PATHOPHYSIOLOGY ASSN 1

RESEARCH ARTICLE

Cross-disorder and disorder-specific deficits

in social functioning among schizophrenia

and alzheimer’s disease patients

Ilja M. J. SarisID 1*, Moji Aghajani1,2, Niels Jongs3, Lianne M. Reus4, Nic J. A. van der

Wee5,6, Amy C. Bilderbeck7, Inge Winter van Rossum8, Celso Arango9,10, Alejandro de la

Torre-Luque10,11, Asad MalikID 7, Andreea Raslescu7, Gerard R. Dawson7, José L. Ayuso-

Mateos10,12, Martien J. KasID 3, Brenda W. J. H. Penninx1

1 Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute,

Amsterdam UMC, Vrije Universiteit and GGZ inGeest, Amsterdam, the Netherlands, 2 Institute of Education

& Child Studies, Section Forensic Family & Youth Care, Leiden University, Leiden, the Netherlands,

3 Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands,

4 Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit

Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands, 5 Department of Psychiatry, Leiden University

Medical Centre, Leiden, the Netherlands, 6 Leiden Institute for Brain and Cognition, Leiden, the Netherlands,

7 P1vital Ltd., Wallingford, Oxfordshire, United Kingdom, 8 Department of Psychiatry, University Medical

Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands, 9 Hospital General Universitario

Gregorio Marañón, CIBERSAM, IiSGM, Universidad Complutense, School of Medicine, Madrid, Spain,

10 Centre of Biomedical Research in Mental Health (CIBERSAM), Barcelona, Spain, 11 Universidad

Complutense de Madrid, Madrid, Spain, 12 Department of Psychiatry, Hospital Universitario la Princesa (IIS-

Princesa), Universidad Autonoma de Madrid, Madrid, Spain

* [email protected], [email protected]

Abstract

Background

Social functioning is often impaired in schizophrenia (SZ) and Alzheimer’s disease (AD).

However, commonalities and differences in social dysfunction among these patient groups

remain elusive.

Materials and methods

Using data from the PRISM study, behavioral (all subscales and total score of the Social

Functioning Scale) and affective (perceived social disability and loneliness) indicators of

social functioning were measured in patients with SZ (N = 56), probable AD (N = 50) and

age-matched healthy controls groups (HC, N = 29 and N = 28). We examined to what extent

social functioning differed between disease and age-matched HC groups, as well as

between patient groups. Furthermore, we examined how severity of disease and mood

were correlated with social functioning, irrespective of diagnosis.

Results

As compared to HC, both behavioral and affective social functioning seemed impaired in SZ

patients (Cohen’s d’s 0.81–1.69), whereas AD patients mainly showed impaired behavioral

social function (Cohen’s d’s 0.65–1.14). While behavioral indices of social functioning were

PLOS ONE

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OPEN ACCESS

Citation: Saris IMJ, Aghajani M, Jongs N, Reus

LM, van der Wee NJA, Bilderbeck AC, et al. (2022)

Cross-disorder and disorder-specific deficits in

social functioning among schizophrenia and

alzheimer’s disease patients. PLoS ONE 17(4):

e0263769. https://doi.org/10.1371/journal.

pone.0263769

Editor: Alejandra Mondragón-Maya, Universidad

Nacional Autonoma de Mexico, MEXICO

Received: May 2, 2021

Accepted: January 26, 2022

Published: April 14, 2022

Copyright: © 2022 Saris et al. This is an open

access article distributed under the terms of the

Creative Commons Attribution License, which

permits unrestricted use, distribution, and

reproduction in any medium, provided the original

author and source are credited.

Data Availability Statement: The data that support

the findings of this study are available from PRISM

(www.prism-project.eu). Restrictions apply to the

availability of these data, which were used under

license for the current study, and are not publicly

available. Data are available with the permission of

PRISM. Necessary data variables for replication are

the baseline characteristics (age, sex, education,

partner status, country); specific disorder

characteristics (medication, PANSS, ADAS-COG),

mood characteristics (QIDS-SR, STAI, PANAS) and

similar across patient groups, SZ patients reported more perceived social disability than AD

patients (Cohen’s d’s 0.65). Across patient groups, positive mood, lower depression and

anxiety levels were strong determinants of better social functioning (p’s <0.001), even more

so than severity of disease.

Conclusions

AD and SZ patients both exhibit poor social functioning in comparison to age- and sex

matched HC participants. Social dysfunction in SZ patients may be more severe than in AD

patients, though this may be due to underreporting by AD patients. Across patients, social

functioning appeared as more influenced by mood states than by severity of disease.

Introduction

Social functioning is crucial for human survival and it has been established that ‘loneliness

kills’ [1, 2]. Social functioning entails a collection of intricate and multi-factorial behavioral

repertoires, which seem to be facilitated by many complex brain network processes [3–5].

Social dysfunction could be broadly defined as inability of the individual to “integrate behav- ioral, cognitive and affective skills to flexibly adapt to diverse social context and demands” [6].

Because of its complexity, social dysfunction often arises as one of the first symptoms in neuro-

psychiatric disorders such as Schizophrenia (SZ) and Alzheimer’s disease (AD) [3]. However,

the origins of social dysfunction in these disorders remain poorly understood [7, 8]. Specifi-

cally, while SZ and AD patients are characterized by distinctive psychopathologies, their psy-

chosocial deficits are deemed partly overlapping. However, empirical data on behavioral and

neurobiological commonalities and differences is practically lacking.

The definition of ‘social dysfunction’ has specific focal points dependent on the disorder

being studied, with a broad range in study methods and outcome measures as a consequence.

The neurobiological underpinnings of the subjective, affective evaluation of social interactions

(i.e. loneliness, self-perceived social capacities) are thought to differ from the ones underlying

the more objective, behavioral aspects of social interactions (i.e. frequency of participating in

social activities, hours spend alone) [4, 9, 10]. We therefore differentiate between behavioral

and affective indicators of social functioning, in line with prior work by our group and other

studies [9, 11–13]. Social dysfunction in SZ is described in a large and growing body of litera-

ture that has identified severe impairments in mentalizing, interpersonal interaction, regulat-

ing emotions and emotion decoding in social situations [14–17]. It has been argued that

higher order affective social processes such as mentalizing are more prone to deficits in SZ

patients than processes which require less mental effort, such as emotion recognition and mir-

roring [14, 18]. In addition, the behavioral pattern of social withdrawal is described as a pro-

dromal symptom of SZ, with an onset up to several years before the first psychotic episode

[19]. In contrast to SZ, empirical data on social dysfunction in AD is arguably more sparse.

Social dysfunction in AD typically starts with initially subtle impairments in social and affec-

tive cognition, which worsen as the disorder progresses [20, 21]. Social impairment has been

described as a distinct constellation of AD symptoms, possibly explained by the degenerative

processes differentially affecting brain regions [22]. More specifically, in AD social dysfunction

seems to be associated with impairments in interpreting cues to others’ emotional states, and

thus identifying others’ emotions, i.e. affective aspects of social dysfunction [21]. In addition, it

has been described that the judgments of AD patients about their own social functioning is

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the social functioning indices (SFS, loneliness

questionnaire, self-rated and external rated

WHODAS).

Funding: The project leading to this application has

received funding from the Innovative Medicines

Initiative 2 Joint Undertaking under grant

agreement No 115916. This Joint Undertaking

receives support from the European Union’s

Horizon 2020 research and innovation programme

and EFPIA. This publication reflects only the

author’s views and neither the IMI 2JU nor EFPIA

nor the European Commission are liable for any

use that may be made of the information contained

therein.

