Skip to main content

Heterogeneity of clinical symptomatology in pediatric patients at clinical high risk for psychosis

Abstract

Objective

Widespread use of diagnostic tools like the Structured Interview for Prodromal Symptoms (SIPS) has highlighted that youth at Clinical High Risk for Psychosis (CHR-P) present with heterogeneous symptomatology. This pilot study aims to highlight the range of clinical characteristics of CHR-P youth, investigate the role of the non-positive (negative, disorganization, and general) symptoms in risk assessment, and determine if specific profiles are associated with severe symptomatology.

Methods

38 participants aged 7–18 were administered the SIPS and designated as CHR-P. Descriptive statistics and mean difference t-tests were used to describe the range in prevalence and severity of SIPS symptoms and to identify symptoms associated with greater overall symptomatology.

Results

Participants who had a greater number of positive symptoms also had significantly more negative, disorganization, and general symptoms. A number of SIPS symptoms were associated with greater number of positive symptoms.

Conclusion

CHR-P youth represent a heterogeneous group, presenting with a wide range in clinical presentation as reflected in both the number of SIPS symptoms and their severity. Though the severity and duration of positive SIPS symptoms determines the CHR-P classification, high ratings on several of the other SIPS negative, disorganization, and general items may be useful indicators of elevated symptomatology.

Peer Review reports

Introduction

There is a growing sense of urgency to investigate and better characterize the prodromal phase of psychosis, known as Clinical High Risk for Psychosis (CHR-P) in order to enhance early identification and prevention efforts [1]. Although it is typical for the onset of psychotic disorders to occur in young adulthood, Early Onset Psychosis (EOP; before age 18) accounts for one-third of cases of psychotic disorders [2]. Early detection of psychosis risk for children is critical since EOP leads to worse outcomes for children as compared to adults [3] and longer duration of untreated psychosis is also associated with worse outcomes [4]. Prospective attempts to identify individuals at-risk for psychosis have been guided by the development of semi-structured interviews to assess prodromal symptoms, the most common in the United States being the Structured Interview for Prodromal Symptoms (SIPS) [5]. The SIPS is intended to provide early identification of psychosis risk, yet work continues to be done to enhance its predictive accuracy for clinical outcomes for CHR-P individuals [6, 7]. For example, reported conversion rates in children at clinical high risk are inconsistent and modest in nature, ranging from 9.5 to 17.5% in the 12–72 months after identification [8,9,10]. Baseline symptomatic heterogeneity in the CHR-P population may be one explanation for the variability in clinical outcomes [11]. The SIPS, including the companion Scale of Prodromal Symptoms (SOPS) and Criteria of Psychosis Risk Syndromes (COPS), identifies three CHR-P risk syndromes: Genetic Risk and Deterioration Syndrome (GRD), Brief Limited Intermittent Psychotic Symptoms (BLIPS), and Attenuated Psychotic Symptoms (APS). In particular, GRD is found to be the least predictive of conversion, BLIPS is considered to be the most predictive of subsequent psychosis, and APS has mixed findings of conversion [12]. The most common risk syndrome, APS, accounts for 85% of CHR-P cases, and is determined based on the presence of one or more attenuated positive symptoms. These criteria are notably broad, with the potential to encompass individuals presenting with only one mild to five or more severe attenuated positive symptoms. Additionally, the SIPS also has the capacity to identify a wide range of clinical symptoms in addition to positive symptoms that at-risk individuals are known to exhibit, including negative, disorganization, and general symptoms [13]. Consequently, focusing exclusively on whether the APS classification criteria is met may overlook the diversity of the CHR-P patients’ overall symptoms and make it more challenging to understand the neurologic underpinnings of symptoms in patients with differing profiles.

The present pilot study (1) describes the heterogeneity of SIPS positive symptom presence and severity in CHR-P youth, (2) investigates the presence and role of the SIPS non-positive (negative, disorganization, and general) symptoms in risk assessment, and (3) compares symptom profiles of CHR-P youth who present with fewer positive attenuated symptoms versus those who have more positive attenuated symptoms, to determine if specific SIPS symptoms are associated with overall more severe symptomatology.

