The burden of disease in early schizophrenia – a systematic literature review

Figures & data

Figure 1. PRISMA study selection schematic. CRD, Centre for Reviews and Dissemination; SLR, systematic literature review.

Figure 2. Summary of included outcome comparisons. Numbers indicate the quantity of studies making a comparison between early schizophrenia and the corresponding comparison group for each outcome of interest.

Table 1. Inpatient hospitalization resource use data in early schizophrenia patient cohorts.

Author and date of publication (Country)	Early schizophrenia and comparator groups (N)	Proportion of patients hospitalized	Mean (SD) number of days hospitalized, per patient	Mean (SD) number of admissions, per patient	Other inpatient hospitalization outcomes
Early vs. Chronic Schizophrenia
Dubois 2014 (Belgium)^40	e-STAR cohort ES: ≤3 years since diagnosis (95) C: >3 years since diagnosis (197)	NR	NR	NR	e-STAR cohort Mean number of hospital stays per patient at baseline: ES: 1 year: 1.24 2 years: 1.11 CS: 1 year: 1.05 2 years: 1.31
	TIMORES cohort ES: <4 episodes (23) C: None				TIMORES cohort Average number of hospital stays per patient at baseline: 0.87 (SD 1.10) No significant difference relative to e-STAR CS group
Garcia-Alvarez 2019 (Spain)^35	ES: Duration of illness <7 years (35) C: Duration of illness >10 years (69)	ES: 61.8% CS: 82.6% (p=.020)^a	NR	ES: 1.86 (2.03) CS: 4.79 (5.85) (p=.028)^a	NR
Kim 2015 (Korea)^39	ES: Duration of illness <5 years (25) C: Duration of illness >5 years (30)	NR	NR	ES: 2.00 (1.29) CS: 6.24 (5.34) (p<.001)	NR
Leung 2011 (China)^24	ES: <2 years from first-episode (50) C: Schizophrenia diagnosis ≥5 years (51)	NR	NR	ES: 0.64 (0.67) CS: 3.02 (3.04) (p<.001)	NR
Matsuda 2014 (Japan)^41	ES: <2 years since psychotic symptom onset (19) C: 5 years since psychotic symptom onset (18)	NR	NR	ES: 0.5 (0.7) CS: 0.8 (1.1)	NR
Mwansisya 2013 (China)^42	ES: Duration of illness <24 months (197) C: Duration of illness >24 months (392)	NR	ES: 166.38 (397.191) CS: 973.20 (1082.015) (p=.001)	NR	NR
Pawelczyk 2015 (Poland)^38	ES: Psychotic symptoms for <2 years (42) C: Chronic schizophrenia (44)	NR	NR	ES: 1.26 (0.497) CS: 4.3 (3.359) (p<.0001)	NR
Early Schizophrenia vs. Other Psychiatric Disorders
Chang 2014 [conference abstract] (Hong Kong, China)^44 Chang 2016 (Hong Kong, China)^34	ES: 3 years from baseline (374) C: First-episode psychotic mania (46)	NR	ES: 79.4 (SD 121.5) Psychotic mania: 96.1 (70.9) (p=.36)	ES: 1.2 (1.1) Psychotic mania: 1.9 (1.4) (p<.01)	Patients with psychotic mania had significantly fewer readmissions (p < .001) than those with schizophrenia
Corker 2015 (Austria, Croatia, Czech Republic, Poland, Romania, Sweden, Turkey)^45	ES: First episode (150) C: First-episode major depressive disorder (176)	ES: • 92.6% (at least once in their lifetime) • 35.8% hospitalized involuntarily MDD: • 43.8% (at least once in their lifetime) • 4.8% hospitalized involuntarily	NR	NR	Longest period spent in hospital ES: mean 41.4 days (SD 49.4) MDD: mean 16.1 days (SD 2.1)
Cotton 2013 (Australia)^26	ES: First episode (283) C: First-episode schizoaffective disorder (64)	ES: 70.7% (inpatient admission) Schizoaffective disorder: 87.5% (p=.008)	NR	ES: 1.6 (1.7) Schizoaffective disorder: 2.2 (1.8) (p=.017)	NR
Crebbin 2008 (UK)^15	ES: First episode (73) C: First-episode psychotic depression (105)	ES: 64.4% Psychotic depression: 77.1% (p=.76)	ES: 231 Psychotic depression: 124 (p=.78)	NR	NR
Crebbin 2009 (UK)^14^b	ES: First episode (27) C: First-episode drug-induced psychosis (35)	ES: 74.1% Drug-induced psychosis: 62.9%	ES: 88.4 Drug-induced psychosis: 25.7	NR	NR
Hui 2015 (Hong Kong, China)^28	ES: First episode (71) C: First-episode delusional disorder (71)	ES: 56.3% (at onset) Delusional disorder: 38.0% (at onset) (p=.029)	NR	NR	Median length of stay at onset ES: 34.5 days (IQR 16.3‒52.5) (p=.107) Delusional disorder: 21 days (IQR 13.0‒36.0)
Laursen 2018 [conference abstract] (NR)^43	ES: Early-onset (349) C: Early-onset bipolar disorder (365)	NR	NR	NR	Incidence ratio of admissions (bipolar disorder vs. ES) IRR 0.44 (95% CI 0.41–0.48) (p<.001)

