INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.

1st Department of Psychiatry Faculty of Medicine School of Health Sciences Aristotle University of Thessaloniki Greece

2nd Department of Psychiatry National and Kapodistrian University of Athens Athens Greece

3rd Department of Psychiatry Faculty of Medicine School of Health Sciences Aristotle University of Thessaloniki Greece

Clinic of Psychiatric Faculty of Medicine Vilnius University Vilnius Lithuania

Clinical Department of Neurology Clinical Centre of Montenegro Dzona Dzeksona bb Podgorica Montenegro

Clinical Department of Psychiatry Clinical Centre of Montenegro Podgorica Montenegro

Deakin University IMPACT Strategic Research Centre School of Medicine Barwon Health Geelong Australia

Deakin University School of Medicine IMPACT Strategic Research Centre Barwon Health Geelong Australia

Department of Adult Psychiatry Poznan University of Medical Sciences Poznan Poland

Department of Medical and Health Sciences Faculty of Health Sciences Linköping University Linköping Sweden

Department of Neurosciences Mental Health and Sensory Organs Suicide Prevention Center Sant'Andrea Hospital Sapienza University of Rome Rome Italy

Department of Psychiatry and Mental Health Santa Maria University Hospital Lisbon Portugal

Department of Psychiatry and Mental Health University of Cape Town Cape Town Western Cape South Africa

Department of Psychiatry and Narcology Riga Stradins University Riga Latvia

Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria

Department of Psychiatry and Psychotherapy Semmelweis University Budapest Hungary

Department of Psychiatry College of Medicine University of Ibadan Nigeria

Department of Psychiatry Lokmanya Tilak Municipal Medical College Mumbai India

Department of Psychiatry National and Kapodistrian University of Athens School of Medicine Eginition Hospital Athens Greece

Department of Psychiatry Queen's University Providence Care Hospital Kingston Ontario Canada

Department of Psychiatry Royal College of Surgeons in Ireland Beaumont Hospital Dublin Ireland

Department of Psychiatry Ruhr University Bochum LWL University Hospital Bochum Germany

Department of Psychiatry Sainte Marguerite University Hospital Marseille France

Department of Psychiatry School of Medicine University of Montenegro Dzona Dzeksona bb Podgorica Montenegro

Department of Psychiatry University of Florida *** FL

Department of Psychiatry University of Oviedo and Centro de Investigación Biomédica en Red de Salud Mental Oviedo Spain

Department of Psychiatry University of Turku Turku Finland

Hallunda Psychiatric Outpatient Clinic Stockholm Psychiatric Southwest Clinic Karolinska Huddinge University Hospital Sweden

Institute of Mental Health Belgrade Serbia

Institute of Mental Health School of Medicine University of Belgrade Belgrade Serbia

Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland Dublin Ireland

MRC Unit on Risk and Resilience in Mental Disorders Department of Psychiatry and Mental Health University of Cape Town Cape Town South Africa

National Institute of Mental Health Klecany Czech Republic

Nyírő Gyula Hospital Budapest Hungary

Orygen The National Centre of Excellence in Youth Mental Health and the Centre for Youth Mental Health the Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry University of Melbourne Parkville Australia

Psychiatry Department Diskapi Yildirim Beyazit Training and Research Hospital Ankara Turkey

Psychosocial Rehabilitation Department of the Vilnius Mental Health Center Department for Psychosis Treatment of the Vilnius Mental Health Center Vilnius Lithuania

Samara State Medical University Department of Psychiatry Samara Psychiatric Hospital Inpatient Unit Russia

Serbian Academy of Sciences and Arts Belgrade Serbia

Timone Institute of Neuroscience CNRS and Aix Marseille University Marseille France

University Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum Sofia Bulgaria

University of Medicine and Pharmacy of Târgu Mures Romania

University of Medicine and Pharmacy of Timisoara Romania

University Psychiatric Centre KU Leuven Kortenberg and Department of Neurosciences KU Leuven Belgium

Western University London Ontario Canada

Zobrazit více v PubMed

Abrams R, Taylor MA, Gaztanaga P (1974) Manic-depressive illness and paranoid schizophrenia. A phenomenologic, family history, and treatment-response study. Arch Gen Psychiatry 31:640–642. PubMed

