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

AbstractTwenty percent of individuals at clinical high risk for psychosis (CHR-P) develop the disorder within 2 years. Extensive research has explored the factors that differentiate those who develop psychosis and those who do not, but the results are conflicting.The current systematic review and meta-analysis comprehensively addresses the consistency and magnitude of evidence for non-purely genetic risk and protective factors associated with the risk of developing psychosis in CHR-P individuals. Random effects meta-analyses, standardized mean difference (SMD) and odds ratio (OR) were used, in combination with an established stratification of evidence that assesses the association of each factor and the onset of psychotic disorders (from class I, convincing evidence to class IV weak evidence), while controlling for several types of biases.A total of 128 original controlled studies relating to 26 factors were retrieved. No factors showed class I-convincing evidence. Two further factors were associated with class II-highly suggestive evidence: attenuated positive psychotic symptoms (SMD = 0.348, 95% CI: 0.280, 0.415) and global functioning (SMD = −0.291, 95% CI: −0.370, −0.211). There was class III-suggestive evidence for negative psychotic symptoms (SMD = 0.393, 95% CI: 0.317, 0.469). There was either class IV-weak or no evidence for all other factors.Our findings suggest that despite the large number of putative risk factors investigated in the literature, only attenuated positive psychotic symptoms, global functioning, and negative psychotic symptoms show suggestive evidence or greater for association with transition to psychosis. The current findings may inform the refinement of clinical prediction models and precision medicine in this field.

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Neural Correlates of Mentalizing in Individuals With Clinical High Risk for Schizophrenia: ALE Meta-Analysis

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.634015 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ksenija Vucurovic ◽

Stéphanie Caillies ◽

Arthur Kaladjian

Keyword(s):

High Risk ◽

Meta Analysis ◽

Mental States ◽

Neural Correlates ◽

Psychotic Symptoms ◽

Middle Temporal Gyrus ◽

Healthy Controls ◽

Clinical High Risk ◽

Temporoparietal Junction ◽

The Right

Psychotic disorder refers to a spectrum of disorders that have multiple etiologies, due to the complex interaction of biological and genetic vulnerability with familial and cultural factors. A clinical high risk (CHR) for schizophrenia is defined as the presence of brief, attenuated, or intermittent psychotic symptoms in non-schizophrenic individuals. The transition to schizophrenia appears significantly more frequent in this at-risk population than in the general population. Moreover, the ability to attribute mental states to others, known as mentalizing or theory of mind, and its neural correlates found in individuals with CHR are similar to those described in patients with schizophrenia. We have therefore explored neurofunctional correlates of mentalizing in individuals with CHR vs. healthy controls, in order to identify the differences in brain activation. A neural coordinate-based activation likelihood estimation meta-analysis of existing neuroimaging data revealed that three regions displayed decreased activation in individuals with CHR, compared with healthy controls: the right temporoparietal junction, the right middle temporal gyrus, and the left precuneus. These results, combined with those in the literature, further support the hypothesis that abnormal activation of posterior brain regions involved in mentalizing correlates with psychotic symptoms in help-seeking individuals.

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Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes

Neuropsychopharmacology ◽

10.1038/s41386-021-01019-0 ◽

2021 ◽

Author(s):

Gemma Modinos ◽

Anja Richter ◽

Alice Egerton ◽

Ilaria Bonoldi ◽

Matilda Azis ◽

...

Keyword(s):

High Risk ◽

Functional Outcomes ◽

Mental States ◽

Adverse Outcomes ◽

Striatal Dopamine ◽

Psychotic Symptoms ◽

Dopamine Synthesis ◽

Clinical High Risk ◽

Hippocampal Activity ◽

The Relationship

AbstractPreclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

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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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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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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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What makes the psychosis ‘clinical high risk’ state risky: psychosis itself or the co-presence of a non-psychotic disorder?

Epidemiology and Psychiatric Sciences ◽

10.1017/s204579602100041x ◽

2021 ◽

Vol 30 ◽

Author(s):

Laila Hasmi ◽

Lotta-Katrin Pries ◽

Margreet ten Have ◽

Ron de Graaf ◽

Saskia van Dorsselaer ◽

...

