Schizophrenia Research

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1 Schizophreni Reserch 145 (2013) Contents lists ville t SciVerse ScienceDirect Schizophreni Reserch journl homepge: Impct of socil nxiety on socil cognition nd functioning in ptients with recent-onset schizophreni spectrum disorders Amélie M. Achim,,, Roslie Ouellet,c, Mrie-Audrey Lvoie,c, Chntl Vllières,d, Philip L. Jckson,c, Mrc-André Roy,,d Centre de recherche de l'institut Universitire en Snté mentle de Quéec, Cnd Déprtement de Psychitrie et neurosciences, Université Lvl, Cnd c École de Psychologie, Université Lvl, Cnd d Clinique Notre-Dme-des-Victoires, Cnd rticle info strct Article history: Received 17 Septemer 2012 Received in revised form 16 Jnury 2013 Accepted 18 Jnury 2013 Aville online 12 Ferury 2013 Keywords: First-episode Theory of mind Socil knowledge Emotion recognition Socil phoi Schizophreni ptients disply importnt rtes of comorid socil nxiety disorder () ut few studies hve directly exmined how ffects the presenttion of schizophreni, notly socil cognition deficits nd functioning. Aims: To compre socil cognition performnce of schizophreni ptients who meet the dignostic criteri for comorid (SZ+) reltive to ptients without such comoridity (SZ ) nd to determine if the impct of socil cognition performnce on functioning is moderted y tht comoridity. Method: Socil cognition performnce (emotion recognition, socil knowledge, nd mentlizing), control non-socil resoning tsk, s well s clinicl symptoms nd functioning were ssessed in 26 ptients with comorid (SZ+), 29 SZ nd 84 helthy controls. Results: Ptient groups significntly differed from ech other on socil knowledge performnce, ut not in levels of symptoms or overll functioning. Reltive to helthy controls, SZ+ were impired uniquely on mentlizing, wheres SZ showed more encompssing socil cognition deficit tht included mentlizing, socil knowledge nd non-socil resoning impirments. ws the est predictor of functioning cross oth ptient groups. Importntly, non-socil resoning negtively influenced mentlizing nd in turn functioning only in the SZ group. Conclusions: The overll pttern of results indictes common mentlizing deficits in SZ+ nd SZ ; however, these deficits pper linked to different underlying deficits nd different pthwys to functionl impct in the two ptient sugroups. This study highlights some distinctive chrcteristics of schizophreni ptients with comorid nd signls need for further investigtions into the sources of the mentlizing nd functioning impirments in SZ+ ptients Elsevier B.V. All rights reserved. 1. Introduction People with schizophreni (SZ) disply importnt rtes of comorid nxiety disorders (Kendler et l., 1996; Cssno et l., 1998; Cosoff nd Hfner, 1998; Pllnti et l., 2004; Voges nd Addington, 2005) nd yet we know little out the reltionship of these comorid disorders with other spects of schizophreni such s positive or negtive symptoms, cognitive deficits, nd functioning. Among nxiety disorders, socil nxiety disorder () seems prticulrly importnt s it ws identified s the most prevlent comorid nxiety disorder in people with SZ in recent met-nlysis (Achim et l., 2011), with pooled prevlence Corresponding uthor t: Centre de recherche de l'institut Universitire en Snté mentle de Quéec (F-4500), 2601 de l Cnrdière, Quéec, PQ, Cnd G1J 2G3. Tel.: ; fx: E-mil ddress: melie.chim@crulrg.ulvl.c (A.M. Achim). of 14.9%, rte much higher thn in the generl popultion (3.6%) (Somers et l., 2006). Comorid ppers erly in the progression of SZ nd cn e detected with similr rtes in first-episode psychosis (13.4%) s in more chronic SZ ptient smples (15.2%) (Achim et l., 2011). In ddition, even higher rtes of (25.6%) hve een oserved in SZ in studies tht relied on expnded clinicl ssessment tools, suggesting tht often goes undetected in SZ when stndrd dignostic tools such s the Structured Clinicl Interview for DSM Disorders (SCID) re used (Achim et l., 2011). Another reson for studying in SZ is the emerging evidence regrding the negtive impcts of this comoridity on SZ ptients, including poorer levels of functioning nd decresed self-esteem (Pllnti et l., 2004; Voges nd Addington, 2005). Given tht cognitive ilities nd especilly socil cognition performnce re recognized s the most importnt predictors of functioninginpeoplewithsz(brune et l., 2007; Fett et l., 2011), it opens the possiility of reltionship etween socil cognition deficits nd comorid in these ptients /$ see front mtter 2013 Elsevier B.V. All rights reserved.

