88 (2006) 82–89www.elsevier.com/locate/schres

Schizophrenia Research

Physical comorbidity, insight, quality of life and global functioningin first episode schizophrenia: A 24-month, longitudinal

outcome study

Kang Sim a,b,⁎, Yiong Huak Chan c, Thiam Hee Chua a, Rathi Mahendran a,Siow Ann Chong b, Patrick McGorry d

a Department of Adult Psychiatry, Woodbridge Hospital/ Institute of Mental Health, 10, Buangkok View, 539747 Singaporeb Department of Early Psychosis Intervention, Woodbridge Hospital/ Institute of Mental Health, Singapore

c Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapored Department of Psychiatry, University of Melbourne and ORYGEN Research Centre, Australia

Received 11 April 2006; received in revised form 7 July 2006; accepted 8 July 2006Available online 14 August 2006

Abstract

This prospective study sought to determine the clinical impact of physical comorbidity on patients with first episodeschizophrenia (FES) and we tested the hypothesis that patients with physical comorbidity were associated with poorer clinical andfunctional outcomes. The severity of psychopathology, insight, social/occupational functioning and quality of life were evaluatedusing Positive And Negative Syndrome Scale (PANSS), Scale to assess Unawareness of Mental Disorder, Global Assessment ofFunctioning Scale (GAF), and World Health Organisation Quality of Life-Bref Scale (WHOQOL-Bref) respectively at baseline andat 6, 12, 18 and 24 months. Out of 142 patients, physical comorbidity was present in 21.8% (n=31) of the patients, and they weremainly related to the cardiovascular, respiratory and endocrine systems. Compared to baseline measurements, patients withphysical comorbidity had greater awareness into the consequences of their psychiatric illness at 12 months, the need for treatmentat 12 and 18 months, and better improvement of PANSS total and general psychopathology subscale scores at 24 months. FESpatients with physical comorbidity also had less reduction in their WHOQOL-Bref scores in the physical health domain at 12 and18 months and greater increase in the GAF scores at 18 and 24 months, indicating better subjective rating of quality of life andobjective measure of their global functioning prospectively. Clinicians need to be aware of the substantial rates of physicalcomorbidity in FES patients which may not be necessarily associated with worse longitudinal outcomes and the findings shouldencourage even greater efforts at early identification and management of these physical conditions.© 2006 Elsevier B.V. All rights reserved.

Keywords: Physical; Comorbidity; First episode; Schizophrenia; Outcome

⁎ Corresponding author. Department of Adult Psychiatry, Wood-bridge Hospital/ Institute of Mental Health, 10, Buangkok View,539747 Singapore. Tel.: +65 63892000; fax: +65 63855900.

E-mail address: kang_sim@imh.com.sg (K. Sim).

0920-9964/$ - see front matter © 2006 Elsevier B.V. All rights reserved.doi:10.1016/j.schres.2006.07.004

1. Introduction

Previous reports have highlighted the presence ofphysical illnesses in patients with psychotic disorderssuch as schizophrenia, with prevalence rates ranging

83K. Sim et al. / Schizophrenia Research 88 (2006) 82–89

from 19% to 57% (Koran et al., 1989; Koranyi, 1979;Hall et al., 1981) which included infective conditions(such as HIV/AIDS) (Cournos et al., 1994; Stefan andCatalan, 1995) and conditions affecting the cardiovas-cular system (such as hypertension, dyslipidaemias)(Kendrick, 1996; Davidson, 2002), endocrine system(such as diabetes, hyperprolactinaemia) (Dixon et al.,2000; Sernyak et al., 2002) and gastrointestinal system(such as irritable bowel syndrome, hepatitis C, H. pyloriinfection) (De Hert et al., 1997; Gupta et al., 1997;Davidson et al., 2001). Despite this, several studies havesuggested that the detection rates of these medicalconditions in patients with serious mental illnessesremained poor. Koran et al. (1989) estimated that up to45% of patients in the Californian public mental healthsystem had physical illness and about half of them wereundiagnosed. Koranyi (1979), similarly found that up to43% of their patients in an outpatient clinic had physicalillnesses and 46% were not detected in the course oftreatment and follow up. Furthermore, these physicalillnesses can potentially impact negatively on thesymptoms of mental illness (Dixon et al., 1999), andresult in greater healthcare burden, and affect attitudestowards treatment as well as the quality of life in theseindividuals (Hofer et al., 2004). This can, in turn, affectthe subsequent management of these medical illnessesin individuals with serious mental illnesses (Sokal et al.,2004).

Most studies of physical comorbidity in psychoticdisorders such as schizophrenia were conducted inpatients with chronic illnesses and to the best of ourknowledge to date, there is a lack of longitudinal dataon the impact of physical comorbidity on the outcomesof these psychotic illnesses. Furthermore, studies ofchronic patients are confounded by the prevailingeffects of psychotropic medications and their inter-actions with the disease process (Meltzer et al., 2002).In this study, we seek to (1) examine the prevalence ofreported physical comorbidity in a cohort of patientswith first episode schizophrenia (FES) within aNational Early Psychosis Intervention Program and(2) systematically evaluate the longitudinal outcomesof these individuals with respect to the clinical(psychopathology, insight, number of hospitalisationand duration of hospitalisation) as well as functionaldomains (psychosocial functioning as measured by theGlobal Assessment of Functioning Scale, quality of lifeas measured by World Health Organisation Qualityof Life-Bref Scale). Based on extant data, we hy-pothesised that patients with physical comorbiditywere associated with poorer clinical and functionaloutcomes.

