerging biomarkers have been investigated in an attempt to stratify CHR-P individuals according to their individual trajectories and refine the diagnostic process. However, heterogeneity across subgroups is a key challenge that has limited the impact of the CHR-P prediction strategies, as the clinical validity of the current research is limited by a lack of external validation across sites and modalities. Despite these challenges, electroencephalography (EEG) biomarkers have been studied in this field and evidence suggests that EEG used in combination with clinical assessments may be a key measure for improving diagnostic and prognostic accuracy in the CHR-P state. The PSYSCAN EEG study is an international, multi-site, multimodal longitudinal project that aims to advance knowledge in this field.MethodsParticipants at 6 international sites take part in an EEG protocol including EEG recording, cognitive and clinical assessments. CHR-P participants will be followed up after 2 years and subcategorised depending on their illness progression regarding transition to psychosis. Differences will be sought between CHR-P individuals and healthy controls and between CHR-P individuals who transition and those who do not transition to psychosis using data driven computational analyses.DiscussionThis protocol addresses the challenges faced by previous studies of this kind to enable valid identification of predictive EEG biomarkers which will be combined with other biomarkers across sites to develop a prognostic tool in CHR-P. The PSYSCAN EEG study aims to pave the way for incorporating EEG biomarkers in the assessment of CHR-P individuals, to refine the diagnostic process and help to stratify CHR-P subjects according to risk of transition. This may improve our understanding of the CHR-P state and therefore aid the development of more personalized treatment strategies.

Hippocampal structural alterations in early-stage psychosis: Specificity and relationship to clinical outcomes

Hippocampal dysfunctions are a core feature of schizophrenia, but conflicting evidence exists whether volumetric and morphological changes are present in early-stage psychosis and to what extent these deficits are related to clinical trajectories. In this study, we recruited individuals at clinical high risk for psychosis (CHR-P) (n = 108), patients with a first episode of psychosis (FEP) (n = 37), healthy controls (HC) (n = 70) as well as a psychiatric control group with substance abuse and affective disorders (CHR-N: n = 38). MRI-data at baseline were obtained and volumetric as well as vertex analyses of the hippocampus were carried out. Moreover, volumetric changes were examined in the amygdala, caudate, nucleus accumbens, pallidum, putamen and thalamus. In addition, we obtained follow-up functional and symptomatic assessments in CHR-P individuals to examine the question whether anatomical deficits at baseline predicted clinical trajectories. Our results show that the hippocampus is the only structure showing significant volumetric decrease in early-stage psychosis, with FEPs showing significantly smaller hippocampal volumes bilaterally alongside widespread shape changes in the vertex analysis. For the CHR-P group, volumetric decreases were confined to the left hippocampus. However, hippocampal alterations in the CHR-P group were not robustly associated with clinical outcomes, including the persistence of attenuated psychotic symptoms and functional trajectories. Accordingly, our findings highlight that dysfunctions in hippocampal anatomy are an important feature of early-stage psychosis which may, however, not be related to clinical outcomes in CHR-P participants.

Prevalence of Individuals at Clinical High-Risk of Psychosis in the General Population and Clinical Samples: Systematic Review and Meta-Analysis.

(1) The consistency and magnitude of the prevalence of Clinical High-Risk for Psychosis (CHR-P) individuals are undetermined, limiting efficient detection of cases. We aimed to evaluate the prevalence of CHR-P individuals systematically assessed in the general population or clinical samples. (2) PRISMA/MOOSE-compliant (PROSPERO: CRD42020168672) meta-analysis of multiple databases until 21/01/21: a random-effects model meta-analysis, heterogeneity analysis, publication bias and quality assessment, sensitivity analysis—according to the gold-standard CHR-P and pre-screening instruments—leave-one-study-out analyses, and meta-regressions were conducted. (3) 35 studies were included, with 37,135 individuals tested and 1554 CHR-P individuals identified (median age = 19.3 years, Interquartile range (IQR) = 15.8–22.1; 52.2% females, IQR = 38.7–64.4). In the general population (k = 13, n = 26,835 individuals evaluated), the prevalence of the CHR-P state was 1.7% (95% Confidence Interval (CI) = 1.0–2.9%). In clinical samples (k = 22, n = 10,300 individuals evaluated), the prevalence of the CHR-P state was 19.2% (95% CI = 12.9–27.7%). Using a pre-screening instrument was associated with false negatives (5.6%, 95% CI = 2.2–13.3%) and a lower CHR-P prevalence (11.5%, 95% CI = 6.2–20.5%) compared to using CHR-P instruments only (28.5%, 95% CI = 23.0–34.7%, p = 0.003). (4) The prevalence of the CHR-P state is low in the general population and ten times higher in clinical samples. The prevalence of CHR-P may increase with a higher proportion of females in the general population and with a younger population in clinical samples. The CHR-P state may be unrecognized in routine clinical practice. These findings can refine detection and preventive strategies.