2 76 A.M. Achim et l. / Schizophreni Reserch 145 (2013) Socil cognition cn e defined s the collection of cognitive processes (e.g. mentlizing, socil knowledge, emotion recognition) tht llow us to understnd others nd tht guide socil interctions (Green et l., 2008). Socil cognition deficits hve een consistently oserved in SZ nd re now recognized to e t the core of the disorder (Sprong et l., 2007; Bor et l., 2009; Kohler et l., 2010). Impirments in socil cognition my lso give rise to high levels of socil nxiety symptoms nd incresed risk of developing comorid (Jcos et l., 2008). In this cse, socil cognition deficits nd socil nxiety disorders would represent common risk fctor for poor functioning in SZ nd worse socil cognition performnce would e expected in SZ ptients tht re ffected with comorid. Though this hypothesis seems logicl nd hs ovious implictions for tretment, no study hs yet looked t socil cognition ilities or its impct on functioning s function of comorid dignosis in people with SZ. To e considered s meeting full dignostic criteri for, ptient with schizophreni hs to present with socil nxiety symptoms tht re not strictly dependent on psychotic symptoms (for instnce ides of reference or persecutory delusions). The few studies tht hve ssessed the reltionships etween socil cognition nd socil nxiety symptoms (Lysker et l., 2010,; Achim et l., 2011) hve not mde this distinction, which could explin the mixed results from these studies. The first im of the current study is to compre the pttern of socil cognition performnce in ptients with SZ spectrum psychotic disorders tht lso meet full criteri for comorid socil nxiety disorder (SZ+) reltive to schizophreni ptients tht do not (SZ ) nd helthy controls. Given the estlished reltionship etween socil cognition nd functioning (Brune et l., 2007; Fett et l., 2011), second im is to ssess the potentil moderting influence of comorid on cognitive pthwys to functioning impirments in people with schizophreni. The first im ws tested using etween group comprisons wheres the second im ws tested using modertion nlyses tht llowed us to determine whether socil cognition performnce hs greter impct on functioning in SZ+ reltive to SZ ptients. We initilly hypothesized tht meeting criteri for comorid would e ssocited with poorer socil cognition performnce (Jcos et l., 2008) nd tht these deficits would ffect functioning to greter extent in SZ+ ptients given tht cognitive models of socil nxiety (Clrk nd Wells, 1995; Wells et l., 1998; Spurr nd Stop, 2002) emphsize the ised ssessments of others' thoughts in this popultion, with recognized impct on socil ehvior nd socil interctions (Spurr nd Stop, 2002, 2003). 2. Mterils nd methods 2.1. Prticipnts Fifty-nine ptients with recent-onset SZ spectrum disorders (men ge=25.7, 51 mles) were recruited from the Clinique Notre-Dmedes-Victoires of the Institut Universitire en Snté Mentle de Quéec. Dignoses included SZ (n=41), schizoffective disorder (n=10), delusionl disorder (n=6) nd psychosis not otherwise specified (n=2). Our decision to include ptients with this rnge of erly dignoses ws sed on previous reports tht these dignoses fll within the SZ spectrum when dignoses re ressessed lter in the course of the illness or sed on fmily studies (Kendler et l., 1995; Schimmelmnn et l., 2005; Mll et l., 2006). Ptients were excluded from the study if they presented with mentl retrdtion (estimted IQ elow 70) or with neurologicl disorder, or if their treting psychitrist judged tht they were not stle enough to provide informed consent for the study. All ptients ut one were tking second-genertion ntipsychotic. In ddition, 16 received ntidepressnts nd 8 received enzodizepines either on dily sis or s needed. The durtion of psychosis since first ntipsychotic tretment rnged from 1 to 68 months, with men of 22 months. Eighty-seven (87) helthy control sujects were recruited from ds in locl medi or pulic plces. They were excluded if they presented with psychosis, mood disorder or neurologicl disorder, hd firstdegree reltive with psychosis, or were tking psychoctive mediction ccording to our screening or SCID-NP (First et l., 1998). This led to the exclusion of three prticipnts with simple phoi, one of whom dditionlly showed gorphoi. The 84 remining helthy prticipnts were included in our nlyses (men ge=24.0, 58 men) Clinicl ssessment of comoridities Clinicl ssessments were performed with comprehensive semistructured interview sed on the SCID-IV (First et l., 1998), which includes ll the SCID questions further supplemented with questions from severl other instruments tht provide detiled coverge of the full rnge of symptoms tht the ptients present with nd the reltionships etween these symptoms nd the conditions eing considered. All the dded instruments (see Supplementry mteril for complete list) hve een vlidted. The resulting semi-structured interview (Roy et l., 2011) notly includes ll the questions from the Lieowitz Socil Anxiety Scle (LSAS) inserted in the SCID module on socil nxiety disorder to further ssess socil nxiety symptoms (Lieowitz, 1987). All interviews were conducted y trined reserch ssistnt nd were susequently reviewed y one of the uthors (MAR) who is n experienced psychitrist Assessment of symptoms nd functioning Positive symptoms, negtive symptoms nd generl psychopthology symptoms were ssessed using the PANSS (Ky et l., 1987), 30-item scle widely used to ssess symptoms of schizophreni. Glol level of functioning ws ssessed with the SOFAS (Americn Psychitric Assocition, 2000), which produces single score reflecting current levels of socil nd occuptionl functioning. The treting psychitrists rted these scles sed on ll ville informtion including interviews with the ptients, informtion from the clinicl interview used for the current project (it includes ll the PANSS questions s well s module on functioning), informtion from fmily memers or from other memers of the stff t the Clinique Notre-Dme-des-Victoires Socil cognition ssessment Socil cognition ws ssessed with the Btterie Intégrée de Cognition Socile (BICS), socil cognition test ttery with good psychometric properties tht includes three min mesures of socil cognition (Achim et l., 2012): 1) The mentlizing test relies on written scenrios. Open questions test the ility to infer the trget chrcter's mentl sttes (26 mentlizing questions). 2) The socil knowledge tsk lso presents hypotheticl situtions, ut no specific chrcter is presented nd nothing is eing expressed. Insted, prticipnts hve to determine how people in generl would feel or rect in 14 different situtions. 3) The emotion recognition tsk consists of consecutive presenttions of 14 stndrdized fcil ffect stimuli (Ekmn nd Friesen, 1976). For ech item, prticipnts select the corresponding emotion from given list of lels (hppy, surprise, sd, ngry, disgust, fer or neutrl). In ddition, the BICS includes control tsk tht ssesses non-socil resoning from 6 stories tht re interspersed within the mentlizing test.

