Psychological Medicine
camb idge.o g/psm
O iginal A icle
Ci e his a icle: González-O ega I e al
(2020). In luence o social cogni ion as a
media o be ween cogni i e ese e and
psychosocial unc ioning in pa ien s wi h i s
episode psychosis. Psychological Medicine 50,
2702–2710. h ps://doi.o g/10.1017/
S0033291719002794
Recei ed: 23 Janua y 2019
Re ised: 9 Augus 2019
Accep ed: 13 Sep embe 2019
Fi s published online: 22 Oc obe 2019
Key wo ds:
Cogni i e ese e; i s episode psychosis;
psychosocial unc ioning; social cogni ion
Au ho o co espondence:
I González-O ega,
E-mail: i xaso.gonzalezo ega@osakide za.eus
©The Au ho (s) 2019. This is an Open Access
a icle, dis ibu ed unde he e ms o he
C ea i e Commons A ibu ion licence (h p://
c ea i ecommons.o g/licenses/by/4.0/), which
pe mi s un es ic ed euse, dis ibu ion, and
ep oduc ion in any medium, p o ided he
o iginal wo k is p ope ly ci ed.
In luence o social cogni ion as a media o
be ween cogni i e ese e and psychosocial
unc ioning in pa ien s wi h i s
episode psychosis
I González-O ega1,2,3,4 , A González-Pin o1,2,3, S Albe ich1,2,3,4, E Echebu úa1,5,
M Be na do1,6, B Cab e a1,6, S Amo e i1,6, A Lobo1,7, C A ango1,8, I Co ipio1,9,
E Vie a1,10, E de la Se na1,11, R Rod iguez-Jimenez1,12, R Sega a1,13,
JM López-Ilundain14, AM Sánchez-To es14, MJ Cues a14, PEPs G oup:
I Zo illa1,2,3, P López1,2,3, M Bioque1,6, G Mezquida1,6, F Ba cones7,15,
C De-la-Cáma a1,7, M Pa ellada1,8, A Espliego1,8, A Alonso-Solís1,9, EM G asa1,9,
C Va o10, L Mon ejo1,10, J Cas o-Fo nieles1,11, I Baeza1,11, M Dompablo1,12,
I To io1,12, A Zabala1,13, JI Eguiluz1,13, L Mo eno-Izco14, J Sanjuan1,16, R Gui ado17,
I Cáce es18, P Ga nie 18, F Con e as1,19,20, J Bobes1,21, S Al-Halabí1,21,22,
J Usall1,23, A Bu josa1,23, S Sa ó1,24, R Landin-Rome o24, A Ibáñez1,25
and G Sel a1,26
1
Cen e o Biomedical Resea ch in he Men al Heal h Ne wo k (CIBERSAM), Mad id, Spain;
2
Depa men o
Psychia y, A aba Uni e si y Hospi al, Bioa aba Resea ch Ins i u e, Vi o ia, Spain;
3
Depa men o Neu osciences,
Uni e si y o he Basque Coun y, Bizkaia, Spain;
4
The Na ional Dis ance Educa ion Uni e si y (UNED), Vi o ia,
Spain;
5
Depa men o Pe sonali y, Assessmen and Psychological T ea men , Uni e si y o he Basque Coun y,
San Sebas ián, Spain;
6
Ba celona Clinic Schizoph enia Uni , Neu oscience Ins i u e, Hospi al Clinic o Ba celona,
Ba celona, Spain;
7
Depa men o Medicine and Psychia y, Uni e si y o Za agoza, A agon Ins i u e o Heal h
Sciences (IIS A agón), Za agoza, Spain;
8
Child and Adolescen Psychia y Depa men , G ego io Ma añón Gene al
Uni e si y Hospi al, School o Medicine, Uni e sidad Complu ense, IiSGM, Mad id, Spain;
9
Depa men o
Psychia y, Ins i u d’In es igació Biomèdica-San Pau (IIB-SANT PAU), Hospi al de la San a C eu i San Pau,
Uni e si a Au ònoma de Ba celona (UAB), Ba celona, Spain;
10
Bipola Diso de s Uni , Hospi al Clinic, Uni e si y o
Ba celona, IDIBAPS, Ba celona, Spain;
11
Child and Adolescen Psychia y Se ice, Hospi al Clinic o Ba celona,
Ba celona, Spain;
12
12 de Oc ub e Hospi al Resea ch Ins i u e (i+12), Mad id, Spain;
13
Depa men o
Neu osciences, Uni e si y o he Basque Coun y, C uces Uni e si y Hospi al, Bioc uces Bizkaia Heal h Resea ch
Ins i u e, Vizcaya, Spain;
14
Depa men o Psychia y, Na a e Hospi al Complex, IdiSNA, Na a e Ins i u e o
Heal h Resea ch, Pamplona, Spain;
15
Depa men o Family Medicine, Hospi al Uni e si a io Miguel Se e ,
Za agoza, Spain;
16
INCLIVA, Uni e si y o Valencia, Hospi al Clinico Uni e si a io o Valencia, Spain;
17
Neu obiology
Uni , Depa men o Cell Biology, In e disciplina y Resea ch S uc u e o Bio echnology and Biomedicine
(BIOTECMED), Uni e si y o Valencia, Valencia, Spain;
18
Depa men o Psychia y, Hospi al del Ma Medical
Resea ch Ins i u e (IMIM), Ba celona, Spain;
19
Psychia y Depa men , Bell i ge Uni e si y Hospi al-IDIBELL,
Ba celona, Spain;
20
Depa men o Clinical Sciences, School o Medicine, Uni e si y o Ba celona, Ba celona,
Spain;
21
Psychia y Depa men , Uni e si y o O iedo, O iedo, Spain;
22
Ins i u e o Neu osciences o he
