PSYCHIATRIC COMORBIDITIES AND SCHIZOPHRENIA1. Peter F. Buckley 1,2, 2. Bri! ". Miller 2, #. D$u%l& S. 'e(rer 3 !) *. D+i) ". C&tle 4,Author Affiliations1.2Department of Psychiatry, Medical College of Georgia, ! "t "e#astian$ay, Augusta, GA 3%122.3$right "tate &ni'ersity (oonshoft "chool of Medicine and the $allace)*ettering +euroscience ,nstitute3.4"-. .incent/s 0ealth and the &ni'ersity of Mel#ourne1.1-o 1hom correspondence should #e addressed2 tel3 !%4)!21)4!1, e)mail3p#uc5ley6mcg.edu. A-&trctPsychiatriccomor#idities arecommonamongpatients 1ithschi7ophrenia. "u#stancea#usecomor#idity predominates. An8iety and depressi'e symptoms are also 'ery common throughoutthe course of illness, 1ith an estimated pre'alence of 19:for panic disorder, 2:forposttraumaticstressdisorder,and23:foro#sessi'e)compulsi'edisorder.,tisestimatedthatcomor#id depression occurs in 9%: of patients, and perhaps ;conser'ati'ely< 4!: of patientsalso ha'e a lifetime diagnosis of comor#id su#stance a#use. -his article chronicles theseassociations, e8amining 1hether these comor#idities are =more than chance> and might represent;distinct< phenotypes of schi7ophrenia. Among the an8iety disorders, the e'idence at present ismost a#undant for anassociation1itho#sessi'e)compulsi'edisorder. Additional studies inne1lydiagnosedantipsychotic)nai'epatientsandtheirfirst)degreerelati'esandsearchesforgenetic and en'ironmental ris5 factors are needed to replicate preliminary findings and furtherin'estigate these associations.-he clinical heterogeneity of schi7ophrenia is indisputa#le. .irtually no 2 patients present 1iththe same constellation of symptoms. Moreo'er, e'en in the same patient, symptoms can sho1dramatic change o'er time, and there is significant interplay #et1een different sets of symptoms3eg, =secondary> negati'e symptoms might #e ameliorated 1ith resolution of positi'e symptoms,1hile core =deficit> negati'e symptoms are more enduring #ut can 1orsen o'er the longitudinalcourse of illness. "uch o#ser'ations gi'e 1ay to considerations that these may e'en constitutegroups of diseases of generallycommonphenotypice8pression#ut of different underlyingetiopathology.1?urther complicating the clinical picture of schi7ophrenia as 1ell as understanding the#oundaries and etiology of this condition is the su#stantial psychiatric comor#idity.2 Depression,an8iety, and su#stance a#use are common accompaniments of the schi7ophrenia condition, andthey in turn pertur# the clinical picture.3 ?or e8ample, depression can cause secondary negati'esymptoms, panic attac5s candri'e paranoia, andcanna#is a#use can1orsenpositi'e anddisorgani7ationsymptoms. Con'ersely, depressi'esymptoms seenintheconte8t of afloridpsychotic relapse often resol'e 1ith treatment of the positi'e symptoms #ut may remerge in the=postpsychotic> state and in turn 1orsen the longitudinal course of the illness.4,9+osologistsha'egreat difficultydealing1ithcomple8setsofsymptoms.3,4,! Generally,animplicit ore8plicit hierarchyisem#raced, suchthat schi7ophrenia=trumps,>depression, andan8iety. @r, if no primacy can #e determined, resort is made to la#els such as =schi7oaffecti'edisorder> or e'en =schi7oo#sessi'e> su#type of schi7ophrenia.3,A An alternati'e approach,reified in Diagnostic and Statistical Manual of Mental Disorders, is to consider these symptomsas part of another a8is , diagnosis that is occurring alongside schi7ophrenia. &nder thisscenario, thepatient has2maBor conditions, andtheseha'eco)occurred;perhapsfor someetiologicalreasoncommonto#othdisorders2 they suggest thatpsychiatric comor#idities are so common that they might #e integral to schi7ophrenia. -o a largee8tent, our current research in clinical trials and neuro#iological studies is increasingly coming inline1iththisproposition#ecauseno1suchstudies support #roadinclusioncriteriaof =allcomers>Dtheschi7ophreniapatients1hom1eseeine'erydayclinicalpractice, 1hoha'eprominent an8iety symptoms, or may also ha'e depressi'e symptoms, and also a#use drugs andalcohol.