Competing interests: I have read the journal’s

policy and the authors of this manuscript have the

following competing interests: CA has been a

consultant to or has received honoraria or grants

from Acadia, Angelini, Gedeon Richter, Janssen

Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage,

Servier, Shire, Schering Plough, Sumitomo

Dainippon Pharma, Sunovion and Takeda. ACB has

received salaries from P1vital Ltd. MK has received

(non-related) research funding from Novartis. BP

has received (non-related) research funding from

Jansen Research and Boehringer Ingelheim. This

does not alter our adherence to PLOS ONE policies

on sharing data and materials.

more positive than according to the perception of the caregiver [20, 23, 24]. In sum, social

functioning in both SZ and AD seems most affected in understanding others [8].

The notion of highly overlapping social functioning deficits in neuropsychiatric disorders

has gained more support and interest in recent years, especially since the launch of the RDoC

framework and the EU-ROAMER initiatives, which advocate a deeper understanding of trans-

diagnostic clinical phenomena and their neurobiobehavioral underpinnings [25, 26]. Cur-

rently, a clear understanding of what transdiagnostic research exactly entails, is still under

debate and clear guidelines are lacking [27, 28]. One of the proposed, stringent guidelines for

transdiagnostic research are the four Mansell criteria: (1) It describes both a clinical, and (2) a

non-clinical sample, (3) it must be present in at least four disorders and (4) the transdiagnostic

construct must be demonstrated in all mental disorders investigated [29]. However, before

being able to examine such underpinnings, it is necessary to more fully grasp the differences

and commonalities in a complex phenomenon such as social dysfunction–including both

behavioral and affective aspects—across neuropsychiatric disorders.

OeHoThe OeHomain aim of the present study is to examine differences and commonalities

in affective and behavioral indicators of social functioning among SZ and AD patients, as com-

pared to age and sex-matched healthy controls (HC), as well as compared to each other (SZ

versus AD). Ultimately this could guide future neurobiological research on the transdiagnostic

domain of social functioning, however, not fulfilling the Mansell criteria in this study, we will

use cross-disorder instead as preferred terminology. The current study is part of the larger EU-

funded PRISM Project (Psychiatric Ratings using Intermediate Stratified Markers), which

examines the neurobiobehavioral underpinnings of social dysfunction in order to advance and

formulate more effective treatment strategies [30]. Whereas SZ and AD differ in core symp-

toms, genetic profile, obvious age difference and underlying neurobiology, they importantly

seem to overlap considerable in social functioning deficits (i.e., social withdrawal, interper-

sonal functioning, loneliness) [30, 31]. A uniform assessment of social functioning is essential

to progress the field of transdiagnostic analyses. Studying patients with distinctively different

neuropsychiatric disorders also aligns nicely with the RDoC perspective that clinical psycho-

logical problems are best defined along functional domains with shared neurobiological sub-

strates, regardless of diagnostic nosologies, to attain novel insights and advance treatment

[25]. We aimed to include patients with a relatively recent disease onset to capture as much as

possible the underlying neurobiology of social dysfunction rather than long-term consequences

of psychopathology or neurodegeneration. A transdiagnostic approach of investigating social

(dys)function with these two discrete clinical entities may thus elucidate both disorder-specific

and cross-disorder deficits.

Material and methods

Participants

Data for the current study were derived from the PRISM study, which examines social dys-

function as a transdiagnostic symptom in individuals with SZ (N = 56), probable AD (N = 52),

and age-matched HC participants (two groups, N = 29 for younger HC (age 18–45) and

N = 28 for older HC (age 50–80) [30]. Two participants (AD patients) did not complete social

functioning questionnaires, leaving 163 participants for analyses.

Participants were recruited between July 2017 and March 2019 from five different recruit-

ing sites across Spain (Hospital General Universitario Gregorio Marañón and Hospital Uni-

versitario de La Princesa) and the Netherlands (University Medical Center Utrecht, VU

University Medical Center Amsterdam and Leiden University Medical Center). The study was

approved by the Ethics Review Board of all participating centers: University Medical Center

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Utrecht, VU University Medical Center Amsterdam, Leiden University Medical Center, Hos-

pital General Universitario Gregorio Marañón and Hospital Universitario de La Princesa. All

participants provided verbal and written informed consent. Rationale and clinical implemen-

tation for the PRISM study is described in depth elsewhere [4, 30, 32].

In- and exclusion criteria

SZ patients were eligible if they had a) a diagnosis of schizophrenia (confirmed using DSM-

based Mini-International Neuropsychiatric Interview (MINI) assessment), b) had a maximum

of 15-year disease duration since diagnosis, c) an age between 18–45 years, and d) a score of

�22 on the 7-item positive subscale of the positive and negative syndrome scale (PANSS) [33]

to rule out an active psychotic episode hampering adequate study participation [32]. SZ

patients were excluded when they were, in the clinician’s judgment, a danger to themselves or

others. AD patients were eligible if they had: a) a diagnosis of probable AD (meeting the

National Institute on Aging and the Alzheimer’s Association criteria), b) a Mini-Mental State

Examination (MMSE) [34] score between 20–26 (indicating mild AD pathology), c) an aged

between 50–80 years. Multiple strokes, either based on clinical judgement, medical history or

imaging results were exclusion criteria for the AD patient group.

Because AD is a progressive disorder with–after diagnosis- a quite variable disease course,

we have included AD patients based on their cognitive abilities as measured by the MMSE

[34]. Since social impairments may also stem from altered social interactions during ‘sick

years’, SZ patients were included with a maximum of 15-year disease duration since diagnosis.

For both the SZ and AD patient groups, we had additional exclusion criteria: a) diagnosis of

a severe, current Major Depressive Disorder (MDD) DSM-IV diagnosis (as assessed with the

MINI) [35] and with a Quick Inventory of Depressive Symptomatology, Self-Rated (QIDS-SR)

[36]�16), b) diagnosis of any other primary psychiatric diagnosis that requires intervention;

c) alcohol or drug abuse/dependence within previous 3 years (as assessed on the MINI), d)

severe Parkinsonism as a consequence of antipsychotic medication (as assessed with a score

�4 on the Extrapyramidal Symptom Rating Scale) [37], e) unstable comorbid somatic disor-

ders potentially affecting the central nervous system (CNS), f) unstable use of medication that

could affect CNS (e.g. start of or changed dosage within last 8 weeks).

We included two HC groups, matching on sex and age with the SZ (between 18–45 years)

and AD (between 50–80 years) groups. Scores on the MMSE for the older HC participants

should be comparable to normative data according to age and years of education. Exclusion

criteria for the HC groups were: a) history of psychiatric Axis-I disorder (as confirmed by the

MINI) or neurological disease associated with cognitive impairment; b) mild or more severe

depression (score >5 on the QIDS-SR); c) current or prior use of antidepressant or anxiolytic

medication including benzodiazepines, or other prescribed medication in the last 6 weeks that

may affect the CNS.

