Introduction
Schizophrenia is characterized by a wide range of symptoms, such as hallucinations, delusions, disorganized speech or behavior, and alteration in cognitive function [
1]. This psychiatric disorder is disabling for the patients and their families because of its early onset and chronic nature [
1]. Negative and cognitive symptoms, such as deficiencies in attention, working memory, or executive function, frequently combine to cause disability. Additionally, positive symptoms including suspicion, hallucinations and delusions might lead to relapse [
1].
The best way to define disorders that progress in a complicated fashion is through stages, which will not only identify a specific point in the disease’s progression but also the best course of treatment at that stage [
2]. This strategy has proven to be quite effective for organizing the treatment in oncology throughout time [
2]. It has been hypothesized that staging models can be crucial for treatment planning for a complicated disorder like schizophrenia [
2]. Various conceptual staging models have been put forth. These models sought to categorize the clinical stages (prodromal, initial episode, acute phase, remission and relapse, chronic phase and residual symptoms) of schizophrenia development.
Among the proposed classifications, some included a premorbid phase or increased risk without frank psychotic symptoms. Fava and Kellner presented a staging model for schizophrenia as follows: Stages 1 and 2 are for prodromal phases and acute episodes respectively, Stage 3 is for residual symptoms, Stage 4 is for subchronic symptoms (lasting between 6 months and 2 years) but more than 6 months), and Stage 5 is for chronic symptoms lasting more than 2 years) [
3].
Lieberman proposed that schizophrenia consists of three pathophysiologic phases divided in four stages [
3]. Stage 1 or the premorbid phase, also known as the neurodevelopmental phase, starts in early adolescence and is characterized by mild cognitive and social abnormalities. The neuroplastic phase, (Stages 2 and 3) includes the prodromal phase followed by the presence of mild psychotic symptoms. Stage 3 is the presence of full-blown psychosis. Finally, the neuro progressive phase is characterized by chronic or residual psychotic symptoms with significant negative and cognitive impairment [
4].
The chronology of psychosis progression is the primary emphasis of Singh and coll. in their staging model. The prodromal phase (stage 1), is split into two phases: a phase of unease (P1) and a phase of non-diagnostic symptoms (P2). Stage 2 begins with the first positive symptoms of psychosis, such as delusions and hallucinations. Stage 3 is a transitional phase characterized by worsening symptoms, followed by Stage 4 that confirms the diagnosis of schizophrenia [
5].
According to Agius et al., the three stages of the development of schizophrenia are the prodrome (stage 1), the initial episode (stage 2), and the chronic phase (stage 3). This author also supports that there exists a premorbid phase prior to the prodromal phase, despite the fact that it was not accounted for as a separate stage [
2].
McGorry and coll., proposed one of the most elaborate staging models of schizophrenia [
3]. Their theoretical model begins with stage 0, when the patient has no symptoms but an elevated risk for psychosis. Then, stage 1 is split into two sub-stages: 1a, which includes mild and non-specific symptoms, and 1b, which includes moderate/subthreshold symptoms. Stage 2 consists of the first episode of psychosis, while stage 3 is divided into three substages: incomplete remission (3a), first relapse (3b), and recurring relapses (3c). Stage 4 indicates a severe and enduring disease. Patients with schizophrenia spectrum disorder as well as other mood disorders including depression or bipolar illness can also benefit from this staging model. The model presented by McGorry et al. also included information on possible therapeutic modalities [
6].
As for Cosci et al., they present a four-stage model, including the prodromes (Stage 1), the acute manifestation (stage 2), the residual symptoms (stage 3), and the chronic phase (stage 4) [
3].
Finally, Fountoulakis et al. (2019) proposed a clinical staging model using the the 5-factor model (5 categories of symptoms related to schizophrenia: positive, negative, affective, cognitive and hostility symptoms) and the Positive and Negative Syndrome Scale (PANSS) [
7] This model identified 4 major clinical stages of schizophrenia after studying a population of stabilized patients diagnosed with schizophrenia with varying ages [
8].
So far, no studies have evaluated the correlation between staging models and clinical presentation and severity among patients with chronic schizophrenia and long-term hospitalizations in psychiatric settings. Among these classification models, the McGorry staging model may be one of the most developed classifications and has the potential to match the clinical stage to the intervention. In this model, the clinical stages are well defined, and the target populations for recruitment are mentioned. Moreover, the sub-stages of McGorry’s classification make this model easily adaptable to the various clinical presentations of schizophrenia, in both outpatient and inpatient settings.
In this context, the formulated research question is the following: Can we use a staging model in a sample of patients diagnosed with schizophrenia, to understand better the clinical presentation, the target treatment, and the functional outcome of this population? So far, only the Diagnostic and Statistical Manual of Mental Disorders (DSM) classification is used in this context and cannot be a comparator for this approach since it cannot determine the outcome, the clinical severity, or the target treatment. Therefore, the present study aims to classify a population of Lebanese in-patients with schizophrenia according to the McGorry staging model and compare factors between the different stages.