P incipali y o As u ias, INEUROPA, O iedo, Spain;
23
Resea ch Uni , Pa c Sani a i San Joan de Déu, Uni e si a de
Ba celona (UB), San Boi de Llob ega , Ba celona, Spain;
24
FIDMAG He manas Hospi ala ias Resea ch Founda ion,
Ba celona, Spain;
25
Psychia y Depa men , Ramón y Cajal Uni e si y Hospi al, Ramón y Cajal Heal h Resea ch
Ins i u e (IRyCIS), Uni e si y o Alcalá, Mad id, Spain and
26
Teaching Uni o Psychia y and Psychological
Medicine, Depa men o Medicine, Uni e si y o Valencia, INCLIVA Heal h Resea ch Ins i u e, Valencia, Spain
Abs ac
Backg ound. Social cogni ion has been associa ed wi h unc ional ou come in pa ien s wi h
i s episode psychosis (FEP). Social cogni ion has also been associa ed wi h neu ocogni ion
and cogni i e ese e. Al hough cogni i e ese e, neu ocogni i e unc ioning, social cogni-
ion, and unc ional ou come a e ela ed, he di ec ion o hei associa ions is no clea .
The e o e, he main aim o his s udy was o analyze he in luence o social cogni ion as a
media o be ween cogni i e ese e and cogni i e domains on unc ioning in FEP bo h a
baseline and a 2 yea s.
Me hods. The sample o he s udy was composed o 282 FEP pa ien s ollowed up o 2 yea s.
To analyze whe he social cogni ion media es he in luence o cogni i e ese e and cogni i e
domains on unc ioning, a pa h analysis was pe o med. The s a is ical signi icance o any
media ion e ec s was e alua ed by boo s ap analysis.
Resul s. A baseline, as nei he cogni i e ese e no he cogni i e domains s udied we e
ela ed o unc ioning, he condi ions o media ion we e no sa is ied. Ne e heless, a 2
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yea s o ollow-up, social cogni ion ac ed as a media o be ween cogni i e ese e and unc-
ioning. Likewise, social cogni ion was a media o be ween e bal memo y and unc ional ou -
come. The esul s o he boo s ap analysis con i med hese signi ican media ions (95%
boo s apped CI (−10.215 o −0.337) and (−4.731 o −0.605) espec i ely).
Conclusions. Cogni i e ese e and neu ocogni ion a e ela ed o unc ioning, and social cog-
ni ion media es in his ela ionship.
In oduc ion
Neu ocogni ion, cogni i e ese e, and social cogni ion ha e all
been ela ed o unc ioning in i s -episode psychosis (FEP).
Speci ically, nume ous s udies ha e ound ha cogni i e de ici s
a e p esen ea ly in psychosis, mani es ing in mul iple cogni i e
domains including wo king memo y, execu i e unc ion, a en-
ion, p ocessing speed, and/o lea ning and memo y (Zabala
e al., 2010; González-O ega e al., 2013; Bo a and Mu ay,
2014). These de ici s ha e been ela ed o poo e psychosocial
unc ioning (Leeson e al., 2011; González-O ega e al., 2013;
G een and Ha ey, 2014; To galsbøen e al., 2015), bu some s ud-
ies ha e no ound his associa ion (K a a i i e al., 2003; S i ling
e al., 2003). O e all, he e is a lack o consensus on how cogni i e
unc ioning changes o e he cou se o he disease and i s ela ion
o unc ional ou come.
Cogni i e ese e has been associa ed wi h he unc ional
cou se o FEP, pa ien s wi h a highe cogni i e ese e showing
a be e ou come (Leeson e al., 2011; Amo e i e al., 2016).
Cogni i e ese e has been de ined as he abili y o a b ain o
cope wi h b ain pa hology and he eby minimize symp oms
(S e n, 2002) and a iables used as measu es o cogni i e ese e
include p emo bid IQ, educa ional le el, and occupa ional a ain-
men (Anaya e al., 2016).
Social cogni ion has also been associa ed wi h unc ional ou -
come. Indeed, i has been sugges ed ha social cogni ion is a be -
e p edic o o unc ional ou come o FEP pa ien s han
neu ocogni ion (Fe e al., 2011; Ohmu o e al., 2016). Social cog-
ni ion includes heo y o mind, social pe cep ion, social knowl-
edge, a ibu ional biases, and emo ion p ocessing, a eas ha a e
a ec ed in FEP pa ien s (Ho an e al., 2012; Bo a and Pan elis,
2013; Bliks ed e al., 2014). I has also been associa ed wi h neu-
ocogni ion and p emo bid IQ (Bliks ed e al., 2014) and he e is
e idence o a ela ionship be ween social cogni ion and neu ocog-
ni ion and ha his may ha e a nega i e in luence on unc ional
ou come o FEP (Schmid e al., 2011).
