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Cognitive predictors of transition and remission of psychosis risk syndrome in a child and adolescent sample: longitudinal findings from the CAPRIS study

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Jordina Tor at Hospital Sant Joan de Déu
Jordina Tor
Inmaculada Baeza at Hospital Clínic de Barcelona
Inmaculada Baeza
Anna Sintes-Estevez
Anna Sintes-Estevez
Anna Sintes-Estevez
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Elena De la Serna at Hospital Clínic de Barcelona
Elena De la Serna
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Abstract and Figures

Cognitive impairments are proposed as predictors in the differentiation between subjects with psychosis risk syndrome (PRS) who will develop a psychotic disorder (PRS-P) and those who will not (PRS-NP). More in-depth study of the PRS-NP group could contribute to defining the role of cognitive alterations in psychosis. This study aims to analyze cognition of children and adolescents with PRS in terms of their clinical outcome at 18-month follow-up (psychosis, remission, and non-remission) and of determinate predictors of transition to psychosis and remission of PRS. The method is two-site, naturalistic, longitudinal study design, with 98 help-seeking adolescents with PRS and 64 healthy controls (HC). PRS-P (n = 24) and PRS-NP (n = 74) participants were clinically and cognitively assessed at baseline, and when full-blown psychotic disorder had developed or at 18-month follow-up. PRS-P subjects showed lower scores at baseline in processing speed, visuospatial memory, attention, and executive function (cognitive flexibility/processing speed) compared to HC. PRS-NP subjects showed lower baseline scores in verbal working memory and verbal fluency compared to HC. This deficit is also observed in the PRS group of participants still presenting attenuated psychotic symptoms at 18-month follow-up, while PRS subjects in remission showed a similar cognitive profile to HC subjects. Baseline score on processing speed, measured with a coding task, appeared to be a predictive variable for the development of a psychotic disorder. Performance in verbal working memory was predictive of remission in the PRS-NP. Post hoc comparisons indicate the need for careful interpretation of cognitive markers as predictors of psychosis. Cognitive impairments are present in both PRS-P and PRS-NP. Those individuals who recover from PRS show baseline cognitive performance comparable to the HC group. Together with sociodemographic variables, this observation could help in the differentiation of a variety of PRS trajectories in children and adolescents.
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European Child & Adolescent Psychiatry (2024) 33:89–104
https://doi.org/10.1007/s00787-022-02137-w
ORIGINAL CONTRIBUTION
Cognitive predictors oftransition andremission ofpsychosis risk
syndrome inachild andadolescent sample: longitudinal findings
fromtheCAPRIS study
JordinaTor1,2 · InmaculadaBaeza3,4,5,6· AnnaSintes‑Estevez1,2· ElenaDelaSerna3,4· OlgaPuig3,5·
DanielMuñoz‑Samons1,2· JavierÁlvarez‑Subiela1,2· GiselaSugranyes3,5· MontserratDolz1,2,4
Received: 24 October 2022 / Accepted: 28 December 2022 / Published online: 4 January 2023
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2023
Abstract
Cognitive impairments are proposed as predictors in the differentiation between subjects with psychosis risk syndrome (PRS)
who will develop a psychotic disorder (PRS-P) and those who will not (PRS-NP). More in-depth study of the PRS-NP group
could contribute to defining the role of cognitive alterations in psychosis. This study aims to analyze cognition of children and
adolescents with PRS in terms of their clinical outcome at 18-month follow-up (psychosis, remission, and non-remission) and
of determinate predictors of transition to psychosis and remission of PRS. The method is two-site, naturalistic, longitudinal
study design, with 98 help-seeking adolescents with PRS and 64 healthy controls (HC). PRS-P (n = 24) and PRS-NP (n = 74)
participants were clinically and cognitively assessed at baseline, and when full-blown psychotic disorder had developed or at
18-month follow-up. PRS-P subjects showed lower scores at baseline in processing speed, visuospatial memory, attention,
and executive function (cognitive flexibility/processing speed) compared to HC. PRS-NP subjects showed lower baseline
scores in verbal working memory and verbal fluency compared to HC. This deficit is also observed in the PRS group of
participants still presenting attenuated psychotic symptoms at 18-month follow-up, while PRS subjects in remission showed
a similar cognitive profile to HC subjects. Baseline score on processing speed, measured with a coding task, appeared to be
a predictive variable for the development of a psychotic disorder. Performance in verbal working memory was predictive of
remission in the PRS-NP. Post hoc comparisons indicate the need for careful interpretation of cognitive markers as predictors
of psychosis. Cognitive impairments are present in both PRS-P and PRS-NP. Those individuals who recover from PRS show
baseline cognitive performance comparable to the HC group. Together with sociodemographic variables, this observation
could help in the differentiation of a variety of PRS trajectories in children and adolescents.
