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October2013 Vol.50 Issue:      4 Table of Contents
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Duration of Untreated Psychosis and Untreated Illness and Their Effect on Clinical Presentation in First Episode Psychosis

Nashaat Adel M. Abdel-Fadeel1, Larry J. Seidman2, Robert W. McCarley3, Mohamed Ayman Abd El-Hameed1, Raquelle Mesholam-Gately3, Joanne Wojcik3, Refaat Mahfouz1

Departments of Psychiatry1, Minia University, Egypt; Psychology2, Psychiatry3, Harvard University, USA


Background: A large sum of research and clinical interest has been given to the duration of untreated psychosis (DUP) and duration of untreated illness (DUI) regarding their implications in disease severity, type and persistence of symptoms, response to treatment and outcome. Objective: This study aimed to evaluate the effect of these two variables on the psychotic symptoms present in a sample of patients with first episode psychosis (n= 137).  Methods: The DUP and DUI were measured for each patient according to definitions. The premorbid functioning of patients of the study was assessed using the Premorbid Adjustment Scale (PAS) and their clinical state at interview was estimated using the Clinical Global Impression scale (CGI). Results: DUP was positively and significantly correlated only to unusual thought content and was negatively and significantly correlated to blunted affect. DUI was positively and significantly correlated only to conceptual disorganization and CGI of the patients. There were no significant correlations between either DUP or DUI and any of the adopted parameters of premorbid functioning in this study. Conclusion: Longer duration of untreated psychosis or duration of untreated illness is limitedly associated with worse clinical presentation of patients. In addition, worse premorbid functioning is not associated with longer DUP or DUI. [Egypt J Neurol Psychiat Neurosurg.  2013; 50(4): 369-375]

Key Words: Duration of untreated psychosis (DUP), Duration of untreated illness (DUI), Schizophrenia, First episode psychosis, Premorbid functioning

Correspondence to Mohamed Ayman Abd ElHameed, Minia Faculty of Medicine, EgyptTel.: +201118994499     Email:



Duration of untreated psychosis is defined as the time from the initial manifestations of the first psychotic symptom to initiation of adequate treatment.1 On the other hand, duration of untreated illness (DUI) is defined as the time from the initial manifestation of early psychiatric symptoms that can be nonspecific, such as anxiety, irritability and anger, poor concentration and reduced functioning, which precede the onset of attenuated (prodromal) or frank psychotic symptoms such as hallucinations and delusions.2

DUP has been shown to influence the clinical presentation in first-episode psychosis.3 Longer DUP is associated with higher general psychopathology scores at presentation, and poor clinical and social outcomes.4 However, the strength of association between DUP and outcome has been found to be only moderately strong.5

A longer DUP may be predicted by poor insight, social isolation and preserved coping skills.6 In addition, Morgan and colleagues in 2006, identified shorter DUP to be predicted by an acute mode of onset, employment prior to evaluation for the first episode (FE) of psychosis and the active involvement of at least one family member in seeking appropriate health care for the patient.7

Schizophrenia outcome has begun to be demonstrated to be more favorable than thought before.8 Most of the patients treated adequately are able to maintain a reasonable quality of life, remain free from stressing symptoms and can function at a moderate level.9,10 Reducing DUP has effects on negative symptom psychopathology and other baseline symptoms in FE schizophrenia.10-12 Early detection programs that allow patients to be involved in treatment earlier may improve outcome of schizophrenia.13,14


Aims of the Study

We aimed to study the duration of untreated psychosis and duration of untreated illness in a sample of patients with first episode psychosis and to study their association with the patients' clinical presentation. In addition, we aimed to study the relationship between the duration of untreated psychosis and duration of untreated illness on one hand and the premorbid adjustment of the sample patients on the other. 




Subjects of this study sample were 137 first episode psychosis patients. Data of these patients was collected from the assessment of first episode patients at the Commonwealth Research Center (CRC), Psychiatry Department, Harvard Medical School, USA.

Both male and female patients were included in the study provided that they were 13-36 years of age, with duration of current first psychotic illness more than one month and less than 5 years, in addition to being able to give written informed consent or the presence of a legal guardian who would agree to give an informed written consent.

Exclusion criteria of the study included past history of psychosis with recovery, non- English speaking, serious suicide risk and serious and unstable medical illness.

The Clinical Global Impression (CGI) scale15; a single rating of severity of illness coded on a 7-point scale (1 = normal, not at all ill to 7 = among the most extremely ill patients). The CGI is completed during the clinical rater's interview. The CGI severity is reliably correlated with the BPRS and the PANSS.16,17 The CGI has been shown to be a valid measure of clinical effectiveness and appropriate for clinical use.18

Duration of Untreated Psychosis (DUP) was measured in weeks based on the difference in dates between the onset of the first psychotic symptom and the first use of antipsychotic medication based on definitions of illness onset in the literature19,20.  

