Schizophrenia – Course, Natural History and Prognosis

Slide introducing the Schizophrenia – Course, Natural History and Prognosis slide deck

Slide introducing the course and prognosis of schizophrenia chapter

Timeline illustrating how genetic, environmental, and neurobiological factors contribute to diverse schizophrenia outcomes.

Slide introducing the Symptom domains and early development in schizophrenia chapter

Slide outlining the five core symptom domains of schizophrenia and illustrating how positive, negative, and cognitive symptoms follow different trajectories over time.

Slide on premorbid functioning and prognosis in schizophrenia, showing distinct patient subgroups at baseline and follow-up

Slide on the neurodevelopmental origins of schizophrenia, linking early developmental risk factors to later illness progression

Slide introducing Early course of schizophrenia chapter

Slide on the critical early course of psychosis, showing the relationship between untreated illness duration and long-term functioning

Slide presenting a transdiagnostic clinical staging framework, showing progression in symptoms, functioning, and neurocognition across illness stages

Slide describing the clinical high-risk state for psychosis and the pathway from population risk to psychosis outcomes

Slide showing cumulative transition risk to psychosis in clinical high-risk individuals across follow-up periods.

Slide describing heterogeneous first-episode psychosis presentations, with symptom network diagrams at baseline and 12-month follow-up

Slide describing the impact of untreated psychosis duration on treatment response and long-term outcomes in first-episode psychosis

Slide introducing Long-term course and progression in schizophrenia chapter

Slide on long-term illness trajectories in first-episode psychosis, showing remission and recovery rates over time

Slide showing 20-year symptom trajectories after first-episode psychosis, including patterns of remission, improvement, relapse, and persistence

Slide summarizing chronic and persistent illness patterns in psychotic disorders, highlighting distinct trajectories and factors influencing long-term functioning

Slide describing heterogeneous long-term schizophrenia outcomes, with four symptom trajectories tracked over ten years of follow-up

Slide on relapse and persistent positive symptoms in schizophrenia, highlighting associations between relapse frequency and long-term outcomes

Slide describing the long-term course of negative symptoms in schizophrenia and their impact on functioning and disability

Slide on cognitive outcomes in psychosis, showing distinct cognitive trajectories and their relationship to clinical and functional outcomes.

Slide introducing Functional outcomes in schizophrenia chapter

Slide on functional outcomes in first-episode psychosis, highlighting predictors of recovery including untreated illness duration, cognition, and symptom remission

Slide showing occupational and functional outcomes following first-episode psychosis.

Slide introducing the Prognostic factors in schizophrenia chapter

Slide showing prognostic factors and outcome predictors across mental disorders

Slide showing the relationship between early treatment response and later clinical outcomes in schizophrenia

Slide showing the relationship between treatment adherence and relapse risk across the course of schizophrenia

Slide showing associations between childhood trauma, social cognition, and functional outcomes in psychotic disorders

Slide showing the prognostic role of negative symptoms in first-episode psychosis and long-term functional outcomes.

Slide showing cognitive impairment and cannabis use as predictors of long-term outcomes in first-episode psychosis

Slide showing the relationship between illness insight and relapse risk in schizophrenia

Slide showing how early intervention services influence clinical and functional outcomes in psychosis.

Slide introducing the Mortality and physical outcomes in schizophrenia chapter

Slide outlining key suicide risk factors and predictors in schizophrenia

Slide describing increased mortality risk and major physical health contributors in schizophrenia

Slide showing increased physical health burden and cause-specific mortality risks in people with schizophrenia

Slide introducing the Modifiers and special topics in schizophrenia chapter

Slide comparing sex differences in the course, prognosis, and mortality of schizophrenia

Slide summarising Course, natural history, and prognosis slide deck

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Schizophrenia is a highly heterogeneous disorder with variable onset, symptom patterns, and long-term outcomes. The onset of schizophrenia is thought to arise from the interaction between neurobiological vulnerability and environmental exposures during development. The disease course is often fluctuating, with episodic exacerbations and periods of remission. Core symptom domains in schizophrenia include positive, negative, disorganization, cognitive, and affective. Each symptom domain of schizophrenia can follow distinct trajectories and may carry prognostic significance across stages of illness.

This slide deck was developed by Professor Dr. Ana Catalán Alcántara, University of the Basque Country, Leioa, Spain; and Professor Dr. Christoph Correll, Charité – Universitätsmedizin Berlin, Germany, in collaboration with Cambridge (a division of Prime, Cambridge, UK).