-he purpose of this article is to =ta5e stoc5> of these ;an8iety, depression, and su#stance a#use to the core disorder, schi7ophrenia2 to ha'e manifested #ecause schi7ophrenia is more common in this core disorder2 or are a conseGuence of some underlying shared lia#ility to #oth sets of disorders.SCHIZOPHRENIA AND AN.IETY-here is an increased pre'alence of an8iety disorders among patients 1ith schi7ophreniacompared1iththegeneral population.13 -heseinclude panicdisorder, posttraumatic stressdisorder ;P-"D effect, such the more canna#isconsumedthegreater theli5elihoodof schi7ophrenia.14 0o1e'er, againthepre'alenceofschi7ophrenia is disproportionate tothe u#iGuitous smo5ingof canna#is, there is noclearassociation #et1een rates of schi7ophrenia and rates of canna#is use in any gi'en population, andmost people 1ho im#i#e canna#is do not de'elop schi7ophrenia. -hus, it seems that canna#is can#e conceptuali7ed as a cumulati'e causal factor in some indi'iduals, acting in concert 1ith other'ulnera#ility factors to promote the manifestation of the illness in some indi'iduals 1ho mightother1ise ha'e remained schi7ophrenia free. -he effect is small, 1ith a population attri#uta#lefractionof9:I!:. Also, it doesnot appear that patients1ithschi7ophreniaandcomor#idcanna#isha'eanyhighergeneticloadingforschi7ophreniathanpatients1ithschi7ophreniaalone.1!Caton et al1A e8amined the relationship #et1een su#stance)induced psychosis andschi7ophrenia #ylongitudinallye'aluatingpatients 1hopresentedacutelypsychotic, all of1hom had a#used drugs or alcohol prior to this first e'er presentation 1ith psychosis. ?orty)fourpercent of patients turned out o'er time to ha'e had a drug)induced psychosis, 1hile 94: ofpatientsultimatelyhadschi7ophreniaastheirprimarydiagnosis. Patients1ithadrug)relatedpsychosis had marginally less positi'e and negati'e symptoms at initial presentation, they 1eremore li5ely toha'e'isual hallucinations,and theirparentshada history ofsu#stancea#use.Caspi et al11 e8amined this issue from a different, complementary perspecti'e. As part of a largeepidemiological study of schi7ophrenia in +e1 Realand, they found that those adolescents 1hopossessed the =faulty> allele ;'al 19A met< polymorphism of the C@M- ;cathechol )@)methyl)transferase< gene 1ere the people 1ho had the 'ulnera#ility to canna#is a#use. -his might helpe8plainthisassociation, 1hichappearsro#ust fromepidemiological data#ut isstill asmalleffect. -hereis a recentstudy of#rainimaging in nonpsychoticcanna#isa#users thatsho1sprogressi'e #rain changes 1ith hea'y and chronic canna#is a#use.1 -he authors report someassociation #et1een paranoid e8periences in a su#set of these patients and greater prominence ofhippocampal changes. As a general o#ser'ation, there ha'e #een fe1 #iological studies of thisdual diagnosis patient population #ecause su#stance a#use is more often than not an e8clusionarycriterion. @n the other hand, there is a gro1ing appreciation of potentially shared neurochemical'ulnera#ility#et1eensu#stancea#useandschi7ophrenia.2%% Animal neurochemical andno1human#rainimagingstudiespointtotheroleofdopamineintheamygdalaas#eing5eytounderstandingdrugcra'ingandre1ard#eha'iors. ,nschi7ophrenia, pleasureandre1ardare#lunted as part of negati'e symptoms. ,t is plausi#le that dopamine dysregulation mightpredispose patients 1ith schi7ophrenia to a#use drugs.14,2%% ,t has also #een e8plained thatpatients 1ith schi7ophrenia 1ho a#use drugs may actually ha'e milder symptoms and that theirpoorer course is more attri#uta#le to the direct effect of drugs on 1orsening symptoms as 1ell asthe associated medication nonadherence. -his is certainly intuiti'e in the sense that patients 1ithmore se'ere illness are less li5ely to ha'e the opportunity and social conte8t to acGuire streetdrugs. ,t has also long #een suggested that patients self medicate either to reduce their symptomsor to counteract the effects of antipsychotic medications.2%1,2%2 Hither association is plausi#leand in accord 1ith clinical e8perience. 0o1e'er, the rate of su#stance a#use comor#idity has notseemedtodiminishinaneraof treatment 1ith"GAs that ha'elessmotor andsecondarynegati'e symptomeffects.2%3 Eegarding treatment of patients 1ith su#stance a#use, thesepatients sho1similar responses to antipsychotic medications as nona#using patients 1ithschi7ophreniaConce they ta5e their medication, a maBor challenge in this patientgroup.2%,2%4 ,ntheclinical antipsychotictrials of inter'entioneffecti'eness ;CA-,H< study,patients 1ithcomor#idsu#stancea#usesho1edcompara#leresponses 1itheach"GAthanpatients 1ithout su#stance a#use.2%9 -here is some e'idence that dual diagnosis patients mightdo #etter on clo7apine, 1ith less relapse into a#use of drugs or alcohol.2%4@'erall, 1hile su#stance a#use comor#idity is remar5a#ly common in schi7ophrenia, thee'idence is lac5ing that this represents some distinct su#group of etiopathological significance.