ITAlian partnership for psychosis prevention (ITAPP): Improving the mental health of young people.

The European impact of the clinical high risk for psychosis (CHR-P) paradigm is constrained by the lack of critical mass (detection) to power prognostic and preventive interventions. An ITAlian partnership for psychosis prevention (ITAPP) was created across CHR-P centers, which were surveyed to describe: (a) service, catchment area, and outreach; (b) service users; and (c) interventions and outcomes. Descriptive statistics and Kaplan-Meier failure function complemented the analyses. The ITAPP included five CHR-P clinical academic centers established from 2007 to 2018, serving about 13million inhabitants, with a recruitment capacity of 277 CHR-P individuals (mean age: 18.7years, SD: 4.8, range: 12-39years; 53.1% females; 85.7% meeting attenuated psychotic symptoms; 85.8% without any substance abuse). All centers were multidisciplinary and included adolescents and young adults (transitional) primarily recruited through healthcare services. The comprehensive assessment of at-risk mental state was the most widely used instrument, while the duration of follow-up, type of outreach, and preventive interventions were heterogeneous. Across 205 CHR-P individuals with follow up (663.7days±551.7), the cumulative risk of psychosis increased from 8.7% (95% CI 5.3-14.1) at 1year to 15.9% (95% CI 10.6-23.3) at 2years, 21.8% (95% CI 14.9-31.3) at 3years, 34.8% (95% CI 24.5-47.9) at 4years, and 51.9% (95% CI 36.3-69.6) at 5years. The ITAPP is one of the few CHR-P clinical research partnerships in Europe for fostering detection, prognosis, and preventive care, as well as for translating research innovations into practice.

No rest for the weary: Prevalence, impact and nature of sleep problems among young people at risk of psychosis.

Sleep problems are common in people with a psychosis-spectrum diagnosis and are associated with worse psychotic symptoms and lower quality of life. Sleep problems are also frequent in individuals at a clinical high risk for psychosis (CHR-P) however, less is known about the prevalence and association with symptoms in this population. This study investigates the prevalence of sleep problems within CHR-P individuals and the associations with attenuated positive symptoms, transition to psychosis, time to transition to psychosis and functioning. The clinical records interactive search (CRIS) tool was used to carry out a retrospective study of 795 CHR-P individuals. Sleep problems, subsequent psychotic diagnoses, attenuated positive symptoms and Health of The Nation Outcome Scale scores were extracted. Regression models were used to examine the association between sleep problems and clinical outcomes. 59.5% of CHR-P individuals experienced sleep problems. Perceptual abnormality severity (OR=1.24, 95% CI=1.05-1.48) and frequency (OR=1.31, 95% CI=1.08-1.58) as measured by the Comprehensive Assessment of At-Risk Mental State interview, predicted sleep problems. Sleep problems were not associated with transition to psychosis; however, they were significantly associated with a shorter time to transition in individuals who developed psychosis (HR=1.4, 95% CI=1.05-1.88) and higher follow-up Health of the Nation Outcome Scale scores (MD=2.26, 95% CI=0.55-3.96). The high prevalence of sleep problems, along with the association with positive symptoms and worse functioning, highlights the need for effective sleep interventions in this population. Further research is needed to better understand the relationship between sleep problems and transition to psychosis.