Al hough cogni i e ese e, neu ocogni i e unc ioning, social
cogni ion, and unc ional ou come a e p obably ela ed, he di ec-
ion o hei associa ions is no clea (Fe e al., 2011; Schmid
e al., 2011; Pinkham and Ha ey, 2012; Hedman e al., 2013;
Lin e al., 2013). In a sys ema ic e iew, Schmid e al.(2011)
ound ha social cogni ion ac s as a media o be ween neu ocog-
ni ion and unc ioning in schizoph enia (Schmid e al., 2011),
hough in indi iduals a clinical high isk o psychosis his was
no obse ed (Ba ba o e al., 2013).
The e o e, o p edic ing he ou come o FEP pa ien s a e he
onse o he disease, i is impo an o explo e he po en ial medi-
a ing ole o social cogni ion in he associa ion be ween neu ocog-
ni ion and unc ioning. In his con ex , ou s udy had he ollowing
objec i es: (1) o assess changes om baseline in cogni i e unc ion-
ing, social cogni ion, and unc ioning a 2 yea s o ollow-up in FEP
pa ien s; (2) o analyze he in luence o cogni i e ese e and cog-
ni i e domains on social cogni ion and unc ioning a baseline
and a 2 yea s o ollow-up; (3) o analyze he in luence o social
cogni ion on unc ioning; and (4) o analyze he in luence o social
cogni ion as a media o be ween cogni i e ese e and cogni i e
domains on unc ioning.
Me hod
Subjec s
This wo k was pa o he ‘Pheno ype-geno ype and en i onmen-
al in e ac ion. Applica ion o a p edic i e model in i s psycho ic
episodes’s udy (PEPs s udy, om i s ac onym in Spanish)
(Be na do e al., 2013).
Pa ien s we e aged be ween 18 and 35 yea s old a he ime o
i s e alua ion and we e equi ed o ha e luen Spanish and o
gi e w i en in o med consen . I pa ien s we e no capable o gi -
ing consen o mino s, a legally au ho ized ep esen a i e was
asked o p o ide consen on hei behal . Mo eo e , i was
equi ed ha pa ien s had a less han 12-mon h his o y o psych-
o ic symp oms.
Exclusion c i e ia o pa ien s we e: men al e a da ion acco d-
ing o he DSM-IV (Ame ican Psychia ic Associa ion, 1994)
(including no only an IQ below 70, as de e mined using he
es desc ibed in Table 1, bu also poo unc ioning), his o y o
head auma wi h he loss o consciousness, and o ganic illness
a ec ing men al heal h. The s udy was app o ed by he clinical
esea ch e hics commi ees o all pa icipa ing cen e s in he
PEPs G oup.
Ini ially, 335 FEP pa ien s we e included in he s udy. O hese,
53 pa ien s we e excluded o no ha ing se en o mo e neu o-
psychological es s comple ed. Thus, he inal s udy sample con-
sis ed o 282 pa ien s.
Da a collec ion
Sociodemog aphic and clinical da a we e collec ed a baseline and
a 2 yea s, while cogni i e assessmen was pe o med a 2 mon hs
o ollow-up, in o de o ensu e he psychopa hological s abili y o
pa ien s, and a 2 yea s o ollow-up. I pa ien s we e ac i ely
psycho ic a he ime o he 2-yea ollow-up, we delayed he
assessmen un il hei condi ion was s abilized. The assessmen
p o ocol was ully desc ibed by Be na do e al.(2013).
Adul pa ien s we e diagnosed wi h FEP using he S uc u ed
Clinical In e iew o DSM-IV Axis I and II Diso de s (Fi s
e al., 1997), while he Schedule o A ec i e Diso de s and
Schizoph enia o school-age child en-P esen and Li e ime e -
sion (Kau man e al., 1997) was used o hose unde 18 yea s
old, ollowing DSM-IV c i e ia.
Func ional impai men o pa ien s was e alua ed using he
unc ional assessmen sho es (FAST) (Rosa e al., 2007), o
which high sco es sugges poo e unc ioning. The FAST is a
measu e o unc ioning ha is alid, eliable, and sensi i e o
change and has been alida ed and widely used in bipola
Psychological Medicine 2703
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diso de (Rosa e al., 2011; Bonnín e al., 2018; Vie a e al., 2018),
a en ion-de ici hype ac i i y diso de (Ro ge e al., 2014), and
FEP (González-O ega e al., 2010).
The subs ance use was assessed using he Eu opean Adap a ion
o a Mul idimensional Assessmen Ins umen o D ug and
Alcohol Dependence (Eu opASI) and pa ien s we e ca ego ized
acco ding o Eu opASI sco es in o ou g oups (no use, use,
abuse, and dependence) (Kokke i and Ha ge s, 1995).
The ollowing cogni i e domains a e assessed: p ocessing
speed, a en ion, e bal memo y, wo king memo y execu i e
unc ion, and p emo bid IQ. The es s and measu es used o
domain summa y sco es a e desc ibed by Be na do e al.(2013)
and Cues a e al.(2015)(Table 1).
Es ima ed p emo bid IQ, educa ional le el, and occupa ional
a ainmen we e used as measu es o cogni i e ese e (Anaya
e al., 2016). IQ was e alua ed wi h he Vocabula y sub es o
Wechsle Adul In elligence Scale (Wechsle , 1997) o Wechsle
In elligence Scale o Child en-IV (Wechsle , 2003), while educa-
ional le el and occupa ional a ainmen a iables we e assessed
wi h he Hollingshead–Redlich Scale (Hollingshead and Redlich,
1958).