Agius M, Goh C, Ulhaq S, McGorry P (2010) The staging model in schizophrenia, and its clinical implications. Psychiatr Danub 22:211–220. PubMed

Albert N, Melau M, Jensen H, Hastrup LH, Hjorthøj C, Nordentoft M (2017) The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders. NPJ Schizophr 3:34. PubMed PMC

Andreasen NC, Liu D, Ziebell S, Vora A, Ho BC (2013) Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am J Psychiatry 170:609–615. PubMed PMC

Angst J. (2002) Historical aspects of the dichotomy between manic-depressive disorders and schizophrenia. Schizophr Res 57:5–13. PubMed

APA (2000) Diagnostic and statistical manual of mental disorders: fourth edition text revision DSM-IV-TR. Washington, DC: American Psychiatric Association.

APA (2013) Diagnostic and statistical manual of mental disorders: DSM-5. Washington, DC: American Psychiatric Association.

Astrup C, Noreik K (1966) Functional psychoses: diagnostic and prognostic models. Springfield, IL: Charles C Thomas.

Barnes TR, Leeson VC, Mutsatsa SH, Watt HC, Hutton SB, Joyce EM (2008) Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia. Br J Psychiatry 193:203–209. PubMed PMC

Berrios GE, Beer D (1994) The notion of a unitary psychosis: a conceptual history. Hist Psychiatry 5:13–36. PubMed

Bora E, Murray RM (2014) Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis? Schizophr Bull 40:744–755. PubMed PMC

Bora E, Yalincetin B, Akdede BB, Alptekin K (2018) Duration of untreated psychosis and neurocognition in first-episode psychosis: a meta-analysis. Schizophr Res 193:3–10. PubMed

Breitborde NJ, Srihari VH, Woods SW (2009) Review of the operational definition for first-episode psychosis. Early Interv Psychiatry 3:259–265. PubMed PMC

Buckley PF, Miller BJ, Lehrer DS, Castle DJ (2009) Psychiatric comorbidities and schizophrenia. Schizophr Bull 35:383–402. PubMed PMC

Bunk D, Eggers C, Klapal M (1999) Symptom dimensions in the course of childhood-onset schizophrenia. Eur Child Adolesc Psychiatry 1(8 Suppl):I29–I35. PubMed

Citrome L, Meng X, Hochfeld M (2011) Efficacy of iloperidone in schizophrenia: a PANSS five-factor analysis. Schizophr Res 131:75–81. PubMed

Compton MT. (2004) Duration of untreated psychosis significantly associated with positive symptoms one year after treatment. Evid Based Ment Health 7:101. PubMed

Conley RR, Ascher-Svanum H, Zhu B, Faries DE, Kinon BJ (2007) The burden of depressive symptoms in the long-term treatment of patients with schizophrenia. Schizophr Res 90:186–197. PubMed PMC

Croughan JL, Robins E (1974) The group of schizoaffective and related psychoses–critique, record, follow-up and family studies. II. Record studies. Arch Gen Psychiatry 31:632–637. PubMed

Cuesta MJ, Peralta V (2011) Testing the hypothesis that formal thought disorders are severe mood disorders. Schizophr Bull 37:1136–1146. PubMed PMC

Cuesta MJ, García de Jalón E, Campos MS, Ibáñez B, Sánchez-Torres AM, Peralta V (2012) Duration of untreated negative and positive symptoms of psychosis and cognitive impairment in first episode psychosis. Schizophr Res 141:222–227. PubMed

Demjaha A, Lappin JM, Stahl D, Patel MX, MacCabe JH, Howes OD, Heslin M, Reininghaus UA, Donoghue K, Lomas B, Charalambides M, Onyejiaka A, Fearon P, Jones P, Doody G, Morgan C, Dazzan P, Murray RM (2017) Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors. Psychol Med 47:1981–1989. PubMed

Dixon L, Green-Paden L, Delahanty J, Lucksted A, Postrado L, Hall J (2001) Variables associated with disparities in treatment of patients with schizophrenia and comorbid mood and anxiety disorders. Psychiatr Serv 52:1216–1222. PubMed