Materials and methods

Participants

In this pilot study, youth ages 7 to 18 were recruited from the outpatient service in a pediatric academic medical center in New England as part of a larger study of neuroplasticity and psychosis [14]. Potential participants were administered the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (KSADS-PL) [15] to rule-out the presence of a psychotic disorder and administered the SIPS to determine CHR-P status. Thirty-eight participants were enrolled on the basis of meeting criteria for at least one of the three CHR-P sub-groups. Exclusion criteria included the presence of a psychotic disorder as determined by the KSADS-PL and clinical chart review identifying substance-induced prodromal symptoms, intellectual disability, history of seizure disorders, and previous traumatic brain injury. Participants provided written informed assent or consent following the guidelines on ethical inclusion of children with psychosis in research described by Frost et al. [16], and all parents/guardians gave written informed consent. The project was approved by the academic institutional review board.

Table 1 Demographics

Measures

As previously noted, the Structured Interview for Prodromal Syndromes (SIPS) is a semi-structured interview that assesses psychotic-like symptoms in four categories: positive, negative, disorganization, and general symptoms. It contains a rating scale for individual symptom severity: The Scale of Prodromal Symptoms (SOPS), which ranges from 0 (absent) to 6 (severe and psychotic) and the Criteria of Psychosis Risk Syndromes (COPS), which determines the CHR-P risk syndrome. To meet criteria for CHR-P Attenuated Positive Symptom (APS) risk syndrome, an individual must receive a rating of 3 to 5 (indicating subthreshold severity) on at least one of the five positive symptoms that began or worsened within the last year and have been present in the last month [5]. The SIPS has demonstrated excellent sensitivity (100%), specificity (74%), and inter-rater reliability for all four subscales [5]. Trained research assistants administered the SIPS. Questions were further clarified and explained to any participant when necessary. Demographic data were obtained via a study specific demographics questionnaire in conjunction with a clinical chart review. Data analyses included descriptive statistics and mean difference t-tests to describe SIPS symptoms and identify symptoms associated with greater overall symptomatology.

Results

Demographic information is summarized in Table 1. All participants met criteria for APS and three participants met criteria for both APS and Genetic Risk and Deterioration (GRD). No participants met criteria for the third psychosis risk syndrome, Brief Intermittent Psychosis (BIPS). Thirty-one (81.6%) participants met criteria for at least one other co-occurring DSM-5 disorder. Nineteen participants (50.0%) met criteria for multiple DSM-5 disorders. On average, participants endorsed 2.74 (SD = 1.13) attenuated positive symptoms (from a possible 1–5 symptoms). The number and severity of symptoms did not differ by gender or age.

The Mean Severity Rating, within a range from 1 (mild) to 6 (severe), for the five positive symptoms was 3.82 (SD = 0.77) across all participants. In addition to positive symptoms, participants presented with an average of 9.39 (SD = 3.28) (out of a possible 14) negative, disorganization, and general, symptoms with a mean severity rating per symptom of 1.74 (SD = 0.95) [within a range from 1 (mild) to 6 (severe)]. Table 2 provides frequencies for all of the SIPS symptoms. From the total list of SIPS symptoms, the most frequently reported symptoms were Trouble with Focus and Attention (D3) (n = 37; 97.4%), Perceptual Abnormalities/Hallucinations (P4) (n = 34; 89.5%), Dysphoric Mood (G2) (n = 34; 89.5%), and Avolition (N2) (n = 30; 78.9%).

Table 2 SIPS symptom frequency and severity ratings

In an effort to understand whether the severity of certain SIPS items was associated with increased psychotic-like symptomatology, participants were categorized into two groups based on the number of positive symptoms endorsed. These two groups were characterized by a higher number of attenuated positive symptoms (3–5) (High APS group) and a lower number of attenuated positive symptoms (1–2) (Low APS group). Independent samples t-tests were conducted to investigate differences in mean SIPS symptoms between the High APS group and the Low APS group. As seen in Table 3, there were significant differences in symptom severity between the High APS (n = 23; 60.53%) and the Low APS (n = 15; 39.47%) groups. The High APS group evidenced significantly higher ratings for Unusual Thought Content/Delusional Ideas (P1), Suspiciousness/Persecutory Ideas (P2), Disorganized Communication (P5), Avolition (N2), Occupational Functioning (N6), Bizarre Thinking (D2), Trouble with Focus and Attention (D3), Motor Disturbances (G3), and Impaired Tolerance to Normal Stress (G4). Table 3 includes t-test scores for all SIPS symptoms. Additionally, the High APS group exhibited significantly more negative symptoms (M = 4.70, SD = 1.69) than the Low APS group (M = 3.40, SD = 1.80), t(36) = -2.25, p =.031, more disorganization symptoms (M = 2.57, SD = 1.12) than the Low APS group (M = 1.80, SD = 1.01), t(36) = -2.13, p =.040, and more general symptoms (M = 3.35, SD = 0.83) than the Low APS group (M = 2.40, SD = 1.12), t(36) = -2.99, p =.005.

