Revista Brasileira de Psiquiatria ISSN print 1516-4446
ISSN on-line 1809-452X
JCR IF 2018: 2.440
Fully open access
No submission fees
No publication charges

Braz J Psychiatry Ahead of Print


Schneider's first-rank symptoms as predictors of remission in antipsychotic-naive first-episode psychosis

Fernando R. Malinowski1,2; Brazilio de C. Tasso3; Bruno B. Ortiz1,2; Cinthia H. Higuchi1; Cristiano Noto1,2; Sintia I. Belangero1; Rodrigo A. Bressan1; Ary Gadelha1,2; Quirino Cordeiro4

1. Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil; https://orcid.org/0000-0002-7452-489X
2. Programa de Esquizofrenia (PROESQ), Departamento de Psiquiatria, UNIFESP, São Paulo, SP, Brazil; https://orcid.org/0000-0002-2706-9118
3. Central Hospital, Centro de Atenção Integrada à Saúde Mental (CAISM), Complexo Hospitalar do Juquery, Franco da Rocha, SP, Brazil
4. Departamento de Psiquiatria, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, SP, Brazil

Ary Gadelha
Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP)
Rua Pedro de Toledo, 669, 3° andar
05039-032, São Paulo, SP, Brazil
E-mail: aryararipe@gmail.com

Received August 1, 2018
Accepted after revision March 7, 2019

Descriptors: Schizophrenia; psychosis; antipsychotics; remission induction; treatment outcome.
Abstract
OBJECTIVE: German psychiatrist Kurt Schneider proposed the concept of first-rank symptoms (FRS) of schizophrenia in 1959. However, their relevance for diagnosis and prediction of treatment response are still unclear. Most studies have investigated FRS in chronic or medicated patients. The present study sought to evaluate whether FRS predict remission, response, or improvement in functionality in antipsychotic-naive first-episode psychosis.
METHODS: Follow-up study of 100 patients at first episode of psychosis (FEP), with no previous treatment, assessed at baseline and after 2 months of treatment. The participants were evaluated with the standardized Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) and for presence of FRS.
RESULTS: Logistic regression analysis showed that, in this sample, up to three individual FRS predicted remission: voices arguing, voices commenting on one's actions, and thought broadcasting.
CONCLUSION: Specific FRS may predict remission after treatment in FEP patients. This finding could give new importance to Kurt Schneider's classic work by contributing to future updates of diagnostic protocols and improving estimation of prognosis.

INTRODUCTION

The diagnosis and treatment of schizophrenia still challenge most psychiatrists.1 Clinical presentation and outcome are widely heterogeneous among patients; insidious onset, early occurrence of negative symptoms, and loss of functionality are associated with poor prognosis.2

A clinical tool capable of predicting prognosis in schizophrenia would allow early, personalized treatment. Through the years, there have been several attempts to create such an instrument. One of the most important authors who endeavored to establish clear criteria for the diagnosis of schizophrenia was Kurt Schneider,3 who, in 1959, described the concept of first-rank symptoms (FRS). According to Schneider, these paranoid symptoms (both hallucinatory and delusional) are particularly prevalent in severe psychotic disorders and hold great importance for the diagnosis of schizophrenia.3 Although other preeminent authors, such as de Clerambault,4 described these symptoms independently, only Schneider proposed that they might hold prognostic value. Many studies5-14 have sought to assess the real utility of FRS as markers for schizophrenia, all of them with inconclusive results. Both the latest version of Schneider's seminal Clinical Psychopathology,3 and Mellor in 19704 described FRS as in Box 1 below; these are the definitions employed in the present study.




The primary objective of this study is to assess the actual capacity of FRS (both the sum of all FRS as a scale and the occurrence of at least one such symptom) to predict remission from first-episode psychosis (FEP) at 2-month follow-up. As secondary objective, we aim to assess the power of FRS to predict treatment response and improvement in function.


METHODS

Participants

This cohort study enrolled 100 drug-naive patients in FEP to undergo reevaluation after 2 months of risperidone therapy. The exclusion criteria were drug-induced psychosis, drug dependence syndrome, severe clinical disease, and/or inability to understand the informed consent form (including inability to name a legally responsible individual capable of understanding the form).

All patients were administered a multidisciplinary protocol for assessment of clinical, neuropsychological, genetic, and neuroimaging data, as part of a broader study approved by the ethics committee of Universidade Federal de São Paulo (UNIFESP) (protocol 0603/10). Participants were recruited from multiple centers in the state of São Paulo, Brazil.