Social cogni ion was assessed wi h unde s anding emo ions,
managing emo ions, and o al emo ional in elligence sco es o
he Maye –Salo ey–Ca uso Emo ional In elligence Tes , which
a e he help ulness o ce ain moods and assess he e ec i eness
o s a egies o manage emo ions (Maye e al., 2009).
S a is ical analyses
Demog aphic a iables a e desc ibed wi h means (±S.D.) and pe -
cen ages. Tes s o pai ed samples we e used o analyze
di e ences in cogni i e pe o mance and unc ioning o pa ien s
be ween baseline and 2 yea s o ollow-up.
To assess he cogni i e domains, we calcula ed he a e age o
he z-sco es o he neu opsychological a iables which co es-
pond o each domain (Table 1). As he sco es o he T ail
Making Tes (Rei an and Wol son, 1985) a e in e se, hey
we e mul iplied by −1 o acili a e he in e p e a ion (highe
sco es indica ing be e pe o mance). The same app oach was
aken o cogni i e ese e, ha is, a e ages o he z-sco es
we e calcula ed o es ima ed p emo bid IQ, educa ional le el,
and occupa ional a ainmen .
To explo e whe he social cogni ion media es he in luence o
cogni i e ese e and cogni i e domains on unc ioning, a h ee-
s ep p ocedu e was used (F azie e al., 2004). Figu e 1 ep esen s
he hypo hesized media ion model. Fi s ly, we analyzed he ela-
ionship be ween cogni i e ese e and cogni i e domains wi h
social cogni ion wi h a linea eg ession (pa h a). Secondly, linea
eg ession models we e buil o explo e he associa ion o cogni i e
ese e and cogni i e domains (independen a iables) wi h unc-
ioning (dependen a iable) (pa h c). All models we e adjus ed
o po en ial con ounde s (namely, age, sex, ci il s a us, socio-
economic le el, educa ional le el, diagnosis, subs ance use, and
amily his o y) wi h a s epwise p ocedu e which only included a i-
ables in he inal model i hey p oduced a signi ican change in he
coe icien o he independen a iable. Finally, social cogni ion was
included as a media o in he mul iple eg essions ound o be sig-
ni ican in he second s ep (pa hs b and c´). I he ela ion o social
cogni ion wi h unc ioning was signi ican and he pa h c associ-
a ion became non-signi ican , condi ions o media ion would be
sa is ied, his sugges ing ha social cogni ion is a media ing a i-
able. The s a is ical signi icance o he media ion was examined
by boo s ap analysis (95% boo s apped con idence in e al (CI)).
Da a analyses we e conduc ed wi h S a a 12.1. The le el o sig-
ni icance was se a p< 0.05, excep o he analyses o he cogni-
ion domains o which we applied he Bon e oni co ec ion o
mul iple compa isons. Fo hese, he le el o signi icance was se
a p< 0.01, calcula ed by di iding 0.05 by i e, he numbe o cog-
ni i e domains.
Resul s
Sociodemog aphic cha ac e is ics, cogni i e, and unc ional
cou se o he sample
Baseline cha ac e is ics o he sample a e summa ized in Table 2.
The o al sample comp ised 192 men (68.1%) wi h a mean age o
Table 1. Desc ip ion o es and measu es used o cogni i e domain summa y
sco es
Cogni i e
domain Neu opsychological sub es s
P emo bid IQ Vocabula y sub es o WAIS-III
a
/WISC-IV
b
P ocessing speed T ail Making Tes
c
- o m A
S oop Tes wo d and colo condi ion
d
A en ion CPT-II
e
Ve bal memo y TAVEC
Wo king memo y Digi Span sub es o he WAIS-III
a
/WISC-IV
b
Le e and numbe sequencing o he WAIS-III
a
/
WISC-IV
b
Execu i e
unc ion
FAS es
g
Animal wo ds
h
T ail Making Tes
c
- o m B
WCST
i
S oop Tes
d
-in e e ence condi ion
a
Wechsle Adul In elligence Scale III (WAIS-III) (Wechsle , 1997).
b
Wechsle In elligence Scale o Child en-IV (WISC-IV) (Wechsle , 2003).
c
T ail Making Tes (Rei an and Wol son, 1985).
d
S oop Tes (Golden, 1978).
e
Conne s’Con inuous Pe o mance Tes (CPT-II) (Conne s, 2004).
Tes de Ap endizaje Ve bal España-Complu ense (TAVEC) (Benede and Alejand e, 1998).
g
Con olled O al Wo d Associa ion Tes (FAS es ) (Loons a e al., 2001).
h
Animal wo ds (Peña-Casano a, 1990).
i
Wisconsin Ca d So ing Tes (WCST) (Hea on e al., 1993).
Fig. 1. Hypo hesized media ion model.
2704 I González-O ega e al.
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23.64 (5.93) yea s. O hese, 123 (43.6%) had a diagnosis o
schizoph enia and 59 (20.9%) had a diagnosis o bipola diso de .
The d ug mos equen ly used was obacco (66.4%) and mos
pa ien s we e single (86.9%).
