Basic Symptoms Are Associated With Age in Patients With a Clinical High-Risk State for Psychosis: Results From the PRONIA Study

Abstract Background The Clinical High Risk state (CHR) concept was implemented to promote the early detection of young help-seeking patients with higher risk of psychotic transition. This category is based on specific clinical criteria (EPA, 2015) and require narrow frequency/duration ratings of subclinical positive psychotic symptoms to allow its definition. Prevalence of CHR “category” appears nevertheless rare in help-seeking young people and the rate of psychotic transition of CHR state is lower than predicted by early studies. Therefore, the binary outcome of transition to psychosis proposed by the “CHR model” actually fails to be an efficient marker to stratify, in neurobiological studies, people with different psychopathological trajectories, notably those who develop psychosis from those who do not. In order to rely on a vulnerability model for schizophrenic psychosis more sensitive to psychosocial functioning and negative dimension, we study prospectively with three years of follow-up a population of help-seekers addressed for clinical suspicion of prodromal state of psychosis. We aimed here to identify subgroups of patients in a sample of subclinical psychotic states using psychological and cognitive outcomes as profiling criteria, focusing not only on transition but also on psychosocial functioning as main outcome. Methods A total of 32 help-seeking adolescents and young adults aged 14 to 35 were referred by health care providers for a specialized evaluation in case of suspicion of a prodromal psychotic state and/or detected by the French version of the Prodromal Questionnaire (PQ-16; cut-off 6/16). Their CHR status was assessed by the Structured Interview for Psychosis-Risk Syndromes (SIPS) and the Schizophrenia Proneness Instrument, Adult (SPI-A). Individuals included in the study presented either a CHR status, a subclinical CHR status or negative symptomatology. All subjects performed an additional neuropsychological battery and blood test for redox markers (Glutathione Peroxidase (GPx) and Glutathione Reductase (GR) activities) (Xin et al, 2016). Based on their clinical profile, we made a stratification of the patients using a Principal Component Analysis. Results Cognitive and psychological outcome stratification of all help-seekers revealed two subgroups (called group1 and group2) of patients with distinct profiles. Individuals in group1 (n=18) had greater levels of basic symptoms and general symptomatology. On the other hand, in group2 (n=14), individuals showed a weaker self-esteem and a lower rate of “living independently”. Cognitive scores for speed processing, attention, verbal learning and social cognition were significantly lower in group2 compared to group1. In addition, these cognitive outcomes were negatively correlated with negative symptoms only in group2. Analysis of redox markers revealed a positive correlation between GPx and GR activities in group1, a correlation disrupted in group2. Discussion Stratification of a cohort of young help-seekers with suspicion of prodromal psychosis, regardless of their CHR status, allowed us to distinguish two subgroups with different clinical profiles: group1 with higher levels of basic symptoms and general symptomatology, and group2 with weaker self-esteem, less autonomy and poorer neurocognition. In addition, analysis of redox markers revealed a redox dysregulation in patients with poorer cognitive profile. Considering the impact of neurocognitive impairment on functioning, special focus to patients of group2 is needed, mostly in clinical practice. Moreover, they might benefit of supplementation with antioxidant compounds such as NAC, which may improve cognitive deficits (Conus et al, 2018).

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Basic symptoms and gray matter volumes of patients at clinical high risk for psychosis

Psychological Medicine ◽

10.1017/s0033291720001282 ◽

2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Daniela Hubl ◽

Chantal Michel ◽

Frauke Schultze-Lutter ◽

Martinus Hauf ◽

Benno G. Schimmelmann ◽

...

Keyword(s):

High Risk ◽

Gray Matter ◽

First Episode ◽

Clinical High Risk ◽

Significant Group ◽

Basic Symptoms ◽

Conversion Rates ◽

Episode Psychosis ◽

Ultra High Risk ◽

Gray Matter Volumes

Abstract Background Clinical high-risk (CHR) for psychosis is indicated by ultra-high risk (UHR) and basic symptom (BS) criteria; however, conversion rates are highest when both UHR and BS criteria are fulfilled (UHR&BS). While BSs are considered the most immediate expression of neurobiological aberrations underlying the development of psychosis, research on neurobiological correlates of BS is scarce. Methods We investigated gray matter volumes (GMV) of 20 regions of interest (ROI) previously associated with UHR criteria in 90 patients from the Bern early detection service: clinical controls (CC), first-episode psychosis (FEP), UHR, BS and UHR&BS. We expected lowest GMV in FEP and UHR&BS, and highest volume in CC with UHR and BS in-between. Results Significantly, lower GMV was detected in FEP and UHR&BS patients relative to CC with no other significant between-group differences. When ROIs were analyzed separately, seven showed a significant group effect (FDR corrected), with five (inferior parietal, medial orbitofrontal, lateral occipital, middle temporal, precuneus) showing significantly lower GM volume in the FEP and/or UHR&BS groups than in the CC group (Bonferroni corrected). In the CHR group, only COGDIS scores correlated negatively with cortical volumes. Conclusions This is the first study to demonstrate that patients who fulfill both UHR and BS criteria – a population that has been associated with higher conversion rates – exhibit more severe GMV reductions relative to those who satisfy BS or UHR criteria alone. This result was mediated by the BS in the UHR&BS group, as only the severity of BS was linked to GMV reductions.