$hilee8planationsto1ardasharedneurochemical, dopamine)mediated'ulnera#ilityto#othschi7ophreniaandsu#stancea#useareintuiti'elyappealing, at present thee'idence#aseisscant.14 Moreo'er, the pre'ailing 'ie1 in #oth the addiction field and in schi7ophrenia researchisthat thisrepresentsaco)occurrenceof2conditionsratherthansomeetiologicallydistinctsu#group of schi7ophrenia patients 1ho are characteri7ed #y a procli'ity to su#stance a#use.Pre'ious "ection +e8t "ectionConclusions-here is clearly an increased pre'alence of an8iety, depressi'e, and su#stance a#use disorders inpatients 1ithschi7ophrenia that occurs ine8cess of that inthe general population. -hesecomor#idities occur at all phases of the course of illness, including in the psychosis prodrome,?HP,andchronicschi7ophrenia.A limited#odyofe'idencesupportstheplausi#ilityofthehypothesisthat an8ietydisordersarepart oftheillnessofschi7ophrenia, 1iththestrongeste'idence #eing for @CD. P-"D, and other an8iety symptoms, 1hile common, do not appear to#e etiologically lin5ed to schi7ophrenia. Depressi'e symptoms are also intrinsic to the illness andimport a poorer outcome, including more psychotic relapses. &nderstanding this relationship isimportant and is also additionally complicated #y #roader perspecti'es a#out the#oundariesFo'erlap#et1eenpsychosis andmooddisorders. "u#stance a#use is particularlycommon and also 1orsens the course of illness, although here this effect is ine8trica#ly lin5ed totreatment noncompliance. ?or each of these comor#idities, their presence is generally associated1ith more se'ere psychopathology and 1ith poorer outcomes. $hat is conspicuous from thisre'ie1 is the relati'e lac5 of in'estigation to1ard a neuro#iological #asis of comor#idity amongpatients1ithschi7ophrenia. -hisisstri5ingin'ie1ofho1commonandchallengingthesecomor#idities are. -here is a conspicuous a#sence of any =smo5ing gun> findings for etiologicalheterogeneityhere.$hiletherehas#eenatleastsomehead1ayintreatmentstudiesof#othpharmacology and nonpharmacology, it is rudimentary and in relation to @CD and schi7ophreniathere is the suggestion that antipsychotic medications might e'en aggra'ate thesesymptoms.3 -here is also, on the other hand, e'idence that antidepressants can not Bust impro'edepressi'e symptoms #ut perhaps also impact fa'ora#ly negati'e and general psychopathologyas 1ell.9-hese o#ser'ations may contri#ute in part to the high rates of polypharmacy that areo#ser'edinthetreatment ofschi7ophrenia.2%! At present, thetherapeuticimplicationsofthisclinical heterogeneityarepoorlyunderstoodandarelargelymanifestedin=trial anderror>treatment choices. -he most parsimonious conclusion at the present time is that thesecomor#idities are certainly more common than chance in schi7ophrenia, #ut theiretiopathological significance and treatment implications thereupon are poorly understood at thepresent time. S -he Author 2%%A. Pu#lished #y @8ford &ni'ersity Press on #ehalf of the MarylandPsychiatric Eesearch Center. All rights reser'ed. ?or permissions, please email3Bournals.permissions6o8fordBournals.org.Pre'ious "ection Eeferences1. 1. 1. *ir5patric5 (, 2. (uchanan E$, 3. Eoss DH, 4. Carpenter $- Or. A separate disease 1ithin the syndrome of schi7ophrenia. Arch Gen Psychiatry 2%%129A3149)1!1.CrossEef Medline $e# of "cience Google "cholar2. 2. 1. Pincus 0A, 2. -e1 D, 3. ?irst M(. Psychiatric comor#idity3 is more lessQ $orld Psychiatry 2%%42331A)23.Medline Google "cholar3. 3. 1. Green A,, 2. Canuso C, 3. (renner MO, 4. $iBci5 OD. Detection and management of comor#idity in schi7ophrenia. Psychiatr Clin +Am 2%%32243119)13.CrossEef Medline $e# of "cience Google "cholar4. 4. 1. "iris ", 2. (ench C. Depression and schi7ophrenia. ,n3 0irsch ", $ein#erger D, editors. "chi7ophrenia. 