Clinical assessment

Demographic information was collected from interviews with participants or caregivers. Diagnosis was assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I).15 Patients were administered the Positive and Negative Syndrome Scale (PANSS),16 a structured interview for assessment of preexisting and current use of drugs (adapted from the ASI17 by the authors), and the Global Assessment of Functioning (GAF) Scale.18 FRS were evaluated by an additional investigator-completed checklist consisting of seven items, scored dichotomously as present or absent: 1) audible thoughts, 2) voices arguing, 3) voices commenting on one's actions, 4) somatic passivity, 5) thought withdrawal, 6) thought broadcasting, and 7) delusional perception. Trained raters assessed all patients at regular meetings.

Antipsychotic treatment during follow-up

All patients were initially treated with risperidone, at doses deemed necessary by their attending physician. After 2 months of regular treatment, patients were reassessed by the same rater, using the same standardized scales. Response to treatment was defined by the percent reduction in PANSS from baseline at 2-month follow-up. Reductions in PANSS were adjusted for a baseline score of 30, according to Leucht.19

Remission, response, and functionality criteria

Remission was defined as a severity of mild or less for the following selected PANSS items (score of 3 on a scale of 1-7): delusions (P1), conceptual disorganization (P2), hallucinatory behavior (P3), unusual thought content (G9), mannerism and posturing (G5), blunted affect (N1), passive/apathetic social withdrawal (N4), and lack of spontaneity and flow of conversation (N6). These are the specific items of the remission criteria developed by the Remission in Schizophrenia Working Group (RSWG).20 The 6-month criterion was not considered in this study, because patients were reassessed after 2 months of therapy.

Response to treatment was considered positive when the subject presented at least a 50% reduction in PANSS score from baseline at 2-month follow-up, while gains in functionality were evaluated by percent improvement in GAF score from baseline at 2-month follow-up.

Outcomes

For the primary outcome, a logistic regression was performed with the seven FRS items, first as independent variables and then as a group, always with remission as the dependent variable. For secondary outcomes, we ran linear regressions: for response analysis, FRS baseline items were the independent variables and percent reduction in PANSS scores after treatment was the dependent variable; when analyzing change in functionality, percent improvement in GAF from baseline was the dependent variable, while FRS baseline items were the independent ones.

Age and gender were the initial control variables; when significant results were found, patient history of any substance abuse (yes or no) and duration of untreated psychosis (DUP) in days were added as control variables as well.

Statistical analysis was conducted in SPSS version 25.21 P-value of 0.05 was considered statistically significant.


RESULTS

The demographic profile of the sample and main results are shown in Table 1.




Respecting the exclusion criteria, 20% of the sample had some history of substance abuse. To make evaluation of diagnosis more objective, we used a categorical approach: 49% of the sample received a diagnosis of schizophrenia, 31% had schizophrenia spectrum disorders, and 20% had mood disorders. The mean (SD) dose of risperidone was 3.39 (1.34) mg per day; dose did not influence response or remission. The mean (SD) PANSS score was 77.29 (25.86) at baseline and 50.52 (28.28) after 2 months of therapy, which represents a 34.6% reduction. The prevalence of FRS in the overall sample is shown in Table 2.




On average, each subject had 3.01 (SD ±2.23) FRS. Sixteen participants did not have any FRS.

Primary outcome

Logistic regression with all diagnosis revealed that three FRS, when absent and considered individually, were capable of predicting remission (Table 3): voices arguing, voices commenting on one's actions, and thought broadcasting. Logistic regression with FRS by diagnostic group showed statistically significant findings as well, but only for voices commenting on one's actions and thought broadcasting (Table 4). When DUP and substance abuse history were added as control variables, these associations did not remain significant.






Regression applied to specific diagnosis groups (schizophrenia alone vs. combined with its spectrum vs. mood disorders alone) failed to present any significant results. Neither complete absence of any FRS nor the number of FRS present (scale 0 to 7), both as independent variables, was able to predict remission.

Secondary outcomes

In the linear regression considering all diagnoses, no single FRS was able to predict response (Table 5). Regression with percent improvement in GAF as the dependent variable excluded single FRS in every scenario. Both regarding response and GAF, the analysis was conducted for FRS individually and within-group FRS. Additional evaluations with subjects segregated by diagnosis also failed to reveal any statistically significant findings. Again, neither the absence of FRS nor the number of FRS present, both as independent variable, was able to predict response nor improvement in functionality. Finally, factor analysis applied to the seven Schneiderian FRS failed to demonstrate any categorical characteristics.




DISCUSSION

Kurt Schneider3 described FRS as experiences where there is loss of the boundaries of the self. Those include passivity, pseudo-hallucinations, and primary interpretation delusion. This description was used in the DSM-III22 under the vague designation of bizarre delusions, in criteria 1 to 6 for schizophrenia. The importance of FRS for this diagnosis remained in DSM-IV,23 as long as criteria B and C were present. The current classification, however, does not consider bizarre delusions as capital criteria for the diagnosis of schizophrenia. The DSM-5 gives much less credit to FRS importance, following the same path.24 Considering the results of the present study, forthcoming diagnosis guides might give renewed importance to FRS.