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Checking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis

European Psychiatry ◽

10.1016/j.eurpsy.2017.05.026 ◽

2017 ◽

Vol 45 ◽

pp. 27-35 ◽

Cited By ~ 10

Author(s):

M.P. Hengartner ◽

K. Heekeren ◽

D. Dvorsky ◽

S. Walitza ◽

W. Rössler ◽

...

Keyword(s):

High Risk ◽

Prediction Model ◽

Sensitivity And Specificity ◽

Predictive Value ◽

Predictive Accuracy ◽

Positive Symptoms ◽

Clinical High Risk ◽

Verbal Iq ◽

Basic Symptoms ◽

Ultra High Risk

AbstractBackground:The aim of this study was to critically examine the prognostic validity of various clinical high-risk (CHR) criteria alone and in combination with additional clinical characteristics.Methods:A total of 188 CHR positive persons from the region of Zurich, Switzerland (mean age 20.5 years; 60.2% male), meeting ultra high-risk (UHR) and/or basic symptoms (BS) criteria, were followed over three years. The test battery included the Structured Interview for Prodromal Syndromes (SIPS), verbal IQ and many other screening tools. Conversion to psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23).Results:Altogether n = 24 persons developed manifest psychosis within three years and according to Kaplan–Meier survival analysis, the projected conversion rate was 17.5%. The predictive accuracy of UHR was statistically significant but poor (area under the curve [AUC] = 0.65, P < .05), whereas BS did not predict psychosis beyond mere chance (AUC = 0.52, P = .730). Sensitivity and specificity were 0.83 and 0.47 for UHR, and 0.96 and 0.09 for BS. UHR plus BS achieved an AUC = 0.66, with sensitivity and specificity of 0.75 and 0.56. In comparison, baseline antipsychotic medication yielded a predictive accuracy of AUC = 0.62 (sensitivity = 0.42; specificity = 0.82). A multivariable prediction model comprising continuous measures of positive symptoms and verbal IQ achieved a substantially improved prognostic accuracy (AUC = 0.85; sensitivity = 0.86; specificity = 0.85; positive predictive value = 0.54; negative predictive value = 0.97).Conclusions:We showed that BS have no predictive accuracy beyond chance, while UHR criteria poorly predict conversion to psychosis. Combining BS with UHR criteria did not improve the predictive accuracy of UHR alone. In contrast, dimensional measures of both positive symptoms and verbal IQ showed excellent prognostic validity. A critical re-thinking of binary at-risk criteria is necessary in order to improve the prognosis of psychotic disorders.

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Clinical High Risk Symptoms and Criteria in the Community: Prevalence, Clinical Significance and Risk Factors for Their Occurrence

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2225 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S226-S226

Author(s):

F. Schultze-Lutter ◽

C. Michel ◽

B.G. Schimmelmann ◽

S. Ruhrmann

Keyword(s):

Risk Factors ◽

High Risk ◽

Clinical Relevance ◽

Clinical Samples ◽

Clinical High Risk ◽

Basic Symptoms ◽

Developmental Models ◽

Increased Risk ◽

Ultra High Risk ◽

Competing Interest

IntroductionIn clinical samples, symptomatic ultra-high risk (UHR) criteria and the basic symptom criterion “cognitive disturbances” perform well in predicting psychosis, and best when both approaches are combined.ObjectiveHowever, little-to-nothing is known about clinical high risk (CHR) and their constituent symptoms in the community.AimsWe studied the prevalence, clinical relevance, and moderators of CHR criteria and symptoms in the community.MethodRegression analyses involved 2683 community participants (age 16–40 years; response rate: 63.4%). Semi-structured telephone interviews were performed by well-trained psychologists.ResultsLifetime and current CHR symptoms were reported by 21.1% and 13.8% of interviewees. Frequency of symptoms was mostly low, only 2.4% met any CHR criterion. A stepwise relationship underlay the association of the two types of CHR symptoms and criteria with the presence of mental disorders and functional deficits, with odds ratios being highest (7.4–31.8) when UHR and basic symptoms occurred together. Report of a family history of mental disorder generally increased risk for CHR symptoms. While younger age increased risk for basic symptoms, lifetime substance misuse and trauma increased risk for UHR symptoms.ConclusionsPrevalence of CHR criteria was within the to-be-expected range from prevalence rates of psychoses. Clinical relevance of both CHR symptoms and criteria increased in a stepwise manner from basic symptoms via UHR symptoms to their combined presence, reinforcing the clinical utility of their combined use. The risk factors selectively associated with basic and UHR symptoms support developmental models relating basic symptoms to neurobiological and UHR symptoms to psychological factors.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Predictors of transition to psychosis in individuals at clinical high-risk for psychosis