Keywords Clinical high risk for psychosis· Cognitive impairment· Neuropsychological profile· Psychosis· Child and
adolescent· Psychosis risk syndrome
* Jordina Tor
jordina.tor@sjd.es
1 Child andAdolescent Mental Health Research Group,
Institut de Recerca Sant Joan de Déu, Santa Rosa, 39-57,
08950EspluguesdeLlobregat, Barcelona, Spain
2 Child andAdolescent Psychiatry andPsychology
Department, Hospital Sant Joan de Déu ofBarcelona, Passeig
Sant Joan de Déu, 002, 08950EspluguesdeLlobregat,
Barcelona, Spain
3 Department ofChild andAdolescent Psychiatry
andPsychology, Hospital Clinic Universitari ofBarcelona,
(2017SGR881), Barcelona, Spain
4 Centro de Investigación Biomédica en Red de Salud Mental,
CIBERSAM, Madrid, Spain
5 Institut d’Investigacions Biomèdiques August Pi Sunyer
(CERCA-IDIBAPS), Barcelona, Spain
6 Health Sciences Division, Department ofPsychiatry
andPsychobiology, University ofBarcelona, Barcelona,
Spain
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... In this clinical high risk for psychosis (CHR) period, cognitive impairments are attenuated compared with what is observed in schizophrenia, but processing speed remains one of the most impaired domains, [6][7][8][9] particularly in individuals who later convert to a psychotic disorder. [10][11][12] As a result, digit symbol coding is a critical component of the North American Prodrome Longitudinal Study (NAPLS) risk calculator, which estimates the vulnerability of converting to psychosis. 7,13 However, in the growing landscape of remote testing, and efforts to ease research burden with measures that are easy to administer and score, there is an increased need for a computerized digit symbol measure that matches the utility of the pen-and-paper versions. ...
Comparing a Computerized Digit Symbol Test to a Pen-and-Paper Classic
Article
Full-text available
  • Sep 2023
Background and Hypothesis Processing speed dysfunction is a core feature of psychosis and predictive of conversion in individuals at clinical high risk (CHR) for psychosis. Although traditionally measured with pen-and-paper tasks, computerized digit symbol tasks are needed to meet the increasing demand for remote assessments. Therefore we: (1) assessed the relationship between traditional and computerized processing speed measurements; (2) compared effect sizes of impairment for progressive and persistent subgroups of CHR individuals on these tasks; and (3) explored causes contributing to task performance differences. Study Design Participants included 92 CHR individuals and 60 healthy controls who completed clinical interviews, the Brief Assessment of Cognition in Schizophrenia Symbol Coding test, the computerized TestMyBrain Digit Symbol Matching Test, a finger-tapping task, and a self-reported motor abilities measure. Correlations, Hedges’ g, and linear models were utilized, respectively, to achieve the above aims. Study Results Task performance was strongly correlated (r = 0.505). A similar degree of impairment was seen between progressive (g = −0.541) and persistent (g = −0.417) groups on the paper version. The computerized task uniquely identified impairment for progressive individuals (g = −477), as the persistent group performed similarly to controls (g = −0.184). Motor abilities were related to the computerized version, but the paper version was more related to symptoms and psychosis risk level. Conclusions The paper symbol coding task measures impairment throughout the CHR state, while the computerized version only identifies impairment in those with worsening symptomatology. These results may be reflective of sensitivity differences, an artifact of existing subgroups, or evidence of mechanistic differences.