Keyword(s):

High Risk ◽

Drug Use ◽

Psychotic Disorder ◽

Positive Family History ◽

Mental Health Service Use ◽

Psychotic Symptoms ◽

Polygenic Risk Score ◽

Clinical High Risk ◽

Drug Use Disorders ◽

Per Se

Abstract Aims Although attenuated psychotic symptoms in the psychosis clinical high-risk state (CHR-P) almost always occur in the context of a non-psychotic disorder (NPD), NPD is considered an undesired ‘comorbidity’ epiphenomenon rather than an integral part of CHR-P itself. Prospective work, however, indicates that much more of the clinical psychosis incidence is attributable to prior mood and drug use disorders than to psychosis clinical high-risk states per se. In order to examine this conundrum, we analysed to what degree the ‘risk’ in CHR-P is indexed by co-present NPD rather than attenuated psychosis per se. Methods We examined the incidence of early psychotic experiences (PE) with and without NPD (mood disorders, anxiety disorders, alcohol/drug use disorders), in a prospective general population cohort (n = 6123 at risk of incident PE at baseline). Four interview waves were conducted between 2007 and 2018 (NEMESIS-2). The incidence of PE, alone (PE-only) or with NPD (PE + NPD) was calculated, as were differential associations with schizophrenia polygenic risk score (PRS-Sz), environmental, demographical, clinical and cognitive factors. Results The incidence of PE + NPD (0.37%) was lower than the incidence of PE-only (1.04%), representing around a third of the total yearly incidence of PE. Incident PE + NPD was, in comparison with PE-only, differentially characterised by poor functioning, environmental risks, PRS-Sz, positive family history, prescription of antipsychotic medication and (mental) health service use. Conclusions The risk in ‘clinical high risk’ states is mediated not by attenuated psychosis per se but specifically the combination of attenuated psychosis and NPD. CHR-P/APS research should be reconceptualised from a focus on attenuated psychotic symptoms with exclusion of non-psychotic DSM-disorders, as the ‘pure' representation of a supposedly homotypic psychosis risk state, towards a focus on poor-outcome NPDs, characterised by a degree of psychosis admixture, on the pathway to psychotic disorder outcomes.

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A Meta-Analysis of Autism and Clinical High-Risk for Psychosis is Too Premature. Comment on: Vaquerizo-Serrano, Salazar de Pablo, Singh & Santosh (2021)

Journal of Autism and Developmental Disorders ◽

10.1007/s10803-021-05345-6 ◽

2021 ◽

Author(s):

Tim Ziermans ◽

Annabeth Groenman ◽

Rik Schalbroeck

Keyword(s):

High Risk ◽

Meta Analysis ◽

Clinical High Risk

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Two-year follow-up of a Chinese sample at clinical high risk for psychosis: timeline of symptoms, help-seeking and conversion

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796016000184 ◽

2016 ◽

Vol 26 (3) ◽

pp. 287-298 ◽

Cited By ~ 21

Author(s):

T. H. Zhang ◽

H. J. Li ◽

K. A. Woodberry ◽

L. H. Xu ◽

Y. Y. Tang ◽

...

Keyword(s):

High Risk ◽

Symptom Onset ◽

Help Seeking ◽

Cox Regression ◽

Clinical Population ◽

Psychotic Symptoms ◽

Clinical High Risk ◽

Chinese Sample ◽

Over Time

Background.Chinese psychiatrists have gradually started to focus on those who are deemed to be at ‘clinical high-risk (CHR)’ for psychosis; however, it is still unknown how often those individuals identified as CHR from a different country background than previously studied would transition to psychosis. The objectives of this study are to examine baseline characteristics and the timing of symptom onset, help-seeking, or transition to psychosis over a 2-year period in China.Method.The presence of CHR was determined with the Structured Interview for Prodromal Syndromes (SIPS) at the participants' first visit to the mental health services. A total of 86 (of 117) CHR participants completed the clinical follow-up of at least 2 years (73.5%). Conversion was determined using the criteria of presence of psychotic symptoms (in SIPS). Analyses examined baseline demographic and clinical predictors of psychosis and trajectory of symptoms over time. Survival analysis (Kaplan–Meier) methods along with Log-rank tests were performed to illustrate the relationship of baseline data to either conversion or non-conversion over time. Cox regression was performed to identify baseline predictors of conversion by the 2-year follow-up.Results.In total 25 (29.1%) of 86 completers transitioned to a psychotic disorder over the course of follow-up. Among the CHR sample, the mean time between attenuated symptom onset and professional help-seeking was about 4 months on average, and converters developed fully psychotic symptoms about 12 months after symptom onset. Compared with those CHR participants whose risk syndromes remitted over the course of the study, converters had significantly longer delays (p = 0.029) for their first visit to a professional in search of help. At baseline assessment, the conversion subgroup was younger, had poorer functioning, higher total SIPS positive symptom scores, longer duration of untreated prodromal symptoms, and were more often given psychosis-related diagnoses and subsequently prescribed antipsychotics in the clinic.Conclusions.Chinese CHR identified primarily by a novel clinical screening approach had a 2-year transition rate comparable with those of specialised help-seeking samples world-wide. Early clinical intervention with this functionally deteriorating clinical population who are suffering from attenuated psychotic symptoms, is a next step in applying the CHR construct in China.

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