Table 3 Mean differences in SIPS symptom ratings

Discussion

As a pilot investigation, this study examined the nature of symptom heterogeneity in a subset of youth exhibiting clinical high risk for psychosis. The results suggest that there is a wide range in clinical presentation as reflected in both the number of SIPS positive symptoms endorsed and their severity. Our results suggest that, in addition to the positive symptoms, high ratings on several of the other SIPS negative, disorganization, and general items (e.g., Avolition, Occupational Functioning, Bizarre Thinking, Trouble with Focus and Attention, Motor Disturbances, and Impaired Tolerance to Normal Stress) may be useful indicators of elevated symptomatology.

The association between number of positive symptoms in the 3–5 range and the severity of attenuated positive symptoms as well as the negative, disorganization, and general SIPS symptoms, suggests the necessity of looking beyond simply the categorical assessment of CHR-P.

These findings provide support for the use of a dimensional conceptualization of psychosis [17]. van Os & Guloksuz [18] posit that given the SIPS already measures symptoms dimensionally (by presence and severity of symptoms), such a dimensional diagnostic method for CHR-P might be useful. The somewhat arbitrary nature of the categorical cut point used in APS criteria has been acknowledged as a limitation for the high-risk paradigm, however, has remained the predominant criteria used [19].

Awareness of the heterogeneity in CHR-P individuals, and youth in particular, has implications for treatment and prevention efforts. This study highlights that all youth at clinical high-risk for psychosis are not alike, have a wide range of presenting symptoms and functional outcomes, and may require distinct types of treatment depending on which symptoms are most prominent and impairing, regardless of actual rates of conversion. As such, it is prudent to discuss not only the SIPS positive symptoms but also negative, disorganization, and general symptoms in the context of clinical high risk.

A number of previous studies have used multivariate prediction models to investigate the predictive validity of the non-positive symptoms in risk for conversion to psychosis [20, 21]. Negative symptom severity [22,23,24,25,26,27], symptoms of disorganization [27,28,29], disordered thought content [30,31,32], and social dysfunction [33,34,35] have all been found to be predictive of conversion to psychosis. These findings indicate the possibility that non-positive symptoms may play a role in psychosis risk.

Consistent with the literature, the majority of CHR-P participants in this study had one or more co-occurring DSM-5 diagnoses, which confirms that most CHR-P individuals are diagnosed with common mental disorders that may persist over time [36, 37], a finding which is consistent for children and adolescents in particular [38]. It is crucial to acknowledge this comorbidity in order to provide specific treatments that are indicated for individuals who have psychotic experiences with co-occurring psychopathology. Moreover, given the heterogeneity of the symptoms evidenced by the participants in this study, additional research on the impact of comorbid disorders on conversion risk is needed, as well as research on the efficacy of treatments for psychosis with specific comorbidities.

Limitations

This pilot study should be interpreted cautiously since it contains several limitations. First, the small sample size and limited demographics, such as predominantly middle to upper class white and non-Hispanic/Latino participants, may adversely affect our ability to more broadly describe the true range in symptom heterogeneity in CHR-P youth. Second, this sample represents only help-seeking individuals. Third, because this was a pilot study, follow-up clinical outcome data such as conversion to psychosis was not collected from the participants. It may not be the case that the presence of more positive symptoms is a marker for increased risk of conversion to psychosis.

Conclusion

While identification of factors that contribute to the risk for conversion to psychosis is needed, it is important to acknowledge that even those who do not convert face challenges and remain vulnerable, with only half remitting over time [23, 39]. Individuals at CHR-P are not only likely to present with persistent comorbid diagnoses, but are likely to experience the onset of additional disorders [37], and often experience persistent functional impairment and attenuated psychosis [40, 41]. In general, CHR-P individuals are likely to experience reduced quality of life [42] and elevated levels of stress, reiterating the need for comprehensive assessment and treatment in this population [43]. It is increasingly apparent that CHR-P youth represent an extremely vulnerable population with heterogeneous clinical presentations. A greater understanding of their clinical profiles will aid in preventing conversion and poor outcomes for these individuals.