3 A.M. Achim et l. / Schizophreni Reserch 145 (2013) Anlyses Ptients were first clssified into two groups ccording to whether they met (the SZ+ group) or not (the SZ group) full dignostic criteri for comorid (Americn Psychitric Assocition, 2000) sed on our clinicl interview. Demogrphic nd clinicl vriles for these two groups were compred using t-tests or Mnn Whitney tests, s pproprite. Next, normlity of the distriutions ws corrected with squre root trnsformtion for mentlizing nd non-socil resoning (see Tle 2 for uncorrected mens), following which the two ptient groups were compred to ech other nd to the controls on ll BICS mesures through nlyses of vrinces performed with gender, ge nd eduction level used s covrites. Then, given the expected impct of socil cognition on functioning (Fett et l., 2011; Achim et l., 2012), we exmined these effects nd ssessed whether comorid cts s modertor 1) of the direct effect of ech BICS mesure on functioning (Fig. 1A) or 2) of the indirect effect of non-socil resoning, socil knowledge or emotion recognition on functioning through their respective effect on mentlizing (Fig. 1B). These nlyses were performed following Hyes' method (Hyes, 2012) for pth nlysis, which relies on stndrd pth nlysis techniques (see tested models in Fig. 1) s well s ootstrpping tests (here 10,000 itertions) to ssess the significnce of the full pth for models such s ours tht include indirect effects. Additionlly, reltionships etween LSAS rtings nd BICS mesures were exmined cross ll ptients using Person correltions to determine whether comorid dignosis nd socil nxiety symptoms showed similr effects on socil cognition performnce in people with SZ. The sme correltions were lso exmined seprtely for ech ptient group. Finlly, we explored the correltions etween LSAS rtings nd the suspiciousness/persecution item from the PANSS (item p6), lso performed seprtely for ech ptient group, which could help A B IV IV w c c w Fig. 1. Models testing for potentil modertion y comorid socil nxiety disorder of the direct nd indirect effects of our trget vriles on functioning. A. Illustrtion of our modertion model. B. Illustrtion of our moderted medition model. For ech independent vrile (IV), the coefficients nd level of significnce of ll model prmeters re reported in Tle 3. =socil nxiety disorder, dichotomous vrile tht distinguishes SZ nd SZ+ ptients. IV=independent vrile from the BICS, including mentlizing, socil knowledge, emotion recognition nd non-socil resoning for model A, nd socil knowledge, emotion recognition nd non-socil resoning for model B. highlight the nture of the socil nxiety symptoms oserved in SZ nd SZ+ ptients. 3. Results 3.1. Comoridity sttus Of the 59 ptients, 29 showed neither prior nor current comorid nd were included in the SZ group, 26 currently met ll dignostic criteri for comorid nd were included in the SZ+ group, wheres the remining four ptients hd history of comorid tht no longer met full dignostic criteri. These four ptients were excluded from further nlyses s there ws no priori reson to include them with either the SZ or the SZ+ group, nd not enough ptients in tht sitution to form seprte group. As shown in Tle 1, the SZ+ group ws older thn the SZ group (p=.018) despite similr durtion of psychosis (p=.390). SZ+ ptients showed higher socil nxiety symptom rtings on the LSAS thn SZ ptients (p.001), ut the two ptient groups did not differ with respect to severity of PANSS positive symptoms, negtive symptoms or generl psychopthology, nd oth groups showed similr levels of functioning (see Tle 1) BICS performnce As shown in Tle 2, SZ+ nd SZ ptients differed significntly only in terms of their performnce on the socil knowledge tsk, with the SZ group producing lower performnce (p=.038). Comprisons of ech ptient group with the controls confirmed tht only the SZ group showed socil knowledge impirment (p=.038) wheres the SZ+ group showed norml performnce on tht mesure. Interestingly, oth the SZ nd SZ+ groups showed impired mentlizing performnce reltive to helthy controls (oth ps.001) while non-socil resoning ws only impired in the SZ group (p=.048) BICS performnce nd functioning in schizophreni As shown in Tle 3 nd Fig. 2A, only mentlizing ws significnt direct predictor of functioning (p=.004), nd the moderting effect of comorid on tht reltionship did not rech significnce (p=.227). As presented in Tle 3 nd Fig. 2(B, C nd D), our moderted medition nlyses reveled indirect effects of oth non-socil resoning nd socil knowledge on functioning through mentlizing ( nd re significnt in oth cses). However, significnt moderting effect of ws