The Premorbid Adjustment Scale (PAS) was used for assessment of premorbid adjustment of the sample patients.21 The PAS comprises 36 items describing levels of functioning before the onset of psychosis. These items cover various domains of functioning over four periods in life (childhood, early adolescence, late adolescence and adulthood). The scoring range is 0-6, with 0 indicating the best level of functioning and 6 the worst.

Brief Psychiatric Rating Scale (BPRS)22 was used for the assessment of positive, negative and disorganized symptoms. Baseline assessment scores were obtained where positive symptoms are represented by hallucinations and unusual thought content; negative symptoms are represented by blunted affect, psychomotor retardation and emotional withdrawal. Disorganized symptoms are represented in BPRS by conceptual disorganization. Each individual BPRS item is scored from 1 to 7 where 1 is symptom not present and 7 is symptom extremely severe. 


Statistical Analysis

Frequencies and percentages were calculated for categorical variables, while means and standard deviations were calculated for continuous variables. Correlations were conducted to study the magnitude, nature and significance of the relationship between the different study variables. All statistical calculations were done using computer programs Microsoft Excel 2003 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 19 for Microsoft Windows.




The mean age of the patients of the study was 22.3±4.4 and most of the patients were males (82.5%) and single (94.2%) (Table 1).

The most prevalent psychotic diagnosis was schizophrenia (66.4%), followed by schizoaffective disorder (19%) and lastly schizophreniform disorder (14.6%) (Table 2).

The age of onset of psychosis for patients of this study was 21.0±4.2, DUP in weeks was 28.6±50.5 while DUI was 91.6±118.3. CGI severity at baseline was 3.9±1.1 (Table 3).  

A significant correlation was found between DUP and unusual thought content and blunted affect. Longer DUP was associated with more severe unusual thought content while shorter DUP was associated with more severe blunted affect. Regarding DUI, longer DUI was significantly correlated with more severe conceptual disorganization (Table 4).

The longer DUI was significantly correlated with more severity in overall symptom presentation as measured by CGI. Age, gender and DUP were not significantly correlated with CGI figures; table 5. No significant correlations were found between either DUP or DUI and premorbid adjustment scale parameters adopted in the current study (Table 6).

Table 1. Demographic characteristics of the patients of the study.


Demographic variables

First episode

Patients (n=137)

Age (years)



Gender: n (%)                   



113 (82.5%)

24 (17.5%)

Marital status: n (%)         





129 (94.2%)

5   (3.6%)

3   (2.2%)

Number of years of education




Table 2. Type of psychosis in first episode patients of the study.








Schizoaffective Disorder



Schizophreniform Disorder







Table 3. Some illness characteristics of the study patients.


Illness characteristics





Age at onset of psychosis (years)





Duration of prodrome (weeks)





Duration of illness (weeks)





DUP (weeks)





DUI  (weeks)





Number of psychiatric Hospitalization





CGI (severity at baseline)





CGI Clinical Global Impression, DUI Duration of Untreated Illness, DUP Duration of Untreated Psychosis, SD Standard Deviation


Table 4. Correlation between age, gender, DUP and DUI with symptoms in first episode psychosis as measured by the Brief Psychiatric Rating Scale (BPRS).


Symptoms of BPRS







Pearson C.










Unusual Thought Content

Pearson C.










Positive symptoms total

Pearson C.










Blunted affect


Pearson C.










Psychomotor retardation

Pearson C.










Emotional withdrawal

Pearson C.










Negative symptoms total

Pearson C.










Conceptual Disorganization

Pearson C.










C Correlation, DUI Duration of Untreated Illness, DUP Duration of Untreated Psychosis

p value significant if <0.05


Table 5. Correlation between age, gender, DUP and DUI with symptoms in first episode psychosis as measured by the Clinical Global Impression (CGI).







CGI                             Pearson C.










DUI Duration of Untreated Illness, DUP Duration of Untreated Psychosis

p value significant if <0.05


Table 6. Correlation between DUP, DUI and PAS study variables.


PAS study variables



Average Socialization

Pear. C.






Average School Functioning

Pear. C.






Average PAS total

Pear. C.






DUI Duration of Untreated Illness, DUP Duration of Untreated Psychosis





The mean age of patients was 22.3 years old; predominantly males (82.5%), and never married (94.2%). These characteristics are consistent with the results of a previous Egyptian FE study23 and with other FE studies.24

The most encountered diagnosis was schizophrenia (66.4%), followed by schizoaffective disorder (19%) and then schizophrenifiorm disorder (14.6%), also confirming the work of Baldwin and colleagues (2005) on epidemiology in FE psychosis.24

The mean age of onset of psychosis was 21 years and this is typical of schizophrenia in that its initial presentation to hospital occurs typically in the late teens to the early 20s25, especially in males.26 This finding also goes with what has been found in an Egyptian sample with a mean age at onset that was 20.3 years. The mean duration of prodrome was 64.4 weeks, which is consistent with what was found by a previous study in 2008 (67.9 weeks).23