Behavioral and affective social functioning indicators

Behavioral indicators of social functioning—The Social Functioning Scale (SFS) consists of

seven subscales; social withdrawal, interpersonal functioning, competence and performance

independence, recreational and prosocial activities, and employment. The subscale ‘employ-

ment’ was not used for total scale analyses, since most participants were retired in the older

HC and AD group introducing a bias as confirmed by the significant association with age and

in line with reporting in a previous study [38]. We conducted Principal Component Analyses

with oblique rotation as the variables are correlated to test if the different subscales represent

one factor (i.e. behavioral social functioning) or two (i.e. affective and behavioral aspects of

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social functioning). In line with other studies using the SFS [38–40], the factor analysis con-

firmed that the six SFS subscales reflect one component (see S1 Table). The social withdrawal

subscale (higher score indicates less social withdrawal) focuses on time spend alone. The inter-

personal functioning subscale includes ability to have rational conversation and difficulty talk-

ing to people. The subscale independence-competence and independence-performance are

two identical lists of activities (e.g. buying items from shops alone) where participants judge

whether they think they are able to do these independently (competence) and following what

they actually independently did in the past three months (performance). The subscales, recrea-

tional and pro-social activities, consist of a list with several activities such as visiting relatives

or playing sports, and the frequency in which participants engage in that activity. We have fol-

lowed the original scoring guidelines [39], which advocate using Social Functioning Scale total

scores (Cronbach’s alpha 0.80), as these better captures underlying social functions/behaviors,

and also safeguards reproducibility across studies. However, since the different subscales

might reflect differences in impairments, we opted to also show the various subscales in subse-

quent supplementary analyses (S2 Table).

Affective indicators of social functioning—Loneliness was assessed with the 11-item de

Jong Gierveld loneliness scale [41], which examines feelings of loneliness (Cronbach’s alpha

0.8). Perceived social disability was measured with an adjusted 5-item ‘getting along’ subdo-

main from the WHODAS 2.0 (WHODAS 2.0: World Health Organization Disability Assess-

ment Schedule 2.0 [42]), which includes questions about difficulties in maintaining

friendships in the last 30 days (Cronbach’s alpha for adjusted ‘getting along’ domain 0.9).

Our division of social dysfunction (behavioral versus affective) is supported by higher inter-

domain than cross-domain correlations between behavioral and affective social indicators

(Table 2).

For patients, perceived social disability (WHO-DAS 2.0) was also assessed by the caregiver

when available (most often parent or partner) and by the research staff conducting the assess-

ment. Consistent with our earlier observations [43], correlations between the caregiver and

researcher rated scores were high (r = .79 for SZ group; r = .79 for AD group, both p’s<0.001,

S3I and S3II Table) and there were some missing values (not all patients participated in the

study with a caregiver). In cases where both scores were available, we computed a ‘rater-per-

ceived’ social disability score by calculating a mean score from both the caregiver and

researcher rated score. In other cases, we used the available score (either caregiver or

researcher rated). Correlations were strong for the SZ and HC groups between their self-rated

perceived social disability score and the rater score (r = .84 for SZ; r = .90 for HC, p’s<0.001).

For AD patients the correlation between the self-rated and rater-score was lower (r = .36). Cor-

responding to our earlier study on the self- and proxy-rated WHODAS scores [43], caregiver/

researcher rated perceived social disability was higher than the rating by the AD patients them-

selves. We included the rater-perceived social disability in our analyses comparing patient

groups.

All instruments are validated for both SZ and AD and were chosen after careful consider-

ation [4].

Severity of disease

Cognitive dysfunction was estimated in AD patients using the Alzheimer’s Disease Assessment

Scale–Cognitive subscale (ADAS-cog) [44] which includes 13 tasks involving both subject-

completed test and observer-based assessments such as word recall, naming objects, and orien-

tation. Current states of positive and negative symptoms of schizophrenia were measured

using the PANSS (positive and negative syndrome scale) [33].

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Mood characteristics

All participants (patients and controls) were asked to complete three mood questionnaires.

The 16-item Quick inventory of Depressive Symptomatology (QIDS-SR) [36], the 20-item

State-Trait Anxiety Inventory (STAI) [45] and the 20-item Positive and Negative Affect Scale

(PANAS) [46] examined depressive symptoms, anxiety symptoms and current positive and

negative affect states, respectively.

Statistical analyses

Demographic and clinical characteristics were described using χ2 for dichotomous variables

and t-tests for continuous variables. The Mann-Whitney test was used as nonparametric test

when assumptions parametric testing were not met. Pearson correlations described associa-

tions between social functioning indicators and continuous demographics (age, years of edu-

cation), point-biserial correlation coefficient described associations for binary demographics

(sex, partner status and country). Analyses of covariance (ANCOVA’s) with post-hoc tests, all

Bonferroni adjusted, compared social functioning indicators among SZ and AD patients, as

well as their age-matched HC groups, while adjusting for age, sex, years of education, partner

status and country. Effect sizes were calculated following Cohen’s formula for estimated differ-

ences [47]. To examine the association of disease severity and mood (the dependent variables)

with behavioral and affective indicators of social functioning (independent variables), linear

regression analyses were conducted, again while adjusting for age, sex, years of education, part-

ner status and country. Statistical analyses were conducted using SPSS (IBM, version 24.0,

IBM Corp., Armonk, NY, USA), and a two-tailed significance level of P < 0.05 was considered

statistically significant.

Results

HC participants had most years of education (17.2 and 16.7 for younger and older HC respec-

tively), whilst both of the patient groups had on average 15.0 years of education (Table 1). SZ

patients were less frequently with a partner (21.4%) as compared to younger HC (51.7%), AD

patients (84.0%) and older HC (82.1%). As expected, psychotropic medication use was high in

SZ patients (e.g. 89.3% used antipsychotics) and 43.8% of AD patients used acetylcholinester-

ase inhibitor and/or a NDMA receptor antagonist.

Current positive and negative symptoms among SZ patients were 11.0 (SD ±3.4) and 14.6

(SD ±6.2) respectively on the PANSS (mean total score 51, SD ±13.1). Mean cognitive dysfunc-

tion of AD was 26.9 (SD ±7.2) on the ADAS-COG. SZ participants had more negative mood

symptoms (i.e. more depressed mood, more anxiety, less positive affect and more negative

affect) than all other groups (AD and both HC groups). Anxiety and negative affect were com-

parable between AD and their matched HC group, but AD patients had more depressive

symptomatology and less positive affect (Table 1).

Correlation analyses (Table 2) across all participants show that age, educational level and

partner status had significant associations with almost all social indices. However, sex and

country had much less consistent associations with social indices (up to three associations

were significant but without consistent direction of association).

Comparison of patient groups with healthy controls

Fig 1 shows unadjusted means for the total SFS score as behavioral indicator, and self-rated

perceived social disability and loneliness as affective social indicators per group with compari-

sons for SZ and AD with their age-matched controls.

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It is clear in Table 3 that the least favorable social functioning outcomes on all measures

were found for the SZ group with large effect sizes (Cohen’s d’s = 0.81–1.69) particularly pro-

nounced for the affective indicators. AD patients showed less favorable outcomes for most

behavioral social functioning indicators as compared to their matched HC group: indepen-

dence-competence and -performance, recreational and prosocial activities and the total SFS

score with medium to large effect sizes (d’s = 0.65–1.14). For both SZ and AD patients the total

SFS was significantly lower from their age-matched controls with large effect sizes (d = 1.80

and 1.14 respectively). Affective social functional indicators of perceived social disability and

loneliness, however, were not significantly different (d’s = 0.17 and d = 0.05 respectively)

between AD and older HC participants. In contrast, the (mean score of caregiver and research

staff) rater-perceived social disability was significantly worse in AD as compared to the older

HC group (p<0.001, d = 1.29).