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Cognitive reserve in patients with first-episode psychosis as outcome predictor at 5-year follow-up
Article
Full-text available
  • Dec 2021
  • EUR CHILD ADOLES PSY
Cognitive reserve (CR) is the premorbid brain capacity to cope with neural damage. People with good CR can tolerate higher levels of pathological brain injuries before displaying clinical symptoms than others. This study aimed to analyze CR in a sample of patients diagnosed with first-episode psychosis (FEP) during childhood or adolescence, comparing them to a community control group (CC) and assessing the predictive value of CR regarding psychosocial functioning, clinical symptoms and neuropsychological variables at the 5-year follow-up. 57 patients diagnosed with FEP during childhood or adolescence and 37 controls completed clinical, neuropsychological, and psychosocial functioning assessments at baseline and 5-year follow-up. CR was assessed in both groups at baseline. The FEP group showed lower CR scores than the CC group. Higher CR in the FEP group was associated with fewer psychotic negative symptoms, total psychotic symptoms and depressive symptoms, higher psychosocial functioning, and less impaired memory and attention at the 5-year follow-up. CR is associated with long-term clinical, neuropsychological and psychosocial functioning outcomes in patients diagnosed with FEP during childhood or adolescence.
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Brain structural trajectories in youth at familial risk for schizophrenia or bipolar disorder according to development of psychosis spectrum symptoms
Article
Full-text available
Background The evaluation of child and adolescent offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) may help understand changes taking place in the brain in individuals at heightened risk for disease during a key developmental period. Methods One hundred twenty‐eight individuals (33 SzO and 46 BpO, considered jointly as ‘Familial High Risk’ (FHR), and 49 controls) aged 6–17 years underwent clinical, cognitive and neuroimaging assessment at baseline, 2‐ and 4‐year follow‐up. Twenty FHR participants (11 SzO and 9 BpO) developed psychotic spectrum symptoms during follow‐up, while 59 FHR participants did not. Magnetic resonance imaging was performed on a 3Tesla scanner; cortical surface reconstruction was applied to measure cortical thickness, surface area and grey matter volume. Results FHR participants who developed psychotic spectrum symptoms over time showed greater time‐related mean cortical thinning than those who did not and than controls. By subgroups, this effect was present in both BpO and SzO in the occipital cortex. At baseline, FHR participants who developed psychotic spectrum symptoms over time had smaller total surface area and grey matter volume than those who did not and than controls. Over time, all FHR participants showed less longitudinal decrease in surface area than controls. In those who developed psychotic spectrum symptoms over time, this effect was driven by BpO, while in those who did not, this was due to SzO, who also showed less grey matter volume reduction. Conclusion The emergence of psychotic spectrum symptoms in FHR was indexed by smaller cross‐sectional surface area and progressive cortical thinning. Relative preservation of surface area over time may signal different processes according to familial risk. These findings lay the foundation for future studies aimed at stratification of FHR youth.
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Annual Research Review: Prevention of psychosis in adolescents -systematic review and meta-analysis of advances in detection, prognosis and intervention
Article
Full-text available
Background: The clinical high-risk state for psychosis (CHR-P) paradigm has facilitated the implementation of psychosis prevention into clinical practice; however, advancements in adolescent CHR-P populations are less established. Methods: We performed a PRISMA/MOOSE-compliant systematic review of the Web of Science database, from inception until 7 October 2019, to identify original studies conducted in CHR-P children and adolescents (mean age <18 years). Findings were systematically appraised around core themes: detection, prognosis and intervention. We performed meta-analyses (employing Q statistics and I2 test) regarding the proportion of CHR-P subgroups, the prevalence of baseline comorbid mental disorders, the risk of psychosis onset and the type of interventions received at baseline. Quality assessment and publication bias were also analysed. Results: Eighty-seven articles were included (n = 4,667 CHR-P individuals). Quality of studies ranged from 3.5 to 8 (median 5.5) on a modified Newcastle-Ottawa scale. Detection: Individuals were aged 15.6 ± 1.2 years (51.5% males), mostly (83%) presenting with attenuated positive psychotic symptoms. CHR-P psychometric accuracy improved when caregivers served as additional informants. Comorbid mood (46.4%) and anxiety (31.4%) disorders were highly prevalent. Functioning and cognition were impaired. Neurobiological studies were inconclusive. Prognosis: Risk for psychosis was 10.4% (95%CI: 5.8%-18.1%) at 6 months, 20% (95%CI: 15%-26%) at 12 months, 23% (95%CI: 18%-29%) at 24 months and 23.3% (95%CI: 17.3%-30.7%) at ≥36 months. Interventions: There was not enough evidence to recommend one specific treatment (including cognitive behavioural therapy) over the others (including control conditions) to prevent the transition to psychosis in this population. Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning. At baseline, 30% of CHR-P adolescents were prescribed antipsychotics and 60% received psychotherapy. Conclusions: It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis. Future interventional research is required.