Dollfus S, Petit M (1995) Stability of positive and negative symptoms in schizophrenic patients: a 3-year follow-up study. Eur Psychiatry 10:228–236. PubMed

Doran AR, Breier A, Roy A (1986) Differential diagnosis and diagnostic systems in schizophrenia. Psychiatr Clin North Am 9:17–33. PubMed

Dragioti E, Wiklund T, Siamouli M, Moutou K, Fountoulakis KN (2017) Could PANSS be a useful tool in the determining of the stages of schizophrenia? A clinically operational approach. J Psychiatr Res 86:66–72. PubMed

Dziuban CD, Shirkey EC (1974) When is a correlation matrix appropriate for factor analysis? Some decision rules. Psychol Bull 81:358–361.

Emmerson LC, Ben-Zeev D, Granholm E, Tiffany M, Golshan S, Jeste DV (2009) Prevalence and longitudinal stability of negative symptoms in healthy participants. Int J Geriatr Psychiatry 24:1438–1444. PubMed

Emsley R, Rabinowitz J, Torreman M; RIS-INT-35 Early Psychosis Global Working Group (2003) The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis. Schizophr Res 61:47–57. PubMed

Emsley R, Rabinowitz J, Medori R; Early Psychosis Global Working Group (2007) Remission in early psychosis: rates, predictors, and clinical and functional outcome correlates. Schizophr Res 89:129–139. PubMed

Escamilla MA. (2001) Diagnosis and treatment of mood disorders that co-occur with schizophrenia. Psychiatr Serv 52:911–919. PubMed

Farde L, Wiesel FA, Stone-Elander S, Halldin C, Nordström AL, Hall H, Sedvall G (1990) D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry 47:213–219. PubMed

Fava GA, Kellner R (1993) Staging: a neglected dimension in psychiatric classification. Acta Psychiatr Scand 87:225–230. PubMed

Fong TC, Ho RT, Wan AH, Siu PJ, Au-Yeung FS (2015) Psychometric validation of the consensus five-factor model of the Positive and Negative Syndrome Scale. Compr Psychiatry 62:204–208. PubMed

Fountoulakis KN. (2017) Therapeutic effect of sertindole on neurocognitive deficit independently of positive and negative symptoms response: a case report. Psychiatry Res 258:618–620. PubMed

Fountoulakis KN, Panagiotidis P, Kimiskidis V, Nimatoudis I, Gonda X (2018a) Prevalence and correlates of neurological soft signs in healthy controls without family history of any mental disorder: a neurodevelopmental variation rather than a specific risk factor? Int J Dev Neurosci 68:59–65. PubMed

Fountoulakis KN, Panagiotidis P, Gonda X, Kimiskidis V, Nimatoudis I (2018b) Neurological soft signs significantly differentiate schizophrenia patients from healthy controls. Acta Neuropsychiatr 30:97–105. PubMed

Fountoulakis KN, Popovic D, Mosheva M, Siamouli M, Moutou K, Gonda X (2017a) Mood symptoms in stabilized patients with schizophrenia: a bipolar type with predominant psychotic features? Psychiatr Danub 29:148–154. PubMed

Fountoulakis KN, Gonda X, Siamouli M, Moutou K, Nitsa Z, Leonard BE, Kasper S (2017b) Higher than recommended dosages of antipsychotics in male patients with schizophrenia are associated with increased depression but no major neurocognitive side effects: results of a cross-sectional pilot naturalistic study. Prog Neuropsychopharmacol Biol Psychiatry 75:113–119. PubMed

Fountoulakis KN, Gonda X, Siamouli M, Panagiotidis P, Moutou K, Nimatoudis I, Kasper S (2018c) Paternal and maternal age as risk factors for schizophrenia: a case-control study. Int J Psychiatry Clin Pract 22:170–176. PubMed

Fresán A, De la Fuente-Sandoval C, Loyzaga C, García-Anaya M, Meyenberg N, Nicolini H, Apiquian R (2005) A forced five-dimensional factor analysis and concurrent validity of the Positive and Negative Syndrome Scale in Mexican schizophrenic patients. Schizophr Res 72:123–129. PubMed