Comparisons across/within patient groups

In the cross-disorder comparison between SZ and AD patients, (Table 4), all behavioral social

indicators were comparable, as well as the total SFS score (p = 0.70, d = 0.31). Perceived social

disability showed a significantly poorer outcome for SZ patients as compared to AD partici-

pants (Cohen’s d = 0.65, p = 0.008). The self-reported perceived social disability was higher in

SZ compared to AD patients, but was not significantly different for the rater-perceived social

disability.

Table 1. Baseline characteristics (N = 163) across patient and control groups.

Schizophrenia patients

N = 56

Younger healthy

controls N = 29

p-value Alzheimer’s disease

patients N = 50

Older healthy

controls N = 28

p-value

Demographics

Age, mean years (SD) 30.8 (6.4) 28.7 (7.4) 0.13 68.6 (7.2) 67.1 (7.0) 0.32

Sex (% female) 28.6% 41.4% 0.23 44.0% 46.4% 0.84

Education, mean years (SD) 15.0 (3.8) 17.2 (2.6) 0.001 15.0 (5.6) 16.7 (4.9) 0.21

Partner status (% with partner) 21.4% 51.7% 0.004 84.0% 82.1% 0.83

Country (% Spain) 39.1% 48.3% 0.43 42.0% 25.0% 0.13

Specific disorder characteristics

Psychotropic medication

Antipsychotic (%) 89.3% 0% 4.0% 0%

Antidepressant (%) 19.6% 0% 16.0% 0%

Acetylcholinesterase inhibitor or NDMA

receptor antagonist (%)

0% 0% 43.8% 0%

Benzodiazepines (%) 10.7% 0% 6.3% 7.1%

Other psychotropics (%) 14.3% 0% 2.1% 3.6%

Severity of disorder

Schizophrenia severity

Positive symptoms, mean PANSS (SD) 11.0 (3.4) NA NA NA

Negative symptoms, mean PANSS (SD) 14.6 (6.2) NA NA NA

AD severity, mean ADAS-Cog (SD) NA NA 26.9 (7.2) NA

Mood characteristics

Depression severity, mean QIDS-SR (SD) 8.0 (5.3) 2.1 (1.5) <0.001 4.1 (2.8) 2.0 (1.3) <0.001

Anxiety severity, mean STAI (SD) 43.5 (11.2) 30.4 (5.9) <0.001 30.7 (8.2) 27.5 (5.8) 0.08

Mood state, PANAS

Positive Affect, mean (SD) 29.5 (6.6) 37.5 (5.9) <0.001 32.5 (5.1) 38.2 (6.1) <0.001

Negative Affect, mean (SD) 18.7 (6.5) 13.9 (3.0) <0.001 13.9 (4.6) 12.7 (3.0) 0.24

https://doi.org/10.1371/journal.pone.0263769.t001

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Table 2. Pearson and point biserial correlations between social indicators and demographics in the overall sample (N = 163).

Behavioral social indicators Affective social indicators

Social

withdrawal

Interpersonal

functioning

Independence

competence

Independence

performance

Recreational

activities

Prosocial

activities

Total

SFS

score

Perceived

social

disability

Rater-

perceived

social

disability

Loneliness

Demographics

Age .273��� .272�� -.162� -.060 .376�� .119 .229�� -.305�� -.135 -.217��

Sex (female = 1;

male = 0)

.160� .036 -.009 .187� .108 .028 .117 -.032 -.060 -.057

Education level .148 .189� .157� .247�� .176� .289�� .272�� -.071 -.261�� -.125

Partner status

(yes = 1; no = 0)

.413�� .372�� .055 .012 .268�� .151 .332�� -.382�� -.342�� -.356��

Country

(Spain = 1;

Netherlands = 0)

-.189� -.120 -.161� -.039 -.140 .027 -.160� -.013 .048 .201�

Behavioral social indicators

Social withdrawal 1

Interpersonal

functioning

.541�� 1

Independence-

competence

.256�� .320�� 1

Independence-

performance

.283�� .361�� .605�� 1

Recreational

activities

.437�� .389�� .359�� .440�� 1

Prosocial

activities

.465�� .482�� .343�� .492�� .564�� 1

Total SFS score .715�� .763�� .595�� .671�� .749�� .755�� 1

Affective social indicators

Perceived social

disability

-.572�� -.681�� -.357�� -.307�� -.414�� -.504�� -.662�� 1

Rater-perceived

social disability

-.560�� -.598�� -.434�� -.483�� -.496�� -.616�� -.730�� .785�� 1

Loneliness -.556�� -.615�� -.296�� -.278�� -.357�� -.393�� -.594�� .615�� .536�� 1

�p-value < 0.05,

�� p-value<0.01,

��� p-value<0.001.

https://doi.org/10.1371/journal.pone.0263769.t002

Fig 1. Unadjusted mean scores for total SFS, loneliness and perceived social disability across psychopathology.

Error bars represent the standard error. Y axis depicts the different scores. �p-value< 0.05, �� p-value<0.01, ��� p-

value<0.001.

https://doi.org/10.1371/journal.pone.0263769.g001

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Linear regression analyses (Table 5) examined the association between clinical characteris-

tics (severity of disorder, mood, positive/negative affect) and social functioning indices among

SZ and AD patients adjusted for aforementioned covariates. Overall, only a few predictors

were found to associate strongly with overall disease severity. More AD symptomatology was

associated with fewer prosocial activities (β = -0.400, p = 0.014). More negative SZ symptom-

atology was associated with less interpersonal functioning (β = -0.330, p = 0.010), and more

Table 3. Mean adjusted† social functioning scores across disorders compared with healthy controls.

Schizophrenia

patients N = 56

Younger healthy

controls N = 29

p-value Effect size

Cohen’s d Alzheimer’s disease

patients N = 50

Older healthy

controls N = 28

p-value Effect size

Cohen’s d Behavioral social functioning indicators

Social withdrawal, mean

(SE)

10.4 (0.5) 13.3 (0.6) <0.001 1.30 12.3 (0.5) 13.1 (0.6) 0.74 0.35

Interpersonal functioning,

mean (SE)

6.4 (0.4) 8.5 (0.4) <0.001 1.33 8.1 (0.4) 8.8 (0.4) 0.43 0.66

Independence-

competence, mean (SE)

36.2 (0.7) 38.7 (0.8) 0.002 0.81 33.9 (0.8) 37.0 (0.8) <0.001 1.06

Independence-

performance, mean (SE)

29.4 (1.1) 34.6 (1.3) <0.001 1.04 28.1 (1.2) 32.4 (1.3) <0.001 0.96

Recreation activities,

mean (SE)

19.3 (1.4) 24.5 (1.7) 0.002 0.81 23.2 (1.6) 28.3 (1.7) 0.002 0.83

Prosocial activities, mean

(SE)

24.8 (2.1) 36.8 (2.6) <0.001 1.25 28.6 (2.4) 34.5 (2.5) 0.030 0.65

Total SFS score, mean

(SE)

111.2 (1.7) 125.3 (2.1) <0.001 1.80 116.5 (1.9) 124.9 (2.0) <0.001 1.14

Affective social functioning indicators

Perceived social disability,

mean (SE)

11.3 (0.8) 6.1 (1.0) <0.001 1.39 6.1 (0.9) 5.5 (1.0) 1.00 0.17

Rater-perceived social

disability, mean (SE)

12.2 (0.8) 5.7 (1.0) <0.001 1.69 10.5 (1.0) 6.0 (1.0) <0.001 1.29

Loneliness, mean (SE) 4.6 (0.6) 0.4 (0.8) <0.001 1.45 2.0 (0.7) 1.8 (0.8) 1.00 0.05

† Adjusted for age, sex, years of education, partner status and country. Bonferroni adjustment for multiple comparisons.

https://doi.org/10.1371/journal.pone.0263769.t003

Table 4. Mean adjusted† social functioning scores across disorders with effect sizes (N = 106).