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Neuropsychological profile of children and adolescents with psychosis risk syndrome: the CAPRIS study
Article
Full-text available
  • Sep 2020
  • EUR CHILD ADOLES PSY
Neuropsychological underperformance is well described in young adults at clinical high risk for psychosis, but the literature is scarce on the cognitive profile of at-risk children and adolescents. The aim of this study is to describe the neuropsychological profile of a child and adolescent sample of patients with psychosis risk syndrome (PRS) compared to healthy controls and to analyze associations between attenuated psychotic symptoms and cognitive impairment. Cross-sectional baseline data analysis from a longitudinal, naturalistic, case–control, two-site study is presented. Eighty-one help-seeking subjects with PRS and 39 healthy controls (HC) aged between 10 and 17 years of age were recruited. PRS was defined by: positive or negative attenuated symptoms, Brief Limited Intermittent Psychotic Symptoms (BLIPS), genetic risk (first- or second-degree relative), or schizotypal personality disorder plus impairment in functioning. A neuropsychological battery was administered to assess general intelligence, verbal and visual memory, visuospatial abilities, speed processing, attention, and executive functions. The PRS group showed lower general neuropsychological performance scores at a multivariate level and lower scores than controls in general intelligence and executive functions. Lower scores on executive function and poorer attention were associated with high scores of positive attenuated psychotic symptoms. No association with attenuated negative symptoms was found. This study provides evidence of cognitive impairment in PRS children and adolescents and shows a relationship between greater cognitive impairment in executive functions and attention tasks and severe attenuated positive symptoms. However, longitudinal studies are needed to clarify the nature of cognitive impairment as a possible vulnerability marker.
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Neurocognition as a predictor of transition to psychotic disorder and functional outcomes in ultra-high risk participants: Findings from the NEURAPRO randomized clinical trial
Article
Full-text available
  • Dec 2018
  • SCHIZOPHR RES
Background: Neurocognitive impairments experienced by individuals at ultra-high risk (UHR) for psychosis are potential predictors of outcome within this population, however there is inconsistency regarding the specific neurocognitive domains implicated. This study aimed to examine whether baseline neurocognition predicted transition to psychosis, or functional outcomes, at medium-term (mean = 3.4 years) follow-up, while controlling for other clinical/treatment variables associated with transition to psychosis. Method: Analysis of data collected as part of a multi-centre RCT of omega-3 fatty acids and cognitive-behavioural case management (NEURAPRO) for UHR individuals was conducted on the 294 participants (134 males, 160 females) who completed neurocognitive assessment (Brief Assessment of Cognition for Schizophrenia) at baseline. Transition to psychosis was determined using the Comprehensive Assessment of At-Risk Mental States (CAARMS), and functioning was measured with the Global Functioning: Social and Role Scales. Results: Mean baseline z-scores indicated that UHR participants performed a quarter to half a standard deviation below normative means in all domains (range mean z = -0.24 to -0.47), except for executive functioning (mean z = 0.16). After adjusting for covariates, poorer Executive (p = .010) and Motor (p = .030) functions were predictive of transition to psychosis. Processing Speed and Verbal Fluency were significant predictors of role functioning at 12 months (p = .004), and social functioning at medium-term follow-up (p = .015), respectively. Conclusions: Neurocognitive abilities are independent predictors of both transition to psychosis and functional outcomes within the UHR population. Further research is needed to determine the best combination of risk variables in UHR individuals for prediction of psychosis transition, functioning and other psychopathology outcomes.