Galderisi S, Mucci A, Bitter I, Libiger J, Bucci P, Fleischhacker WW, Kahn RS; Eufest Study Group (2013) Persistent negative symptoms in first episode patients with schizophrenia: results from the European First Episode Schizophrenia Trial. Eur Neuropsychopharmacol 23:196–204. PubMed

Gard DE, Kring AM, Gard MG, Horan WP, Green MF (2007) Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure. Schizophr Res 93:253–260. PubMed PMC

Garriga M, et al. (2016) Assessment and management of agitation in psychiatry: expert consensus. World J Biol Psychiatry 17:86–128. PubMed

Gift TE, Strauss JS, Kokes RF, Harder DW, Ritzler BA (1980) Schizophrenia: affect and outcome. Am J Psychiatry 137:580–585. PubMed

Harvey PD. (2011) Mood symptoms, cognition, and everyday functioning: in major depression, bipolar disorder, and schizophrenia. Innov Clin Neurosci 8:14–18. PubMed PMC

Hayashi N, Igarashi Y, Yamashina M, Suda K (2002) Is there a gender difference in a factorial structure of the positive and negative syndrome scale? A test by structural equation modeling. Psychopathology 35:28–35. PubMed

Helfer B, Samara MT, Huhn M, Klupp E, Leucht C, Zhu Y, Engel RR, Leucht S (2016) Efficacy and safety of antidepressants added to antipsychotics for schizophrenia: a systematic review and meta-analysis. Am J Psychiatry 173:876–886. PubMed

Hill M, Crumlish N, Clarke M, Whitty P, Owens E, Renwick L, Browne S, Macklin EA, Kinsella A, Larkin C, Waddington JL, O’Callaghan E (2012) Prospective relationship of duration of untreated psychosis to psychopathology and functional outcome over 12 years. Schizophr Res 141:215–221. PubMed

Ho BC, Alicata D, Ward J, Moser DJ, O’Leary DS, Arndt S, Andreasen NC (2003) Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia. Am J Psychiatry 160:142–148. PubMed

Holmboe R, Noreik K, Astrup C (1968) Follow-up of functional psychoses at two Norwegian mental hospitals. Acta Psychiatr Scand 44:298–310. PubMed

Hwu HG, Chen CH, Hwang TJ, Liu CM, Cheng JJ, Lin SK, Liu SK, Chen CH, Chi YY, Ou-Young CW, Lin HN, Chen WJ (2002) Symptom patterns and subgrouping of schizophrenic patients: significance of negative symptoms assessed on admission. Schizophr Res 56:105–119. PubMed

Kant O. (1940) Types and analyses of the clinical pictures of recovered schizophrenics. Psychiat Q 14:676–700.

Kasanin J. (1933) The acute schizoaffective psychoses. Am J Psychiatry 13:97–126. PubMed

Kasanin J.[1933] (1994) The acute schizoaffective psychoses. Am J Psychiatry 151:144–154. PubMed

Kay SR. (1990) Positive-negative symptom assessment in schizophrenia: psychometric issues and scale comparison. Psychiatr Q 61:163–178. PubMed

Kay SR, Sevy S (1990) Pyramidical model of schizophrenia. Schizophr Bull 16:537–545. PubMed

Kay SR, Sandyk R (1991) Experimental models of schizophrenia. Int J Neurosci 58:69–82. PubMed

Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276. PubMed

Kay SR, Opler LA, Lindenmayer JP (1988) Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res 23:99–110. PubMed

Kelley ME, White L, Compton MT, Harvey PD (2013) Subscale structure for the Positive and Negative Syndrome Scale (PANSS): a proposed solution focused on clinical validity. Psychiatry Res 205:137–142. PubMed PMC

Keshavan MS, Schooler NR (1992) First-episode studies in schizophrenia: criteria and characterization. Schizophr Bull 18:491–513. PubMed

Keshavan MS, Tandon R, Boutros NN, Nasrallah HA (2008) Schizophrenia, “just the facts”: what we know in 2008 Part 3: neurobiology. Schizophr Res 106:89–107. PubMed