uniquely oserved on the pth from non-socil resoning to mentlizing ( w, p=.021), nd ssessment of the significnce of the indirect effect ( pth) seprtely for ech ptient group using ootstrpping procedures nd percentile-sed confidence intervls reveled significnt indirect effect in SZ (95% CI=1.2 to 13.1) ut not in SZ+ (95% CI= 0.8 to 4.0) Socil nxiety symptoms nd BICS performnce None of the correltions etween LSAS rtings nd BICS mesures reched significnce (ll ps>.26), e it cross ll SZ ptients or when ssessed seprtely for the SZ or the SZ+ groups. Within the SZ sugroup, 9 ptients reported socil nxiety symptoms tht could correspond to DSM-IV criterion A for (importnt fer of socil or performnce situtions) ut were nonetheless included in the SZ group s these fers were limited to the topic of their psychotic symptoms nd hence did not meet ll other dignostic criteri for (i.e. socil nxiety symptoms were not independent of psychotic symptoms). The socil cognition performnce of these 9 SZ ptients did not differ from the other 20 SZ ptients (ll ps>.30) while trend

4 78 A.M. Achim et l. / Schizophreni Reserch 145 (2013) Tle 1 Demogrphic nd clinicl chrcteristics (men nd SD) of the schizophreni groups. SZ+ SZ SZ+ vs. SZ Controls SZ+ vs. Controls SZ vs. Controls N/% 26/44.1% 29/49.2% 84 Age 27.0 (4.2) 24.0 (4.8) t= 2.44, 24.0 (3.6) t=3.54, t=0.03, p=.018 p=.001 p=.979 Gender (men/women) 21/5 26/3 Z= 0.93, 58/26 Z= 1.26, Z= 2.82, p=.355 p=.207 p=0.23 Eduction 3.8 (1.1) 4.1 (0.9) t=0.98, 2.96 (1.0) t=3.74, t=5.38, p=.333 p.001 p.001 Durtion of psychosis (months) 23.6 (18.9) 19.6 (15.7) t= 0.87, p=.390 PANSS Positive 14.6 (3.6) 14.8 (5.0) t=0.18, p=.857 Negtive 16.7 (5.7) 17.0 (7.1) t=0.18, p=.859 Generl 32.2 (6.6) 30.6 (9.0) t= 0.75, p=.455 LSAS 57.8 (21.2) 32.8 (18.7) t= 4.62, p.001 SOFAS 56.9 (12.1) 56.7 (12.8) t= 0.07, p=.943 SZ =ptients with schizophreni without comorid socil nxiety disorder; SZ+=ptients with schizophreni with comorid socil nxiety disorder; PANSS=Positive nd Negtive Symptom Scle; SOFAS=socil nd occuptionl functioning ssessment scle, LSAS=Lieowitz socil nxiety scle. Eduction ctegories from the Hollingshed two-fctor index of socil position (Miller, 1991) on 7-point scle. Lower numers indicte higher eduction. A score of 4 is equivlent to completed high school wheres score of 3 is equivlent to technicl course or n unfinished chelor degree. The SOFAS ws missing for one SZ ptient nd the LSAS for nother SZ ptient. Indictes significnt effect (p.05). for lower socil knowledge performnce ws oserved in these 9 ptients reltive to the SZ+ group (p=.08) Socil nxiety symptoms nd suspiciousness/persecution The correltion etween socil nxiety symptoms nd the suspiciousness/persecution item from the PANSS (item p6) ws significnt in the SZ group (r=.41, p=.029) ut clerly sent in the SZ+ group (r=.08, p=.706), despite higher verge p6 rtings in the SZ+ reltive to the SZ group (respectively 3.2 nd 2.4, t(53)= 2.8, p=.008). 4. Discussion This study investigted the clinicl nd socil cognitive chrcteristics of ptients with recent-onset schizophreni spectrum disorders who lso met full DSM-IV criteri for comorid socil nxiety disorder (SZ+ group) compred to schizophreni ptients without comorid (SZ group) nd helthy controls. Our thorough clinicl evlution llowed us to oserve socil nxiety symptoms meeting dignostic criteri for comorid in 44.1% of our ptients. This high prevlence reltive to other studies supports our previous finding (Achim et l., 2011) tht supplementing the SCID with dditionl tools improves the detection of comorid nxiety disorders in SZ. Consistent with previous studies (Pllnti et l., 2004; Michil nd Birchwood, 2009), our SZ+ nd SZ groups did not differ in their levels of PANSS symptoms, ut our results reveled different ptterns of socil cognition impirment. Contrry to our expecttions, the SZ+ ptients were impired only on mentlizing wheres the SZ group showed more encompssing socil cognition deficit tht included mentlizing impirments ut lso socil knowledge nd generl resoning impirments. Importntly, the two ptient groups significntly differed from ech other with respect to their socil knowledge performnce, with etter performnce in the SZ+ group. The finding tht socil knowledge ws intct in the SZ+ group is intriguing s these ptients, who re dditionlly urdened y, showed less rther thn more encompssing socil cognition deficits. Interestingly, we showed tht socil knowledge performnce specificlly vried s function of dignosis, regrdless of levels of socil nxiety symptoms mesured using the LSAS. This pttern of results is consistent with the ide tht schizophreni