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Cognitive Deficits in Psychotic Disorders: A Lifespan Perspective
Article
Full-text available
  • Dec 2018
  • NEUROPSYCHOL REV
Individuals with disorders that include psychotic symptoms (i.e. psychotic disorders) experience broad cognitive impairments in the chronic state, indicating a dimension of abnormality associated with the experience of psychosis. These impairments negatively impact functional outcome, contributing to the disabling nature of schizophrenia, bipolar disorder, and psychotic depression. The robust and reliable nature of cognitive deficits has led researchers to explore the timing and profile of impairments, as this may elucidate different neurodevelopmental patterns in individuals who experience psychosis. Here, we review the literature on cognitive deficits across the life span of individuals with psychotic disorder and psychotic-like experiences, highlighting the dimensional nature of both psychosis and cognitive ability. We identify premorbid generalized cognitive impairment in schizophrenia that worsens throughout development, and stabilizes by the first-episode of psychosis, suggesting a neurodevelopmental course. Research in affective psychosis is less clear, with mixed evidence regarding premorbid deficits, but a fairly reliable generalized deficit at first-episode, which appears to worsen into the chronic state. In general, cognitive impairments are most severe in schizophrenia, intermediate in bipolar disorder, and the least severe in psychotic depression. In all groups, cognitive deficits are associated with poorer functional outcome. Finally, while the generalized deficit is the clearest and most reliable signal, data suggests specific deficits in verbal memory across all groups, specific processing speed impairments in schizophrenia and executive functioning impairments in bipolar disorder. Cognitive deficits are a core feature of psychotic disorders that provide a window into understanding developmental course and risk for psychosis. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
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Neurocognitive Functioning in Individuals at Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis
Article
  • Jun 2021
Importance Neurocognitive functioning is a potential biomarker to advance detection, prognosis, and preventive care for individuals at clinical high risk for psychosis (CHR-P). The current consistency and magnitude of neurocognitive functioning in individuals at CHR-P are undetermined. Objective To provide an updated synthesis of evidence on the consistency and magnitude of neurocognitive functioning in individuals at CHR-P. Data Sources Web of Science database, Cochrane Central Register of Reviews, and Ovid/PsycINFO and trial registries up to July 1, 2020. Study Selection Multistep literature search compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology performed by independent researchers to identify original studies reporting on neurocognitive functioning in individuals at CHR-P. Data Extraction and Synthesis Independent researchers extracted the data, clustering the neurocognitive tasks according to 7 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and 8 CHR-P domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. Main Outcomes and Measures The primary effect size measure was Hedges g of neurocognitive functioning in individuals at CHR-P (1) compared with healthy control (HC) individuals or (2) compared with individuals with first-episode psychosis (FEP) or (3) stratified for the longitudinal transition to psychosis. Results A total of 78 independent studies were included, consisting of 5162 individuals at CHR-P (mean [SD; range] age, 20.2 [3.3; 12.0-29.0] years; 2529 [49.0%] were female), 2865 HC individuals (mean [SD; range] age, 21.1 [3.6; 12.6-29.2] years; 1490 [52.0%] were female), and 486 individuals with FEP (mean [SD; range] age, 23.0 [2.0; 19.1-26.4] years; 267 [55.9%] were female). Compared with HC individuals, individuals at CHR-P showed medium to large deficits on the Stroop color word reading task (g = −1.17; 95% CI, −1.86 to −0.48), Hopkins Verbal Learning Test–Revised (g = −0.86; 95% CI, −1.43 to −0.28), digit symbol coding test (g = −0.74; 95% CI, −1.19 to −0.29), Brief Assessment of Cognition Scale Symbol Coding (g = −0.67; 95% CI, −0.95 to −0.39), University of Pennsylvania Smell Identification Test (g = −0.55; 95% CI, −0.97 to −0.12), Hinting Task (g = −0.53; 95% CI, −0.77 to −0.28), Rey Auditory Verbal Learning Test (g = −0.50; 95% CI, −0.78 to −0.21), California Verbal Learning Test (CVLT) (g = −0.50; 95% CI, −0.64 to −0.36), and National Adult Reading Test (g = −0.52; 95% CI, −1.01 to −0.03). Individuals at CHR-P were less impaired than individuals with FEP. Longitudinal transition to psychosis from a CHR-P state was associated with medium to large deficits in the CVLT task (g = −0.58; 95% CI, −1.12 to −0.05). Meta-regressions found significant effects for age and education on processing speed. Conclusions and Relevance Findings from this meta-analysis support neurocognitive dysfunction as a potential detection and prognostic biomarker in individuals at CHR-P. These findings may advance clinical research and inform preventive approaches.
