Health related quality of life in patients having schizophrenia negative symptoms – a systematic review

Figures & data

Table 1. Schizophrenia negative symptom qualification.

SNS	Definition
Prominent negative symptoms [7,33,34]	Moderate symptom severity of ≥4 on at least 3 negative PANSS subscore items or moderately severe symptom severity of ≥5 on at least 2 negative PANSS subscore.
Predominant negative symptoms	• If using the SANS: the score of ≥60 on the SANS and of ≤50 on the SAPS, or if the score corresponds to less than moderately ill on the CGI-S [7,35]. • If using the PANSS: the total negative subscore of >20 including a score of >4 in at least one of N1-N7 items, reduction of <10% on PANSS negative subscore, and stable medication for 2 weeks before an intervention [36,37].
Predominant and persistent negative symptoms [38,39]	The total negative score of >20 points on the PANSS including a score of ≥4 in at least one of the PANSS-negative items – N1–N7 (range 1–7) (at least moderate, clinically relevant negative symptoms) [40]. Stable antipsychotic medication for 2 weeks before an intervention with reduction of <10% on PANSS negative subscore over this time. The total positive score of <20 points on PANSS including a score of ≥5 (‘‘marked’’ severity or higher) in at least one of the PANSS-positive items – P1–P6 [40]. The total negative score of ≥4 on the CGI-S [41]. A score of >9 on the CDSS [42]. A score of ≥3 on the clinical global impression of ESRS at screening [43].

Abbreviations: CDSS – Calgary Depression Scale for Schizophrenia; CGI-S – Clinical Global Impressions-Severity; ESRS – Parkinsonism of the Extrapyramidal Symptom Rating Scale; PANSS – Positive and Negative Syndrome Scale; SANS – Scale for the Assessment of Negative Symptoms; SAPS – Scale for the Assessment of Positive Symptoms

Table 2. Definitions of psychometric properties and subcategories.

	Definition
The validity of an instrument	It is the most important property of an instrument. The validity is the state that proves that the instrument is able to measure what it is aimed to measure. Several types of validity exist [18,44,45]. Construct validity is the ability of a test to measure a theoretical construct. It is about generalization of a construct or results from a study to the large concept of this study. It includes convergent and discriminant validity. Face validity addresses time of filling of an instrument, the missing rate, the ceiling and floor effect, etc. It is a general impression determining if the operationalization seems like a good translation of the construct or not. Content validity checks the relationship between the content domain and the purpose of the instrument. The aim of this validation is to have a good description of the content. Criterion-related validity is the ability to test if a measure is able to predict a variable that is designated as a criterion or not. Predictive validity is the fact of predicting the future measure or a result from a current measurement. It measures the extent to which a future level of a variable can be predicted from a current measurement. This includes correlation with measurements made with different instruments. Concurrent validity is the fact of measuring the existing relationship between the new measure and an existing test which is the criterion.
Reliability of an instrument	It is the degree to which assessed tool produces stable and consistent measurements. It includes the internal consistency and the test retest reliability [18,46,47]. Reproducibility or test-retest reliability is obtained by administrating the same instrument twice over a period of time (this period varies from one instrument to another). To evaluate the stability of the test retest reliability over time, a correlation between the first and the second score is calculated. Internal consistency is a method of reliability measure evaluating the degree to which all items included in the same domain evaluate the same construct and produce a score. The combination of this score with the score of the other domains of the same instrument produces an overall score.
Ability to detect change	It is the ability to measure the degree and the latency of the change between two measurements and to give the evidence that the tool is equally sensitive to the change independently of the duration of break between them [18,48,49].

Figure 1. Flow chart.

Table 3. HRQoL instruments used in patients with schizophrenia.

