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

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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Lab-Based and Self-Reported Indices of Fitness Show Lowered Fitness and Insight into Fitness in Individuals at Clinical High Risk for Psychosis

10.1101/2020.04.30.060244 ◽

2020 ◽

Author(s):

Katherine S. F. Damme ◽

Richard P. Sloan ◽

Matthew N. Bartels ◽

Alara Ozsan ◽

Luz H. Ospina ◽

...

Keyword(s):

High Risk ◽

Healthy Volunteers ◽

Negative Symptoms ◽

Population Characteristics ◽

Self Report ◽

Positive Symptoms ◽

Clinical High Risk ◽

Laboratory Findings ◽

Exercise Interventions ◽

Intensity Of Exercise

AbstractIntroductionExercise is a promising intervention for clinical high-risk for psychosis (CHR) populations, who have attenuated positive symptoms, but evidence suggests that these youth may require tailored exercise interventions. Presently, the scope of the problem is unknown, as these youth may not be reliable reporters on fitness. This issue is compounded by the fact that there have been no investigations that utilized a formal fitness assessment in this critical population. The present study aims to determine the level of fitness in CHR youth with lab-based measures, test how effectively self-report measures characterize objective fitness indices, and explore clinical factors that may be interrupting reliable self-report-an important tool if these interventions are to be taken to scale.MethodsForty CHR individuals completed an exercise survey and lab-based indices of fitness (i.e., VO2max and BMI). Forty healthy volunteers completed lab indices of fitness and a structured clinical interview ruling out the presence of psychiatric illness.ResultsCHR youth showed greater BMI and lower VO2max compared to healthy volunteers. In the CHR group, abstract self-report items (perceived fitness) did not reflect lab indices of fitness, whereas specific exercise behaviors (intensity of exercise) showed stronger correlations with laboratory-based fitness measurements. Exploratory analyses suggested that positive symptoms involving grandiosity, and negative symptoms such as avolition, correlated with discrepancy between self-perception and laboratory findings of fitness.DiscussionResults suggest that CHR individuals are less objectively fit than matched controls, and that it will be important to consider unique population characteristics when weighing self-report data.

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Individualized risk components guiding antipsychotic delivery in patients with a clinical high risk of psychosis: application of a risk calculator

Psychological Medicine ◽

10.1017/s0033291721000064 ◽

2021 ◽

pp. 1-10

Author(s):

TianHong Zhang ◽

LiHua Xu ◽

HuiJun Li ◽

HuiRu Cui ◽

YingYing Tang ◽

...

Keyword(s):

High Risk ◽

Negative Symptoms ◽

Psychotic Symptoms ◽

Risk Level ◽

Antipsychotic Treatment ◽

Positive Symptoms ◽

General Function ◽

Clinical High Risk ◽

Risk Calculator ◽

Personal Risk

Abstract Background Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics. Methods Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher). Results In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment. Conclusions Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.

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Reduced willingness to expend effort for rewards is associated with risk for conversion and negative symptom severity in youth at clinical high-risk for psychosis

Psychological Medicine ◽

10.1017/s003329172100204x ◽

2021 ◽

pp. 1-8

Author(s):

Gregory P. Strauss ◽

Lisa A. Bartolomeo ◽

Lauren Luther

Keyword(s):

High Risk ◽

Negative Symptom ◽

Symptom Severity ◽

High Probability ◽

Negative Symptoms ◽

Positive Symptoms ◽

Clinical High Risk ◽

Risk Calculator ◽

Cross Sectional ◽

High Effort

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 predictive of conversion to illness. Mechanisms underlying negative symptoms are unclear in the CHR population. Methods The current study evaluated whether CHR participants demonstrated deficits in the willingness to expend effort for rewards and whether these impairments are associated with negative symptoms and greater risk for conversion. Participants included 44 CHR participants and 32 healthy controls (CN) who completed the Effort Expenditure for Reward Task (EEfRT). Results Compared to CN, CHR participants displayed reduced likelihood of exerting high effort for high probability and magnitude rewards. Among CHR participants, reduced effort expenditure was associated with greater negative symptom severity and greater probability of conversion to a psychotic disorder on a cross-sectional risk calculator. Conclusions Findings suggest that effort-cost computation is a marker of illness liability and a transphasic mechanism underlying negative symptoms in the SZ spectrum.

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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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Transdiagnostic Dimensions of Psychiatric Comorbidity in Individuals at Clinical High Risk for Psychosis: A Preliminary Study Informed by HiTOP

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.614710 ◽

2021 ◽

Vol 11 ◽

Author(s):

Henry R. Cowan ◽

Vijay A. Mittal

Keyword(s):

High Risk ◽

Negative Symptom ◽

Negative Symptoms ◽

Psychiatric Comorbidity ◽

Psychotic Disorders ◽

Comparison Group ◽

Dimensional Structure ◽

Psychotic Symptoms ◽

Positive Symptoms ◽

Clinical High Risk

Background: Although psychiatric comorbidity is the norm among individuals at clinical high risk for psychotic disorders (CHR), research has yet to examine transdiagnostic dimensional models of comorbidity in this critical population.Methods: This study analyzed quantitative measures of eleven psychiatric syndromes in a group at CHR (n = 71) and a matched healthy comparison group (n = 73) to determine these syndromes' dimensional structure and relationships to cognition, functioning, and risk of conversion to psychotic disorders.Results: Relative to the comparison group, the CHR group was elevated on all eleven psychiatric syndromes. Exploratory factor analysis found three psychopathology dimensions: internalizing, negative symptoms, and positive symptoms. Depression cross-loaded onto the internalizing and negative symptom dimensions. Hypomania loaded positively on positive symptoms but negatively on negative symptoms. The negative symptom factor was associated with poorer cognition and functioning and a higher risk of conversion to psychosis.Conclusions: These dimensions align with internalizing, detachment, and thought disorder, three of the five spectra in higher-order models such as the Hierarchical Taxonomy of Psychopathology (HiTOP). In the CHR state, detachment appears to be particularly insidious and predictive of psychosis. Further research is required to distinguish depression and hypomania from attenuated psychotic symptoms in this population.

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Faculty Opinions recommendation of Efficacy and Acceptability of Interventions for Attenuated Positive Psychotic Symptoms in Individuals at Clinical High Risk of Psychosis: A Network Meta-Analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733520235.793567538 ◽

2019 ◽

Author(s):

Vijay Mittal

Keyword(s):

High Risk ◽

Meta Analysis ◽

Psychotic Symptoms ◽

Clinical High Risk

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

Journal of Autism and Developmental Disorders ◽

10.1007/s10803-021-05046-0 ◽

2021 ◽

Author(s):

Julio Vaquerizo-Serrano ◽

Gonzalo Salazar de Pablo ◽

Jatinder Singh ◽

Paramala Santosh

Keyword(s):

Systematic Review ◽

High Risk ◽

Literature Search ◽

Meta Analysis ◽

Autism Spectrum ◽

Clinical High Risk ◽

Psychotic Experiences ◽

Attenuated Psychosis Syndrome ◽

The Mean ◽

Spectrum Disorders

AbstractPsychotic 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.

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