Data availability

The dataset that supports the findings of this study is not publicly available due to its containing identifiable information that could compromise the privacy of research participants but is potentially available from the corresponding author [E.D.] upon reasonable request.

References

  1. Yung AR, McGorry PD, McFarlane CA, Jackson HJ, Patton GC, Rakkar A. Monitoring and care of young people at incipient risk of psychosis. Schizophr Bull. 1996;22(2):283–303.

    Article  CAS  PubMed  Google Scholar 

  2. Madaan V, Dvir Y, Wilson DR. Child and adolescent schizophrenia: pharmacological approaches. Expert Opin Pharmacother. 2008;9(12):2053–68.

    Article  CAS  PubMed  Google Scholar 

  3. Armando M, Pontillo M, Vicari S. Psychosocial interventions for very early and early-onset schizophrenia: a review of treatment efficacy. Curr Opin Psychiatry. 2015;28(4):312–23.

    Article  PubMed  Google Scholar 

  4. Díaz-Caneja CM, Pina-Camacho L, Rodríguez-Quiroga A, Fraguas D, Parellada M, Arango C. Predictors of outcome in early-onset psychosis: a systematic review. Npj Schizophrenia. 2015;1(1):1–10.

    Article  Google Scholar 

  5. Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Cannon T, Ventura J, et al. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull. 2003;29(4):703–15.

    Article  PubMed  Google Scholar 

  6. Cannon TD, Cornblatt B, McGorry P. Editor’s introduction: the empirical status of the Ultra high-risk (prodromal) research paradigm. Schizophr Bull. 2007;33(3):661–4.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cornblatt BA, Carrión RE, Auther A, McLaughlin D, Olsen RH, John M, et al. Psychosis Prevention: a modified clinical high risk perspective from the Recognition and Prevention (RAP) program. Am J Psychiatry. 2015;172(10):986–94.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lång U, Yates K, Leacy FP, Clarke MC, McNicholas F, Cannon M, et al. Systematic review and meta-analysis: psychosis risk in children and adolescents with an at-risk mental state. J Am Acad Child Adolesc Psychiatry. 2022;61(5):615–25.

    Article  PubMed  Google Scholar 

  9. Raballo A, Poletti M, Preti A, McGorry P. Clinical high risk for psychosis in children and adolescents: a meta-analysis of transition prevalences. Schizophr Res. 2022;243:254–61.

    Article  PubMed  Google Scholar 

  10. Ruhrmann S, Schultze-Lutter F, Salokangas RK, Heinimaa M, Linszen D, Dingemans P, et al. Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study. Arch Gen Psychiatry. 2010;67(3):241–51.

    Article  PubMed  Google Scholar 

  11. Lencz T, Smith CW, Auther A, Correll CU, Cornblatt B. Nonspecific and attenuated negative symptoms in patients at clinical high-risk for schizophrenia. Schizophr Res. 2004;68(1):37–48.

    Article  PubMed  Google Scholar 

  12. Fusar-Poli P, Cappucciati M, Borgwardt S, Woods SW, Addington J, Nelson B, et al. Heterogeneity of psychosis risk within individuals at clinical high risk: a meta-analytical stratification. JAMA Psychiatry. 2016;73(2):113–20.

    Article  PubMed  Google Scholar 

  13. McGlashan T, Walsh B, Woods S. The psychosis-risk syndrome: handbook for diagnosis and follow-up. Oxford University Press; 2010.

  14. Gonzalez-Heydrich J, Enlow MB, D’Angelo E, Seidman LJ, Gumlak S, Kim A, et al. N100 repetition suppression indexes neuroplastic defects in clinical high risk and psychotic youth. Neural Plast. 2016;2016:4209831.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36(7):980–8.

    Article  CAS  PubMed  Google Scholar 

  16. Frost KH, Lincoln SH, Norkett EM, Jin MX, Gonzalez-Heydrich J, D’Angelo EJ. The ethical inclusion of children with psychotic disorders in research: recommendations for an educative, multimodal assent process. Ethics Behav. 2016;26(2):163–75.