Du ing 2 yea s o ollow-up, all he cogni i e domain sco es
imp o ed signi ican ly, excep wo king memo y and execu i e
unc ion. Social cogni ion, cogni i e ese e, and unc ioning
we e also signi ican ly be e a 2 yea s (Table 3).
Co ela ions be ween cogni i e and unc ional a iables a e
p esen ed in a Supplemen a y Table.
Rela ionship be ween cogni i e ese e, social cogni ion,
gene al cogni ion, and unc ioning
Table 4 epo s he esul s o he analysis o he basic pa h models
a bo h baseline and 2 yea s. A baseline, cogni i e ese e was sig-
ni ican ly associa ed wi h social cogni ion. Rega ding baseline
cogni i e domain sco es, a e he Bon e oni co ec ion, only
p ocessing speed and e bal memo y showed a signi ican associ-
a ion wi h social cogni ion a baseline (pa h a). Social cogni ion
was no signi ican ly associa ed wi h unc ioning a baseline
(pa h b). Nei he cogni i e ese e no he cogni i e domains
we e ela ed o unc ioning a baseline (pa h c).
A 2 yea s o ollow-up, in addi ion o baseline cogni i e
ese e and e bal memo y, baseline execu i e unc ion was also
associa ed wi h social cogni ion a 2 yea s, while p ocessing
speed became non-signi ican a his ime poin (pa h a).
Fu he mo e, social cogni ion a bo h baseline and 2 yea s was
signi ican ly associa ed wi h unc ioning a he end o he
ollow-up (pa h b). Cogni i e ese e was signi ican ly ela ed o
unc ioning a 2 yea s. Rega ding baseline cogni i e domain
sco es, a e applying he Bon e oni co ec ion, only a en ion
and e bal memo y we e signi ican ly ela ed o unc ioning a
2 yea s (pa h c).
The in luence o social cogni ion as a media o be ween
cogni i e ese e and cogni i e domains on unc ioning
A baseline, as nei he cogni i e ese e no cogni i e domain
sco es we e ela ed o unc ioning (pa h c), he condi ions o
media ion we e no sa is ied.
A 2 yea s o ollow-up, a e including social cogni ion a
baseline in he inal model, all signi ican ela ions o baseline
cogni i e domains and cogni i e ese e wi h FAST a 2 yea s
emained signi ican . Fu he , hei coe icien s inc eased a e
he inclusion o social cogni ion, and he e o e, baseline social
cogni ion did no media e in hese ela ions. Ne e heless, ele-
an esul s we e ob ained a e including social cogni ion a 2
yea s in he model. Social cogni ion a 2 yea s was a signi ican
media o be ween cogni i e ese e and unc ioning a 2 yea s
(Fig. 2). In ac , i s associa ion wi h unc ioning was signi ican
(pa h b), while he ela ion be ween cogni i e ese e and unc-
ioning became non-signi ican (pa h c´). These indings sugges
a signi ican ull media ion o social cogni ion, i media ing 20.8%
o he e ec (95% boo s apped CI −10.215 o −0.337).
Wi h espec o cogni i e domains, a e including social cog-
ni ion a 2 yea s in he eg ession model be ween baseline a en-
ion and unc ioning a 2 yea s, social cogni ion had a signi ican
associa ion wi h unc ioning (pa h b) and a en ion emained sig-
ni ican , i s coe icien inc easing (b= 3.445, p= 0.006). The e o e,
he condi ions o he media ion o social cogni ion we e no sa -
is ied. Rega ding baseline e bal memo y, his domain los i s sig-
ni ican associa ion wi h unc ioning a 2 yea s when including
social cogni ion a 2 yea s in he model (pa h c´), while he la e
had a signi ican associa ion wi h unc ioning (pa h b) (Fig. 3).
Thus, social cogni ion a 2 yea s appea s o be a signi ican ull
media o , i media ing 25.2% o he e ec (95% boo s apped
CI −4.731 o −0.605).
Discussion
The main inding o his s udy is ha social cogni ion ac ed as a
media o be ween cogni i e ese e and unc ioning a 2 yea s o
ollow-up. Likewise, social cogni ion was a media o be ween e -
bal memo y and unc ional ou come. These indings sugges ha
social cogni ion is in ol ed and indeed plays a c ucial ole in he
unc ional ou come o FEP pa ien s. The e is li le p e ious
esea ch on his media ion, al hough in a sys ema ic e iew
Schmid e al.(2011) also ound ha social cogni ion media ed
he ela ionship be ween neu ocogni ion and unc ioning in
schizoph enia. Ou indings a e om a sample o pa ien s wi h
FEP and ake in o accoun he ole o cogni i e ese e.
Mo eo e , ou s udy has a longi udinal design.
The e is ex ensi e e idence o social cogni i e de ici s in FEP
(Ho an e al., 2012; Bo a and Pan elis, 2013; Bliks ed e al.,
Table 2. Baseline cha ac e is ics o he sample
Va iable To al sample (n= 282)
Sex
Male 192 (68.1%)
Age, yea s 23.64 (5.93)
Ci il s a us
Single 245 (86.9%)
Ma ied 20 (7.1%)
O he 17 (6%)
Socioeconomic le el
Low 124 (44.6%)
Medium 69 (24.8%)
High 85 (30.6%)
Table 3. Means o cogni ion and FAST du ing ollow-up (n= 186)
Va iable Baseline 2 yea s
A en ion −0.38 (0.99) −0.21 (0.87)
P ocessing speed −0.96 (1.06) −0.69 (1.00)
Ve bal memo y −1.07 (1.24) −0.65 (1.11)
Wo king memo y −0.71 (0.76) −0.67 (0.86)
Execu i e unc ion −0.43 (0.50) −0.16 (0.62)
Social cogni ion −0.72 (0.89) −0.58 (0.95)
Cogni i e ese e −0.45 (0.56) 0.04 (0.56)
FAST 26.01 (16.16) 19.40 (15.40)
p alue <0.05 excep o he cogni i e domains o which he Bon e oni co ec ion was
applied ( p< 0.01). Bold alues ep esen he signi ican alues.