Abbreviations. C, comparator; CI, confidence interval; CS, chronic schizophrenia; ES, early schizophrenia; IQR, interquartile range; MDD, major depressive disorder; NR, not reported; SD, standard deviation.

^aNot significant after adjusting for age.

^bSubpopulation of the Crebbin 2008 study (injection drug users).

Table 2. Social functioning data in early schizophrenia patient cohorts.

Author and date of publication (Country)	Early schizophrenia and comparator groups (N)	Mean (SD) Social and Occupational Functioning Assessment Scale^a	Mean (SD) Social Functioning Scale^b	Mean (SD) other social functioning measures
Early Schizophrenia vs. Healthy Controls
Agid 2012 (Canada)^54	ES: First episode (31) C: Age and sex-matched controls (29)	ES in symptomatic remission: 49.8 (7.96) HC: 84.0 (5.16) (p<.001)	NR	NR
Agid 2014 [conference abstract] (Canada)^55	ES: First episode (65) C: NR (NR)	NR	Patients with ES experienced significant impairment in social engagement, interpersonal communication, recreation, pro-social and enjoyment domains (p<.05)	NR
Ballon 2007 (USA)^56	ES: First episode within last year (16) C: Comparison subjects from the community (34)	NR	NR	Social Adjustment Scale – Self Report^c: ES: 2.46 (0.56) HC: 1.58 (0.28) (p<.05)
Jaracz 2007 (Poland)^59	ES: Up to 13-months' follow-up from first episode (74) C: Age and sex-matched controls (86)	NR	ES: 104.4 (10.6) HC: 117.0 (6.6) (p<.001)	NR
Early vs. Chronic Schizophrenia
Bougie 2017 [conference abstract] (Canada)^57	ES: Original diagnosis ≤5 years (103) C: Original diagnosis >5 years (52)	Baseline: ES: 50.3 CS: 49.8	NR	NR
Garcia-Alvarez 2019 (Spain)^35	ES: Duration of illness <7 years (35) C: Duration of illness >10 years (69)	NR	NR	Personal and Social Performance Scale: ES: 47.77 (18.70) CS: 49.33 (15.50) (p=.652)
Higuchi 2017 (Japan)^58	ES: Duration of illness <1 year (38) C: Duration of illness ≥1 year (135)	ES: 44.4 (11.7) CS: 54.9 (14.4) (p=.11)	NR	NR
Kim 2015 (Korea)^39	ES: Duration of illness ≤5 years (25) C: Duration of illness >5 years (30)	NR	NR	Personal and Social Performance Scale: ES: 60.92 (11.24) CS: 60.23 (10.42) (p=.822)
Early Schizophrenia vs. Other Psychiatric Disorders
Chang 2014 [conference abstract] (Hong Kong, China)^44; Chang 2016 (Hong Kong, China)^34	ES: 3 years from baseline (374) C: First-episode psychotic mania (46)	ES: 62.4 (14.4) Psychotic mania: 68.8 (11.9) (p<.01)	NR	NR
Higuchi 2017 (Japan)^58	ES: Duration of illness <1 year (38) C: Other psychiatric disorders with psychosis (19)	ES: 44.4 (11.7) Other psychoses: 42.5 (16.8) (p=.11)	NR	NR
Hui 2015 (Hong Kong, China)^28	ES: First episode (71) C: First-episode delusional disorder (71)	ES: 57.6 (11.1), Delusional disorder: 56.6 (15.5) (p=.673)	NR	NR
Lee 2016 (Hong Kong, China)^60	ES: First episode (157) C: First-episode brief psychotic disorder (42)	ES: 57.06 (12.16), Brief psychotic disorder: 64.74 (14.31) (p=.001)	NR	NR