Characterising cognitive heterogeneity in individuals at clinical high-risk for psychosis: a cluster analysis with clinical and functional outcome prediction

Schizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes.

Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis.

BackgroundLittle is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals.MethodsPubMed and Web of Science were searched until November 2020 in this PRISMA compliant meta-analysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were two-tailed with α=0.05.Findings75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges’ g=0.753, 95%CI=0.495-1.012) and 24 (Hedges’ g=0.836, 95%CI=0.463-1.209), but not ≥36 months (Hedges’ g=0.315. 95%CI=-0.176–0.806). Negative symptoms improved at 12 (Hedges’ g=0.496, 95%CI=0.315–0.678), but not 24 (Hedges’ g=0.499, 95%CI=-0.137–1.134) or ≥36 months (Hedges’ g=0.033, 95%CI=-0.439–0.505). Depressive symptoms improved at 12 (Hedges’ g=0.611, 95%CI=0.441–0.782) and 24 (Hedges’ g=0.583, 95%CI=0.364–0.803), but not ≥36 months (Hedges’ g=0.512 95%CI=-0.337–1.361). Functioning improved at 12 (Hedges’ g=0.711, 95%CI=0.488–0.934), 24 (Hedges’ g=0.930, 95%CI=0.553–1.306) and ≥36 months (Hedges’ g=0.392, 95%CI=0.117–0.667). Remission from CHR-P status occurred in 33.4% (95%CI=22.6–44.1%) at 12 months, 41.4% (95%CI=32.3–50.5%) at 24 months and 42.4% (95%CI=23.4–61.3%) at ≥36 months. Heterogeneity across the included studies was significant and ranged from I2=53.6% to I2=96.9%. The quality of the included studies (mean±SD) was 4.6±1.1 (range=2-8).InterpretationCHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. Prolonged duration of care may be needed for this patient population to optimize outcomes.FundingNone.

Negative Prognostic Effect of Baseline Antipsychotic Exposure in Clinical High Risk for Psychosis (CHR-P): Is Pre-Test Risk Enrichment the Hidden Culprit?

IntroductionSample enrichment is a key factor in contemporary early-detection strategies aimed at the identification of help-seekers at increased risk of imminent transition to psychosis. We undertook a meta-analytic investigation to ascertain the role of sample enrichment in the recently highlighted negative prognostic effect of baseline antipsychotic (AP) exposure in clinical high-risk (CHR-P) of psychosis individuals.MethodsSystematic review and meta-analysis of all published studies on CHR-P were identified according to a validated diagnostic procedure. The outcome was the proportion of transition to psychosis, which was calculated according to the Freeman‐Tukey double arcsine transformation.ResultsThirty-three eligible studies were identified, including 16 samples with details on AP exposure at baseline and 17 samples with baseline AP exposure as exclusion criterion for enrollment. Those with baseline exposure to AP (n = 395) had higher transition rates (29.9%; 95% CI: 25.1%–34.8%) than those without baseline exposure to AP in the same study (n = 1289; 17.2%; 15.1%–19.4%) and those coming from samples that did not include people who were exposed to AP at baseline (n = 2073; 16.2%; 14.6%–17.8%; P < .05 in both the fixed-effects and the random-effects models). Heterogeneity within studies was substantial, with values above 75% in all comparisons.ConclusionsSample enrichment is not a plausible explanation for the higher risk of transition to psychosis of CHR-P individuals who were already exposed to AP at the enrollment in specialized early-detection programs. Baseline exposure to AP at CHR-P assessment is a major index of enhanced, imminent risk of psychosis.

Autism Spectrum Disorder and Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis

Psychotic experiences can occur in autism spectrum disorders (ASD). Some of the ASD individuals with these experiences may fulfil Clinical High-Risk for Psychosis (CHR-P) criteria. A systematic literature search was performed to review the information on ASD and CHR-P. A meta-analysis of the proportion of CHR-P in ASD was conducted. The systematic review included 13 studies. The mean age of ASD individuals across the included studies was 11.09 years. The Attenuated Psychosis Syndrome subgroup was the most frequently reported. Four studies were meta-analysed, showing that 11.6% of CHR-P individuals have an ASD diagnosis. Symptoms of prodromal psychosis may be present in individuals with ASD. The transition from CHR-P to psychosis is not affected by ASD.