Khan A, Lindenmayer JP, Opler M, Yavorsky C, Rothman B, Lucic L (2013a) A new Integrated Negative Symptom structure of the Positive and Negative Syndrome Scale (PANSS) in schizophrenia using item response analysis. Schizophr Res 150:185–196. PubMed

Khan A, Yavorsky C, Liechti S, Opler M, Rothman B, DiClemente G, Lucic L, Jovic S, Inada T, Yang L (2013b) A rasch model to test the cross-cultural validity in the positive and negative syndrome scale (PANSS) across six geo-cultural groups. BMC Psychol 1:5. PubMed PMC

Kitamura T, Okazaki Y, Fujinawa A, Yoshino M, Kasahara Y (1995) Symptoms of psychoses. A factor-analytic study. Br J Psychiatry 166:236–240. PubMed

Kurtz MM. (2005) Neurocognitive impairment across the lifespan in schizophrenia: an update. Schizophr Res 74:15–26. PubMed

Lake CR. (2008) Hypothesis: grandiosity and guilt cause paranoia; paranoid schizophrenia is a psychotic mood disorder; a review. Schizophr Bull 34:1151–1162. PubMed PMC

Lake CR, Hurwitz N (2006) Schizoaffective disorders are psychotic mood disorders; there are no schizoaffective disorders. Psychiatry Res 143:255–287. PubMed

Lang FU, Kösters M, Lang S, Becker T, Jäger M (2013) Psychopathological long-term outcome of schizophrenia – a review. Acta Psychiatr Scand 127:173–182. PubMed

Langfeldt G. (1937) The prognosis of schizophrenia and the factors influencing the course of the disease. Acta Psychiatr Neurol Scand Suppl 13:1–128.

Leucht S, Kissling W, McGrath J (2004) Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry 65:177–186. PubMed

Leung A, Chue P (2000) Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand 101:3–38. PubMed

Liemburg E, Castelein S, Stewart R, van der Gaag M, Aleman A, Knegtering H; Genetic Risk and Outcome of Psychosis (GROUP) Investigators (2013) Two subdomains of negative symptoms in psychotic disorders: established and confirmed in two large cohorts. J Psychiatr Res 47:718–725. PubMed

Lin CY, Tsai GE, Lane HY (2014) Assessing and treating cognitive impairment in schizophrenia: current and future. Curr Pharm Des 20:5127–5138. PubMed

Lincoln C, Harrigan S, McGorry PD (1998) Understanding the topography of the early psychosis pathways. An opportunity to reduce delays in treatment. Br J Psychiatry Suppl 172:21–25. PubMed

Lindenmayer JP, Kay SR, Friedman C (1986) Negative and positive schizophrenic syndromes after the acute phase: a prospective follow-up. Compr Psychiatry 27:276–286. PubMed

Llorca PM, Blanc O, Samalin L, Bosia M, Cavallaro R; EGOFORS Initiative (2012) Factors involved in the level of functioning of patients with schizophrenia according to latent variable modeling. Eur Psychiatry 27:396–400. PubMed

Lorr M, McNair DM, Klett CJ, Lasky JJ (1962) Evidence of ten psychotic syndromes. J Consult Psychol 26:185–189. PubMed

Lykouras L, Oulis P, Psarros K, Daskalopoulou E, Botsis A, Christodoulou GN, Stefanis C (2000) Five-factor model of schizophrenic psychopathology: how valid is it? Eur Arch Psychiatry Clin Neurosci 250:93–100. PubMed

Maat A, van Montfort SJ, de Nijs J, Derks EM, Kahn RS, Linszen DH, van Os J, Wiersma D, Bruggeman R, Cahn W, de Haan L, Krabbendam L, Myin-Germeys I; GROUP Investigators (2015) Emotion processing in schizophrenia is state and trait dependent. Schizophr Res 161:392–398. PubMed

Maier W, Zobel A, Wagner M (2006) Schizophrenia and bipolar disorder: differences and overlaps. Curr Opin Psychiatry 19:165–170. PubMed

Marder SR, Davis JM, Chouinard G (1997) The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J Clin Psychiatry 58:538–546. PubMed