The mean DUP was 28.6 weeks, and that is shorter than what was found previously in India27 (48 weeks) and in western countries, such as an American study which reported DUP to be 84 weeks.28 Differences may reflect ascertainment procedures in our study, measurement of DUP or other cultural factors. For example, in a developing country (India) where stigma is a problem, awareness is poor, and there is limited mental health resources, DUP may be longer. However, longer DUP has also been reported in the west countries.3

Regarding the association between DUP and symptoms of psychosis, significant correlations were limited in the current study. This is in contrast to the view that "untreated psychosis is biologically toxic".29,30 In addition, previous studies for early detection and intervention of psychosis placed a lot of significance on the issue of DUP. 31-35

The significant correlations in our study were between DUP and unusual thought content, and blunted affect, in which longer DUP was associated with more severe unusual thought content while shorter DUP was associated with more severe blunted affect. Shorter DUP was found to be associated with more severe negative symptoms and overall severity as indicated by CGI score, but none of these correlations were statistically significant. That is consistent with what was concluded by Robinson and colleagues (1999) who found only a tendency for prediction of outcome by psychosis duration.36

In the present study, a significant positive correlation was found between longer DUI and more severe conceptual disorganization and more severity in overall symptom presentation as measured by CGI. Thus, we could be conclud that longer DUP or DUI are correlated more with positive and disorganized symptoms than they are with negative symptoms. That is consistent with the results of Syzmanski and colleagues (1996).37 But, this is in contrast to the view that prolonged DUI may predict more negative symptoms.38

Fresan and colleagues (2003) found an association between long DUP and poor premorbid functioning.39 Consistent with that , we found that worse PAS scores (higher scores) in the socialization and school functioning domains, as well as total PAS scores were related to longer DUP but none of those correlations were statistically significant.

The lack of a significant correlation between premorbid functioning and DUP is also consistent with a previous study in 1996 that failed to observe a significant relationship between premorbid functioning and DUP.20



In conclusion, results of the current study do not indicate that longer duration of untreated psychosis or duration of untreated illness is associated with worse clinical presentation of patients with first episode psychosis with the exception of a limited number of psychotic symptoms. In addition, these results do not indicate that worse premorbid functioning is associated with longer DUP or DUI.


[Disclosure: Authors report no conflict of interest]




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الملخص العربى


مدة الذهان و المرض قبل التدخل العلاجى و تأثيرها على أعراض الحالة الإكلينيكية

فى مرضى النوبة الأولى من الاضطراب الذهانى


تم إجراء هذا البحث على عينة من مرضى النوبة الأولى للذهان سواء المصابين بالفصام أو الأمراض الذهانية الأخرى ذات العلاقة, أجرى البحث فى مركز كومنولث للأبحاث بقسم الأمراض النفسية بكلية الطب، جامعة هارفارد بالولايات المتحدة الأمريكية. واشتملت الدراسة على عينة مكونة من 137 شخصا (113 من الذكور و 24 من الإناث) وكان متوسط أعمارهم 22.3 سنة. وهدف البحث غلى دراسة كل من: تأثير طول مدة المرض قبل العلاج على الأعراض الإكلينيكية لهؤلاء المرضى (وذلك من خلال قياس هذه الأعراض وشدتها باستخدام مقياس التقييم النفسى المختصر ومعدل الانطباع الاكلينيكى العام)، وكذلك تقييم العلاقة بين مدى تكيف المرضى قبل حدوث المرض وطول مدة الذهان قبل التدخل العلاجى.

أبرزت نتائج البحث وجود ارتباط كبير بين مدة الذهان قبل التدخل العلاجى ومحتوى الفكر غير العادى (0.017) و التبلد المزاجي (0.045) بينما ارتبطت مدة المرض قبل التدخل العلاجى مع تشوش المفهوم عند المرضى (0.025) و نتيجة معدل الانطباع الاكلينيكى (0.041) و لكن ليس مع غيرهما من المقاييس. وبالتالى لم تؤكد الفرضية التى تنص على ارتباط طول مدة المرض أو الذهان قبل التدخل العلاجى مع شدة الأعراض الايجابية و السلبية للمرض الذهانى. ولم يتم العثور على علاقات ذات دلالات إحصائية بين مستوى تكيف المرضى قبل المرض ومدة الذهان أو المرض قبل التدخل العلاجى، وهكذا كانت هذه النتيجة معارضة للفرضية القائلة بأن هناك علاقة بين مستوى تكيف المرضى قبل المرض من ناحية و مدة الذهان أو المرض قبل التدخل العلاجى من الناحية الأخرى.

وخلص البحث إلى انه بالرغم من وجود ارتباط ذو دلالة إحصائية بين مدة الذهان و المرض قبل التدخل العلاجى وبين بعض المقاييس الخاصة بالأعراض الايجابية والسلبية فى المرض الذهانى إلا أن ذلك لا يمكن تعميمه على البقية الغالبة من هذه الأعراض. وكذلك لا توجد علاقة ذات دلالة بين مستوى تكيف المرضى قبل المرض ومدة الذهان أو المرض قبل التدخل العلاجى. 


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