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Index for
slide deck

Course, natural history, and prognosis

Course, natural history, and prognosis

Course, natural history, and prognosis

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Overview of the course and prognosis of schizophrenia

The course and prognosis of schizophrenia

The course and prognosis of schizophrenia

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The course and prognosis of schizophrenia

The course and prognosis of schizophrenia

References:
1. McCutcheon RA, Reis Margques R, Howes OD. Schizophrenia-an overview. JAMA Psychiatry 2020; 77: 201–210.
2. Leucht S, Siafis S, McGrath JJ, et al. Schizophrenia. Nat Rev Dis Primers 2025; 11: 83.
3. Jauhar S, Johnstone M, McKenna PJ. Schizophrenia. Lancet 20…

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Symptom domains and early development in schizophrenia

Symptom domains and early development in schizophrenia

Symptom domains and early development in schizophrenia

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Symptom domains in schizophrenia

Symptom domains in schizophrenia

The Liddle framework identifies psychomotor poverty (e.g., reduced speech and movement), disorganization (e.g., thought disorder and inappropriate affect), and reality distortion (e.g., delusions and hallucinations) as distinct but related syndromes.² This model expanded …

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Premorbid functioning and prognosis

Premorbid functioning and prognosis

References:
1. Amoretti S, Verdolini N, Mezquida G, et al. Identifying clinical clusters with distinct trajectories in first-episode psychosis through an unsupervised machine learning technique. Eur Neuropsychopharmacol 2021; 47: 112–129.
2. Chan CC, Shanahan M, Ospina L…

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Neurodevelopmental origins of schizophrenia

Neurodevelopmental origins of schizophrenia

References:
1. Birnbaum & Weinberger. The genesis of schizophrenia: an origin story. Am J Psychiatry 2024;181; 482–492.
2. Murray RM, Bhavsar V, Tripoli G, Howes DD. 30 Years on: how the neurodevelopmental hypothesis of schizophrenia morphed into the developmental risk fa…

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Early course of schizophrenia

Early course of schizophrenia

Early course of schizophrenia

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Global mean duration of untreated psychosis

Global mean duration of untreated psychosis

References:
1. Salazar de Pablo G, Aymerich C, Guinart D. What is the duration of untreated psychosis worldwide? – A meta-analysis of pooled mean and median time and regional trends and other correlates across 369 studies. Psychol Med 2024; 54: 652–662.

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Early-course critical period of psychosis

Early-course critical period of psychosis

References:
1. Crumlish N, Whitty P, Clarke M, et al. Beyond the critical period: longitudinal study of 8-year outcome in first-episode non-affective psychosis. Br J Psychiatry 2009; 194:18–24.
2. Fusar-Poli McGorry PD, Kane JM. Improving outcomes of first-episode psychos…

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Transdiagnostic clinical staging

Transdiagnostic clinical staging

Traditional clinical staging is unidirectional and fails to account for the dynamic course of schizophrenia.¹ Dynamic models may enhance prognosis prediction and guide individualized treatment, within and across stages.¹

References:
1. Scott J, Iorfino F, Capon W, et al. …

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Clinical high-risk for psychosis

Clinical high-risk for psychosis

Several assessment tools have been developed to identify individuals at clinical high risk for psychosis, particularly in the early stages before a full psychotic disorder emerges. Three key assessment tools are described below.

The CAARMS is a semi-structured interview …

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Transition risk for individuals at clinical high-risk for psychosis

Transition risk for individuals at clinical high-risk for psychosis

References:
1. Salazar de Pablo G, Radua J, Pereira J, et al. Probability of transition to psychosis in individuals at clinical high risk: an updated meta-analysis. JAMA Psychiatry 2021; 78: 970–978.
2. Catalan et al. Annual research review: prevention of psychosis in ado…

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Initial presentation in first-episode psychosis

Initial presentation in first-episode psychosis

In the figure, each circle (node) represents a symptom, and the lines between nodes represent statistical associations between symptoms.² Symptoms are grouped by clinical scale: orange nodes represent depressive symptoms from the CDSS, blue nodes represent negative sympto…

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Duration of untreated psychosis and early treatment response

Duration of untreated psychosis and early treatment response

References:
1. Salazar de Pablo G, Guinart D, Armendariz A, et al. Duration of untreated psychosis and outcomes in first-episode psychosis: systematic review and meta-analysis of early detection and intervention strategies. Schizophr Bull 2024; 50: 771–783.
2. Catalan A, …

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