Marneros A. (1983) Kurt Schneider’s ‘Zwischen-Fälle’, ‘mid-cases’ or ‘cases in between’. Psychiatr Clin (Basel) 16:87–102. PubMed

Marneros A. (2003) The schizoaffective phenomenon: the state of the art. Acta Psychiatr Neurol Scand Suppl 29–33. PubMed

McGlashan TH. (2006) Is active psychosis neurotoxic? Schizophr Bull 32:609–613. PubMed PMC

McGorry PD, Bell RC, Dudgeon PL, Jackson HJ (1998) The dimensional structure of first episode psychosis: an exploratory factor analysis. Psychol Med 28:935–947. PubMed

McGorry PD, Nelson B, Goldstone S, Yung AR (2010) Clinical staging: a heuristic and practical strategy for new research and better health and social outcomes for psychotic and related mood disorders. Can J Psychiatry 55:486–497. PubMed

Melle I, Larsen TK, Haahr U, Friis S, Johannesen JO, Opjordsmoen S, Rund BR, Simonsen E, Vaglum P, McGlashan T (2008) Prevention of negative symptom psychopathologies in first-episode schizophrenia: two-year effects of reducing the duration of untreated psychosis. Arch Gen Psychiatry 65:634–640. PubMed

Mojtabai R. (1999) Duration of illness and structure of symptoms in schizophrenia. Psychol Med 29:915–924. PubMed

Möller HJ. (2008) Systematic of psychiatric disorders between categorical and dimensional approaches: Kraepelin’s dichotomy and beyond. Eur Arch Psychiatry Clin Neurosci 258(Suppl 2):48–73. PubMed

Möller HJ, Werner-Eilert K, Wüschner-Stockheim M, von Zerssen D (1982) [Relevant predictors of the 5 year outcome of patients with schizophrenic or similar paranoid psychoses (author’s transl)]. Arch Psychiatr Nervenkr (1970) 231:305–322. PubMed

Monteiro LC, Silva VA, Louzã MR (2008) Insight, cognitive dysfunction and symptomatology in schizophrenia. Eur Arch Psychiatry Clin Neurosci 258:402–405. PubMed

Müller MJ, Wetzel H, Szegedi A, Benkert O (1999) Three dimensions of depression in patients with acute psychotic disorders: a replication study. Compr Psychiatry 40:449–457. PubMed

Murray RM, Sham P, Van Os J, Zanelli J, Cannon M, McDonald C (2004) A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder. Schizophr Res 71:405–416. PubMed

Nakaya M, Suwa H, Ohmori K (1999a) Latent structures underlying schizophrenic symptoms: a five-dimensional model. Schizophr Res 39:39–50. PubMed

Nakaya M, Suwa H, Komahashi T, Ohmori K (1999b) Is schizophrenic symptomatology independent of the phase of the illness? Psychopathology 32:23–29. PubMed

Noreik K, Astrup C, Dalgard OS, Holmboe R (1967) A prolonged follow-up of acute schizophrenic and schizophreniform psychoses. Acta Psychiatr Scand 43:432–443. PubMed

Norman RM, Lewis SW, Marshall M (2005) Duration of untreated psychosis and its relationship to clinical outcome. Br J Psychiatry Suppl 48:s19–s23. PubMed

Oorschot M, Lataster T, Thewissen V, Lardinois M, Wichers M, van Os J, Delespaul P, Myin-Germeys I (2013) Emotional experience in negative symptoms of schizophrenia–no evidence for a generalized hedonic deficit. Schizophr Bull 39:217–225. PubMed PMC

Pandurangi AK, Sax KW, Pelonero AL, Goldberg SC (1994) Sustained attention and positive formal thought disorder in schizophrenia. Schizophr Res 13:109–116. PubMed

Penttilä M, Jääskeläinen E, Hirvonen N, Isohanni M, Miettunen J (2014) Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis. Br J Psychiatry 205:88–94. PubMed

Peralta V, Cuesta MJ (1994) Psychometric properties of the positive and negative syndrome scale (PANSS) in schizophrenia. Psychiatry Res 53:31–40. PubMed

Peralta V, Cuesta MJ (1995) Negative symptoms in schizophrenia: a confirmatory factor analysis of competing models. Am J Psychiatry 152:1450–1457. PubMed

