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

AbstractBasic 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.

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The trait‐state distinction between schizotypy and clinical high risk: results from a one‐year follow‐up

World Psychiatry ◽

10.1002/wps.20595 ◽

2019 ◽

Vol 18 (1) ◽

pp. 108-109 ◽

Cited By ~ 7

Author(s):

Chantal Michel ◽

Rahel Flückiger ◽

Jochen Kindler ◽

Daniela Hubl ◽

Michael Kaess ◽

...

Keyword(s):

High Risk ◽

Clinical High Risk ◽

One Year

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Baseline Cortical Thickness Reductions in Clinical High Risk for Psychosis: Brain Regions Associated with Conversion to Psychosis Versus Non-Conversion as Assessed at One-Year Follow-Up in the Shanghai-At-Risk-for-Psychosis (SHARP) Study

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa127 ◽

2020 ◽

Author(s):

Elisabetta C Del Re ◽

William S Stone ◽

Sylvain Bouix ◽

Johanna Seitz ◽

Victor Zeng ◽

...

Keyword(s):

High Risk ◽

Language Processing ◽

Cortical Thickness ◽

Brain Regions ◽

Group Differences ◽

Clinical High Risk ◽

Pars Opercularis ◽

One Year ◽

First Time

Abstract Objective To assess cortical thickness (CT) and surface area (SA) of frontal, temporal, and parietal brain regions in a large clinical high risk for psychosis (CHR) sample, and to identify cortical brain abnormalities in CHR who convert to psychosis and in the whole CHR sample, compared with the healthy controls (HC). Methods Magnetic resonance imaging, clinical, and cognitive data were acquired at baseline in 92 HC, 130 non-converters, and 22 converters (conversion assessed at 1-year follow-up). CT and SA at baseline were calculated for frontal, temporal, and parietal subregions. Correlations between regions showing group differences and clinical scores and age were also obtained. Results CT but not SA was significantly reduced in CHR compared with HC. Two patterns of findings emerged: (1) In converters, CT was significantly reduced relative to non-converters and controls in the banks of superior temporal sulcus, Heschl’s gyrus, and pars triangularis and (2) CT in the inferior parietal and supramarginal gyrus, and at trend level in the pars opercularis, fusiform, and middle temporal gyri was significantly reduced in all high-risk individuals compared with HC. Additionally, reduced CT correlated significantly with older age in HC and in non-converters but not in converters. Conclusions These results show for the first time that fronto-temporo-parietal abnormalities characterized all CHR, that is, both converters and non-converters, relative to HC, while CT abnormalities in converters relative to CHR-NC and HC were found in core auditory and language processing regions.

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Subtypes of Clinical High Risk for Psychosis that Predict Antipsychotic Effectiveness in Long-Term Remission

Pharmacopsychiatry ◽

10.1055/a-1252-2942 ◽

2020 ◽

Vol 54 (01) ◽

pp. 23-30

Author(s):

TianHong Zhang ◽

JunJie Wang ◽

LiHua Xu ◽

YanYan Wei ◽

XiaoChen Tang ◽

...

Keyword(s):

High Risk ◽

Cognitive Deficits ◽

Negative Symptoms ◽

Treatment Decision ◽

Positive Symptom ◽

Clinical High Risk ◽

Clinical Value ◽

Medication History ◽

Treatment Decision Making

Abstract Introduction In a previous report, we used canonical correlation analysis to classify individuals with clinical high risk (CHR) of psychosis into the 3 subtypes: subtype-1, characterized by extensive negative symptoms and cognitive deficits, appeared to have the highest risk for conversion to psychosis; subtype-2, characterized by thought and behavioral disorganization, with moderate cognitive impairment; subtype-3, characterized by the mildest symptoms and cognitive deficits. The present study attempted to identify these subtypes’ response to antipsychotic (AP) treatment. Methods A total of 289 individuals with CHR were identified and followed up for 2 years. Individuals with CHR were classified by subtype. Use of APs was examined at 2-month, 1-year, and 2-year follow-up interviews that inquired after the subjects’ medication history since the first visit. The main outcome was remission, determined according to global assessment of function (GAF) score (i. e., functional outcome) and SIPS positive symptom score (symptomatic outcome) at the follow-up points. Results Among the 289 individuals with CHR included in the current analysis, 223 (77.2%) were treated using APs for at least 2 weeks during the follow-up period. Individuals with CHR tended to show significant improvement in both symptoms and function after 2 years, but subtypes exhibited significantly different trajectories. Subtype status can predict AP treatment outcome in terms of remission. The likelihood of remission differed significantly among the subtype groups. The remission rates for individuals with subtypes 1–3 treated using AP were 13.5%, 36.1%, and 67.0%, respectively. Discussion These subtypes may be of clinical value in AP treatment decision-making in the CHR population.