ptients showing socil nxiety symptoms tht meet full dignostic criteri (i.e. the socil nxiety symptoms tht they report re not strictly dependent on psychotic symptoms) form distinct sugroup of ptient. Our results suggest Tle 2 Performnce (men nd SD), etween group nlyses, nd post-hoc group comprisons. SZ SZ+ Controls SZ+ vs SZ SZ+ vs Controls SZ vs Controls Between group Socil knowledge (/14) 9.6 (2.7) 11.0 (1.6) 11.2 (1.7) F=4.54, F=1.03, F=4.39, F=4.41, p=.038* p=.312 p=.038* p=.014* Emotion recognition (/14) 10.6 (1.8) 10.6 (1.7) 11.0 (1.3) F=0.08, F=1.846 F=1.44, F=1.49, p=.779 p=.177 p=.233 p=.230 (/52) 37.2 (8.6) 38.0 (7.1) 44.7 (4.4) F=0.07, F=11.91, F=12.05, F=9.54, p=.793 p=.001** p=.001** p.001** Non-socil resoning (/12) 9.8 (1.8) 10.4 (1.6) 10.9 (1.3) F=2.42, F=1.91, F=4.02, F=3.03, p=.126 p=.170 p=.048* p=.052 *p.05; **p.005; SZ =ptients with schizophreni without comorid socil nxiety disorder; SZ+=ptients with schizophreni with comorid socil nxiety disorder; CO=helthy controls. There were two ptients for whom the comined story tsk ws not ville due to incomplete testing, one in the SZ group nd one in the SZ+ group. Even though uncorrected mens re reported here, the nlyses for mentlizing nd non-socil resoning were performed on scores tht hd previously een trnsformed (squre-root trnsformtion) to correct the normlity of the distriutions. Group comprisons were performed with gender, ge nd eduction level s covrites. The sme nlyses performed without demogrphic covrites led to similr pttern of results with the exception tht the overll group effect for non-socil resoning reched significnce (p=.007).

5 A.M. Achim et l. / Schizophreni Reserch 145 (2013) Tle 3 Results for the direct nd indirect effect models. Model nd prmeter (see Fig. 2) Unstndrdized pth coefficient SE t p Direct effect models MTZ-functioning c c w SK-functioning c c w ER-functioning c c w NSR-functioning c c w Indirect effect models SK-MTZ-functioning w c ER-MTZ-functioning w c NSR-MTZ-functioning w c MTZ=mentlizing; SK=socil knowledge; ER=emotion recognition; NSR=non-socil resoning. p.05. p.01. tht this sugroup of ptients could show greter sensitivity to others, showing symptoms of socil nxiety ut lso mking them less prone to socil knowledge deficits. Though the literture does not provide much evidence regrding socil knowledge performnce in people with primry (Pln et l., in preprtion), enhnced empthy hs een reported in primry ptients (Tii-Elhnny nd Shmy-Tsoory, 2011). Given tht good numer of our ptients were receiving ntidepressnts or enzodizepines nd tht these ptients were more likely to e in the SZ+ group, n lterntive possiility is these tretments hve n effect on socil cognition nd eventully on functioning, which could explin why our SZ+ ptients showed etter socil knowledge performnce nd lso why they did not show dditionl functioning difficulties such s in previous studies (Pllnti et l., 2004; Voges nd Addington, 2005). Further work will definitely e required to understnd the distinctions etween SZ+ nd SZ ptients, including their tretment needs to chieve optiml functioning, nd to determine whether SZ+ ptients re etter conceived s hving two reltively independent dignoses or rther represent sugroup of schizophreni ptients tht differ from oth SZ ptients nd ptients with primry (i.e. not in the context of psychotic disorder). The fct tht we oserved similr levels of functioning in SZ nd SZ+ ptients could lso e relted to the fct tht different spects of functioning my e differentilly ffected in SZ nd SZ+ nd tht the SOFAS, very glol mesure, ws not sufficiently sensitive to detect such differences. Pllnti et l. (2004) previously reported worse functioning in SZ+ reltive to SZ in some res of functioning (e.g. work, sociliztion nd personl well-eing) ut not ll (e.g. they found etter fmily djustment). More comprehensive mesures of functioning should thus e used in future studies. Even though our two ptient groups did not differ in their levels of functioning, mjor finding from the current study is tht non-socil resoning hd n importnt indirect effect on functioning through its effect on mentlizing in SZ ptients, ut not in SZ+ ptients. Furthermore, though socil knowledge influenced mentlizing cross oth ptient groups, it ws only impired in the SZ group nd ws thus more likely to show negtive (rther thn positive) influence on mentlizing nd functioning in SZ ptients. Overll, non-socil resoning nd socil knowledge deficits re two trget processes linked to mentlizing impirments nd in turn to impired functioning in SZ, wheres the specific processes t ply in the mentlizing deficits