Abbreviations. C, comparator; CI, confidence interval; CS, chronic schizophrenia; ES, early schizophrenia; HC, healthy control; NR, not reported; SD, standard deviation.

^a Score ranging from 0–100, with 100 indicating superior functioning in all domains⁷⁴.

^b Composed of 79 items and 7 subscales. Scores range from 55–135 with a higher score representing better functioning⁷⁵.

^c Scale used to measure a person’s satisfaction with their social situation, considering work/school role, social/leisure time, family outside of the home, primary relationship, parental role and family unit domains. Higher scores indicate greater social dysfunction⁵⁶.

Table 3. Quality of life data in early schizophrenia patient cohorts.

Author and date of publication (Country)	Early schizophrenia and comparator groups (N)	Mean (SD) quality of life measures	Mean (SD) happiness measures
Early Schizophrenia vs. Healthy Controls
Agid 2012 (Canada)^54	ES: First episode (31) C: Age and sex-matched controls (29)	Satisfaction with Life Scale^a (5–35): ES: 24.3 (7.40) HC: 22.76 (4.81) (p=.349)	Subjective Happiness Scale^b (1–7): ES: 5.16 (1.01) HC: 4.80 (0.68) (p=.113) Single-Item Happiness Question^c (0–10): ES: 7.61 (1.67) HC: 7.21 (0.94) (p=.254) World Values Survey^d (1–4): ES: 3.23 (0.76) HC: 3.03 (0.42) (p=.238)
Agid 2015 (Canada)^63	ES: First episode (54) C: Age and sex-matched controls (55)	NR	Subjective Happiness Scale^b, score >4 (/7), n (%): ES: 25 (46) HC: 34 (62) (p=.09) Satisfaction With Life Scale, score >25 (/35), n (%): ES: 22 (41) HC: 31 (57) (p=.09)
Law 2005 (Hong Kong, China)^65	ES: First episode (117) C: Age-matched controls (117)	SF-36 (Chinese version): Physical function: ES 88.4 (14.1) HC 97.1 (6.0) (p<.001) Role-physical: ES: 46.2 (39.3) HC: 83.3 (29.9) (p<.001) Bodily pain: ES: 74.2 (26.7) HC: 85.6 (21.5) (p<.001) General health: ES: 52.2 (20.9) HC: 63.3 (20.5) (p<.001) Vitality: ES: 49.4 (19.7) HC: 59.5 (19.6) (p<.001) Social functioning: ES: 60.6 (30.0) HC: 87.1 (17.4) (p<.001) Role-emotional: ES: 37.6 (41.0) HC: 54.1 (42.9) (p=.003) Mental health: ES: 48.8 (22.1) HC: 70.5 (18.8) (p<.001)	NR
Early vs. Chronic Schizophrenia
Kim 2015 (Korea)^39	ES: Duration of illness ≤5 years (25) C: Duration of illness >5 years (30)	Schizophrenia Quality of Life Scale: ES: 42.52 (16.26) CS: 39.17 (20.36) (p=.509)	NR
Makanjuola 2007 (Nigeria)^52	ES: Onset of illness (100) C: Illness duration >2 years (100)	WHOQOL-BREF on subjective quality of life, overall quality of life and general health, n (%): ES: Good, 19 (19); Poor, 81 (81) CS: Good, 7 (7); Poor, 93 (93) (p=.02)	NR
