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

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

EClinicalMedicine ◽

10.1016/j.eclinm.2021.100909 ◽

2021 ◽

Vol 36 ◽

pp. 100909

Author(s):

Gonzalo Salazar de Pablo ◽

Filippo Besana ◽

Vincenzo Arienti ◽

Ana Catalan ◽

Julio Vaquerizo-Serrano ◽

...

Keyword(s):

High Risk ◽

Negative Symptoms ◽

Meta Analysis ◽

Positive Symptoms ◽

Clinical High Risk ◽

Longitudinal Outcome

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Secondary sources of negative symptoms in those meeting criteria for a clinical high-risk syndrome

Biological Psychiatry Global Open Science ◽

10.1016/j.bpsgos.2021.05.008 ◽

2021 ◽

Author(s):

Tina Gupta ◽

Gregory P. Strauss ◽

Henry R. Cowan ◽

Andrea Pelletier-Baldelli ◽

Lauren M. Ellman ◽

...

Keyword(s):

High Risk ◽

Negative Symptoms ◽

Clinical High Risk ◽

Secondary Sources

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Association of baseline inflammatory markers and the development of negative symptoms in individuals at clinical high risk for psychosis

Brain Behavior and Immunity ◽

10.1016/j.bbi.2018.11.315 ◽

2019 ◽

Vol 76 ◽

pp. 268-274 ◽

Cited By ~ 18

Author(s):

David R. Goldsmith ◽

Ebrahim Haroon ◽

Andrew H. Miller ◽

Jean Addington ◽

Carrie Bearden ◽

...

Keyword(s):

High Risk ◽

Inflammatory Markers ◽

Negative Symptoms ◽

Clinical High Risk

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Negative symptoms in individuals at clinical high risk of psychosis

Psychiatry Research ◽

10.1016/j.psychres.2012.02.018 ◽

2012 ◽

Vol 196 (2-3) ◽

pp. 220-224 ◽

Cited By ~ 138

Author(s):

Danijela Piskulic ◽

Jean Addington ◽

Kristin S. Cadenhead ◽

Tyrone D. Cannon ◽

Barbara A. Cornblatt ◽

...

Keyword(s):

High Risk ◽

Negative Symptoms ◽

Clinical High Risk

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S69. CLINICAL HIGH RISK STATE: STRATIFICATION BASED ON CLINICAL PROFILE AND REDOX STATUS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.135 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S60-S60

Author(s):

Martine Cleusix ◽

Ines Khadimallah ◽

Elodie Toffel ◽

Paul Klauser ◽

Kim Q Do ◽

...

Keyword(s):

High Risk ◽

Psychosocial Functioning ◽

Help Seeking ◽

Verbal Learning ◽

Self Esteem ◽

Cognitive Outcomes ◽

Clinical Profile ◽

Clinical High Risk ◽

Basic Symptoms ◽

The Impact

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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Delay discounting in youth at clinical high-risk for psychosis and adults with schizophrenia

Psychological Medicine ◽

10.1017/s0033291720000677 ◽

2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Lisa A. Bartolomeo ◽

Hannah C. Chapman ◽

Ian M. Raugh ◽

Gregory P. Strauss

Keyword(s):

High Risk ◽

Delay Discounting ◽

Negative Symptoms ◽

Chronic Phase ◽

Reward Processing ◽

Positive Symptoms ◽

Clinical High Risk ◽

Symptom Scale ◽

Processing Mechanism ◽

Value Representation

Abstract Background Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and highly predictive of conversion to illness. Mechanisms underlying negative symptoms in the CHR population are unclear. Two studies were conducted to evaluate whether abnormalities in a reward processing mechanism thought to be core to negative symptoms in SZ, value representation, also exist in CHR individuals and whether they are associated with negative symptoms transphasically. Methods Study 1 included 33 individuals in the chronic phase of illness who have been diagnosed with schizophrenia or schizoaffective disorder (SZ) and 40 healthy controls (CN). Study 2 included 37 CHR participants and 45 CN. In both studies, participants completed the delay discounting (DD) task as a measure of value representation and the Brief Negative Symptom Scale was rated to measure negative symptoms. Results Results indicated that patients with SZ had steeper discounting rates than CN, indicating impairments in value representation. However, CHR participants were unimpaired on the DD task. In both studies, steeper discounting was associated with greater severity of negative symptoms. Conclusions These findings suggest that deficits in value representation are associated with negative symptoms transphasically.

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