quality assessment · web view25 90 8.2 huepe 2012 18 4.7 2.9 14 5 1.9 mendoza 2011 109 0.93 0.11...

Supplementary documents

Contents

Protocol and search terms

Quality Assessment Tool

Screening checklist

Data collection template

PRISMA Checklist

Table of quality assessment scores for included studies

Results for separate emotions

Results from meta-regression

Forrest plot for neutral valence meta-analysis

Page number

2

5

6

7

8

10

11

20

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1

Protocol and search terms

Review question

The aim of this systematic review is to examine the relationship between genetic risk for schizophrenia (based on molecular genetics or family history) and cognitive biases that are associated with psychosis.

Searches

EMBASE, MEDLINE, MEDLINE-in-process, PSYCHinfo will be searched from the beginning of their records up to the present date using the keyword search terms listed below.

Hand searches will be conducted of reference sections of eligible studies.

Searches will be made using the following search terms:

Genetic high risk: polygenic OR “risk profile score” OR gene* AND (risk OR liability OR susceptib* OR predispos*) OR “high risk”

Family history high risk: “first degree relati*” OR “famil* risk”

Schizophrenia: Schizoph* OR psychosis OR psychotic OR hallucinat* OR delusion* OR paranoi* OR schizoaffective OR schizotypy

Cognintive bias: (bias* OR deficit OR reason*) AND (cognition OR cognitive OR meta cog* OR metacog* OR attention* OR process* OR perceptual OR information processing OR perception)

Source Monitoring: (source OR reality OR self OR external) AND (memory OR monitoring OR recognition) OR “self generated speech” OR “external misattribut*” OR “externali* bias”

Jumping to Conclusions bias: jump* adj2 conclusion* OR “data gathering” OR beads adj2 task OR “probability reas*”

External attribution bias: “external attribut*” “internal attribut*” OR “Locus of control” OR “attribut* style”

Top-down processing: “Top-down processing” OR “top down processing” OR “auditory feedback” OR “visual feedback”

Belief inflexibility: “belief inflex*” OR “belief flex*” OR BADE OR disconfirm* adj2 bias OR “evidence integrat*”

Emotion recognition: (emotion* OR affect* OR facial) AND (recogni* OR perception OR perceive OR process*)

The final search term structure will be:

High risk (genetics/family history) AND Schizophrenia AND one of cognitive/perceptual biases

2

Types of study to be included

Any study design that includes a comparison between participants and control groups.

Condition or domain being studied

Cognitive biases

Participants/population

General population

Exposure(s)

Genetic risk for schizophrenia (based on molecular genetics or family history).

This is defined as a person having a high number of risk alleles for schizophrenia, having copy number variants associated with schizophrenia, or having one or more first degree relatives with schizophrenia.

Comparator(s)/control(s)

Participants not at high genetic risk for schizophrenia based on either molecular genetics or family history

Context

Any setting.

Primary outcome(s)

Performance on tasks that test for cognitive biases associated with psychotic symptoms. Cognitive biases and perceptual biases that are associated with psychosis are those that have been reported as supporting the development and maintenance of psychosis.

This is defined as the following in these tasks:

The jumping-to-conclusions bias: This should either be the beads task or a conceptual equivalent.

Externalizing bias: A task that tests for a bias for misattributing internal thoughts or spoken words to an external source

Top-down processing: A task that tests for a top-down processing bias associated with hallucinations

External attribution bias: A task that tests for participants’ bias to attribute negative events to external sources

Belief inflexibility Bias: A task that tests for a bias against disconfirmatory evidence

Emotion recognition: Tasks that assess for affect perception deficits or facial emotion recognition task, such as the Penn Emotion Recognition Task.

Tasks that explicitly state that the outcome is a perceptual or cognitive bias associated with psychosis that is not one of the above mentioned tasks will be identified and included.

3

Secondary outcome(s)

None.

Data extraction (selection and coding)

Titles and abstracts of studies retrieved using the search strategy and those from additional sources will be screened to identify studies that potentially meet the inclusion criteria outlined above. The full texts of these potentially eligible studies will then be retrieved and independently assessed for eligibility by two review team members. Any disagreements between them over the eligibility of particular studies will be resolved through discussion with a third reviewer.