Schizophrenia patients N = 56 Alzheimer’s disease patients N = 50 p-value Effect size d Behavioral social indicators

Social withdrawal, mean (SE) 10.4 (0.5) 12.3 (0.5) 0.27 0.40

Interpersonal functioning, mean (SE) 6.4 (0.4) 8.1 (0.4) 0.08 0.28

Independence-competence, mean (SE) 36.2 (0.7) 33.9 (0.8) 0.54 0.33

Independence-performance, mean (SE) 29.4 (1.1) 28.1 (1.2) 1.00 0.13

Recreational activities, mean (SE) 19.3 (1.4) 23.2 (1.6) 0.98 0.27

Pro-social activities, mean (SE) 24.8 (2.1) 28.6 (2.4) 1.00 0.18

Total SFS score, mean (SE) 111.2 (1.7) 116.5 (1.9) 0.70 0.31

Affective social indicators

Perceived social disability, mean (SE) 11.3 (0.8) 6.1 (0.9) 0.008 0.65

Rater-perceived social disability, mean (SE) 12.2 (0.8) 10.5 (1.0) 1.00 0.20

Loneliness, mean (SE) 4.6 (0.6) 2.0 (0.7) 0.21 0.41

† Adjusted for age, sex, years of education, partner status and country. Bonferroni adjustment for multiple comparisons.

https://doi.org/10.1371/journal.pone.0263769.t004

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positive SZ symptoms related to more loneliness (β = 0.278, p = 0.049). Disease severity was

not associated with the total SFS.

More consistent associations were found for mood state indicators (Table 5). Across both

diagnostic groups, positive affect was associated with all behavioral and affective social func-

tioning indicators, except for independence-competence and -performance. More favorable

social functioning was found for those with less depressive symptomatology, less anxiety and

better mood state. Across patient groups, positive mood and lower depression and anxiety lev-

els were thus strongly associated with better social functioning, even more so than severity of

disease per patient group.

Discussion

The current study presents novel findings from the pan-European PRISM project on cross-dis-

order and disorder-specific deficits in social functioning among SZ and AD patients. As com-

pared to HC, both behavioral and affective social functioning are clearly poorer in SZ patients

(Cohens d’s 0.81–1.69), whereas AD patients have mostly poorer behavioral social function

(Cohen’s d’s 0.65–1.14). Behavioral indices of social functioning were fairly similar across

patient groups, SZ patients have more feelings socially disability than AD patients (Cohen’s d 0.65). Across patient groups, positive mood, lower depression and anxiety levels were strong

determinants of better social functioning (p’s <0.001), even more so than severity of disease.

Overall, this indicates that SZ and AD patients have rather similar social functioning levels in

terms of behavior, but affective social functioning is different.

Table 5. Adjusted† associations of clinical characteristics and various social functioning indicators within the group of patients (AD N = 50, SZ = 56).

ADAS-Cog AD

only β PANSS positive

symptoms SZ only β PANSS negative

symptoms SZ only β Depression severity

AD and SZ β Anxiety severity

AD and SZ β PANAS positive

affect AD and SZ

β

PANAS negative

affect AD and SZ

β

Behavioral social indicators

Social withdrawal 0.173 -0.224 -0.053 -0.555��� -0.413��� 0.414��� -0.355��

Interpersonal

functioning

-0.059 -0.072 -0.330� -0.522��� -0.424��� 0.468��� -0.309��

Independence-

competence

-0.166 0.009 -0.224 -0.151 -0.132 0.158 -0.175

Independence-

performance

-0.158 -0.039 -0.151 -0.102 -0.121 0.166 -0.091

Recreational

activities

-0.263 -0.124 -0.021 -0.166 -0.169 0.395��� -0.158

Pro-social activities -0.400� -0.054 -0.077 -0.312�� -0.165 0.366��� -0.043

Total SFS score -0.242 -0.111 -0.205 -0.498��� -0.399��� 0.561��� -0.310��

Affective social indicators

Perceived social

disability

0.194 -0.082 0.238 0.650��� 0.423��� -0.516��� 0.274��

Rater-perceived

social disability

0.322 -0.274 0.177 0.424��� 0.232� -0.336�� 0.125

Loneliness -0.163 0.278� 0.227 0.653��� 0.495��� -0.370�� 0.445���

† adjusted for sex, age, educational years, partner status and country.

�p-value < 0.05,

�� p-value<0.01,

��� p-value<0.001.

https://doi.org/10.1371/journal.pone.0263769.t005

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Consistent with our earlier observations [43], we observed a putative lack of insight among

AD patients, who perceive their social disability on the same level as healthy controls, whereas

AD informants and research staff perceive their social disability as significantly more impaired.

By contrast the current data suggest that SZ patients are more aware of their own social disabil-

ities than AD patients, an observation that warrants further investigation in future studies

[48]. Findings are in line with previous research in AD patients where it was shown that a

strong self-concept was associated with larger social dysfunction discrepancy comparing self-

rating with caregiver rating [24]. Interestingly, social functioning in both diagnostic groups

was found to be more strongly associated with mood than by current state of the disorders.

For SZ patients impairments in behavioral social functioning are consistently described

[14, 49, 50], as are impairments in affective social functioning, such as feeling lonely and

socially impaired [51–53]. Our results seem consistent with and replicate this previous SZ

research. Findings for AD patients are less unequivocal. Impairments in behavioral social

functioning for AD patients are described as rather subtle in an early stage of the disease [21,

23]. In our study, however, AD patients differed from their matched HC group on most behav-

ioral social functioning indices. It is possible that broad assessment of social functioning as

implemented here could easier reveal subtle differences in specific aspects of social behavior.

Among affective social indicators, feelings of loneliness were similar between AD and their

matched healthy controls, as was found before [54].

When comparing SZ and AD patients on behavioral social functioning, a highly similar pat-

tern of (dys)functioning emerged. This was especially true for the combined SFS outcomes.

The largest differences between the patient groups emerged for the affective social indicators.

For instance, patients with SZ evaluated themselves as less capable in social contact than AD

patients. This suggests that patients have quite similar social functioning behavior but may

evaluate this differently. It has been shown that feelings of loneliness are not necessarily

reflected by objective social isolation [51, 55]. AD patients evaluated their perceived social dis-

ability on the same level as their matched healthy controls, whereas an informant evaluated

their social abilities as strongly impaired. This suggest that AD patients may have an overly

positive view of their own social functioning, possibly leading to underreporting of their

impairments. This overestimation of their own social functioning, as compared to informants,

has been described before [24, 43] and has been linked to loss of awareness due to AD [23].

Lack of awareness of social dysfunction is related to greater distress among the caregivers of

AD patients [20, 23]. Mood influenced social functioning to a large extent, especially the affec-

tive indicators, with better mood associated with more favorable affective social outcomes. The

large impact of anxiety and depressive disorders on social functioning has been described

before, although the underlying pathophysiological mechanisms remain largely unknown.