Psychological Medicine 2705
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2014; Langdon e al., 2014;Hoe al., 2015) and ela ed condi ions
(Lahe a e al., 2015; Va o e al., 2017). Impai men s in social
unc ioning ha e been ela ed o de ici s in emo ion ecogni ion,
emo ional in elligence/social pe cep ion, and social knowledge
o FEP pa ien s (Adding on e al., 2010), because o hei di icul-
ies managing speci ic si ua ions and p edic ing social conse-
quences, as well as in ecognizing changes in beha io al
meaning (Mon euil e al., 2010). Mo eo e , i is conside ed
ha de e io a ion in social cogni ion has been ela ed o poo
unc ioning, especially poo wo k and social unc ioning as well
as in e pe sonal and p oblem sol ing skills (Adding on e al.,
2010; Fe e al., 2011; Ho an e al., 2012).
A second majo inding o ou s udy is ha social cogni ion
may be a po en ial ma ke o p edic ing he unc ional ou come
o pa ien s. P e ious s udies ha e also ound ha social cogni ion
may be a ai ma ke o psychosis (Bo a e al., 2008; Bo a and
Pan elis, 2013). In ac , i has been seen ha social cogni ion
could be a be e p edic o o unc ional ou come han neu ocog-
ni ion wi h a signi ican impac on gene al unc ioning o pa ien s
(Fe e al., 2011; Ohmu o e al., 2016). In ou sample o FEP
pa ien s, al hough baseline social cogni ion was ela ed o unc-
ioning a 2 yea s, i was no a media o be ween cogni ion and
unc ional ou come; howe e , social cogni ion 2 yea s la e was
a signi ican media o . This inding is p obably ela ed o he
s a e and ai na u e o social cogni ion. Social dys unc ion has
been desc ibed as a s a e ma ke ela ed o symp oms o schizo-
ph enia, and some s udies sugges ha i is no impai ed a e
symp om eco e y (Co co an e al., 1995; D u y e al., 1998).
None heless, se e al s udies ha e demons a ed de ici s in social
cogni ion in emi ed pa ien s (He old e al., 2002; Janssen
e al., 2003; Inoue e al., 2006). I is possible ha pa ien s ha e
social cogni ion de ici s as a ai ma ke , and in addi ion, hese
de ici s may wo sen wi h symp oms, indica ing ha i is bo h a
ai and a s a e a iable. Mo eo e , social cogni i e de ici s a e
Table 4. S a is ical analyses o he pa hs a and b
Pa h a (cogni i e domains/CR a baseline →social cogni ion) Social cogni ion a baseline Social cogni ion a 2 yea s
Cogni i e ese e b= 0.462, p< 0.001 b= 0.491, p< 0.001
A en ion b=−0.016, p= 0.461 b= 0.057, p= 0.463
P ocessing speed b= 0.159, p= 0.004 b= 0.138, p= 0.051
Ve bal memo y b= 0.148, p= 0.002 b= 0.185, p= 0.003
Wo king memo y b= 0.146, p= 0.051 b= 0.206, p= 0.039
Execu i e unc ion b= 0.420, p= 0.059 b= 0.910, p= 0.006
Pa h b (social cogni ion →FAST) FAST a baseline FAST a 2 yea s
Social cogni ion a baseline b=−1.862, p= 0.077 b=−3.410, p= 0.006
Social cogni ion a 2 yea s –b=−3.347, p= 0.007
Pa h c (cogni i e domains/CR a baseline →FAST) FAST a baseline FAST a 2 yea s
Cogni i e ese e b=−2.105, p= 0.195 b=−3.849, p= 0.048
A en ion b=0.125, p= 0.725 b= 3.257, p= 0.005
P ocessing speed b=−1.347, p= 0.125 b=−0.961, p= 0.364
Ve bal memo y b=−1.459, p= 0.059 b=−2.451, p= 0.007
Wo king memo y b=−2.881, p= 0.014 b=−2.062, p= 0.162
Execu i e unc ion b=−6.669, p= 0.057 b=−9.594, p= 0.016
p alue <0.05 excep o he cogni i e domains o which he Bon e oni co ec ion was applied ( p< 0.01). Bold alues ep esen he signi ican alues.
Fig. 2. Media ion o social cogni ion be ween cogni i e ese e and unc ioning a 2
yea s.
Fig. 3. Media ion o social cogni ion be ween e bal memo y and unc ioning a 2
yea s.
2706 I González-O ega e al.
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al eady p esen e en in pa ien s a isk o psychosis (Thompson
e al., 2012; Ohmu o e al., 2016; Zhang e al., 2016) and de ici s
ha e e en been ound in una ec ed i s -deg ee ela i es (Bo a
and Pan elis, 2013), his highligh ing i s ai p ope ies.