Peralta V, Cuesta MJ (1999) Dimensional structure of psychotic symptoms: an item-level analysis of SAPS and SANS symptoms in psychotic disorders. Schizophr Res 38:13–26. PubMed

Peralta V, Cuesta MJ (2000) Duration of illness and structure of symptoms in schizophrenia. Psychol Med 30:481–483. PubMed

Peralta V, Cuesta MJ (2001) How many and which are the psychopathological dimensions in schizophrenia? Issues influencing their ascertainment. Schizophr Res 49:269–285. PubMed

Perkins DO, Gu H, Boteva K, Lieberman JA (2005) Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry 162:1785–1804. PubMed

Pope HG Jr, Lipinski JF Jr (1978) Diagnosis in schizophrenia and manic-depressive illness: a reassessment of the specificity of ‘schizophrenic’ symptoms in the light of current research. Arch Gen Psychiatry 35:811–828. PubMed

Primavera D, Bandecchi C, Lepori T, Sanna L, Nicotra E, Carpiniello B (2012) Does duration of untreated psychosis predict very long term outcome of schizophrenic disorders? Results of a retrospective study. Ann Gen Psychiatry 11:21. PubMed PMC

Qin H, Zhang J, Wang Z, Min H, Yan C, Chen F, Fu W, Zhang M (2014) Duration of untreated psychosis and clinical outcomes of first-episode schizophrenia: a 4-year follow-up study. Shanghai Arch Psychiatry 26:42–48. PubMed PMC

Rummel C, Kissling W, Leucht S (2005) Antidepressants as add-on treatment to antipsychotics for people with schizophrenia and pronounced negative symptoms: a systematic review of randomized trials. Schizophr Res 80:85–97. PubMed

Rummel C, Kissling W, Leucht S (2006) Antidepressants for the negative symptoms of schizophrenia. Cochrane Database Syst Rev CD005581. PubMed PMC

Rund BR. (2014) Does active psychosis cause neurobiological pathology? A critical review of the neurotoxicity hypothesis. Psychol Med 44:1577–1590. PubMed

Salokangas RK. (1997) Structure of schizophrenic symptomatology and its changes over time: prospective factor-analytical study. Acta Psychiatr Scand 95:32–39. PubMed

Schneider K. (1973) Klinische psychopathologie. 10th ed. Stuttgart, Germany: Thieme.

Specht G. (1905) Chronic mania and paranoia. Zbl Nervenheilk 590.

Stochl J, Jones PB, Plaistow J, Reininghaus U, Priebe S, Perez J, Croudace TJ (2014) Multilevel ordinal factor analysis of the positive and negative syndrome scale (PANSS). Int J Methods Psychiatr Res 23:25–35. PubMed PMC

Strutz T. (2016) Data Fitting and Uncertainty (A practical introduction to weighted least squares and beyond): Springer Vieweg.

Sullivan SA, Carroll R, Peters TJ, Amos T, Jones PB, Marshall M, Birchwood M, Fowler D, Johnson S, Fisher HL, Major B, Rahaman N, Joyce J, Chamberlain-Kent N, Lawrence J, Moran P, Tilling K (2019) Duration of untreated psychosis and clinical outcomes of first episode psychosis: an observational and an instrumental variables analysis. Early Interv Psychiatry 13:841–847. PubMed

Targum SD. (1983) Neuroendocrine dysfunction in schizophreniform disorder: correlation with six-month clinical outcome. Am J Psychiatry 140:309–313. PubMed

Taylor M, Perera U (2015) NICE CG178 psychosis and schizophrenia in adults: treatment and management - an evidence-based guideline? Br J Psychiatry 206:357–359. PubMed

Taylor PJ. (1985) Motives for offending among violent and psychotic men. Br J Psychiatry 147:491–498. PubMed