2nded. @8ford, &*3 (lac51ell2 2%%3. p. 142)14!.Google "cholar9. 9. 1. Moller 0O. Drug treatment of depressi'e symptoms in schi7ophrenia. Clin "chi7ophr EelatPsychoses 2%%!21332A)34%.Google "cholar4. 4. 1. *endell EH. -he classification of depressions3 a re'ie1 of contemporary confusion. (r OPsychiatry 1!4212319)2A.?EHH?ull -e8t!. !. 1. Pierre OM. Deconstructing schi7ophrenia for D"M).3 challenges for clinical and research agendas. Clin"chi7ophr Eelat Psychoses 2%%A223144)1!4.CrossEef Google "cholarA. A. 1. $ing O, 2. Agra1al +. Concepts and classification of schi7ophrenia. ,n3 0irsch ",$ein#erger D,editors. "chi7ophrenia. 2nd ed. @8ford, &O*3 (lac51ell2 2%%3. p. 3)14.Google "cholar. . American Psychiatric Association. Diagnostic and "tatistical Manual of MentalDisorders. ?ourth edition, -e8t Ee'ision. $ashington, DC3 American PsychiatricAssociation2 2%%%.1%. 1%. 1. (uc5ley P?. Pre'alenceandconseGuencesofthedual diagnosisofsu#stancea#useandse'erementalillness. O Clin Psychiatry 2%%424!39).CrossEef Medline $e# of "cience Google "cholar11. 11. 1. Caspi A, 2. Moffitt -H, 3. Cannon M, 4. et al. Moderation of the effect of adolescent)onset canna#is use on adult psychosis #y a functionalpolymorphisminthecatechol)%)methyltransferasegene3 longitudinal e'idenceof agene8en'ironment interaction. (iol Psychiatry 2%%929!3111!)112!.CrossEef Medline $e# of "cience Google "cholar12. 12. 1. (erman7ohn PC, 2. Porto M, 3. Arlo1 P(, 4. Pollac5 ", 9. "tronger E, 4. "iris "G. 0ierarchical diagnosis in chronic schi7ophrenia3 a clinical study of co)occurringsyndromes."chi7ophr (ull. 2%%%224391!)929.A#stractF ?EHH?ull -e8t13. 13. 1. Po5os ., 2. Castle DO. Pre'alenceofcomor#idan8ietydisordersinschi7ophreniaspectrumdisorders3 aliteraturere'ie1. Curr Psychiatry Ee' 2%%42232A9)3%!.CrossEef Google "cholar14. 14. 1. (oyd O0. &se of mental health ser'ices for the treatment of panic disorder. Am OPsychiatry 1A421433194)19!4.Medline $e# of "cience Google "cholar19. 19. 1. Good1in E, 2. Myons O", 3. Mc+ally EO. Panic attac5s in schi7ophrenia. "chi7ophr Ees 2%%229A3213)22%.CrossEef Medline $e# of "cience Google "cholar14. 14. 1. (oyd O0, 2. (ur5e OD Or, 3. Gruen#erg H, 4. et al. H8clusion criteria of D"M),,,. A study of co)occurrence of hierarchy)free syndromes. ArchGen Psychiatry 1A42413A3)A.CrossEef Medline $e# of "cience Google "cholar1!. 1!. 1. Eo#ins M+, 2. Eegier DA. +e1 Kor5, +K3 -he ?ree Press2 11. Psychiatric Disorders in America3 the HpidemiologicalCatchment Area "tudy.Google "cholar1A. 1A. 1. Argyle +. Panic attac5s in chronic schi7ophrenia. (r O Psychiatry1%219!343%)433.A#stractF ?EHH?ull -e8t1. 1. 1. (aylT ?O, 2. *re#s M@, 3. Hpel#aum C, 4. Me'y D, 9. 0ardy P. Clinical features of panic attac5s in schi7ophrenia. Hur Psychiatry 2%%1214334)393.CrossEef Medline $e# of "cience Google "cholar2%. 2%. 1. (land EC, 2. +e1man "C, 3. @rn 0. "chi7ophrenia3 lifetime co)mor#idity in a community sample. Acta Psychiatr"cand 1A!2!933A3)31.CrossEef Medline $e# of "cience Google "cholar21. 21. 1. Cassano G(, 2. Pini ", 3. "aettoni M, 4. Eucci P, 9. Dell)@sso M. @ccurrence andclinical correlates of psychiatric comor#idityinpatients 1ith psychoticdisorders. O Clin Psychiatry 1A2934%)4A.Medline $e# of "cience Google "cholar22. 22. 1. Chen CK, 2. Miu CK, 3. Kang KK. Correlation of panic attac5s and hostility in chronic schi7ophrenia. Psychiatry Clin+eurosci 2%%129933A3)3A!.Medline Google "cholar23. 23. 1. Ciapparelli A, 2. Paggini E, 3. Mara77iti D, 4. et al. Comor#idity 1ith a8is , an8iety disorders in remitted psychotic patients 1 year afterhospitali7ation. C+" "pectr2%%!212313)1.Medline $e# of "cience Google "cholar24. 24. 1. Craig -, 2. 01ang MK, 3. (romet HO. @#sessi'e)compulsi'e and panic symptoms in patients 1ith first)admission psychosis. Am OPsychiatry 2%%2219392)9A.CrossEef Medline $e# of "cience Google "cholar29. 29. 1. Cosoff "O, 2. 0afner EO. -hepre'alenceofcomor#idan8ietyinschi7ophrenia, schi7oaffecti'edisorderand#ipolardisorder. Aust + R O Psychiatry 1A23234!)!2.CrossEef Medline $e# of "cience Google "cholar24. 24. 1. Cutler OM, 2. "iris "G. =Panic)li5e> symptomatology in schi7ophrenic and schi7oaffecti'e patients 1ith postpsychoticdepression3 o#ser'ations and implications. Compr Psychiatry 112323449)4!3.CrossEef Medline $e# of "cience Google "cholar2!. 