One hypothesis argues that imbalanced brain network function (especially in the brain’s

default mode network [56]) not only impedes adaptive social functioning, but also interferes

with maintenance of stable (positive) mood [9, 57, 58]. Current severity of disease in SZ and

AD had only minor influence on social functioning indicators, as was previously found for AD

[22] and SZ [49], although the reverse has been described as well [50, 54].

The PRISM study described here is unique in its comparison of two patient groups with dis-

tinctive pathologies and age-ranges, in relation to various indicators of social functioning.

Transdiagnostic research is limited by the fact that similar, uniform instruments are often not

used in different disease populations. We argue that such standardization of specific outcomes

is necessary to progress the transdiagnostic research field. It could be that underlying contrib-

uting factors to social functioning are not perse similar across different disease conditions, but

this does not mean that certain outcomes, like social functioning, cannot be measured in a uni-

form way. Some limitations inherent to the study should be mentioned. First, our data are

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PLOS ONE | https://doi.org/10.1371/journal.pone.0263769 April 14, 2022 11 / 16

cross-sectional, thereby not allowing for causal interpretations. Second, data is based on self-

or informer-based evaluation, which may have resulted in biased responding. Passive monitor-

ing of social behavior is a promising development to objectively measure ambulatory behavior

and tackle possible self-report bias. Smartphone technology such as the BEHAPP-app [43, 59,

60] will allow the comparison of perceived social functioning with objective measurements.

Third, we excluded the employment subscale of the SFS, since most AD patients and older

HC’s were retired or not working, in line with other research [38]. However, inclusion of the

employment subscale would arguably increase differences in social functioning between youn-

ger SZ patients and younger HC’s. Fourth, we made a distinction between behavioral (i.e.

more quantitative) and affective (i.e. more perceptions of own social dysfunction) social indi-

cators, which bears some clear benefits and is supported by prior work, but may ultimately

pose an oversimplification of a complex phenomenon. Future work is therefore warranted to

further explore and validate the findings and interpretations of the current study.

In summary, the present study reveals that behavioral aspects of social functioning are

rather similarly affected in SZ and AD, whilst the affective perception of this behavior seems

partly different in the two patient groups. Patients diagnosed with AD evaluate their interper-

sonal relations as only mildly impaired, whereas patients diagnosed with SZ have a more nega-

tive perspective of their own social functioning. AD patients may underreport their

impairments in social functioning. Future research on social functioning should make a dis-

tinction between behavioral and affective indicators of social functioning, as these may associ-

ate differentially with pathophysiology. Findings further suggest that mood is highly associated

with social functioning. This study may serve as a point of departure for future cross-disorder

studies into the neurobiological underpinnings of social impairments in SZ and AD.

Supporting information

S1 Table. Factor analyses of the six subscales of the social functioning scale.

(DOCX)

S2 Table. Mean scaled social functioning scale scores (N = 163).

(DOCX)

S3 Table. I. Perceived social disability (WHO-DAS score) availability across patient groups.

II. Perceived social disability correlations across groups.

(DOCX)

Acknowledgments

We thank the editor and the reviewers for their constructive feedback to improve the quality

and understanding of the study.

Author Contributions

Conceptualization: Nic J. A. van der Wee, Amy C. Bilderbeck, Inge Winter van Rossum,

Celso Arango, Gerard R. Dawson, José L. Ayuso-Mateos, Martien J. Kas, Brenda W. J. H.

Penninx.

Data curation: Niels Jongs, Lianne M. Reus, Alejandro de la Torre-Luque.

Formal analysis: Ilja M. J. Saris, Alejandro de la Torre-Luque, Asad Malik, Brenda W. J. H.

Penninx.

PLOS ONE Social functioning among schizophrenia and alzheimer’s disease patients

PLOS ONE | https://doi.org/10.1371/journal.pone.0263769 April 14, 2022 12 / 16

Funding acquisition: Nic J. A. van der Wee, Celso Arango, Gerard R. Dawson, José L. Ayuso-

Mateos, Martien J. Kas, Brenda W. J. H. Penninx.

Investigation: Ilja M. J. Saris, Niels Jongs, Nic J. A. van der Wee, Inge Winter van Rossum,

Gerard R. Dawson, Brenda W. J. H. Penninx.

Project administration: Lianne M. Reus, Amy C. Bilderbeck, Inge Winter van Rossum, Ale-

jandro de la Torre-Luque, Asad Malik, Andreea Raslescu, Martien J. Kas.

Supervision: Moji Aghajani, Martien J. Kas, Brenda W. J. H. Penninx.

Writing – original draft: Ilja M. J. Saris, Moji Aghajani, Brenda W. J. H. Penninx.

Writing – review & editing: Ilja M. J. Saris, Moji Aghajani, Niels Jongs, Lianne M. Reus, Nic J.

A. van der Wee, Amy C. Bilderbeck, Inge Winter van Rossum, Celso Arango, Alejandro de

la Torre-Luque, Asad Malik, Andreea Raslescu, Gerard R. Dawson, José L. Ayuso-Mateos,

Martien J. Kas, Brenda W. J. H. Penninx.

References 1. Holt-Lunstad J, Smith TB, Layton JB. Social relationships and mortality risk: A meta-analytic review.

PLoS Med. 2010; 7. https://doi.org/10.1371/journal.pmed.1000316 PMID: 20668659

2. Hawkley LC, Cacioppo JT. Loneliness Matters: A Theoretical and Empirical Review of Consequences

and Mechanisms. Ann Behav Med. 2010; 40. https://doi.org/10.1007/s12160-010-9210-8 PMID:

20652462

3. Adolphs R. The social brain: neural basis of social knowledge. Annu Rev Psychol. 2009; 60: 693–716.

https://doi.org/10.1146/annurev.psych.60.110707.163514 PMID: 18771388

4. van der Wee NJA, Bilderbeck AC, Cabello M, Ayuso-Mateos JL, Saris IMJ, Giltay EJ, et al. Working def-

initions, subjective and objective assessments and experimental paradigms in a study exploring social

withdrawal in schizophrenia and Alzheimer’s disease. Neuroscience and Biobehavioral Reviews. 1 Feb

2019 97: 38–46. https://doi.org/10.1016/j.neubiorev.2018.06.020 PMID: 29949732

5. Cacioppo JT, Cacioppo S, Capitanio JP, Cole SW. The Neuroendocrinology of Social Isolation. Annu

Rev Psychol. 2015; 66: 733–67. https://doi.org/10.1146/annurev-psych-010814-015240 PMID:

25148851

6. Bierman KL, Welsh JA. Assessing Social Dysfunction: the Contributions of Laboratory and Perfor-

mance-Based Measure. J Clin Child Psychol. 2000; 29: 526–539. https://doi.org/10.1207/

S15374424JCCP2904_6 PMID: 11126631

7. Cullen KR, Westlund MK, Klimes-Dougan B, Mueller BA, Houri A, Eberly LE, et al. Abnormal amygdala

resting-state functional connectivity in adolescent depression. JAMA Psychiatry. 2014; 71: 1138–1147.

https://doi.org/10.1001/jamapsychiatry.2014.1087 PMID: 25133665

8. Porcelli S, Van Der Wee N, van der Werff S, Aghajani M, Glennon JC, van Heukelum S, et al. Social

brain, social dysfunction and social withdrawal. Neurosci Biobehav Rev. 2019; 97: 10–33. https://doi.

org/10.1016/j.neubiorev.2018.09.012 PMID: 30244163

9. Saris IMJ, Aghajani M, Werff SJA, Wee NJA, Penninx BWJH. Social functioning in patients with depres-

sive and anxiety disorders. Acta Psychiatr Scand. 2017; 136: 352–361. https://doi.org/10.1111/acps.