Risk of bias (quality) assessment

The quality of individual studies will be assessed by two independent reviewers using an assessment checklist which the reviewing team have developed based on the Newcastle-Ottawa Quality Assessment. Any discrepancies will be resolved by discussion with a third reviewer. The quality assessment for each study will inform the decision of whether to include the studies in data analysis and will add to the discussion of the quality of data available and therefore the potential areas for further research.

Strategy for data synthesis

We will provide a narrative synthesis of the findings from the included studies, or a meta-analysis if data allows.

4

Quality Assessment Tool (based on Newcastle-Ottawa Quality Assessment)

1) Selection of Participants

a) Reported as randomly or consecutively sampled (1 point)

b) No description or not random or consecutively sampled

2) Selection of recruited participants

a) Response rate reported (1 point)

c) No reported response rate

3) Comparability

a) The study controls for any potential confounding factors (1 points)

c) did not address any possible confounding factors

4) Selection of the low genetic risk group

a) Drawn from the same community and representative of the exposed cohort (1 point)

b) Drawn from a different source

c) No description of the derivation of the non-exposed cohort

Screening checklist

5

Is the paper published in a peer-reviewed journal?

Y/N

Does the paper include people at high risk for developing schizophrenia based on family history or genetics?

High risk based on family history should refer to first degree relatives with schizophrenia.

Y/N

Does the study measure a cognitive bias listed in the protocol or specifically state that it measures a cognitive bias associated with psychosis?

Y/N

Does the study compare participants that are or are not at high risk for developing schizophrenia, based on genetics or family history, on a cognitive bias task?

Y/N

6

Data collection template

Author_Year

Cognitive Bias

Country

Setting

Design

Criteria used to define high risk group

Sampling strategy

Response rate (if stated)

High risk (HR): n, mean age, %male, mean, SD

Low risk (control): n, mean age, %male, mean, SD

Cognitive bias test used

Comments on results

Confounders adjusted for

7

Prisma checklist

Section/topic # Checklist item Reported on page #

TITLE Title 1 Identify the report as a systematic review, meta-analysis, or both. 1ABSTRACT Structured summary 2 Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria,

participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.

1

INTRODUCTION Rationale 3 Describe the rationale for the review in the context of what is already known. 1

Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

1

METHODS Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide

registration information including registration number. 2

Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

2

Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

2

Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

Sup. 2

Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

2

Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

3

Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

Supp. 6

Section/topic # Checklist item Reported on page #

8

Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

3

Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

4

RESULTS Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for

exclusions at each stage, ideally with a flow diagram. Figure 1

Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

Tables 1

Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). Table 1Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each

intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. 5 – 6 (Figure 2-10)

Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency. 5 – 6, (Figure 2-10)

Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15). 1Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item

16]). 2

DISCUSSION Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance

to key groups (e.g., healthcare providers, users, and policy makers). 8 - 9

Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

10

Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

10

FUNDING Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for

the systematic review. 10

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097

9

Table S1: Quality assessment results

Study

Sam

plin

g st

rate

gyRe

spon

se

rate

Adju

sted

fo

r con

-Se

lect

ion

of c

ontro

l

Tota

l sco

re

Confounders adjusted

Albacete (Albacete et al., 2016) 0 0 0 0 0 None

Alfimova et al., 2013 (Alfimova et al., 2013) 0 0 1 0 1 Sex, age, education

(Allott et al., 2015) 0 0 1 1 2 Age, IQ, symptoms

Andersen (Andersen et al., 2016) et al., 2016 0 0 1 0 1 Age, sex

Andric (Andric et al., 2016)et al., 2016 0 0 1 0 1 Age, gender, IQ, general facial recognition

Ay (Ay et al., 2016) et al., 2016 0 0 0 0 0 None

Bediou (Bediou et al., 2007)et al., 2007 0 0 1 0 1 Depression, age, education

Bolte (Bolte and Poustka, 2003) and Poustka, 2003 1 1 1 0 3 Gender, age, IQ

Calkins (Calkins et al., 2010)et al., 2010 0 0 1 1 2 Sex, age

Cella (Cella et al., 2015) et al., 2015 0 0 1 0 1 Age, gender, education, IQ, cognitive function

Coleman (Coleman et al., 2017) et al., 2017 1 1 1 1 4 White western European ancestry