Early Schizophrenia vs. Other Psychiatric Disorders
Al-Bataineh 2016 (Europe)^64	ES: First episode (242) C: First-episode schizophreniform disorder (182) C: First-episode schizoaffective disorder (31)	Manchester Short Assessment of Quality of Life: • Patients with schizophrenia performed significantly worse at 12 months for quality of life compared with schizophreniform disorder (U = 10,176, p=.014) and schizoaffective patients (U = 1669, p=.036)	NR
Owoeye 2013 (Ireland)^19	ES: First episode (45) C: First-episode major depressive disorder (28) C: First-episode bipolar disorder (37)	Quality of Life Scale^e (6–112): ES: 65.5 (20.6) MDD: 76.1 (28.0) (p=ns) Bipolar disorder: 100.3 (22.3) (p<.001)	NR
Rowland 2019 (UK)^27	ES: First episode (227) C: First-episode delusional disorder (36)	EQ-5D health thermometer, baseline: ES: 61.63 (22.36) Delusional disorder: 60.00 (24.11) (p=.689)	NR
Sim 2007 (Singapore)^53	ES: First episode (254) C: First-episode schizoaffective disorder (24)	WHOQOL-BREF: Overall quality of life: ES 3.26 (1.03) Schizoaffective disorder: 3.25 (1.29) (p=.78)	NR

Abbreviations. C, comparator; CS, chronic schizophrenia; EQ-5D, EuroQol 5-dimensions; ES, early schizophrenia; HC, healthy control; MDD, major depressive disorder; NR, not reported; ns, not significant; SD, standard deviation; SF-36, 36-item short form survey; WHOQOL, World Health Organization Quality of Life.

^a Self-report questionnaire to assess satisfaction with life with a minimum score of 5 (dissatisfied) and a maximum score of 35 (satisfied)⁷⁶.

^b Scale runs from 1 (not happy) to 7 (most happy), averaged over four items⁷⁷.

^c Scale of 0 (not happy) to 10 (most happy)⁵⁴.

^d Scale from 1 (most happy) to 4 (not happy)⁵⁴.

^e Scale ranging from 6–112⁷⁸.

Dubois V, Peuskens J, Geerts P, et al. Clinical outcomes of long-acting risperidone in recent versus long-term diagnosed Belgian schizophrenic patients: results from electronic Schizophrenia Treatment Adherence Registry (e-STAR) and Trial for the Initiation and Maintenance Of REmission in Schizophrenia with risperidone (TIMORES). Early Intervent Psychiatry. 2014;8(1):39–49.

 PubMed Web of Science ®Google Scholar

García-Álvarez L, Garcia-Portilla MP, Caso JR, et al. Early versus late stage schizophrenia. What markers make the difference? World J Biol Psychiatry. 2019;20(2):159–165.

 Google Scholar

Kim SJ, Shim JC, Kong BG, et al. Differences in cognitive function and daily living skills between early- and late-stage schizophrenia. Int J Psychiatry Clin Pract. 2015;19(4):245–251.