2!. 1. Gar'ey M, 2. +oyes E Or, 3. Anderson D, 4. Coo5 (. H8aminationofcomor#idan8ietyinpsychiatricinpatients. ComprPsychiatry 1123232!!)2A2.CrossEef Medline $e# of "cience Google "cholar2A. 2A. 1. Good1in ED, 2. Amador U?, 3. Malaspina D, 4. Kale "A, 9. Goet7 EE, 4. Gorman OM. An8iety and su#stance use comor#idity among inpatients 1ith schi7ophrenia. "chi7ophrEes2%%32413A)9.CrossEef Medline $e# of "cience Google "cholar2. 2. 1. 0eun E, 2. Maier $. Eelation of schi7ophrenia and panic disorder3 e'idence from a controlled family study. Am OMed Genet 1924%312!)132.CrossEef Medline $e# of "cience Google "cholar3%. 3%. 1. 0iguchi 0, 2. *amata M, 3. Koshimoto M, 4. "himisu -, 9. 0ishi5a1a K. Panic attac5s in patients 1ith chronic schi7ophrenia3 a complication of long)term neuroleptictreatment. Psychiatry Clin +eurosci 129331)4.Medline Google "cholar31. 31. 1. Ma##ate MA, 2. Koung PC, 3. Arana G$. Panic disorder in schi7ophrenia. Can O Psychiatry 124434AA)4%.Medline $e# of "cience Google "cholar32. 32. 1. Myons MO, 2. 0uppert O, 3. -oomey E, 4. et al. Mifetime pre'alence of mood and an8iety disorders in t1in pairs discordant forschi7ophrenia. -1in Ees 2%%%2332A)32.CrossEef Medline Google "cholar33. 33. 1. Moorey 0, 2. "oni "D. An8iety symptoms in sta#le chronic schi7ophrenics. O Ment 0ealth 1423329!)242.CrossEef Google "cholar34. 34. 1. Pallanti ", 2. Vuercioli M, 3. 0ollander H. "ocial an8iety in outpatients 1ith schi7ophrenia3 a rele'ant cause of disa#ility. AmOPsychiatry 2%%42141393)9A.CrossEef Medline $e# of "cience Google "cholar39. 39. 1. "tra5o1s5i "M, 2. -ohen M, 3. "toll AM, 4. et al. Comor#idity in psychosis at first hospitali7ation. Am O Psychiatry 13219%3!92)!9!.Medline $e# of "cience Google "cholar34. 34. 1. -i##o P, 2. "1ainson O, 3. Chue P, 4. MeMelledo OM. Pre'alence and relationship to delusions and hallucinations of an8iety disorders inschi7ophrenia. Depress An8iety2%%321!349)!2.CrossEef Medline $e# of "cience Google "cholar3!. 3!. 1. &las 0, 2. Alpte5in *, 3. A5dede ((, 4. et al. Panic symptoms in schi7ophrenia3 comor#idity and clinical correlates. Psychiatry Clin+eurosci 2%%!24134!A)4A%.Medline Google "cholar3A. 3A. 1. Rarate E. Miami (each3 ?la2 +o'em#er 1!. -he comor#idity#et1een schi7ophrenia and an8ietydisorders. Paperpresentedat3 31stAnnual Meetingofthe Associationfor Ad'ancement of(eha'ior -herapy.Google "cholar3. 3. 1. (raga EO, 2. Mendlo1ic7 M., 3. Marrocos EP, 4. ?igueira ,M. An8iety disorders in outpatients 1ith schi7ophrenia3 pre'alence and impact on the su#Becti'eGuality of life. O Psychiatr Ees 2%%92334%)414.CrossEef Medline $e# of "cience Google "cholar4%. 4%. 1. *aterndahl DA, 2. Eealini OP. Mifetime pre'alence of panic states. Am O Psychiatry13219%3244)24.Medline $e# of "cience Google "cholar41. 41. 1. Grant (?, 2. 0asin D", 3. "tinson ?", 4. et al. -he epidemiology of D"M),. panic disorder and agorapho#ia in the &nited "tates3 resultsfrom the +ational Hpidemiologic "ur'ey on Alcohol and Eelated Conditions. O ClinPsychiatry2%%424!3343)3!4.Medline $e# of "cience Google "cholar42. 42. 1. -ien AK, 2. Haton $$. Psychopathologic precursors and sociodemographic ris5 factors for the schi7ophreniasyndrome. Arch Gen Psychiatry 122433!)44.CrossEef Medline $e# of "cience Google "cholar43. 43. 1. (erman7ohn PC, 2. Arlo1 P(, 3. Pitch EO, 4. "iris "G. Panic and paranoia. O Clin Psychiatry 1!29A3329)324.Medline $e# of "cience Google "cholar44. 44. 1. 0ofmann "G. Eelationship #et1een panic and schi7ophrenia. Depress An8iety1231%1)1%4.CrossEef Medline Google "cholar49. 49. 1. "iris "G, 2. Mason "H, 3. "hu1all MA. 0istories of su#stance a#use, panic andsuicidal ideationinschi7ophrenic patients 1ithhistories of post)psychotic depression. Prog +europsychopharmacol (iolPsychiatry 1321!34%)41!.CrossEef Medline Google "cholar44. 44. 1. ?ial5o M, 2. ?reeman D, 3. (e##ington P, 4. et al. &nderstanding suicidal ideation in psychosis3 findings from the psychological pre'ention ofrelapse in psychosis ;PEP< trial. Acta Psychiatr "cand 2%%4211431!!)1A4.CrossEef Medline $e# of "cience Google "cholar4!. 4!. 1. $eissman MM, 2. ?yer AO, 3. 