of SZ+ ptients nd tht negtively influence their functioning remin unidentified. Since ttriution ises hve een reported in people with primry (i.e. not in the context of SZ ) (Clrk et l., 1997; Amin et l., 1998; Pln et l., in preprtion), one possiility is tht such ises re lso present in SZ+ nd negtively ffect mentlizing nd functioning. In ny cse, our study suggests tht different pthwys led to mentlizing nd functioning deficits in SZ+ nd SZ ptients. Overll, this study thus highlights the relevnce of tking socil nxiety into ccount to further our understnding of the pthwys to mentlizing nd functioning impirments in people with SZ nd suggests tht further investigtions into the neurocognitive processes t ply re wrrnted. If the distinctions etween the cognitive deficits of SZ+ nd SZ ptients cn e confirmed, tretments tht trget cognitive or socil cognitive deficits in ptients with schizophreni (e.g. Moritz nd Woodwrd, 2007; Horn et l., 2009; Aghotor et l., 2010; Horn et l., 2011; Moritz et l., 2011) should e dpted in consequence. Another interesting oservtion is tht no significnt reltionship emerged etween LSAS scores nd socil cognition performnce in this study. This oservtion is consistent with previous study tht found no significnt reltionship etween socil nxiety symptoms nd emotion recognition performnce in SZ (Lysker et l., 2010). We hve previously oserved significnt negtive reltionship etween LSAS rtings nd empthic perspective-tking, defined s the tendency to tke the perspective of others in socil situtions (Achim et l., 2011). However, in tht study rtings on perspective-tking were cquired using self-rting questionnire nd it is possile tht perceived ilities differ from ctul ilities in SZ ptients. Generlly, socil nxiety symptom rtings should e interpreted with cre in SZ s high rtings cn sometimes e strictly oserved in the context of psychotic suspiciousness or other psychotic symptoms (Lysker et l., 2010). The reltionship etween suspiciousness rtings nd LSAS scores tht ws here uniquely oserved in our SZ group supports the ide tht socil nxiety symptoms re of different nture in SZ+ nd SZ ptients. These results lso support the vlidity of our clssifiction of ptients into the SZ+ nd SZ groups, since ptients for whom high levels of socil nxiety symptoms could e explined y psychotic suspiciousness were ppropritely included into the SZ group. The limittions of this study include the lck of sensitivity of our emotion recognition test, which did not llow us to highlight n emotion recognition deficit tht hs often een reported in SZ (Chn et l., 2010; Kohler et l., 2010). Emotion recognition deficits hve however not een systemticlly oserved in recent-onset or first-episode SZ ptients nd could e relted to durtion of psychosis (Achim et l., 2012). The reltionship etween emotion recognition nd comorid in SZ thus deserves further investigtion in more chronic smples or using more sensitive mesures. A relted limittion is tht our functioning mesure, the SOFAS, did not llow us to investigte seprte res of functioning. Another limittion is tht the design nd the smple size of this study did not llow us to ssess the effect of djunct mediction such s ntidepressnts or enzodizepines on socil cognition or functioning. Also, the smll smple size of this study did not provide optiml

6 80 A.M. Achim et l. / Schizophreni Reserch 145 (2013) A Significnt Not sign. B w c c w Socil knowledge C D w w Emotion recognition Non-socil resoning Fig. 2. Models testing for potentil modertion y comorid socil nxiety disorder of the direct nd indirect effects of our trget vriles on functioning. Illustrtion of the results for our direct effect nd indirect effect models, for which ll prmeters re presented in Tle 3. A. Results for the model testing the direct effect of mentlizing on functioning, significnt direct reltionship tht is not moderted y the presence or sence of comorid socil nxiety disorder (). B. Indirect effect of socil knowledge on functioning through mentlizing, significnt indirect effect tht is not moderted y the presence or sence of comorid. C. Indirect effect of socil knowledge on functioning through mentlizing, showing no effect of our emotion recognition mesure on our mentlizing tsk, nd no modertion y the presence or sence of comorid. D. Indirect effect of non-socil resoning on functioning through mentlizing, significnt indirect effect tht is however significntly moderted y the presence or sence of comorid. = socil nxiety disorder, dichotomous vrile tht distinguishes SZ nd SZ+ ptients. The prmeters (, w,,,c,c w or c ) re presented in Tle 3 for ll our models. power to detect