12774 PMID: 28767127

10. Cacioppo S, Grippo AJ, London S, Goossens L, Cacioppo JT. Loneliness: Clinical Import and Interven-

tions. Perspect Psychol Sci. 2015; 10: 238–249. https://doi.org/10.1177/1745691615570616 PMID:

25866548

11. Dickens A.; Richards S.; Greaves C. & Campbell J. Interventions targeting social isolation in older peo-

ple: a systematic review. BMC Public Health. 2011; 11: 647. https://doi.org/10.1186/1471-2458-11-647

PMID: 21843337

12. Cacioppo JT, Hughes ME, Waite LJ, Hawkley LC, Thisted RA. Loneliness as a specific risk factor for

depressive symptoms: Cross-sectional and longitudinal analyses. Psychol Aging. 2006; 21: 140–151.

https://doi.org/10.1037/0882-7974.21.1.140 PMID: 16594799

13. Rico-Uribe LA, Caballero FF, Olaya B, Tobiasz-Adamczyk B, Koskinen S, Leonardi M, et al. Loneliness,

social networks, and health: A cross-sectional study in three countries. PLoS One. 2016. https://doi.org/

10.1371/journal.pone.0145264 PMID: 26761205

PLOS ONE Social functioning among schizophrenia and alzheimer’s disease patients

PLOS ONE | https://doi.org/10.1371/journal.pone.0263769 April 14, 2022 13 / 16

14. Green MF, Horan WP, Lee J. Social cognition in schizophrenia. Nat Rev Neurosci. 2015; 16: 620–631.

https://doi.org/10.1038/nrn4005 PMID: 26373471

15. Galderisi S, Mucci A, Buchanan RW, Arango C. Negative symptoms of schizophrenia: new develop-

ments and unanswered research questions. The lancet Psychiatry. 2018; 5: 664–677. https://doi.org/

10.1016/S2215-0366(18)30050-6 PMID: 29602739

16. Yang C, Qi A, Yu H, Guan X, Wang J, Liu N, et al. Different levels of facial expression recognition in

patients with firstepisode schizophrenia: A functional MRI study. Gen Psychiatry. 2018; 31: 1–6. https://

doi.org/10.1136/gpsych-2018-000014 PMID: 30582127

17. Maat A, van Haren NEM, Bartholomeusz CF, Kahn RS, Cahn W. Emotion recognition and theory of

mind are related to gray matter volume of the prefrontal cortex in schizophrenia. Eur Neuropsychophar-

macol. 2016; 26: 255–264. https://doi.org/10.1016/j.euroneuro.2015.12.013 PMID: 26711688

18. Addington J, Addington D. Social and cognitive functioning in psychosis. Schizophr Res. 2008; 99:

176–181. https://doi.org/10.1016/j.schres.2007.07.004 PMID: 17681756

19. Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016; 388: 86–97. https://doi.org/10.1016/

S0140-6736(15)01121-6 PMID: 26777917

20. Belfort T, Simões P, de Sousa MFB, Santos RL, Barbeito I, Torres B, et al. The Relationship Between

Social Cognition and Awareness in Alzheimer Disease. J Geriatr Psychiatry Neurol. 2018; 31: 27–33.

https://doi.org/10.1177/0891988717743587 PMID: 29187026

21. Henry JD, Von Hippel W, Molenberghs P, Lee T, Sachdev PS. Clinical assessment of social cognitive

function in neurological disorders. Nat Rev Neurol. 2016; 12: 28–39. https://doi.org/10.1038/nrneurol.

2015.229 PMID: 26670297

22. Cosentino S, Zahodne LB, Brandt J, Blacker D, Albert M, Dubois B, et al. Social cognition in Alzheimer’s

disease: A separate construct contributing to dependence. Alzheimer’s Dement. 2014; 10: 818–826.

https://doi.org/10.1016/j.jalz.2013.12.021 PMID: 24656839

23. Nelis SM, Clare L, Martyr A, Markova I, Roth I, Woods RT, et al. Awareness of social and emotional

functioning in people with early-stage dementia and implications for carers. Aging Ment Heal. 2011; 15:

961–969. https://doi.org/10.1080/13607863.2011.575350 PMID: 21722021

24. Clare L, Nelis SM, Martyr A, Roberts J, Whitaker CJ, Markova IS, et al. The influence of psychological,

social and contextual factors on the expression and measurement of awareness in early-stage demen-

tia: Testing a biopsychosocial model. Int J Geriatr Psychiatry. 2012; 27: 167–177. https://doi.org/10.

1002/gps.2705 PMID: 21425345

25. Insel T, Cuthbert B, Garvey M, Heinssen R, Pine D, Quinn K, et al. Research Domain Criteria (RDoC):

Toward a New Classification Framework for Research on Mental Disorders. Am J Psychiatry Online.

2010; 167: 748–751. https://doi.org/10.1176/appi.ajp.2010.09091379 PMID: 20595427

26. Haro JM, Ayuso-Mateos JL, Bitter I, Demotes-Mainard J, Leboyer M, Lewis SW, et al. ROAMER: Road-

map for mental health research in Europe. Int J Methods Psychiatr Res. 2014; 23: 1–14. https://doi.org/

10.1002/mpr.1406 PMID: 24375532

27. Fusar-Poli P, Solmi M, Brondino N, Davies C, Chae C, Politi P, et al. Transdiagnostic psychiatry: a sys-

tematic review.

28. Sauer-Zavala S, Gutner CA, Farchione TJ, Boettcher HT, Bullis JR, Barlow DH. Current Definitions of

“Transdiagnostic” in Treatment Development: A Search for Consensus. Behav Ther. 2017; 48: 128–

138. https://doi.org/10.1016/j.beth.2016.09.004 PMID: 28077216

29. Mansell M, Harvey A, Watkins E, Shafran R. Conceptual foundations of the transdiagnostic approach to

CBT. J Cogn Psychother. 2009; 23: 6–19.

30. Kas MJ, Penninx B, Sommer B, Serretti A, Arango C, Marston H. A quantitative approach to neuropsy-

chiatry: The why and the how. Neurosci Biobehav Rev. 2019; 97: 3–9. https://doi.org/10.1016/j.

neubiorev.2017.12.008 PMID: 29246661

31. Cuthbert BN. The PRISM project: Social withdrawal from an RDoC perspective. Neurosci Biobehav

Rev. 2019; 97: 34–37. https://doi.org/10.1016/j.neubiorev.2018.08.006 PMID: 30107226

32. Bilderbeck AC, Penninx BWJH, Arango C, van der Wee N, Kahn R, Winter-van Rossum I, et al. Over-

view of the clinical implementation of a study exploring social withdrawal in patients with schizophrenia

and Alzheimer’s disease. Neurosci Biobehav Rev. 2019; 97: 87–93. https://doi.org/10.1016/j.neubiorev.

2018.06.019 PMID: 29940238

33. Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia.