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

Psychiatry Research ◽

10.1016/j.psychres.2021.113942 ◽

2021 ◽

pp. 113942

Author(s):

Tor Gunnar Værnes ◽

Jan Ivar Røssberg ◽

Ingrid Melle ◽

Barnaby Nelson ◽

Kristin Lie Romm ◽

...

Keyword(s):

High Risk ◽

Functional Outcomes ◽

Clinical High Risk ◽

One Year

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Erratum to: Baseline Cortical Thickness Reductions in Clinical High Risk for Psychosis: Brain Regions Associated with Conversion to Psychosis Versus Non-Conversion as Assessed at One-Year Follow-up in the Shanghai-At-Risk-for-Psychosis (SHARP) Study

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa154 ◽

2020 ◽

Keyword(s):

At Risk ◽

High Risk ◽

Cortical Thickness ◽

Brain Regions ◽

Clinical High Risk ◽

One Year

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O6.6. MULTIMODAL PROGNOSIS OF NEGATIVE SYMPTOM SEVERITY IN INDIVIDUALS WITH INCREASED RISK OF DEVELOPING PSYCHOSIS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa028.035 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S15-S16

Author(s):

Daniel Hauke ◽

André Schmidt ◽

Erich Studerus ◽

Christina Andreou ◽

Anita Riecher-Rössler ◽

...

Keyword(s):

High Risk ◽

Negative Symptom ◽

Symptom Severity ◽

Negative Symptoms ◽

Risk Group ◽

Sequential Testing ◽

Clinical High Risk ◽

Moderate Severity ◽

Symptom Progression

Abstract Background Precise prognosis of clinical outcomes in individuals at clinical high-risk (CHR) of developing psychosis is imperative to guide treatment selection. While much effort has been put into the prediction of transition to psychosis in CHR individuals, prognostic models focusing on negative symptom progression in this population are widely missing. This is a major oversight bearing in mind that 82% of CHR individuals exhibit at least one negative symptom in the moderate to severe range at first clinical presentation, whereas 54% still meet this criteria after 12 months. Negative symptoms are strong predictors of poor functional outcome irrespective of other symptoms such as depression or anxiety. Prognostic tools are therefore urgently required to track negative symptom progression in CHR individuals in order to guide early personalized interventions. Here, we applied machine-learning to multi-site data from five European countries with the aim of predicting negative symptoms of at least moderate severity 9-month after study inclusion. Methods We analyzed data from the ‘Personalized Prognostic Tools for Early Psychosis Management’ (PRONIA; www.pronia.eu) study, which consisted of 94 individuals at clinical high-risk of developing psychosis (CHR). Predictive models either included baseline level of negative symptoms, measured with the Structured Interview for Prodromal Syndromes, whole-brain gyrification pattern, or both to forecast negative symptoms of moderate severity or above in CHR individuals. Using data from the clinical and gyrification model, further sequential testing simulations were conducted to stratify CHR individuals into different risk groups. Lastly, we assessed the models’ ability to predict functional outcomes in CHR individuals. Results Baseline negative symptom severity alone predicted moderate to severe negative symptoms with a balanced accuracy (BAC) of 68%, whereas predictive models trained on gyrification measures achieved a BAC of 64%. Stacking the two modalities allowed for an increased BAC of 72%. Additional sequential testing simulations suggested, that CHR patients could be stratified into a high risk group with 83% probability of experiencing at least moderate negative symptoms at follow-up and a medium/low risk group with a risk ranging from 25 to 38%, when using the two models sequentially. Furthermore, the models trained to predict negative symptom severity from baseline symptoms were less predictive of role (60% BAC) and social (62% BAC) functioning at follow-up. However, the model trained on gyrification data also predicted role (74% BAC) and social (73% BAC) functioning later on. The stacking model predicted role, and social functioning with 64% BAC and 66% BAC respectively. Discussion To the best of our knowledge this is the first study using state-of-the-art predictive modelling to prospectively identify CHR subjects with negative symptoms in the moderate to above moderate severity range who potentially require further therapeutic consideration. While the predictive performance will need to be validated in other samples and may be improved by expanding the models with additional predictors, we believe that this pragmatic approach will help to stratify individual risk profiles and optimize personal interventions in the future.

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Real-world effectiveness of antipsychotic treatment in psychosis prevention in a 3-year cohort of 517 individuals at clinical high risk from the SHARP (ShangHai At Risk for Psychosis)

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867420917449 ◽

2020 ◽

Vol 54 (7) ◽

pp. 696-706 ◽

Cited By ~ 4

Author(s):

TianHong Zhang ◽

LiHua Xu ◽

XiaoChen Tang ◽

YanYan Wei ◽

Qiang Hu ◽

...