The relationship between cognitive deficits and impaired short-term functional outcome in clinical high-risk for psychosis participants: A machine learning and modelling approach

Poor functional outcomes are common in individuals at clinical high-risk for psychosis (CHR-P), but the contribution of cognitive deficits remains unclear. We examined the potential utility of cognitive variables in predictive models of functioning at baseline and follow-up with machine learning methods. Additional models fitted on baseline functioning variables were used as a benchmark to evaluate model performance.Data were available for 1) 146 CHR-P individuals of whom 118 completed a 6- and/or 12-month follow-up, 2) 47 participants not fulfilling CHR criteria (CHR-Ns) but displaying affective and substance use disorders and 3) 55 healthy controls (HCs). Predictors of baseline global assessment of functioning (GAF) scores were selected by L1-regularised least angle regression and then used to train classifiers to predict functional outcome in CHR-P individuals.In CHR-P participants, cognitive deficits together with clinical and functioning variables explained 41% of the variance in baseline GAF scores while cognitive variables alone explained 12%. These variables allowed classification of functional outcome with an average balanced accuracy (BAC) of 63% in both mixed- and cross-site models. However, higher accuracies (68%–70%) were achieved using classifiers fitted only on baseline functioning variables.Our findings suggest that cognitive deficits, alongside clinical and functioning variables, displayed robust relationships with impaired functioning in CHR-P participants at baseline and follow-up. Moreover, these variables allow for prediction of functional outcome. However, models based on baseline functioning variables showed a similar performance, highlighting the need to develop more accurate algorithms for predicting functional outcome in CHR-P participants.

Prevalence and predictors of suicidality and non-suicidal self-harm among individuals at clinical high-risk for psychosis: Results from a community-recruited sample.

AimSuicidal thoughts and behaviours are prevalent in individuals with schizophrenia. However, research examining the prevalence and predictors of suicidality and self‐harm in participants at clinical high‐risk for psychosis (CHR‐P) is limited and mostly focuses on help‐seeking participants recruited through clinical pathways. The current study sought to assess the prevalence of suicidality and self‐harm and identify predictors of current suicidal ideation in community‐recruited CHR‐P participants.MethodsData were available for 130 CHR‐P participants, 15 participants with first‐episode psychosis (FEP), 47 participants not fulfilling CHR‐P criteria (CHR‐Ns) and 53 healthy controls. Current and lifetime suicidality and self‐harm were assessed using the Mini‐International Neuropsychiatric Interview and the Comprehensive Assessment of At‐Risk Mental States (CAARMS). Multivariable logistic regression analysis was used to determine predictors of current suicidal ideation in the CHR‐P group.ResultsA considerable proportion of CHR‐P participants disclosed current suicidal ideation (34.6%). Overall, FEP individuals were at greatest risk, with considerably high prevalence rates for current suicidal ideation (73.3%), lifetime self‐harm behaviour (60.0%) and lifetime suicide attempt (60.0%). In the CHR‐P sample, current suicidal ideation was predicted by lifetime suicide attempts, lower CAARMS severity, impaired social functioning and greater comorbidity.ConclusionsOur findings suggest that suicidality and self‐harm are highly prevalent in community‐recruited CHR‐P and FEP individuals. Accordingly, these results highlight the importance of further research into the determinants of suicidality and self‐harm during at‐risk and early stages of psychosis, and the implementation of intervention strategies to reduce adverse outcomes in these populations.

Altered Autonomic Function in Individuals at Clinical High Risk for Psychosis.