0aghighi ?, 4. et al. Potential panic disorder syndrome3 clinical and genetic lin5age e'idence. AmO MedGenet 2%%%24324)39.CrossEef Medline $e# of "cience Google "cholar4A. 4A. 1. "hi O, 2. (adner OA, 3. Gershon H", 4. Miu C. AllelicassociationofG!2FG3%1ithschi7ophreniaand#ipolar disorder3 acomprehensi'emeta)analysis. "chi7ophr Ees2%%A2A3A)!.Medline $e# of "cience Google "cholar4. 4. 1. Morgan C, 2. ?isher 0. Hn'ironment and schi7ophrenia3 en'ironmental factors in schi7ophrenia3 childhood traumaCacritical re'ie1. "chi7ophr (ull 2%%!23333)1%.A#stractF ?EHH?ull -e8t9%. 9%. 1. "ha1 *, 2. Mc?arlane AC, 3. (oo5less C, 4. Air -. -he etiology of postpsychotic posttraumatic stress disorder follo1ing a psychotic episode. O-rauma "tress2%%221933)44.CrossEef Medline $e# of "cience Google "cholar91. 91. 1. *ennedy (M, 2. Dhali1al +, 3. Pedley M, 4. "ahner C, 9. Green#erg E, 4. Manshadi M". Post)traumatic stress disorder in su#Bects 1ith schi7ophrenia and #ipolar disorder. O *y MedAssoc 2%%221%%339)3.Medline Google "cholar92. 92. 1. ?rame M, 2. Morrison AP. Causes of posttraumatic stress disorder in psychotic patients. Arch GenPsychiatry 2%%129A33%9)3%4.CrossEef Medline $e# of "cience Google "cholar93. 93. 1. McGorry PD, 2. Chanen A, 3. McCarthy H, 4. .an Eiel E, 9. Mc*en7ie D, 4. "ingh (".Posttraumatic stress disorder follo1ing recent)onset psychosis. An unrecogni7ed postpsychoticsyndrome. O +er' Ment Dis 1121!3293)29A.CrossEef Medline $e# of "cience Google "cholar94. 94. 1. "ha1 *, 2. Mc?arlane A, 3. (oo5less C. -he phenomenology of traumatic reactions to psychotic illness. O +er' MentDis 1!21A93434)441.CrossEef Medline $e# of "cience Google "cholar99. 99. 1. Calhoun P", 2. "techucha5 *M, 3. "trauss O, 4. (os1orth 0(, 9. Mar8 CH, 4. (utterfield M,.,nterpersonal trauma, 1ar7onee8posure, andposttraumaticstressdisorderamong'eterans1ith schi7ophrenia. "chi7ophr Ees. 2%%!21321%)214.CrossEef Medline $e# of "cience Google "cholar94. 94. 1. ?an U, 2. 0enderson DC, 3. +guyen DD, 4. et al. Posttraumatic stress disorder, cogniti'e function and Guality of life in patients 1ithschi7ophrenia. Psychiatry Ees2%%A219314%)144.CrossEef Medline $e# of "cience Google "cholar9!. 9!. 1. Gearon O", 2. *altman ",, 3. (ro1n C, 4. (ellac5 A". -raumatic life e'ents and P-"D among 1omen 1ith su#stance use disorders andschi7ophrenia. Psychiatr "er'2%%32943923)92A.CrossEef Medline $e# of "cience Google "cholar9A. 9A. 1. *ilcommons AM, 2. Morrison AP. Eelationships#et1eentraumaandpsychosis3 ane8plorationofcogniti'eanddissociati'efactors. Acta Psychiatr "cand2%%921123391)39.CrossEef Medline $e# of "cience Google "cholar9. 9. 1. Meyer 0, 2. -aiminen -, 3. .uori -, 4. AiBWlW A, 9. 0elenius 0. Posttraumatic stress disorder symptoms related to psychosis and acute in'oluntaryhospitali7ation in schi7ophrenic and delusional patients. O +er' Ment Dis 121A!3343)392.CrossEef Medline $e# of "cience Google "cholar4%. 4%. 1. Mueser *-, 2. Goodman M(, 3. -rum#etta "M, 4. et al. -rauma and posttraumatic stress disorder in se'ere mental illness. O Consult ClinPsychol 1A244343)4.CrossEef Medline $e# of "cience Google "cholar41. 41. 1. Mueser *-, 2. "alyers MP, 3. Eosen#erg "D, 4. et al. 9 "ite 0ealth and Eis5 "tudy Eesearch Committee. ,nterpersonal trauma and posttraumaticstress disorder in patients 1ith se'ere mental illness3 demographic, clinical, and healthcorrelates."chi7ophr (ull. 2%%423%349)9!.A#stractF ?EHH?ull -e8t42. 42. 1. +eria K, 2. (romet HO, 3. "ie'ers ", 4. Ma'elle O, 9. ?ochtmann MO. -rauma e8posure and posttraumatic stress disorder in psychosis3 findings froma first)admission cohort. O Consult Clin Psychol 2%%22!%3244)291.CrossEef Medline $e# of "cience Google "cholar43. 43. 1. Prie#e ", 2. (rN5er M, 3. Gun5el ". ,n'oluntary admission and posttraumatic stress disorder symptoms in schi7ophreniapatients. Compr Psychiatry 1A23322%)224.CrossEef Medline $e# of "cience Google "cholar44. 44. 1. Eesnic5 "G, 2. (ond GE, 3. Mueser *-. -rauma and posttraumatic stress disorder in people 1ith schi7ophrenia. O A#normPsychol 2%%321123419)423.CrossEef Medline $e# of "cience Google "cholar49. 49. 1. "eedat ", 2. ?ritelli ., 3. @osthui7en P, 4. Hmsley EA, 9. "tein DO. Measuring an8iety in patients 1ith schi7ophrenia. O +er' Ment Dis 2%%!219332%)324.CrossEef Medline $e# of "cience Google "cholar44. 44. 