Davalos (Davalos et al., 2004) et al., 2004 0 0 0 0 0 None

de Achaval (de Achaval et al., 2010)et al., 2010 1 0 1 0 2 Age, cognitive performance, education

Erol (Erol et al., 2010) et al., 2010 0 0 0 0 0 None

Germine (Germine et al., 2016) et al., 2016 1 0 1 1 3 white non-Hispanic ancestry

Goghari (Goghari et al., 2011)et al., 2011 0 0 1 0 1 Age

Goghari (Goghari et al., 2017) et al., 2017 0 0 1 0 1 age, sex, education, handedness, vocabulary

score, matric reasoning scoreGoldschmidt (Goldschmidt et

al., 2014) et al., 2014 0 0 0 0 0 None

Horton (Horton et al., 2017)et al., 2017 0 0 1 0 1 Age

Huepe (Huepe et al., 2012)et al., 2012 0 0 0 0 0 None

Ibanez (Ibanez et al., 2012)et al., 2012 0 0 1 0 1 Age

Kee (Kee, 2004), 2004 0 0 0 0 0 None

Kohler (Kohler et al., 2014)et al., 2014 0 0 1 1 2 family clusters, age, sex and psych history

Lavoie (Lavoie et al., 2014)et al., 2014 0 0 1 0 1 IQ, non-social reasoning, age, gender, SES

Leppanen (Leppanen et al., 2008) et al., 2008 0 0 0 0 0 Gender

Li (Li et al., 2010) et al., 2010 0 0 0 0 0 None

Li (Li et al., 2012) et al., 2012 0 0 0 0 0 None

McCown (McCown et al., 1989) et al., 1989 0 0 0 1 1 Gender

10

Mendoza (Mendoza et al., 2011) et al., 2011 0 0 1 0 1 Age, gender, education

Ruocco (Ruocco et al., 2014) et al., 2014 0 0 1 0 1 Age, race and sex

Spilka (Spilka and Goghari, 2017) and Goghari, 2017 0 0 0 0 0 None

Toomey (Toomey et al., 1999) et al., 1999 0 0 0 0 0 None

Wolf (Wolf et al., 2011) et al., 2011 0 0 1 0 1 None

Yang (Yang et al., 2015) et al., 2015 0 0 1 0 1 None

Footnote: see Quality Assessment Tool for details on how points were awarded.

Split emotions results

Anger

Study Control High riskN1 M1 SD1 N2 M2 SD2

Allott 2015 30 66.7 26.3 27 70.4 23.3Andric 2016 51 78.83 17.59 55 73.77 16.86Goghari 2011 36 88 12 23 90 12Goghari 2017 21 80.4 11.5 25 76 13.1Huepe 2012 18 5.5 1.5 14 5.5 2.1Leppanen 2008 22 0.8 0.23 23 0.7 0.31Mendoza 2011 109 0.95 0.12 110 0.9 0.21Ruocco 2014 380 0 1 332 -0.3 0.06

Meta-analysis results

Pooled SMD = 0.271 (95% CI = 0.126 to 0.417) Heterogeneity chi-squared = 8.72 (d.f. = 7) p = 0.273 I-squared (variation in SMD attributable to heterogeneity) = 19.7% Estimate of between-study variance Tau-squared = 0.0085 Test of SMD=0 : z= 3.65 p = 0.000

11

Forest plot

Disgust recognition

Study Control High risk N Mean SD N Mean SD

Allott 2015 30 74.4 28.6 27 71.6 27.3Huepe 2012 18 4 1.9 14 3.7 1.9Mendoza 2011 109 0.95 0.07 110 0.88 0.17


SMD = 0.365 (95% CI = 0.065 - 0.666) Heterogeneity chi-squared = 2.72 (d.f. = 2) p = 0.257 I-squared (variation in SMD attributable to heterogeneity) = 26.5% Estimate of between-study variance Tau-squared = 0.0211 Test of SMD=0 : z= 2.39 p = 0.017

12

Forest plot

NOTE: Weights are from random effects analysis

. (-2.32, 3.05)with estimated predictive interval

Overall (I-squared = 26.5%, p = 0.257)

Mendoza 2011

Study

Allott 2015

Huepe 2012

0.37 (0.07, 0.67)