Acronyms	Complete label	No of items	No of dimensions	Include patients with SNS		Studies
Generic HRQoL instruments
EQ-5D	EuroQol-5D	5	5		No	Prieto 2003 [50]
SF-36	Short Form 36 Health Survey	36	8		No	Ware 1993 [51]
WHOQOL-100	The World Health Organization Quality of Life Scale	100	6		No	The WHOQOL Group 1998 [52]
WHOQOL-Bref		26	4		No	Skevington 2004 [53]
Severe mental illness HRQoL instruments
QoLI	The brief Quality of Life Interview	74	8		Yes	Lançon 2000 [54]
LQOLP	Lancashire Quality of Life Profile	24	9		No	Oliver 1996 [55]
MANSA	Manchester Short Assessment of Quality of Life	12	NA		No	Priebe 1999 [56]
SWN	Subjective Well-being under Neuroleptics Scale	38	5		Yes	Naber 2001 [57]
SWN-20		20	5		Yes	de Hann 2002 [58]
TOOL	The Tolerability and Quality of Life questionnaire	8	8		Yes	Montejo 2009/2011 [59,60]
WQLI	Wisconsin Quality of Life Index	47	8		No	Diaz 1991[61]
S.QUA.L.A	Subjective Quality of Life Analysis	22	44		Yes	Nadalet 2005 [62]
Q-LES-Q	Quality of Life Enjoyment and Satisfaction Questionnaire	60	7		No	Pitkänen 2012 [63]
Q-LES-Q-18		18	5		Yes	Ritsner 2005 [64]
Schizophrenia specific HRQoL
S-QoL	Quality-of-life Questionnaire in Schizophrenia	41	8		No	Auquier 2002 [23]
S-Qol-18		18			Yes	Boyer 2010 [19]
SQLS	Schizophrenia Quality of Life Scale	30	3		No	Wilkinson 2000 [65]
		30	3		No	Kaneda 2002 [66]
SLDS	Satisfaction with Life Domains Scale	15	15		Yes	Carlson 2009 [20]
QLiS	Schizophrenia-Specific Quality-of-life Scale	52	12		Yes	Franz 2012, 2013 [21,22]

Table 4. Psychometric validation of schizophrenia-specific HRQoL instruments.

	validity
Acronyms	Face validity/Content validity	Construct validity (internal validity)	Construct validity (external validity)	Cross-cultural validity	Reliability internal consistency	Reliability reproducibility (test-retest)	Sensitivity to change	Studies
S-Qol-18	Face validity • Floor effects from 10.2% to 28.8% • Ceiling effects from 12.7% to 35.1% • Missing data 2–10%	Discriminant validity • Items intern consistency >0.4 • Satisfactory internal consistency (from 0.80 to 0.93)	• High correlation between S-QoL-18 and S-QoL 41 >0.80 • Negative correlation between S-QoL 18 dimension scores, CGI and CDSS scores (except CGI-RFa and CDSS-RFa)	• NA	• Cronbach’s alpha: from 0.72 to 0.84	• Satisfactory test–retest reliability for 72 stable patients	• Study on 28 patients: Improved health status (reduced total PANSS≥ 20%) after 6 months	Boyer 2010 [19]
SLDS	Face validity • Filling time: 10 min Content validity • Pilot study to check comprehensibility of the instrument	• NA	Divergent validity • No correlations between SLDS and other instruments that evaluated different constructs. Correlation between SLDS and PANSS, general subscale and with the score in the Strauss and carpenter (r = 0.2)	• Translation and back-translation of SLDS by 2 natives Discrepancies: approved by consensus	• Cronbach’s alpha: 0.84	• High intraclass correlation coefficient for all domains except for 3 (<0.60).	• NA	Carlson 2009 [20]
QLiS	Content validity • FStructured open-ended interview • Literature review	• NA	• Positive correlation between QLiS and WHOQOL-BREF dimensions Variance for non-QLiS QoL instruments was >20% after controlling for global life satisfaction	• NA	• Cronbach’s alpha: >0.70 with the exception of 1 subscale	• Reproducibility assessed between (D1 and D7 or D14) Positive correlation between PANSS scores and the GAF global score	• NA	Franz 2012, 2013 [21,22]

Abbreviations: S-Qol-18 – Quality of Life Questionnaire in Schizophrenia – Short Form; RFa – Family relationships; PANSS – Positive and Negative Syndrome Scale; WHOQOL – The World Health Organisation Quality of Life Scale; CGI – Clinical Global Impressions Scale; SLDS – Satisfaction with Life Domains Scale; QLiS – Schizophrenia-specific Quality of Life Scale; GAF – Global Assessment of Functioning.