    Article  Google Scholar 

  17. Phalen P, Millman Z, Rouhakhtar PR, Andorko N, Reeves G, Schiffman J. Categorical versus dimensional models of early psychosis. Early Interv Psychiat. 2022;16(1):42–50.

    Article  Google Scholar 

  18. van Os J, Guloksuz S. A critique of the ultra-high risk and transition paradigm. World Psychiatry. 2017;16(2):200–6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yung AR, Nelson B, Thompson A, Wood SJ. The psychosis threshold in Ultra High Risk (prodromal) research: is it valid? Elsevier; 2010. pp. 1–6.

  20. Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rössler A, Schultze-Lutter F, et al. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013;70(1):107–20.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Studerus E, Ramyead A, Riecher-Rössler A. Prediction of transition to psychosis in patients with a clinical high risk for psychosis: a systematic review of methodology and reporting. Psychol Med. 2017;47(7):1163–78.

    Article  CAS  PubMed  Google Scholar 

  22. Cannon TD, Yu C, Addington J, Bearden CE, Cadenhead KS, Cornblatt BA, et al. An individualized risk calculator for research in prodromal psychosis. Am J Psychiatry. 2016;173(10):980–8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Salazar de Pablo G, Catalan A, Serrano JDV, Pedruzo B, Alameda L, Armendariz A et al. Negative symptoms in children and adolescents with Eearly-Onset pychosis and at clinical high-risk for psychosis: systematic review and Meta-analysis. Br J Psychiatry Open. 2022.

  24. Devoe D, Lu L, Cannon T, Cadenhead K, Cornblatt B, McGlashan T, et al. Persistent negative symptoms in youth at clinical high risk for psychosis: a longitudinal study. Schizophr Res. 2021;227:28–37.

    Article  CAS  PubMed  Google Scholar 

  25. Piskulic D, Addington J, Cadenhead KS, Cannon TD, Cornblatt BA, Heinssen R, et al. Negative symptoms in individuals at clinical high risk of psychosis. Psychiatry Res. 2012;196(2–3):220–4.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Valmaggia L, Stahl D, Yung A, Nelson B, Fusar-Poli P, McGorry P, et al. Negative psychotic symptoms and impaired role functioning predict transition outcomes in the at-risk mental state: a latent class cluster analysis study. Psychol Med. 2013;43(11):2311–25.

    Article  CAS  PubMed  Google Scholar 

  27. Zhang T, Xu L, Tang Y, Li H, Tang X, Cui H, et al. Prediction of psychosis in prodrome: development and validation of a simple, personalized risk calculator. Psychol Med. 2019;49(12):1990–8.

    Article  PubMed  Google Scholar 

  28. Demjaha A, Valmaggia L, Stahl D, Byrne M, McGuire P. Disorganization/cognitive and negative symptom dimensions in the at-risk mental state predict subsequent transition to psychosis. Schizophr Bull. 2012;38(2):351–9.

    Article  PubMed  Google Scholar 

  29. Raballo A, Nelson B, Thompson A, Yung A. The comprehensive assessment of at-risk mental states: from mapping the onset to mapping the structure. Schizophr Res. 2011;127(1–3):107–14.

    Article  PubMed  Google Scholar 

  30. Addington J, Liu L, Buchy L, Cadenhead KS, Cannon TD, Cornblatt BA, et al. North American Prodrome Longitudinal Study (NAPLS 2): the prodromal symptoms. J Nerv Ment Dis. 2015;203(5):328–35.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ciarleglio AJ, Brucato G, Masucci MD, Altschuler R, Colibazzi T, Corcoran CM, et al. A predictive model for conversion to psychosis in clinical high-risk patients. Psychol Med. 2019;49(7):1128–37.

    Article  PubMed  Google Scholar 

  32. Perkins DO, Jeffries CD, Cornblatt BA, Woods SW, Addington J, Bearden CE, et al. Severity of thought disorder predicts psychosis in persons at clinical high-risk. Schizophr Res. 2015;169(1–3):169–77.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Cornblatt BA, Carrión RE, Addington J, Seidman L, Walker EF, Cannon TD, et al. Risk factors for psychosis: impaired social and role functioning. Schizophr Bull. 2012;38(6):1247–57.