On he o he hand, ano he ele an inding o ou s udy is
ha cogni i e ese e and neu ocogni ion p edic ed social cogni-
ion, bo h a baseline and 2 yea s. Bliks ed e al.(2014) also ound
a co ela ion be ween social cogni ion and IQ, hough hey dis in-
guish be ween a complex e sion o social cogni i e de ici s linked
wi h IQ and ano he e sion ela ed o simple o ms o social
cogni ion ha a e independen o IQ. Rega ding cogni i e
domains, p ocessing speed and e bal memo y showed a signi i-
can associa ion wi h social cogni ion a baseline. A 2 yea s o
ollow-up, e bal memo y and execu i e unc ion we e associa ed
wi h social cogni ion. P e ious s udies ha e also ound ha cog-
ni i e unc ioning is ela ed o social cogni ion. Theo y o mind
disabili ies ha e been ela ed o gene al cogni i e impai men
(Bo a e al., 2008) and mo e speci ically, Fe nandez-Gonzalo
e al.(2013,2014) showed ha execu i e unc ion was ela ed o
heo y o mind in FEP pa ien s. Fu he , Sachs e al.(2004)
ound a co ela ion be ween emo ion disc imina ion and e bal
memo y and language p ocessing cogni i e domains.
As we hypo hesized, a 2 yea s o ollow-up he e was an
imp o emen in social cogni ion, cogni i e unc ioning, and gen-
e al unc ioning o pa ien s. The e is ex ensi e e idence o he
in ol emen o cogni i e impai men in he unc ional ou come
o FEP pa ien s (Lepage e al., 2014; To galsbøen e al., 2015).
Neu ocogni i e de ici s ha e been iden i ied as a co e symp om
o schizoph enia and may be mo e ela ed o unc ional eco e y
o pa ien s han clinical symp oms (Lepage e al., 2014). I has
been sugges ed ha cogni i e impai men appea s soon a e o
e en be o e he i s episode o psychosis (Bo a and Mu ay,
2014), and while some s udies a gue ha he e is de e io a ion
in cogni i e unc ions in he ollow-up (Mo ison e al., 2006;
A ango e al., 2012), o he s pos ula e an imp o emen in cogni i e
unc ion (Rod íguez-Sánchez e al., 2008; Becke e al., 2010). Ou
indings sugges ha cogni i e impai men in FEP is no p og es-
si e a e he onse o illness, bu a he imp o es in he ollow-up,
which lends suppo o he neu ode elopmen al model o cogni-
ion. Al hough he e ec s o ea men s we e no analyzed in he
s udy, i is possible ha ea men e ec s and/o clinical s abiliza-
ion con ibu e o cogni i e imp o emen s in FEP. In ou sample
o FEP pa ien s, cogni i e unc ioning imp o ed signi ican ly a
he 2-yea ollow-up in all cogni i e domains, excep wo king
memo y and execu i e unc ion. Simila ly, Lepage e al.(2014)
ound ha e bal and wo king memo y a e he cogni i e domains
mos a ec ed in FEP. This sugges s ha speci ic cogni i e
domains may be mo e sensi i e han o he s o p edic ing long-
e m unc ional ou come, ha is, some may be mo e impai ed
and may be mo e closely ela ed o pa ien ou come.
Speci ically, in ou FEP sample, e bal memo y p edic ed he
unc ional ou come a he 2-yea ollow-up. In ela ion o his,
To galsbøen e al.(2015) ound ha a en ion/ igilance and e -
bal lea ning p edic ed emission a 6 mon hs o ollow-up,
whe eas a en ion/ igilance and wo king memo y p edic ed unc-
ional ou come.
Cogni i e ese e was also associa ed wi h unc ional ou -
come. This esul has also been ound in o he s udies.
Speci ically, i has been concluded ha pa ien s wi h a be e
cogni i e ese e will ha e be e ou comes in ollow-up.
Ba ne e al.(2006) concluded ha pa ien s wi h be e cogni-
i e ese e could ha e be e easoning skills and unc ional
capaci y o use compensa o y o ms and inhibi abno mal neu al
p ocessing, which ansla es in o g ea e insigh and ea men
adhe ence. O he s udies also ound ha cogni i e ese e can
p edic bo h he isk o illness as symp oms emi and unc ional
imp o emen (Ba ne e al., 2006;Fo cadae al., 2015;G ande
e al., 2017). Amo e i e al.(2016) ha e shown ha cogni i e
ese e p edic s neu opsychological ou come, nega i e symp-
oms, and unc ioning a 2 yea s o ollow-up, and hence, cogni-
i e ese e can be used as a eliable indica o o he cou se o
FEP pa ien s (Amo e i e al., 2018).
The indings o ou s udy ha e impo an implica ions o
clinical p ac ice. An unde s anding o he associa ion be ween
neu ocogni ion, cogni i e ese e, and unc ioning and o he
media ing ole o social cogni ion is impo an o p edic ing
he ou come o FEP pa ien s a e illness onse . I is essen ial
o conside he ela ionship be ween illness ou come in pa ien s
and hei IQ, bo h p emo bid alues and changes he ein, o
iden i y he need o a speci ic ea men o imp o e he unc-
ional ou come o FEP pa ien s. Specially, pa ien s wi h lowe
cogni i e ese e may be mo e likely o need unc ional ehabili-
a ion o help o imp o e hei p ognosis. In addi ion, people
wi h highe cogni i e ese e can be o ien ed o mo e ‘no mal’
wo k o educa ion. Likewise, i is essen ial ha he ea men
o hese pa ien s ocuses on social cogni i e de ici s o imp o e
hei unc ional ou come.