Van den Oord EJ, Rujescu D, Robles JR, Giegling I, Birrell C, Bukszár J, Murrelle L, Möller HJ, Middleton L, Muglia P (2006) Factor structure and external validity of the PANSS revisited. Schizophr Res 82:213–223. PubMed

van der Gaag M, Cuijpers A, Hoffman T, Remijsen M, Hijman R, de Haan L, van Meijel B, van Harten PN, Valmaggia L, de Hert M, Wiersma D (2006) The five-factor model of the Positive and Negative Syndrome Scale I: confirmatory factor analysis fails to confirm 25 published five-factor solutions. Schizophr Res 85:273–279. PubMed

van Os J. (2009) ‘Salience syndrome’ replaces ‘schizophrenia’ in DSM-V and ICD-11: psychiatry’s evidence-based entry into the 21st century? Acta Psychiatr Scand 120:363–372. PubMed

Van Os J. (2010) Are psychiatric diagnoses of psychosis scientific and useful? The case of schizophrenia. J Mental Health 19:305–317. PubMed

van Os J. (2011) From schizophrenia metafacts to non-schizophrenia facts. Schizophr Res 127:16–17. PubMed

Van Os J, Gilvarry C, Bale R, Van Horn E, Tattan T, White I, Murray R (1999) A comparison of the utility of dimensional and categorical representations of psychosis. UK700 Group. Psychol Med 29:595–606. PubMed

van Os J, Kapur S (2009) Schizophrenia. Lancet 374:635–645. PubMed

van Os J, Linscott RJ (2012) Introduction: the extended psychosis phenotype–relationship with schizophrenia and with ultrahigh risk status for psychosis. Schizophr Bull 38:227–230. PubMed PMC

van Os J, Fahy TA, Jones P, Harvey I, Sham P, Lewis S, Bebbington P, Toone B, Williams M, Murray R (1996) Psychopathological syndromes in the functional psychoses: associations with course and outcome. Psychol Med 26:161–176. PubMed

Wallwork RS, Fortgang R, Hashimoto R, Weinberger DR, Dickinson D (2012) Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia. Schizophr Res 137:246–250. PubMed PMC

Walsh E, Buchanan A, Fahy T (2002) Violence and schizophrenia: examining the evidence. Br J Psychiatry 180:490–495. PubMed

Walsh-Messinger J, Antonius D, Opler M, Aujero N, Goetz DM, Goetz R, Malaspina D (2018) Factor structure of the Positive and Negative Syndrome Scale (PANSS) differs by sex. Clin Schizophr Relat Psychoses 11:207–213. PubMed

Welner A, Welner Z, Leonard MA (1977a) Bipolar manic-depressive disorder: a reassessment of course and outcome. Compr Psychiatry 18:327–332. PubMed

Welner A, Croughan J, Fishman R, Robins E (1977b) The group of schizoaffective and related psychoses: a follow-up study. Compr Psychiatry 18:413–422. PubMed

White L. (2005) Interpreting the PANSS: measures, factors and models. Schizophr Res 79:349–351. PubMed

White L, Harvey PD, Opler L, Lindenmayer JP (1997) Empirical assessment of the factorial structure of clinical symptoms in schizophrenia. A multisite, multimodel evaluation of the factorial structure of the Positive and Negative Syndrome Scale. The PANSS Study Group. Psychopathology 30:263–274. PubMed

Willem Van der Does AJ, Dingemans PM, Linszen DH, Nugter MA, Scholte WF (1995) Dimensions and subtypes of recent-onset schizophrenia. A longitudinal analysis. J Nerv Ment Dis 183:681–687. PubMed

Wójciak P, Remlinger-Molenda A, Rybakowski J (2016) Stages of the clinical course of schizophrenia - staging concept. Psychiatr Pol 50:717–730. PubMed

Wolthaus JE, Dingemans PM, Schene AH, Linszen DH, Knegtering H, Holthausen EA, Cahn W, Hijman R (2000) Component structure of the positive and negative syndrome scale (PANSS) in patients with recent-onset schizophrenia and spectrum disorders. Psychopharmacology (Berl) 150:399–403. PubMed

Wu BJ, Lan TH, Hu TM, Lee SM, Liou JY (2015) Validation of a five-factor model of a Chinese Mandarin version of the Positive and Negative Syndrome Scale (CMV-PANSS) in a sample of 813 schizophrenia patients. Schizophr Res 169:489–490. PubMed

Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ (2013) Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry 70:913–920. PubMed