Introduction: Alterations in autonomic functioning in individuals diagnosed with schizophrenia are well-documented. Yet, it is currently unclear whether these dysfunctions extend into the clinical high-risk state. Thus, we investigated resting heart rate (RHR) and heart rate variability (HRV) indices in individuals at clinical high-risk for psychosis (CHR-P).Methods: We recruited 117 CHR-P participants, 38 participants with affective disorders and substance abuse (CHR-N) as well as a group of 49 healthy controls. CHR-P status was assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). We obtained 5 min, eyes-open resting-state MEG data, which was used for the extraction of cardiac field-related inter-beat-interval data and from which heart-rate and heart-rate variability measures were computed.Results: Compared to both CHR-N and healthy controls, CHR-P participants were characterized by an increased RHR, which was not explained by differences in psychopathological comorbidity and medication status. Increased RHR correlated with the presence of subthreshold psychotic symptoms and associated distress. No differences between groups were found for heart-rate variability measures, however. Furthermore, there was an association between motor-performance and psychophysiological measures.Conclusion: The current study provides evidence of alterations in autonomic functioning as disclosed by increased RHR in CHR-P participants. Future studies are needed to further evaluate this characteristic feature of CHR-P individuals and its potential predictive value for psychosis development.

Lower speech connectedness linked to incidence of psychosis in people at clinical high risk

BackgroundFormal thought disorder is a cardinal feature of psychotic disorders, and is also evident in subtle forms before psychosis onset in individuals at clinical high-risk for psychosis (CHR-P). Assessing speech output or assessing expressive language with speech as the medium at this stage may be particularly useful in predicting later transition to psychosis. MethodSpeech samples were acquired through administration of the Thought and Language Index (TLI) in 24 CHR-P participants, 16 people with first-episode psychosis (FEP) and 13 healthy controls. The CHR-P individuals were then followed clinically for a mean of 7 years (s.d. = 1.5) to determine if they transitioned to psychosis. Non-semantic speech graph analysis was used to assess the connectedness of transcribed speech in all groups. ResultsSpeech was significantly more disconnected in the FEP group than in both healthy controls (p < .01) and the CHR-P group (p < .05). Results remained significant when IQ was included as a covariate. Significant correlations were found between speech connectedness measures and scores on the TLI, a manual assessment of formal thought disorder. In the CHR-P group, lower scores on two measures of speech connectedness were associated with subsequent transition to psychosis (8 transitions, 16 non-transitions; p < .05). ConclusionThese findings support the utility and validity of speech graph analysis methods in characterizing speech connectedness in the early phases of psychosis. This approach has the potential to be developed into an automated, objective and time-efficient way of stratifying individuals at CHR-P according to level of psychosis risk.

Acute oxytocin effects in inferring others\u2019 beliefs and social emotions in people at clinical high risk for psychosis

Social deficits are key hallmarks of the Clinical High Risk for Psychosis (CHR-P) state and of established psychotic disorders, and contribute to impaired social functioning, indicating a potential target for interventions. However, current treatments do not significantly ameliorate social impairments in CHR-P individuals. Given its critical role in social behaviour and cognition, the oxytocinergic (OT) system is a promising target for novel interventions in CHR-P subjects. In a double-blind, placebo-controlled, crossover design, 30 CHR-P males were studied using functional magnetic resonance imaging (fMRI) on two occasions, once after 40IU self-administered intranasal OT and once after placebo. A modified version of the Sally-Anne task was used to assess brain activation during inferring others’ beliefs and social emotions. The Reading the Mind in the Eyes Test was acquired prior to the first scan to test whether OT effects were moderated by baseline social-emotional abilities. OT did not modulate behavioural performances but reduced activation in the bilateral inferior frontal gyrus compared with placebo while inferring others’ social emotions. Furthermore, the relationship between brain activation and task performance after OT administration was moderated by baseline social-emotional abilities. While task accuracy during inferring others’ social emotion increased with decreasing activation in the left inferior frontal gyrus in CHR-P individuals with low social-emotional abilities, there was no such relationship in CHR-P individuals with high social-emotional abilities. Our findings may suggest that acute OT administration enhances neural efficiency in the inferior frontal gyrus during inferring others’ social emotions in those CHR-P subjects with low baseline social-emotional abilities.