0.54 (0.27, 0.81)

SMD (95% CI)

0.10 (-0.42, 0.62)

0.16 (-0.54, 0.86)

100.00

58.57

Weight

25.62

%

15.80

0.37 (0.07, 0.67)

0.54 (0.27, 0.81)

SMD (95% CI)

0.10 (-0.42, 0.62)

0.16 (-0.54, 0.86)

100.00

58.57

Weight

25.62

%

15.80

0-.857 0 .857

Fear recognition


Allott 2015 30 73.3 25.4 27 50.6 29.8Andric 2016 51 66.44 17.14 55 63.55 16.83Goghari 2011 36 86 11 23 91 11Goghari 2017 21 69.4 15.7 25 68.8 16.2Huepe 2012 18 4.3 2.2 14 3.5 1.8Li 2012 12 78.33 10.08 12 78.75 7.11Mendoza 2011 109 0.98 0.05 110 0.87 0.23Ruocco 2014 380 0 1 332 -0.06 0.06


13

SMD 0.227 (95% CI -0.046 to 0.500) Heterogeneity chi-squared = 25.35 (d.f. = 7) p = 0.001 I-squared (variation in SMD attributable to heterogeneity) = 72.4% Estimate of between-study variance Tau-squared = 0.0955 Test of SMD=0 : z= 1.63 p = 0.103

Forest plot

Happy

Study Control High riskN Mean SD N Mean SD

Allott 2015 30 100 0 27 96.3 10.7Andric 2016 51 87.03 10.22 55 89.57 12.14Goghari 2011 36 93 9 23 95 9Goghari 2017 21 93.4 6.1 25 93.3 6.4

14

Huepe 2012 18 7.8 0.5 14 7.07 1.8Li 2012 12 88.75 11.89 12 95 9.77Leppanen 2008 22 0.84 0.26 23 0.91 0.08Mendoza 2011 109 0.99 0.02 110 0.97 0.11Ruocco 2014 380 0 1 332 -0.1 0.05



Forest plot

Neutral recognition

Study Control High risk 15

N Mean SD N Mean SDAllott 2015 30 88.9 18.2 27 88.9 22.6Andric 2016 51 80.66 16.29 55 80.82 17Ruocco 2014 380 0 1 332 -0.34 0.07

Meta-analysis


Forest plot

16

Sad recognition


Allott 2015 30 78.9 23.9 27 66.7 32Goghari 2011 36 87 11 23 91 11Goghari 2017 21 88.1 11.6 25 90 8.2Huepe 2012 18 4.7 2.9 14 5 1.9Mendoza 2011 109 0.93 0.11 110 0.85 0.18Ruocco 2014 380 0 1 332 0 0.06



Forest plot

17

Surprise recognition


Allott 2015 30 82.2 25.9 27 85.2 19.2Huepe 2012 18 6.7 1.3 14 6.2 1.4Mendoza 2011 109 0.98 0.05 110 0.94 0.14



Forest plot

NOTE: Weights are from random effects analysis

. (-2.76, 3.25)with estimated predictive interval

Overall (I-squared = 33.1%, p = 0.224)

Allott 2015

Study

Mendoza 2011

Huepe 2012

0.24 (-0.08, 0.56)

-0.13 (-0.65, 0.39)

SMD (95% CI)

0.38 (0.11, 0.65)

0.37 (-0.33, 1.08)

100.00

26.90

Weight

56.18

16.92

%

0.24 (-0.08, 0.56)

-0.13 (-0.65, 0.39)

SMD (95% CI)

0.38 (0.11, 0.65)

0.37 (-0.33, 1.08)

100.00

26.90

Weight

56.18

16.92

%

0-1.08 0 1.08

18

Forrest plot for neutral valence meta-analysis

19

Table 3 – results from meta-regression

Variable Coefficient Confidence interval P value Residual I2 (%)Quality score 0.1664494 -0.0105193 to 0.3434182 0.064 39.02%

Time limited test 0.0849263 -0.1979217 to 0.3677743 0.539 47.47Validated test 0.039321 -0.2579279 to 0.3365698 0.786 49.24%

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quality assessment · web view25 90 8.2 huepe 2012 18 4.7 2.9 14 5 1.9 mendoza 2011 109 0.93 0.11...

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