Table 5. Negative symptoms in HRQoL validation studies.

Acronyms	instrument assessing SNS	Correlation between 2 instruments	Score of patients with SNS in this instrument (mean± SD)	Studies
QoLI	PANSS	• Significant correlation between PANSS Negative symptoms and ‘satisfaction with leisure activities’, ‘satisfaction with life in general’, ‘friendships’ and ‘state of health’ dimensions of the QoLI	• PANSS total score: 84.6 ± 20.8 Positive factor: 18.2 ± 7.0 Negative factor: 24.5 ± 6.9 General psychopathology: 41.7 ± 10.2	Lançon 2000 [54]
SWN-38	PANSS	• Negative correlations between SWN-38 domains and PANSS negative score	• PANSS positive factor: 21.09 ± 5.84 PANSS negative factor: 23.69 ± 6.40 PANSS general psychopathology: 90.51 ± 18.72	Naber 2001 [57]
SWN-38 and SWN-20	PANSS	• Negative correlations between dimensions of SWN-38 and PANSS Negative score (−0.28) Native correlation between dimensions of SWN-20 – PANSS negative score (−0,3)	• NA	De Hann 2002 [58]
TOOL	PANSS	• NA	• PANSS positive factor: 19.91V7.94 PANSS negative factor: 19.91 ± 7.94 PANSS general psychopathology: 32.76 ± 12.09	Montejo 2011 [59]
S.QUA.L.A	PANSS	• NA	• PANSS total score: 43.74 ± 16.71 PANSS positive factor: 9.58 ± 4.38 PANSS negative factor: 15.25 ± 11.22 PANSS general psychopathology: 22.40 ± 7.94	Nadalet 2005 [62]
Q-LES-Q-18	PANSS	• Negative correlation between ‘subjective feeling’ and ‘social relationship’ and PANSS negative scores. Positive correlation between ‘leisure activities’, ‘physical health and general index’	• NA	Ritsner 2005 [64]
S-QoL-18	PANSS	• Negative correlations between 5 dimensions of S-QoL-18 dimension scores PANSS- negative factor. Three significant correlations between ‘relationships with friends’, ‘resilience and autonomy’ dimensions of S-QoL-18 and PANSS- negative factor.	• PANSS total score: 69.6 ± 18.4 Positive factor: 15.7 ± 6.1 Negative factor: 19.2 ± 6.9 General psychopathology: 35.8 ± 9.6	Boyer 2010 [19]
SLDS	• PANSS	Negative correlations between SLDS dimensions and PANSS negative factor.	• NA	Carlson 2009 [20]
QLiS	PANSS	• NA	• PANSS positive factor: 13.2 ± 5.5 PANSS negative factor: 15.0 ± 5.5 PANSS general psychopathology: 28.7 ± 7.3	Franz 2012 [21]

Abbreviations: MANSA – Manchester Short Assessment of Quality of Life; PANSS – Positive and Negative Syndrome Scale; SWN – Subjective Well-being under Neuroleptics Scale; TOOL – The Tolerability and Quality of Life questionnaire; WQLI – Wisconsin Quality of Life Index; S.QUA.L.A – Subjective Quality of Life Analysis; Q-LES-Q-18 – Quality of Life Enjoyment and Satisfaction Questionnaire short form; S-QoL-18 – Quality of Life Questionnaire in Schizophrenia – Short Form; SLDS – Satisfaction with Life Domains Scale; QLiS – Schizophrenia-specific Quality of Life Scale; QoLI – The brief Quality of Life Interview.

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