This s udy has some limi a ions and s eng hs ha should be
conside ed. Ou s udy had a ollow-up o 2 yea s, and a longe
ollow-up pe iod should be conside ed in u u e esea ch.
Ano he limi a ion is he a iabili y ac oss s udies in how IQ is
measu ed. Al hough we used c i e ia based on p e ious s udies,
he e is no speci ic ins umen alida ed o measu e cogni i e
ese e. Finally, u u e s udies should include a con ol g oup.
The s udy also has impo an s eng hs. Fi s , he esul s can be
conside ed gene alizable because i is a mul icen e s udy ha
included a la ge sample o pa ien s ec ui ed in nume ous
Spanish psychia ic admission cen e s o acu e psychosis.
Second, he wide age ange o he pa ien s means ha he sample
is ep esen a i e o he a ge popula ion, wi h an a e age age
(23.63 ± 5.9 yea s), lowe han ha o o he s udies wi h la ge
FEP coho s which did no include child and adolescen pa ien s
(OPUS ial: 26.6 ± 6.4; Be elsen e al., 2008; and EUFEST ial:
26 ± 5.6; Kahn e al., 2008). Thi d, he neu opsychological ba e y
used was ex ensi e and co e ed he a eas p oposed by he
NIMH-MATRICS consensus (excep isual memo y) (Ke n
e al., 2008; Nuech e lein e al., 2008; Nuech e lein and G een,
2009).
To conclude, al hough u he s udies a e equi ed, ou ind-
ings sugges ha cogni i e ese e and neu ocogni ion a e ela ed
o unc ioning, and social cogni ion plays a media ing ole.
Supplemen a y ma e ial. The supplemen a y ma e ial o his a icle can
be ound a h ps://doi.o g/10.1017/S0033291719002794
Acknowledgemen s. We would like o hank he au ho s o he PEPs g oup
who pa icipa ed in he de elopmen o his manusc ip .
Financial suppo . This wo k was suppo ed by he Ca los III Ins i u e o
Heal h and Eu opean Fund o Regional De elopmen (PI08/1213, PI11/
01977, PI14/01900, PI08/01026, PI11/02831, PI14/01621, PI08/1161, PI16/
00359, PI16/01164, PI18/00805), he Basque Founda ion o Heal h Inno a ion
and Resea ch (BIOEF), he Sec e a ia d´Uni e si a s I Rece ca del
Depa amen d´Economia I Coneixemen (2017 SGR 1365), and R&D ac i i ies
in Biomedicine, Mad id Regional Go e nmen and S uc u al Funds o he
Eu opean Union (S2017/BMD-3740 (AGES-CM 2-CM)).
Psychological Medicine 2707
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Con lic o in e es . A González-Pin o has ecei ed g an s om o se ed as
consul an , ad iso o CME speake o he ollowing en i ies: Almi all,
As aZeneca, B is ol-Mye s Squibb, Cephalon, Eli Lilly, Glaxo-Smi h-Kline,
Janssen-Cilag, Fe e , Johnson & Johnson, Lundbeck, Me ck, O suka, P ize ,
Sano i-A en is, Se ie , She ing-Plough, Sol ay, he Spanish Minis ies o
Science and Inno a ion ( h ough CIBERSAM) and o Science ( h ough he
Ca los III Ins i u e o Heal h), he Basque Go e nmen , he S anley Medical
Resea ch Ins i u e, and Wye h.
C A ango has been a consul an o o has ecei ed ees o g an s om Abbo ,
Amgen, As aZeneca, B is ol-Mye s-Squibb, Caja Na a a, CIBERSAM, he
Alicia Koplowi z Founda ion, he Ca los III Ins i u e o Heal h, Janssen Cilag,
Lundbeck, Me ck, he Spanish Minis ies o Science and Inno a ion, o
Heal h, and o Economy and Compe i i eness, Mu ua Mad ileña, O suka,
P ize , Roche, Se ie , Shi e, Takeda, and Sche ing-Plough.
E Vie a has ecei ed g an s om o se ed as consul an , ad iso o CME
speake o he ollowing en i ies: AB-Bio ics, Alle gan, Angelini, Fe e ,
Gedeon Rich e , Janssen, Lundbeck, O suka, Sano i-A en is, Suno ion, he
Ca los III Ins i u e o Heal h, he Eu opean Union’s 7 h F amewo k P og am
and Ho izon 2020, he B ain and Beha iou Founda ion (NARSAD), and he
S anley Medical Resea ch Ins i u e.
R Rod iguez-Jimenez has been a consul an o , spoken in ac i i ies o , o
ecei ed g an s om: he Ca los III Ins i u e o Heal h, he Spanish Heal h
Resea ch Fund (FIS), CIBERSAM, Mad id Regional Go e nmen (S2010/
BMD-2422 AGES), JanssenCilag, Lundbeck, O suka, P ize , Fe e , Jus e, and
Takeda
The o he au ho s ha e no con lic s o in e es o decla e.
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