 PubMed Web of Science ®Google Scholar

Leung JS, Lee TM, Lee CC. Facial emotion recognition in Chinese with schizophrenia at early and chronic stages of illness. Psychiatry Res. 2011;190(2–3):172–176.

 PubMed Web of Science ®Google Scholar

Matsuda Y, Sato S, Hatsuse N, et al. Neurocognitive functioning in patients with first-episode schizophrenia 1 year from onset in comparison with patients 5 years from onset. Int J Psychiatry Clin Pract. 2014;18(1):63–69.

 PubMed Web of Science ®Google Scholar

Mwansisya TE, Yi W, Wang Z, et al. Comparison of psychosocial determinants in inpatients with first-episode and chronic schizophrenia in China. Arch Psychiatr Nurs. 2013;27(1):32–41.

 PubMed Web of Science ®Google Scholar

Pawelczyk T, Szymanska B, Grancow-Grabka M, et al. Telomere length in blood cells is related to the chronicity, severity, and recurrence rate of schizophrenia. Neuropsychiatr Dis Treat. 2015;11:1493–1503.

 PubMed Web of Science ®Google Scholar

Chang CW, Lau ES, Hui LM, et al. Three-year outcome comparison between patients presenting with first-episode psychotic mania and schizophrenia to easy program in Hong Kong. Schizophr Res. 2014;153:S304-S305.

 Google Scholar

Chang WC, Lau ESK, Chiu SS, et al. Three-year clinical and functional outcome comparison between first-episode mania with psychotic features and first-episode schizophrenia. J Affect Disord. 2016;200:1–5

 PubMed Web of Science ®Google Scholar

Corker EA, Beldie A, Brain C, et al. Experience of stigma and discrimination reported by people experiencing the first episode of schizophrenia and those with a first episode of depression: the FEDORA project. Int J Soc Psychiatry. 2015;61(5):438–445.

 PubMed Web of Science ®Google Scholar

Cotton SM, Lambert M, Schimmelmann BG, et al. Differences between first episode schizophrenia and schizoaffective disorder. Schizophr Res. 2013;147(1):169–174.

 PubMed Web of Science ®Google Scholar

Crebbin K, Mitford E, Paxton R, et al. First-episode psychosis: An epidemiological survey comparing psychotic depression with schizophrenia. J Affect Disorders. 2008;105(1–3):117–124.

 PubMed Web of Science ®Google Scholar

Crebbin K, Mitford E, Paxton R, et al. First-episode drug-induced psychosis: a medium term follow up study reveals a high-risk group. Soc Psychiatry Psychiatr Epidemiol. 2009;44(9):710–715.

 PubMed Web of Science ®Google Scholar

Hui CL, Lee EH, Chang WC, et al. Delusional disorder and schizophrenia: a comparison of the neurocognitive and clinical characteristics in first-episode patients. Psychol Med. 2015;45(14):3085–3095.

 PubMed Web of Science ®Google Scholar

Laursen MF, Licht R, Valentin JB, et al. Prognosis of early-onset bipolar disorder compared to early-onset schizophrenia and healthy controls in a nationwide register based study. Early Intervent Psychiatry. 2018;12(Supplement 1):152.

 Google Scholar

Agid O, McDonald K, Siu C, et al. Happiness in first-episode schizophrenia. Schizophr Res. 2012;141(1):98–103.

 PubMed Web of Science ®Google Scholar

Agid O, Siu C, Harvey PD, et al. Treatment outcomes, insight and recovery in first-episode schizophrenia. Schizophr Res. 2014;153:S165–S166.

 Web of Science ®Google Scholar

Ballon JS, Kaur T, Marks II, et al. Social functioning in young people at risk for schizophrenia. Psychiatry Res. 2007;151(1–2):29–35.

 PubMed Web of Science ®Google Scholar

Jaracz K, Górna K, Rybakowski F. Social functioning in first-episode schizophrenia. A prospective follow-up study. Arch Psychiatry Psychotherapy. 2007;4:19–27.