Since Schneider's original publication, a number of studies have tried to validate the diagnostic significance of the FRS; however, few clearly established the definition of each symptom. Furthermore, in clinical psychiatry, different practitioners consider and evaluate FRS using their personal impressions. As this lack of objective criteria may result in biased results,15 studies exploring FRS should establish their definitions clearly.

In our sample, three FRS showed significant discriminative power to predict remission: hearing voices arguing, hearing voices commenting on one's actions, and thought broadcasting. This finding suggests that, when detected, these symptoms may somehow be associated with worse outcomes. The most common FRS in our study, delusional perception, was not the most frequent in all relevant publications that explored the topic. Although Bland in 1980 found the same result,13 Lewine et al. (1982) mentioned thought broadcast as the most common,25 while Ndetei et al. (1983) found audible thoughts,26 and Chandrasena (1987), voices arguing.27 Interestingly, Gureje & Bamgboye (1987) found delusional perception to be the least common FRS, and passivity the most frequent.28 These discrepancies are probably related to differences in sample; in fact, the study that also found delusional perception to be the most common FRS used a sample of patients with schizophrenia during first hospitalization, a somewhat similar profile to that of our FEP subjects. Moreover, as mentioned before, different studies apply different definitions of each FRS, which hinders comparisons.

As the importance of FRS for diagnosis and prognosis has been under discussion for decades, with consistent argumentation on both sides,22,23,29 the results of this study provide additional evidence supporting FRS as an aspect to be considered. Clinical observation suggests that FRS can be found in a wide range of mental disorders where psychosis is present; this empirical view is supported by our heterogeneous sample, which included patients with schizophrenia, polymorphic psychosis, psychotic bipolar disorder, schizoaffective disorder, and even some mood disorders.30,31 However, our secondary analysis failed to find any association of FRS with treatment response or functionality outcomes.

Schneider regarded the loss of the boundaries of the self as the core symptom of schizophrenia. However, in our sample, symptoms related to self-disorder were present in less than 50% of participants, which is in line with other studies reporting the low sensitivity of FRS.29,31,32 In addition, we observed that only 11% of subjects presented all seven FRS, while 20% had two, 14.8% had three, 10% had four, 12% had five, 5% had six, and 16% did not have any FRS. This suggests that FRS can be widely distributed among patients and, as our factor analysis revealed, cannot be clearly divided into two or more dimensions.

It is important to note that DUP and positive history of substance abuse, when used as control variables, nullified the statistically significant results of initial logistic regression. This finding reinforces the clinical and research impressions that both variables influence remission prognosis in psychosis.

A number of limitations should be acknowledged. Our sample was relativity small and consisted only of first-episode patients, although this homogeneity could also be considered a strength of the study. Most patients originally studied by Kurt Schneider were chronically institutionalized individuals. In addition, the FRS were evaluated by their presence or absence, instead of measuring their intensity. The 6-months of symptom stability proposed by Andreasen et al. as a remission criterion20 could not be assessed, because patients were evaluated only at 2-month follow-up. Finally, we included other psychotic disorders rather than selecting only patients with schizophrenia, although this could also be considered a strength.

In conclusion, our results suggests, even considering the aforementioned limitations and the lack of positive findings regarding treatment response and functionality, specific FRS have some capacity to predict remission in a heterogeneous group of patients in first-episode psychosis. These findings may indicate a possible path for future research into basic psychopathology, regarding both diagnosis and prognosis. Finally, forthcoming studies which use the FRS should define each symptom clearly so as to minimize subjective bias and help other publications structure their own criteria.


REFERENCES

1. Kyziridis TC. Notes on the history of schizophrenia. German J Psychiatry. 2005;8:42-8.

2. van Os J, Kapur S. Schizophrenia. Lancet. 2009;374:635-45.

3. Schneider K. Psicopatologia clínica. São Paulo: Mestre Jou; 1968.

4. Mellor CS. First rank symptoms of schizophrenia. I. The frequency in schizophrenics on admission to hospital. II. Differences between individual first rank symptoms. Br J Psychiatry. 1970;117:15-23.

5. Carpenter WT Jr, Strauss JS. Cross-cultural evaluation of Schneider's first-rank symptoms of schizophrenia: a report from the International Pilot Study of Schizophrenia. Am J Psychiatry. 1974;131:682-7.

6. Ramperti N, Anwar M, Renwick L, Jackson D, Foley S, McWilliams S, et al. First rank symptoms in first episode psychosis and their relationship to the duration of untreated illness. J Nerv Ment Dis. 2010;198:820-3.