Keyword(s):

High Risk ◽

Real World ◽

Negative Symptoms ◽

Low Dose ◽

Antipsychotic Treatment ◽

Positive Symptoms ◽

Clinical High Risk ◽

Small Subgroup ◽

Conversion Rates

Objective: Antipsychotics are widely used for treating psychosis, but it is unclear whether they can also prevent psychosis. This study attempted a longitudinal evaluation of antipsychotics under real-world conditions in China to evaluate their effect on the rate of conversion to psychosis in individuals with a clinical high risk (CHR) of psychosis. Method: A total of 517 CHR individuals were recruited between 2011 and 2016 and followed up for 3 years. Among these, 450 (87.0%) individuals completed follow-up, 108 (24.0%) showed conversion to psychosis and 309 (68.7%) received antipsychotics. The main outcome was conversion to psychosis. The sample was further stratified according to the severity of positive symptoms. Results: Patients who did not receive antipsychotics showed a lower conversion rate than those who did (17.7% vs 26.9%; odds ratio [OR] = 0.660, 95% confidence interval [CI] = [0.442, 0.985], p = 0.035). In mild CHR cases, antipsychotic treatment was more likely to be associated with conversion to psychosis, compared with the no-antipsychotics group, with no such difference observed in severe CHR cases. Among those who received antipsychotics, monotherapy or low-dose treatment was associated with lower conversion rates. Our results did not favor any specific type of antipsychotics and suggested that a very small subgroup of CHR individuals with severe positive and general symptoms but mild negative symptoms may benefit from antipsychotic treatment. Conclusions: Administration of antipsychotics to CHR patients is potentially harmful with no preventive benefits. We do not recommend antipsychotic treatment for CHR individuals, which is practiced widely in China, and strongly advise caution if these drugs are used.

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

European Archives of Psychiatry and Clinical Neuroscience ◽

10.1007/s00406-021-01315-2 ◽

2021 ◽

Author(s):

Kate Haining ◽

Ruchika Gajwani ◽

Joachim Gross ◽

Andrew I. Gumley ◽

Robin A. A. Ince ◽

...

Keyword(s):

Cluster Analysis ◽

High Risk ◽

Functional Outcomes ◽

Early Stage ◽

Psychotic Symptoms ◽

First Episode ◽

Cognitively Impaired ◽

Clinical High Risk ◽

Global Functioning

AbstractSchizophrenia 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.

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Meta-analyzing the prevalence and prognostic effect of antipsychotic exposure in clinical high-risk (CHR): when things are not what they seem

Psychological Medicine ◽

10.1017/s0033291720004237 ◽

2020 ◽

pp. 1-9

Author(s):

Andrea Raballo ◽

Michele Poletti ◽

Antonio Preti

Keyword(s):

High Risk ◽

Meta Analysis ◽

Prognostic Impact ◽

Clinical High Risk ◽

Qualitative Synthesis ◽

Prognostic Effect ◽

Inverse Variance ◽

Arcsine Transformation ◽

Estimate Prevalence

Abstract Background The clinical high-risk (CHR) for psychosis paradigm is changing psychiatric practice. However, a widespread confounder, i.e. baseline exposure to antipsychotics (AP) in CHR samples, is systematically overlooked. Such exposure might mitigate the initial clinical presentation, increase the heterogeneity within CHR populations, and confound the evaluation of transition to psychosis at follow-up. This is the first meta-analysis examining the prevalence and the prognostic impact on transition to psychosis of ongoing AP treatment at baseline in CHR cohorts. Methods Major databases were searched for articles published until 20 April 2020. The variance-stabilizing Freeman-Tukey double arcsine transformation was used to estimate prevalence. The binary outcome of transition to psychosis by group was estimated with risk ratio (RR) and the inverse variance method was used for pooling. Results Fourteen studies were eligible for qualitative synthesis, including 1588 CHR individuals. Out of the pooled CHR sample, 370 individuals (i.e. 23.3%) were already exposed to AP at the time of CHR status ascription. Transition toward full-blown psychosis at follow-up intervened in 112 (29%; 95% CI 24–34%) of the AP-exposed CHR as compared to 235 (16%; 14–19%) of the AP-naïve CHR participants. AP-exposed CHR had higher RR of transition to psychosis (RR = 1.47; 95% CI 1.18–1.83; z = 3.48; p = 0.0005), without influence by age, gender ratio, overall sample size, duration of the follow-up, or quality of the studies. Conclusions Baseline AP exposure in CHR samples is substantial and is associated with a higher imminent risk of transition to psychosis. Therefore, such exposure should be regarded as a non-negligible red flag for clinical risk management.

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