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Cognitive dysfunction in a psychotropic medication-naïve, clinical high-risk sample from the ShangHai-At-Risk-for-Psychosis (SHARP) study: Associations with clinical outcomes
Article
  • Jul 2020
  • SCHIZOPHR RES
Objectives 1) to assess generalizability of neurocognitive deficits reported in previous Western clinical high-risk (CHR) for psychosis studies in a prodromal program in Shanghai, China; and 2) to investigate neurocognition in CHR subjects in relation to a broader range of clinical outcomes (e.g. remission) than presence or absence of psychosis. Method Baseline neurocognitive assessments of CHR (n = 217) and healthy control (HC; n = 133) subjects were compared based on 1-year follow-up clinical status using MANOVA. CHR subjects were first divided into ‘converter’ (CHR-C; n = 41) and ‘non-converter’ (CHR-NC; n = 155) to psychosis groups and compared to HC and to each other. CHR subjects were then divided into ‘remission’ (i.e. achieved remission; n = 102), ‘symptomatic’ (persistent positive symptoms in the absence of conversion; n = 37) and ‘poor-outcome’ (converted and symptomatic subjects who did not respond to treatment; n = 57) groups. Results CHR neurocognitive performance was broadly impaired compared to HC; CHR-C subjects showed lower performance in processing speed and visual learning than CHR-NC. CHRs with poor clinical outcomes showed lower performance on most MCCB tasks compared to HC, particularly in learning and processing speed, as clinical outcome worsened from remission to symptomatic to poor outcome groups. Conclusions Level and pattern of baseline neurocognitive weaknesses in SHARP CHR subjects were similar to those in NAPLS-2. Outcome stratification into remission, symptomatic and poor groups was associated with increasing cognitive deficits in learning and processing speed. These findings support cross-cultural generalizability and advance understanding of CHR neurocognitive heterogeneity associated with 1-year clinical outcomes.
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Characterization of children and adolescents with psychosis risk syndrome: The Children and Adolescents Psychosis Risk Syndrome (CAPRIS) study
Article
  • Nov 2018
Aim Despite the interest in psychosis risk syndrome (PRS) in children and adolescents, information on the syndrome in this population is scarce. Methods Prospective naturalistic multi‐site study in which 10‐ to 17‐year‐old help‐seeking subjects who met PRS criteria (positive or negative attenuated symptoms; brief limited intermittent psychotic symptoms; genetic risk or schizotypal personality disorder plus impairment in functioning) were included, along with 45 age and sex‐matched healthy controls (HC). All subjects were clinically and functionally assessed. Results Ninety‐one PRS subjects (PRSS) with a mean age of 15.5 ± 1.4 met inclusion criteria (IC). Compared with HC, PRSS presented worse global and academic functioning in the previous year, had experienced more psychiatric and psychological problems, and presented gestational ages outside the normal range. More than 80% of PRSS met ≥2 IC, with 65.9% having one Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis, and 61.7% of those having ≥2 diagnoses. Some 49.5% of PRSS had a first‐ or second‐degree family history (FH) of psychosis. Patients with first‐ and second‐degree FH do not differ in their clinical expression. Conclusions Children and adolescents with PRS are a patient group with a pattern of neurodevelopmental impairment and clinical complexity similar to patients with schizophrenia spectrum disorders, highlighting the importance of assessing these variables in child and adolescent samples. PRSS with first‐ and second‐degree relatives with FH do not present differences in their clinical presentation, suggesting that including these two groups of patients in the genetic risk criteria would enrich knowledge of these criteria.
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