 Google Scholar

Bougie JK, Malla A, Miguelez M, et al. Real life assessment of abilify maintena (reliam): interim analysis from a Canadian naturalistic study of aripiprazole long-acting injectable in patients with schizophrenia. Value Health. 2017;20(5):A293.

 Google Scholar

Higuchi Y, Sumiyoshi T, Seo T, et al. Associations between daily living skills, cognition, and real-world functioning across stages of schizophrenia; a study with the Schizophrenia Cognition Rating Scale Japanese version. Schizophr Res Cogn. 2017;7:13–18.

 PubMedGoogle Scholar

Lee EH, Hui CL, Chang WC, et al. Letter to the editor: comparison of cognitive functions, pre-morbid conditions and clinical characteristics between brief psychotic disorder and schizophrenia. Psychol Med. 2016;46(9):2011–2013.

 PubMed Web of Science ®Google Scholar

Ivarsson T, Broberg AG, Arvidsson T, et al. Bullying in adolescence: psychiatric problems in victims and bullies as measured by the Youth Self Report (YSR) and the Depression Self-Rating Scale (DSRS). Nord J Psychiatry. 2005;59(5):365–373.

 PubMed Web of Science ®Google Scholar

Birchwood M, Smith J, Cochrane R, et al. The social functioning scale the development and validation of a new scale of social adjustment for use in family intervention programmes with schizophrenic patients. Br J Psychiatry. 1990;157(6):853–859.

 PubMed Web of Science ®Google Scholar

Agid O, McDonald K, Fervaha G, et al. Values in first-episode schizophrenia. Can J Psychiatry. 2015;60(11):507–514.

 PubMed Web of Science ®Google Scholar

Law CW, Chen EY, Cheung EF, et al. Impact of untreated psychosis on quality of life in patients with first-episode schizophrenia. Qual Life Res. 2005;14(8):1803–1811.

 PubMed Web of Science ®Google Scholar

Bamiso Makanjuola A, Ademola Adeponle B, Ayodele Obembe O. A comparison of quality-of-life in schizophrenia and affective disorder patients in a Nigerian tertiary hospital. Transcult Psychiatry. 2007;44(1):65–78.

 PubMedGoogle Scholar

Al-Bataineh R, Crasan A, Purnichi T, et al. Is diagnosis indeed prognosis? 12 months outcome for schizophrenia, schizophreniform and schizoaffective disorder. Eur Neuropsychopharmacol. 2016;26(Suppl. 1):S49–S50.

 Web of Science ®Google Scholar

Owoeye O, Kingston T, Scully PJ, et al. Epidemiological and clinical characterization following a first psychotic episode in major depressive disorder: comparisons with schizophrenia and bipolar I disorder in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). Schizophr Bull. 2013;39(4):756–765.

 PubMed Web of Science ®Google Scholar

Rowland T, Birchwood M, Singh S, et al. Short-term outcome of first episode delusional disorder in an early intervention population. Schizophr Res. 2019;204:272–303.

 Web of Science ®Google Scholar

Sim K, Chan YH, Chong SA, et al. A 24-month prospective outcome study of first-episode schizophrenia and schizoaffective disorder within an early psychosis intervention program. J Clin Psychiatry. 2007;68(9):1368–1376.

 PubMed Web of Science ®Google Scholar

Diener E, Emmons RA, Larsen RJ, et al. The satisfaction with life scale. J Pers Assess. 1985;49(1):71–75.

 PubMed Web of Science ®Google Scholar

Lyubomirsky S, Lepper HS. A measure of subjective happiness: preliminary reliability and construct validation. Social Indicators Res. 1999;46(2):137–155.

 Web of Science ®Google Scholar

Burckhardt CS, Anderson KL. The Quality of Life Scale (QOLS): reliability, validity, and utilization. Health Qual Life Outcomes. 2003;1(1):60.

 PubMedGoogle Scholar