    Article  PubMed  Google Scholar 

  34. Fusar-Poli P, Byrne M, Valmaggia L, Day F, Tabraham P, Johns L, et al. Social dysfunction predicts two years clinical outcome in people at Ultra high risk for psychosis. J Psychiatr Res. 2010;44(5):294–301.

    Article  CAS  PubMed  Google Scholar 

  35. Jang JH, Shin NY, Shim G, Park HY, Kim E, Jang G-E, et al. Longitudinal patterns of social functioning and conversion to psychosis in subjects at ultra-high risk. Australian New Z J Psychiatry. 2011;45(9):763–70.

    Article  Google Scholar 

  36. Fusar-Poli P, Nelson B, Valmaggia L, Yung AR, McGuire PK. Comorbid depressive and anxiety disorders in 509 individuals with an at-risk mental state: impact on psychopathology and transition to psychosis. Schizophr Bull. 2014;40(1):120–31.

    Article  PubMed  Google Scholar 

  37. Lin A, Wood SJ, Nelson B, Beavan A, McGorry P, Yung AR. Outcomes of nontransitioned cases in a sample at ultra-high risk for psychosis. Am J Psychiatry. 2015;172(3):249–58.

    Article  PubMed  Google Scholar 

  38. Tor J, Dolz M, Sintes A, Muñoz D, Pardo M, de la Serna E, et al. Clinical high risk for psychosis in children and adolescents: a systematic review. Eur Child Adolesc Psychiatry. 2018;27(6):683–700.

    Article  PubMed  Google Scholar 

  39. Millman ZB, Pitts SC, Thompson E, Kline ER, Demro C, Weintraub MJ, et al. Perceived social stress and symptom severity among help-seeking adolescents with versus without clinical high-risk for psychosis. Schizophr Res. 2018;192:364–70.

    Article  PubMed  Google Scholar 

  40. Addington J, Cornblatt BA, Cadenhead KS, Cannon TD, McGlashan TH, Perkins DO, et al. At clinical high risk for psychosis: outcome for nonconverters. Am J Psychiatry. 2011;168(8):800–5.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Schlosser DA, Jacobson S, Chen Q, Sugar CA, Niendam TA, Li G, et al. Recovery from an at-risk state: clinical and functional outcomes of putatively prodromal youth who do not develop psychosis. Schizophr Bull. 2012;38(6):1225–33.

    Article  PubMed  Google Scholar 

  42. Fusar-Poli P, Rocchetti M, Sardella A, Avila A, Brandizzi M, Caverzasi E, et al. Disorder, not just state of risk: meta-analysis of functioning and quality of life in people at high risk of psychosis. Br J Psychiatry. 2015;207(3):198–206.

    Article  PubMed  Google Scholar 

  43. Pruessner M, Iyer SN, Faridi K, Joober R, Malla AK. Stress and protective factors in individuals at ultra-high risk for psychosis, first episode psychosis and healthy controls. Schizophr Res. 2011;129(1):29–35.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to the Tommy Fuss Fund and the Linda and Timothy O’Neill Foundation for their support of this research.

Funding

The data used in this study were collected as part of a research study funded by the Tommy Fuss Fund and the Linda and Timothy O’Neill Foundation.

Author information

Authors and Affiliations

Authors

Contributions

L.S.R., D.C., M.W., and E.D. conceived the study and determined the research design and methodology. E.D. and J.G.H. facilitated participant recruitment and data collection. L.S.R., D.C., and E.D. contributed to analysis and interpretation of data. L.S.R. assumed the lead in writing the manuscript. All authors contributed to editing the manuscript and received the final manuscript before submitting for publication.

Corresponding author

Correspondence to Eugene D’Angelo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study protocol was reviewed and approved by the Boston Children’s Hospital Institutional Review Board, approval number IRB-P00000875. Participants provided written informed assent or consent following the guidelines on ethical inclusion of children with psychosis in research described by Frost et al. [16], and all parents/guardians of minors gave written informed consent. Authors confirm that all methods were performed in accordance with the World Medical Association Declaration of Helsinki ethics principles for medical research involving human subjects and all other relevant guidelines and regulations.

Consent for publication

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rintell, L.S., Carroll, D., Wales, M. et al. Heterogeneity of clinical symptomatology in pediatric patients at clinical high risk for psychosis. BMC Res Notes 17, 88 (2024). https://doi.org/10.1186/s13104-024-06742-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13104-024-06742-7

Keywords