Discussion
Patients in our study belonged to stages 3b (43%), 3c (47.5%), and 4 (9.5%) only. In our study, higher positive, negative, and general psychopathology PANSS subscales scores, a higher number of antipsychotics, and a higher mean chlorpromazine equivalent dose were significantly associated with severe illness (Stage 4 compared to the other groups). These results are consistent with previous reports that suggest that there is a 25% increase in the PANSS total score before relapse [
20]. Concerning the chlorpromazine equivalent dose, this result is consistent with the report that intensive antipsychotic dosage has great importance in the treatment of chronic schizophrenia [
21]. However, a significantly higher mean GAF scale was found among participants in stage 3b as compared to the other groups, which is consistent with the McGorry staging model that shows a higher GAF score in stage 1b (< 70) than in stage 2 (GAF 30–50) [
22].
The staging model would gain specificity if one or more quantifiable biological markers could be identified [
23]. Several biomarkers reflecting possible causal mechanisms and/or consequences of the pathophysiology are candidates for integration into the clinical staging model of psychiatric illnesses [
23]. Electroencephalography (EEG) can be used to measure the most important brain function impairments in the psychosis spectrum and severe mood disorders [
23]. In clinical psychiatry, this could involve not only a cross-sectional biological definition but also a wider biopsychosocial definition of extent or progression [
6]. Other motor indications, and neurocognitive disturbances could be included. Non-invasive biological markers, such as changes in brain volume can be detected using Magnetic Resonance Imaging (MRI). Genetic variables like Catechol-O-Methyl transferase (COMT) and serotonin-transporter gene, and other endocrine markers may be displayed to reflect progression or greater severity of the disorder may eventually be included. For biological phenomena, such as hippocampal atrophy in individuals with depression or schizophrenia, this may be related to the duration of untreated illness. A clinical staging model could then be used to determine which biological markers could ultimately be useful in treatment selection and prognosis [
22]. The model could be further tailored for use in psychiatry, by including social factors, such as social isolation or vocational failure, which typically flows from poorly or mistreated treated illness. In any case, a person who presents for initial treatment with a great deal of collateral personal and social damage is less likely to respond to interventions (i.e. be more treatment resistant at that point whether primary or secondary) and hence more likely to have a worse prognosis [
22].
Clinical implications
Each stage in the McGorry staging model of schizophrenia is associated with well-defined clinical presentations. Staging system help in deciding appropriate treatment. The concept of a staging approach to the treatment of schizophrenia is gaining prominence [
8,
24,
25]. Clinical staging is widely used in different medical specialties. Using such models in psychiatry can improve the diagnostic process and potential therapeutic interventions for patients suffering from mental disorders. If staging was applied at a large scale for psychiatric disorders such as schizophrenia, we would be able to assess treatment efficacy according to their ability to prevent progression from earlier to later stages. The use of a standardized model of staging would ensure that treatments that are offered earlier are effective, safe, acceptable, and affordable [
2,
6].
Limitations
For the limitations, we can mention the issue of sufficient awareness and training in phenomenological informed assessment of psychopathology [
24]. A second related issue is that of inter-rater reliability. One significant challenge in connection with earlier pre-psychotic illness stages is that clinical ultra-high-risk patients may be quite heterogeneous concerning the pathophysiology and pathogenesis of psychotic disorders. Another challenge is associated with the transition from clinical to pathophysiological stage definitions [
26]. For example, to date, it has been difficult to demonstrate robust and replicable relationships between brain abnormalities in schizophrenia patients and the severity of their clinical or neurocognitive impairments. In this study, we did not find stages 1, 2, and 3a, which is considered a limitation. The data was collected at a specific point in time. The follow-up of the patients was not evaluated. Data was collected from one hospital in Lebanon. Finally, rehabilitation and psychotherapeutic approaches may have had an impact on the prognosis of psychosis, hence on the clinical stage classification. In our study, all included subjects are considered as long-term inpatients (hospitalization for at least one year), and benefited from non-specific supportive group therapy, along with medical and psychiatric care. This may be a limitation, even though no specific individual psychotherapy or rehabilitation program was implemented for specific participants.
Conclusion
The Staging model focuses primarily on dividing the course of the disorder into recognizable stages based on seriousness, development, and symptom characteristics to better predict prognosis. On the clinical side, defining discrete stages creates a framework for the evolution of interventions oriented toward prevention. In this study, we were able to classify 158 patients hospitalized for schizophrenia according to the McGorry staging model. This classification must aid clinicians select treatments that are particularly relevant to each stage. When considering the application of staging models to psychiatric disorders, applying such strategies to patients at earlier stages where intervention is more efficient to limit the progression of the illness, which is not the case in our study. Further studies must consider the indicative biological and endophenotypic markers, social, and protective factors for better classification.
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