Schizophr Bull. 1987; 13: 261–275. https://doi.org/10.1093/schbul/13.2.261 PMID: 3616518

34. Tombaugh TN, McIntyre NJ. The Mini-Mental State Examination: A Comprehensive Review. J Am Ger-

iatr Soc. 1992; 40: 922–935. https://doi.org/10.1111/j.1532-5415.1992.tb01992.x PMID: 1512391

PLOS ONE Social functioning among schizophrenia and alzheimer’s disease patients

PLOS ONE | https://doi.org/10.1371/journal.pone.0263769 April 14, 2022 14 / 16

35. Sheehan D V., Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International

Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychi-

atric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998; 59: 22–33. PMID: 9881538

36. Rush AJ, Gullion CM, Basco MR, Jarrett RB, Trivedi MH. The Inventory of Depressive Symptomatology

(IDS): psychometric properties. Psychol Med. 1996; 26: 477–86. https://doi.org/10.1017/

s0033291700035558 PMID: 8733206

37. Chouinard G, Margolese HC. Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophr

Res. 2005; 76: 247–265. https://doi.org/10.1016/j.schres.2005.02.013 PMID: 15949657

38. Vázquez Morejón AJ, Jiménez G-Bóveda R. Social Functioning Scale: New contributions concerning

its psychometric characteristics in a Spanish adaptation. Psychiatry Res. 2000; 93: 247–256. https://

doi.org/10.1016/s0165-1781(99)00123-7 PMID: 10760383

39. Birchwood M, Smith J, Cochrane R, Wetton S, Copestake S. The Social Functioning Scale. The devel-

opment and validation of a new scale of social adjustment for use in family intervention programmes

with schizophrenic patients. Br J Psychiatry. 1990; 157: 853–859. https://doi.org/10.1192/bjp.157.6.853

PMID: 2289094

40. Iffland JR, Lockhofen D, Gruppe H, Gallhofer B, Sammer G, Hanewald B. Validation of the German ver-

sion of the Social Functioning Scale (SFS) for schizophrenia. PLoS One. 2015; 10: 1–18. https://doi.

org/10.1371/journal.pone.0121807 PMID: 25837711

41. de Jong-Gierveld J, Kamphuis F, Kamphuls F. The Development of a Rasch-Type Loneliness Scale.

Appl Psychol Meas. 1985; 9: 289–299. https://doi.org/10.1177/014662168500900307

42. Üstün TB, Chatterji S, Kostanjsek N, Rehm J, Kennedy C, Jordan JE, et al. Developing the World Health

Organization Disability Assessment Schedule 2.0. Bull World Health Organ. 2010; 88: 815–823. https://

doi.org/10.2471/BLT.09.067231 PMID: 21076562

43. Jongs N, Penninx B, Arango C, Ayuso-Mateos JL, van der Wee N, van Rossum IW, et al. Effect of dis-

ease related biases on the subjective assessment of social functioning in Alzheimer’s disease and

schizophrenia patients. J Psychiatr Res. 2020. https://doi.org/10.1016/j.jpsychires.2020.11.013 PMID:

33221026

44. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry. 1984;

141: 1356–1364. https://doi.org/10.1176/ajp.141.11.1356 PMID: 6496779

45. Spielberger CD, Gorsuch RL, Lushene R, Vagg PR, Jacobs GA. Manual for the State-Trait Anxiety

Inventory. Palo Alto, CA: Consulting Psychologists Press. 1983.

46. Watson D, Clark LA, Tellegen A. Development and Validation of Brief Measures of Positive and Nega-

tive Affect: The PANAS Scales. J Pers Soc Psychol. 1988; 54: 1063–1070. https://doi.org/10.1037//

0022-3514.54.6.1063 PMID: 3397865

47. Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale: Lawrence Erlbaum Associ-

ates; 1988.

48. Parellada M, Boada L, Fraguas D, Reig S, Castro-Fornieles J, Moreno D, et al. Trait and state attributes

of insight in first episodes of early-onset schizophrenia and other psychoses: A 2-year longitudinal

study. Schizophr Bull. 2011; 37: 38–51. https://doi.org/10.1093/schbul/sbq109 PMID: 20884756

49. Lysaker PH, McCormick BP, Snethen G, Buck KD, Hamm JA, Grant M, et al. Metacognition and social

function in schizophrenia: Associations of mastery with functional skills competence. Schizophr Res.

2011; 131: 214–218. https://doi.org/10.1016/j.schres.2011.06.011 PMID: 21745724

50. Simons CJP, Bartels-Velthuis AA, Pijnenborg GHM. Cognitive Performance and Long-Term Social

Functioning in Psychotic Disorder: A Three-Year Follow-Up Study. PLoS One. 2016; 11: e0151299.

https://doi.org/10.1371/journal.pone.0151299 PMID: 27082629

51. Trémeau F, Antonius D, Malaspina D, Goff DC, Javitt DC. Loneliness in schizophrenia and its possible

correlates. An exploratory study. Psychiatry Res. 2016; 246: 211–217. https://doi.org/10.1016/j.

psychres.2016.09.043 PMID: 27721059

52. Eglit GML, Palmer BW, Martin AS, Tu X, Jeste D V. Loneliness in schizophrenia: Construct clarification,

measurement, and clinical relevance. PLoS One. 2018; 13: 1–20. https://doi.org/10.1371/journal.pone.

0194021 PMID: 29566046

53. Green MF, Horan WP, Lee J, McCleery A, Reddy LF, Wynn JK. Social Disconnection in Schizophrenia

and the General Community. Schizophr Bull. 2018; 44: 242–249. https://doi.org/10.1093/schbul/sbx082

PMID: 28637195

54. Balouch S, Rifaat E, Chen HL, Tabet N. Social networks and loneliness in people with Alzheimer’s

dementia. Int J Geriatr Psychiatry. 2019; 34: 666–673. https://doi.org/10.1002/gps.5065 PMID:

30706526

55. Holwerda TJ, Deeg DJH, Beekman ATF, Van Tilburg TG, Stek ML, Jonker C, et al. Feelings of loneli-

ness, but not social isolation, predict dementia onset: Results from the Amsterdam Study of the Elderly

PLOS ONE Social functioning among schizophrenia and alzheimer’s disease patients

PLOS ONE | https://doi.org/10.1371/journal.pone.0263769 April 14, 2022 15 / 16

(AMSTEL). J Neurol Neurosurg Psychiatry. 2014; 85: 135–142. https://doi.org/10.1136/jnnp-2012-

302755 PMID: 23232034

56. Spreng RN, Andrews-Hanna JR. The Default Network and Social Cognition. Brain Mapping: An Ency-

clopedic Reference. Elsevier Inc.; 2015. pp. 165–169.

57. Kupferberg A, Bicks L, Hasler G. Social functioning in major depressive disorder. Neurosci Biobehav

Rev. 2016; 69: 313–332. https://doi.org/10.1016/j.neubiorev.2016.07.002 PMID: 27395342

58. Santini ZI, Koyanagi A, Tyrovolas S, Mason C, Haro JM. The association between social relationships

and depression: A systematic review. J Affect Disord. 2015; 175: 53–65. https://doi.org/10.1016/j.jad.

2014.12.049 PMID: 25594512

59. Eskes P, Spruit M, Brinkkemper S, Vorstman J, Kas MJ. The sociability score: App-based social profil-

ing from a healthcare perspective. Comput Human Behav. 2016; 59: 39–48.

60. Jongs N, Jagesar R, Van Haren NEM, Penninx BWJH, Reus L, Visser PJ, et al. A framework for

assessing neuropsychiatric phenotypes by using smartphone-based location data. Transl Psychiatry.

2020; 10. https://doi.org/10.1038/s41398-020-00893-4 PMID: 32612118

PLOS ONE Social functioning among schizophrenia and alzheimer’s disease patients

PLOS ONE | https://doi.org/10.1371/journal.pone.0263769 April 14, 2022 16 / 16

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