modertion effects nd did not llow us to use structurl eqution modeling to ssess ll potentil direct nd indirect effects in single, more comprehensive nlysis. In conclusion, our results support the distinction of the SZ versus SZ+ groups nd highlight the importnce of tking the prevlent comoridity into ccount given tht SZ+ ptients differed from SZ ptients t lest in terms of their pttern of socil cognition performnce nd pthwys to functionl impct. Such deficits hve ecome importnt trgets for new tretments nd our results provide potentilly helpful informtion for the design of dpted tretment for SZ ptients presenting with or without comorid. Supplementry dt to this rticle cn e found online t dx.doi.org/ /j.schres Role of funding source This work ws supported y Cndin Institutes of Helth Reserch (CIHR) postdoctorl fellowship to AMA nd CIHR operting grnt (#MOP-77647) to MAR. PJ ws supported y slry grnt from CIHR. Contriutors Amélie M Achim ws implicted in ll phses of the project including the design of the study, the conception nd vlidtion of the tools used in this study, the testing nd the nlyses. She lso wrote the mnuscript. Roslie Ouellet ws lso implicted in the conception nd vlidtion of the socil cognition test ttery, she performed some testing nd edited the mnuscript. Mrie-Audrey Lvoie did some testing, helped with the nlyses nd edited the mnuscript. Chntl Vllières ws implicted in the recruitment phse, she did some testing nd edited the mnuscript. Philip L. Jckson ws implicted in the project design, provided support for ll spects of the project nd edited the mnuscript. Mrc-André Roy ws implicted in the design of the tools, prticulrly for clinicl ssessment, provided support throughout the project nd helped AMA with the writing of the mnuscript. Conflict of interest None. Acknowledgments We would like to thnk the clinicl nd reserch tem from Clinique Notre-Dme des Victoires for their support. References Achim, A.M., Mzide, M., Rymond, E., Olivier, D., Merette, C., Roy, M.A., How prevlent re nxiety disorders in schizophreni? A met-nlysis nd criticl review on significnt ssocition. Schizophr. Bull. 37 (4), Achim, A.M., Ouellet, R., Roy, M.A., Jckson, P.L., Assessment of empthy in firstepisode psychosis nd met-nlytic comprison with previous studies in schizophreni. Psychitry Res. 190 (1), 3 8. Achim, A.M., Ouellet, R., Roy, M.A., Jckson, P.L., in first-episode psychosis. Psychitry Res. 196 (2 3), Aghotor, J., Pfueller, U., Moritz, S., Weisrod, M., Roesch-Ely, D., Metcognitive trining for ptients with schizophreni (MCT): fesiility nd preliminry evidence for its efficcy. J. Behv. Ther. Exp. Psychitry 41 (3), Americn Psychitric Assocition, Dignostic nd Sttisticl Mnul of Mentl Disorders, Fourth edition. Amin, N., Fo, E.B., Coles, M.E., Negtive interprettion is in socil phoi. Behv. Res. Ther. 36 (10), Bor, E., Yucel, M., Pntelis, C., Theory of mind impirment in schizophreni: met-nlysis. Schizophr. Res. 109 (1 3), 1 9. Brune, M., Adel-Hmid, M., Lehmkmper, C., Sonntg, C., Mentl stte ttriution, neurocognitive functioning, nd psychopthology: wht predicts poor socil competence in schizophreni est? Schizophr. Res. 92 (1 3), Cssno, G.B., Pini, S., Settoni, M., Rucci, P., Dell'Osso, L., Occurrence nd clinicl correltes of psychitric comoridity in ptients with psychotic disorders. J. Clin. Psychitry 59, Chn, R.C., Li, H., Cheung, E.F., Gong, Q.Y., Impired fcil emotion perception in schizophreni: met-nlysis. Psychitry Res. 178 (2), Clrk, D.M., Wells, A., A cognitive model of socil phoi. In: Heimerg, R.G., Lieowitz, M.R., Hope, D., Schneier, F. (Eds.), Socil Phoi: Dignosis, Assessment nd Tretment. Guilford, New York, pp

7 A.M. Achim et l. / Schizophreni Reserch 145 (2013) Clrk, D.M., Slkovskis, P.M., Ost, L.G., Breitholtz, E., Koehler, K.A., Westling, B.E., Jevons, A., Gelder, M., Misinterprettion of ody senstions in pnic disorder. J. Consult. Clin. Psychol. 65 (2), Cosoff, S.J., Hfner, J., The prevlence of comorid nxiety in schizophreni, schizoffective disorder nd ipolr disorder. Aust. N. Z. J. Psychitry 32, Ekmn, P., Friesen, W.V., Pictures of Fcil Affect. Consulting Psychologists Press, Plo Alto, CA. Fett, A.K., Viechtuer, W., Dominguez, M.D., Penn, D.L., vn Os, J., Krendm, L., The reltionship etween neurocognition nd socil cognition with functionl outcomes in schizophreni: met-nlysis. Neurosci. Bioehv. Rev. 35 (3), First, M.B., Spitzer, R.L., Gion, M., Willims, J.B., Structured Clinicl Interview for DSM-IV Axis I Disorders Ptient Edition (SCID-I/P V nd SCID-I/NP Version 2.0). Americn Psychitric Pulishing, Inc., New