7. Andreasen NC, Flaum M. Schizophrenia: the characteristic symptoms. Schizophr Bull. 1991;17:27-49.

8. Rosen C, Grossman LS, Harrow M, Bonner-Jackson A, Faull R. Diagnostic and prognostic significance of Schneiderian first-rank symptoms: a 20-year longitudinal study of schizophrenia and bipolar disorder. Compr Psychiatry. 2011;52:126-31.

9. Thorup A, Petersen L, Jeppesen P, Nordentoft M. Frequency and predictive values of first rank symptoms at baseline among 362 young adult patients with first-episode schizophrenia results from the Danish OPUS study. Schizophr Res. 2007;97:60-7.

10. Hoenig J. Schneider's first rank symptoms and the tabulators. Compr Psychiatry. 1984;25:77-87.

11. Mellor CS, Sims AC, Cope RV. Change of diagnosis in schizophrenia and first-rank symptoms: an eight-year follow-up. Compr Psychiatry. 1981;22:184-8.

12. Bland RC, Orn H. Schizophrenia: Schneider's first-rank symptoms and outcome. Br J Psychiatry. 1980;137:63-8.

13. Idrees M, Khan I, Sarwar R, Irfan M. Frequency of first rank symptoms in patients of schizophrenia: a hospital-based study. Gomal J Med Sci. 2010;8:50-3.

14. Nordgaard J, Arnfred SM, Handest P, Parnas J. The diagnostic status of first-rank symptoms. Schizophr Bull. 2008;34:137-54.

15. First MB, Gibbon M. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). In: Hilsenroth MJ, Segal DL, editors. Comprehensive handbook of psychological assessment. Hoboken: John Wiley & Sons; 2004. Vol 2. Personality assessment. p. 134-43.

16. Kay SR, Opler LA, Lindenmayer JP. The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiatry Suppl. 1989;7:59-67.

17. Kessler F, Cacciola J, Alterman A, Faller S, Souza-Formigoni ML, Cruz MS, et al. Psychometric properties of the sixth version of the Addiction Severity Index (ASI-6) in Brazil. Braz J Psychiatry. 2012;34:24-33.

18. Aas IH. Global Assessment of Functioning (GAF): properties and frontier of current knowledge. Ann Gen Psychiatry. 2010;9:20.

19. Leucht S. Measurements of response, remission, and recovery in schizophrenia and examples for their clinical application. J Clin Psychiatry. 2014;75 Suppl 1:8-14.

20. Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162:441-9.

21. IBM Corp. IBM SPSS Statistics for Windows. Version 25.0. Armonk: IBM Corp; 2017.

22. Heinz A, Voss M, Lawrie SM, Mishara A, Bauer M, Gallinat J, et al. Shall we really say goodbye to first rank symptoms? Eur Psychiatry. 2016;37:8-13.

23. Pichot P. [DSM-III: the 3d edition of the Diagnostic and Statistical Manual of Mental Disorders from the American Psychiatric Association]. Rev Neurol (Paris). 1986;142:489-99.

24. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Publishing; 2013.

25. Lewine R, Renders R, Kirchhofer M, Monsour A, Watt N. The empirical heterogeneity of first rank symptoms in schizophrenia. Br J Psychiatry. 1982;140:498-502.

26. Ndetei DM, Singh A. Schneider's first rank symptoms of schizophrenia in Kenyan patients. Acta Psychiatr Scand. 1983;67:148-53.

27. Chandrasena R. Schneider's First Rank Symptoms: an international and interethnic comparative study. Acta Psychiatr Scand. 1987;76:574-8.

28. Gureje O, Bamgboye EA. A study of Schneider's first-rank symptoms of schizophrenia in Nigerian patients. Br J Psychiatry. 1987;150:867-9.

29. Preiser M, Jeffrey W. Schizophrenic patients and Schneiderian first-rank symptoms. Am J Psychiatry. 1979;136:323-6.

30. Tanenberg-Karant M, Fennig S, Ram R, Krishna J, Jandorf L, Bromet EJ. Bizarre delusions and first-rank symptoms in a first-admission sample: a preliminary analysis of prevalence and correlates. Compr Psychiatry. 1995;36:428-34.

31. Oliva F, Dalmotto M, Pirfo E, Furlan PM, Picci RL. A comparison of thought and perception disorders in borderline personality disorder and schizophrenia: psychotic experiences as a reaction to impaired social functioning. BMC Psychiatry. 2014;14:239.

32. Ihara K, Morgan C, Fearon P, Dazzan P, Demjaha A, Lloyd T, et al. The prevalence, diagnostic significance and demographic characteristics of Schneiderian first-rank symptoms in an epidemiological sample of first-episode psychoses. Psychopathology. 2009;42:81-91.