1. "tra5o1s5i "M, 2. *ec5 PH Or, 3. McHlroy "M, 4. Monc7a5 0", 9. $est "A. Chronology of comor#id and principal syndromes in first)episode psychosis. ComprPsychiatry1923431%4)112.CrossEef Medline $e# of "cience Google "cholar4!. 4!. 1. *essler EC, 2. "onnega A, 3. (romet H, 4. 0ughes M, 9. +elson C(. Posttraumatic stress disorder in the +ational Comor#idity "ur'ey. Arch GenPsychiatry 1929231%4A)1%4%.CrossEef Medline $e# of "cience Google "cholar4A. 4A. 1. "trauss OM, 2. Calhoun P", 3. Mar8 CH, 4. et al. Comor#id posttraumatic stress disorderis associated1ithsuicidality inmale'eterans1ithschi7ophrenia or schi7oaffecti'e disorder. "chi7ophr Ees 2%%42A43149)14.CrossEef Medline $e# of "cience Google "cholar4. 4. 1. Calhoun P", 2. (os1orth 0(, 3. "techucha5 *A, 4. "trauss O, 9. (utterfield M,. -he impact of posttraumatic stress disorder on Guality of life and health ser'ice utili7ationamong 'eterans 1ho ha'e schi7ophrenia. O -rauma "tress 2%%421333)3!.CrossEef Medline $e# of "cience Google "cholar!%. !%. 1. "cheller)Gil5ey G, 2. Moynes *, 3. Cooper ,, 4. *ant C, 9. Miller A0. Harly life stress and P-"D symptoms in patients 1ith comor#id schi7ophrenia and su#stancea#use."chi7ophr Ees 2%%424314!)1!4.CrossEef Medline $e# of "cience Google "cholar!1. !1. 1. Goodman C, 2. ?in5el (, 3. +aser M, 4. et al. +eurocogniti'e deterioration in elderly chronic schi7ophrenia patients 1ith and 1ithoutP-"D. O +er' Ment Dis2%%!2193419)42%.Medline $e# of "cience Google "cholar!2. !2. 1. (erman ,, 2. *alino1s5i A, 3. (erman "M, 4. Mengua O, 9. Gren A,. @#sessi'e and compulsi'e symptoms in chronic schi7ophrenia. Compr Psychiatry 1923434)1%.CrossEef Medline $e# of "cience Google "cholar!3. !3. 1. Hisen OM, 2. (eer DA, 3. Pato M-, 4. .enditto -A, 9. Easmussen "A. @#sessi'e)compulsi'e disorder in patients 1ith schi7ophrenia or schi7oaffecti'e disorder. AmO Psychiatry1!219432!1)2!3.Medline $e# of "cience Google "cholar!4. !4. 1. ?a#isch *, 2. ?a#isch 0, 3. Mangs G, 4. $ieselmann G, 9. Rapotoc75y 0G. @#sessi'e)compulsi'e symptoms in schi7ophrenia. "chi7ophr Ees 1!224319.Google "cholar!9. !9. 1. ?a#isch *, 2. ?a#isch 0, 3. Mangs G, 4. 0u#er 0P, 9. Rapotoc75y 0G. ,ncidence of o#sessi'e)compulsi'e phenomena inthe course of acute schi7ophrenia andschi7oaffecti'e disorder. "chi7ophr Ees 2%%12143334)341.Google "cholar!4. !4. 1. ?enton $", 2. McGlashan -0. -he prognostic significance of o#sessi'e)compulsi'e symptoms in schi7ophrenia. AmOPsychiatry 1A42143343!)441.Medline $e# of "cience Google "cholar!!. !!. 1. *arno M, 2. Golding OM, 3. "orensen "(, 4. (urnam MA. -he epidemiologyof o#sessi'e)compulsi'e disorder in fi'e &"communities. Arch GenPsychiatry1AA24931%4)1%.CrossEef Medline $e# of "cience Google "cholar!A. !A. 1. *ayahan (, 2. @7tur5 @, 3. .e7nedaroglu (, 4. Hraslan D. @#sessi'e)compulsi'e symptoms in schi7ophrenia3 pre'alence and clinicalcorrelates. Psychiatry Clin +eurosci 2%%929321)29.Medline Google "cholar!. !. 1. *rXger ", 2. (rWunig P, 3. 0Nffler O, 4. "hugar G, 9. (Nrner ,, 4. Mang5rWr O. Pre'alence of o#sessi'e)compulsi'e disorder inschi7ophrenia andsignificance of motorsymptoms. O +europsychiatry Clin +eurosci 2%%%212314)24.Medline $e# of "cience Google "cholarA%. A%. 1. Meghani "E, 2. Penic5 HC, 3. +ic5el HO. Paper presented at3 191st Annual Meeting of the American Psychiatric Association. -oronto,@+2 1A. "chi7ophrenia patients 1ith and 1ithout @CD.Google "cholarA1. A1. 1. Mohammadi ME, 2. Ghani7adeh A, 3. Moini E. Mifetime comor#idity of o#sessi'e)compulsi'e disorder 1ith psychiatric disorders in acommunity sample. Depress An8iety 2%%!22434%2)4%!.CrossEef Medline $e# of "cience Google "cholarA2. A2. 1. +echmad A, 2. Eat7oni G, 3. Poyuro's5y M, 4. et al. @#sessi'e)compulsi'e disorder in adolescent schi7ophrenia patients. Am OPsychiatry 2%%3214%31%%2)1%%4.CrossEef Medline $e# of "cience Google "cholarA3. A3. 1. Porto M, 2. (erman7ohn PC, 3. Pollac5 ", 4. Morrissey E, 9. "iris "G. A profile of o#sessi'e)compulsi'e symptoms in schi7ophrenia. C+" "pectrum 1!22321)29.Google "cholarA4. A4. 1. Poyuro's5y MD, 2. ?uchs C, 3. $ei7man A. @#sessi'e)compulsi'e disorder in patients 1ith first)episode schi7ophrenia. Am OPsychiatry 1219431A)2%%%.Medline $e# of "cience Google "cholarA9. A9. 1. Poyuro's5y M, 2. 