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1651 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s838-s838

Author(s):

M. Skuhareuskaya ◽

O. Skugarevsky

Keyword(s):

High Risk ◽

Visual Memory ◽

Negative Symptoms ◽

Cox Regression ◽

Neuropsychological Test ◽

Psychotic Episode ◽

Clinical High Risk ◽

Basic Symptoms ◽

Role Function ◽

Thought Disorders

ObjectiveClinical high risk (CHR) for psychosis state is characterized by presence of potentially prodromal for schizophrenia symptoms. The aim of this study was to assess the predictors of transition to first psychotic episode.MethodsThe study included 123 CHR subjects. All the subjects were characterized by the presence of one of the group of criteria: (1) UHR criteria, (2) basic symptoms criteria and (3) negative symptoms and formal thought disorders (FTD). The presence of FTD in clinical high-risk individuals was assessed with methods of experimental pathopsychology. The mean length of follow-up was 26 months (SD 18). All subjects were males, mean age = 20.2 (SD: 2.1). We examined the subjects’ performance using the Cambridge automated neuropsychological test battery. We applied survival analyses to determine associations between a transition to psychosis and sociodemographic, clinical and neurocognitive parameters. To determine which items are the best predictors, Cox regression analyses were applied.ResultsThe psychosis developed in 39 subjects (31.7%). Global assessment of functioning, positive symptoms, blunted affect, social isolation, impaired role function, disorganizing/stigmatizing behavior, basic symptoms (thought pressure, unstable ideas of reference), neurocognitive parameters (visual memory and new learning, decision making, executive function) significantly influenced the transition to psychosis. A prediction model was developed and included unusual thought content (Wald = 12.386, P < 0.0001, HR = 2.996), perceptual abnormalities (Wald = 4.777, P = 0.029, HR = 1.43) and impaired role function (Wald = 1.425, P < 0.028, HR = 4.157).ConclusionClinical measures are important predictors for transition to psychosis in high-risk individuals.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Duration of basic and attenuated-psychotic symptoms in individuals at clinical high risk for psychosis: pattern of symptom onset and effects of duration on functioning and cognition

BMC Psychiatry ◽

10.1186/s12888-021-03267-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lorna Staines ◽

Ruchika Gajwani ◽

Joachim Gross ◽

Andrew I. Gumley ◽

Stephen M. Lawrie ◽

...

Keyword(s):

High Risk ◽

Cognitive Deficits ◽

Psychotic Symptoms ◽

Healthy Controls ◽

Clinical High Risk ◽

Basic Symptoms ◽

Secondary Objective ◽

Secondary Phenomenon ◽

The Relationship ◽

At Risk Mental State

Abstract Introduction Duration of risk symptoms (DUR) in people at clinical high risk for psychosis (CHR-P) has been related to poorer clinical outcomes, such as reduced functioning, but it is currently unclear how different symptoms emerge as well as their link with cognitive deficits. To address these questions, we examined the duration of basic symptoms (BS) and attenuated psychotic symptoms (APS) in a sample of CHR-P participants to test the hypothesis that BS precede the manifestation of APS. As a secondary objective, we investigated the relationship between DUR, functioning and neuropsychological deficits. Methods Data from 134 CHR-P participants were assessed with the Comprehensive Assessment of At-Risk Mental State and the Schizophrenia Proneness Interview, Adult Version. Global, role and social functioning and neurocognition were assessed and compared to a sample of healthy controls (n = 57). Results In CHR-P participants who reported both APS and BS, onset of BS and APS was not significantly related. When divided into short and long BS duration (</> 8 years), CHR-P participants with a longer duration of BS showed evidence for an onset of BS preceding APS (n = 8, p = 0.003). However, in the short BS duration group, APS showed evidence of preceding BS (n = 56, p = 0.020). Finally, there were no significant effects of DUR on cognition or functioning measures. Conclusion The present findings do not support the view that APS constitute a secondary phenomenon to BS. Moreover, our data could also not confirm that DUR has a significant effect on functioning and cognitive deficits. These findings are discussed in the context of current theories regarding emerging psychosis and the importance of DUR.

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