York. Green, M.F., Penn, D.L., Bentll, R., Crpenter, W.T., Geel, W., Gur, R.C., Kring, A.M., Prk, S., Silverstein, S.M., Heinssen, R., Socil cognition in schizophreni: n NIMH workshop on definitions, ssessment, nd reserch opportunities. Schizophr. Bull. 34 (6), Hyes, A.F., PROCESS: verstile computtionl tool for oserved vrile medition, modertion, nd conditionl process modeling [White pper]. Retrieved from Horn, W.P., Kern, R.S., Shokt-Fdi, K., Sergi, M.J., Wynn, J.K., Green, M.F., Socil cognitive skills trining in schizophreni: n initil efficcy study of stilized outptients. Schizophr. Res. 107 (1), Horn, W.P., Kern, R.S., Tripp, C., Hellemnn, G., Wynn, J.K., Bell, M., Mrder, S.R., Green, M.F., Efficcy nd specificity of socil cognitive skills trining for outptients with psychotic disorders. J. Psychitr. Res. 45 (8), Jcos, M., Snow, J., Gerci, M., Vythilingm, M., Blir, R.J., Chrney, D.S., Pine, D.S., Blir, K.S., Assocition etween level of emotionl intelligence nd severity of nxiety in generlized socil phoi. J. Anxiety Disord. 22, Ky, S.R., Fiszein, A., Opler, L.A., The positive nd negtive syndrome scle (PANSS) for schizophreni. Schizophr. Bull. 13 (2), Kendler, K.S., Nele, M.C., Wlsh, D., Evluting the spectrum concept of schizophreni in the Roscommon Fmily Study. Am. J. Psychitry 152 (5), Kendler, K.S., Gllgher, T.J., Aelson, J.M., Kessler, R.C., Lifetime prevlence, demogrphic risk fctors, nd dignostic vlidity of nonffective psychosis s ssessed in US community smple. Arch. Gen. Psychitry 53, Kohler, C.G., Wlker, J.B., Mrtin, E.A., Heley, K.M., Moerg, P.J., Fcil emotion perception in schizophreni: met-nlytic review. Schizophr. Bull. 36 (5), Lieowitz, M.R., Socil phoi. Mod. Prol. Phrmcopsychitry 22, Lysker, P.H., Slvtore, G., Grnt, M.L., Proccci, M., Olesek, K.L., Buck, K.D., Nicolo, G., Dimggio, G., Deficits in theory of mind nd socil nxiety s independent pths to prnoid fetures in schizophreni. Schizophr. Res. 124 (1 3), Lysker, P.H., Ynos, P.T., Outclt, J., Roe, D., Assocition of stigm, self-esteem, nd symptoms with concurrent nd prospective ssessment of socil nxiety in schizophreni. Clin. Schizophr. Relt. Psychoses 4 (1), Mll, A., Normn, R., Schmitz, N., Mnchnd, R., Béchrd-Evns, L., Tkhr, J., Hrichrn, R., Predictors of rte nd time to remission in first-episode psychosis: two-yer outcome study. Psychol. Med. 36 (5), Michil, M., Birchwood, M., Socil nxiety disorder in first-episode psychosis: incidence, phenomenology nd reltionship with prnoi. Br. J. Psychitry 195 (3), Miller, D.C., Hollingshed's two fctors Index of Socil Position, In: Miller, D.C. (Ed.), Hndook of reserch design nd socil mesurement, 5th ed. Sge Pulictions, Newury Prk, C, pp Moritz, S., Woodwrd, T.S., Metcognitive trining in schizophreni: from sic reserch to knowledge trnsltion nd intervention. Curr. Opin. Psychitry 20 (6), Moritz, S., Kerstn, A., Veckenstedt, R., Rndjr, S., Vitzthum, F., Schmidt, C., Heise, M., Woodwrd, T.S., Further evidence for the efficcy of metcognitive group trining in schizophreni. Behv. Res. Ther. 49 (3), Pllnti, S., Quercioli, L., Hollnder, E., Socil nxiety in outptients with schizophreni: relevnt cuse of disility. Am. J. Psychitry 161 (1), Pln, I., Lvoie, M.A., Achim, A.M., in preprtion. A scoping review nd met-nlysis of socil cognition performnce in nxiety disorders. Roy, M.A., Achim, A.M., Bouchrd, R.H., Demers, M.F., Le, A., Merette, C., Mzide, M., Anxiety disorders nd sustnce use disorders in first-episode psychosis. Schizophr. Bull. 37 (1), 7. Roy, M.A., Achim, A., Vllières, C., Lé, A., Mérette, C., Mzide, M., Demers, M.F., Bouchrd, R.H., in preprtion. Comoridity etween nxiety disorders nd psychotic disorders. Schimmelmnn, B.G., Conus, P., Edwrds, J., McGorry, P.D., Lmert, M., Dignostic stility 18 months fter tretment initition for first-episode psychosis. J. Clin. Psychitry 66 (10), Somers, J.M., Goldner, E.M., Wrich, P., Hsu, L., Prevlence nd incidence studies of nxiety disorders: systemtic review of the literture. Cn. J. Psychitry 51 (2), Sprong, M., Schothorst, P., Vos, E., Hox, J., vn Engelnd, H., Theory of mind in schizophreni: met-nlysis. Br. J. Psychitry 191, Spurr, J.M., Stop, L., Self-focused ttention in socil phoi nd socil nxiety. Clin. Psychol. Rev. 22, Spurr, J.M., Stop, L., The oserver perspective: effects on socil nxiety nd performnce. Behv. Res. Ther. 41, Tii-Elhnny, Y., Shmy-Tsoory, S.G., Socil cognition in socil nxiety: first evidence for incresed empthic ilities. Isr. J. Psychitry Relt. Sci. 48 (2), Voges, M., Addington, J., The ssocition etween socil nxiety nd socil functioning in first episode psychosis. 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