0ramen5o' ", 3. ,sa5o' .. @#sessi'e)compulsi'e disorder in hospitali7ed patients 1ith chronic schi7ophrenia. PsychiatryEes 2%%121%234)9!.CrossEef Medline $e# of "cience Google "cholarA4. A4. 1. -i##o P, 2. *roetsch M, 3. Chue P, 4. $arne5e M. @#sessi'e)compulsi'e disorder in schi7ophrenia. O Psychiatr Ees. 2%%%234313)144.CrossEef Medline $e# of "cience Google "cholarA!. A!. 1. -i##o P, 2. $arne5e M. @#sessi'e)compulsi'e disorder in schi7ophrenia3 epidemiologic and #iologic o'erlap. OPsychiatry +eurosci 1224319)24.Medline $e# of "cience Google "cholarAA. AA. 1. Muc5a ,, 2. ?ry7e M, 3. Ce#ella A, 4. "tas7e1sa5 H. Prodromal symptoms of schi7ophrenics syndrome in children and adolescents. PsychiatrPol 2%%2234suppl32A3)2A4.Medline Google "cholarA. A. 1. ,ida O, 2. ,1asa5a 0, 3. 0irao ?, 4. et al. Clinical features of childhood)onset schi7ophrenia 1ith o#sessi'e)compulsi'e symptomsduring the prodromal phase.Psychiatry Clin +eurosci 192432%1)2%!.Medline Google "cholar%. %. 1. "hioiri -, 2. "hinada *, 3. *u1a#ara 0, 4. "omeya -. Harly prodromal symptoms and diagnoses #efore first psychotic episode in 21 inpatients 1ithschi7ophrenia.Psychiatry Clin +eurosci 2%%!241334A)394.Medline Google "cholar1. 1. 1. Poyuro's5y M, 2. ?aragian ", 3. "ha#eta A, 4. *oso' A. Comparison of clinical characteristics, co)mor#idity and pharmacotherapy in adolescentschi7ophrenia patients 1ith and 1ithout o#sessi'e)compulsi'e disorder. PsychiatryEes2%%A2193133)13.CrossEef Medline $e# of "cience Google "cholar2. 2. 1. Poyuro's5y M, 2. ?uchs C, 3. ?aragian ", 4. et al. Preferential aggregation of o#sessi'e)compulsi'e spectrum disorders in schi7ophrenia patients1ith o#sessi'e)compulsi'e disorder. Can O Psychiatry 2%%42913!44)!94.Medline $e# of "cience Google "cholar3. 3. 1. EaB5umar EP, 2. Eeddy KC, 3. *anda'el -. Clinical profile of =schi7o)o#sessi'e> disorder3 a comparati'e study. ComprPsychiatry 2%%A243242)24A.CrossEef Medline $e# of "cience Google "cholar4. 4. 1. (erman ,, 2. Merson A, 3. .iegner (, 4. Mosonc7y M?, 9. Pappas D, 4. Green A,. @#sessions and compulsions as a distinct cluster of symptoms in schi7ophrenia3 aneuropsychological study. O +er' Ment Dis 1A21A4319%)194.CrossEef Medline $e# of "cience Google "cholar9. 9. 1. $hitney *A, 2. ?astenau P", 3. H'ans OD, 4. Mysa5er P0. Comparati'e neuropsychological function in o#sessi'e)compulsi'e disorder and schi7ophrenia1ith and 1ithout o#sessi'e)compulsi'e symptoms. "chi7ophr Ees 2%%4243!9)A3.CrossEef Medline $e# of "cience Google "cholar4. 4. 1. "e'inco5 M, 2. A5oglu A, 3. *o5cu ?. "uicidality in schi7ophrenia patients 1ith and 1ithout o#sessi'e)compulsi'edisorder. "chi7ophr Ees 1%%22%31A)2%2.CrossEef Google "cholar!. !. 1. Poyuro's5y M, 2. *riss ., 3. $eisman G, 4. et al. ?amilial aggregation of schi7ophrenia)spectrum disorders and o#sessi'e)compulsi'eassociateddisordersinschi7ophreniapro#ands1ithand1ithout @CD. AmOMedGenet(+europsychiatr Genet 2%%92133331)34.Google "cholarA. A. 1. Poyuro's5y M, 2. Michaelo's5y H, 3. ?risch A, 4. et al. C@M-.al19AMet polymorphisminschi7ophrenia1itho#sessi'e)compulsi'edisorder3 acase)control study. +eurosci Mett 2%%923A321)24.CrossEef Medline $e# of "cience Google "cholar. . 1. (ottas A, 2. Coo5e EG, 3. Eichter MA. Comor#idity and pathophysiology of o#sessi'e)compulsi'e disorder in schi7ophrenia3 is theree'idence for a schi7o)o#sessi'e su#type of schi7ophreniaQ O Psychiatry +eurosci 2%%923%31A!)13.Medline $e# of "cience Google "cholar1%%. 1%%. 1. Mahendran E, 2. Mie1 H, 3. "u#ramaniam M. De no'o emergence of o#sessi'e)compulsi'e symptoms 1ith atypical antipsychotics in asianpatients 1ith schi7ophrenia or schi7oaffecti'e disorder3 a retrospecti'e, cross)sectional study. OClin Psychiatry 2%%!24A3942)949.Medline $e# of "cience Google "cholar1%1. 1%1. 1. Hrtugrul A, 2. Anil Kagcioglu AH, 3. Hni +, 4. Ka7ici *M. @#sessi'e)compulsi'e symptoms in clo7apine)treated schi7ophrenic patients. Psychiatry Clin+eurosci2%%929;2 antipsychotic agents. Am OPsychiatry 2%%%219!313!)13A.CrossEef Medline $e# of "cience Google "cholar1A4. 1A9. 1. -ollefson GD, 2. "anger -m, 3. Mu K, 4. -hieme MH. Depressi'e signs and symptoms in schi7ophrenia3 a prospecti'e #linded trial of olan7apine andhaloperidol. Arch Gen Psychiatry 1A299;3