2. Methods

2.1. Participants and study design

This longitudinal study report is part of a largerresearch project evaluating the impact of psychiatric andphysical comorbidities in patients with first episodepsychotic disorders (Early Psychosis and ComorbidityProject). The study population consisted of 142 consec-utive subjects enrolled in the Early Psychosis InterventionProgram at the Institute of Mental Health/WoodbridgeHospital in Singapore from March 2001 to March 2003fulfilling the following criteria: 1) age between 18 and40 years, 2) English speaking, 3) presentation with a firstepisode schizophrenia and had no previous psychiatrichospitalisation or antipsychotic treatment. The Institute ofMental Health/Woodbridge Hospital is the only statepsychiatric hospital which also serves as a principaltreatment and follow up facility for patients suffering fromsevere mental illnesses including the psychotic disorders.The subjects were excluded in this study if the psychoticsymptoms: 1) were secondary to acute intoxication orwithdrawal from alcohol or other psychoactive substances(Strakowski et al., 1995) or 2) resulted entirely from amedical illness as determined by a comprehensivemedicaland neurological evaluation which is further elaboratedbelow. The study has the approval of the Hospital EthicsCommittee and all participants providedwritten, informedconsent after a full explanation of the nature of the study.

All new psychiatric admissions were reviewed dailyand at index hospitalisation, a total of 240 potential studyparticipants were identified, of whom 162 (67.5%) metinclusion and exclusion criteria. Of these, 142 (59.2%)provided written, informed consent for the study. Allefforts were taken to ensure completeness of follow updata and this was assisted by the use of case managementapproach within the clinical cum research program toenhance regularity with review appointments. Neverthe-less, default rates of different individuals at differentpoints in time occurred at 6 (14.8%), 12 (17.6%), 18(19.0%) and 24 (23.9%) months and were taken intoaccount in the mixed-model repeated measurementanalyses. There were no significant differences in thebasic demographic variables (age and sex) of patients whowere willing or not willing to participate in the study.

2.2. Diagnostic assessment

Axis I psychiatric diagnoses were assessed by psy-chiatrists at the index hospitalisation and at 24months bymeans of the Structured Clinical Interview for DSM IV-Axis I Disorders, Patient Edition (SCID-P) (First et al.,

84 K. Sim et al. / Schizophrenia Research 88 (2006) 82–89

1994). In completing the SCID-P, combined symptominformation was obtained from various sources includ-ing clinical interviews with the subjects as well assignificant others, medical records and other primary,treating clinicians whenever necessary. All recruitedpatients underwent a thorough physical and neurologicalexamination and standard basic laboratory investigations(including full blood count, renal, thyroid function testsand other investigations whenever indicated) were per-formed to rule out prior or concurrent physical illnesses.Physical comorbidity was defined as the presence of allantecedent or concurrent medical or surgical illnesses,excluding substance abuse or dependence, and based onthe standardized history taking protocol, mental statusexamination, physical examination and basic laboratoryinvestigations. Clinical details of physical comorbiditywere further corroborated with information obtainedfrom medical records or consultations with colleaguesfrom the relevant medical or surgical disciplines,whenever indicated (such as history of previous medicalconsultations as reported by subjects or new medicalreferrals which were initiated by the attending psychi-atrist or treatment team). During the period of the followup, subjects with physical comorbidity who weredetermined at baseline were included in the group withphysical comorbidity at the various points of assessmentif they continue to receive treatment or require ongoingmedical surveillance for their physical illnesses. Therewas good inter-rater reliability for the principal Axis Idiagnoses and physical comorbidity (both kappa above0.90), as determined by the clinician-investigators (K.S.and T.H.C.).

2.3. Rating scales for clinical and functionalassessments

The Positive And Negative Syndrome Scale (PANSS)(Kay et al., 1987), Scale to assess Unawareness of MentalDisorders (SUMD) (Amador et al., 1994) and the GlobalAssessment of Functioning Scale (SCID Axis V) wereused to assess the severity of psychopathology, level ofinsight and psychosocial functioning respectively. Inter-rater reliability was obtained by rating 16 subjects by tworaters (K.S. and T.H.C.) with intraclass coefficient (ICC)above 0.80 for all the observer rated scales.

The subjective QOL at baseline was assessed using the26-item World Health Organization Quality of Life-BrefScale (WHOQOL-BREF), an abbreviated version of theWHOQOL-100 assessment instrument (The WHOQOLGroup, 1998). It is a valid and reliable self-rated instru-ment which is sensitive to the health-related QOL insubjects with psychotic illnesses (Herrman et al., 2002)

and has been well validated in Asian subjects (Saxena etal., 2001; Yao et al., 2002). The 26 items produce scoresfor four domains related to QOL, namely physical health(activities of daily living, dependence on medical treat-ment, energy and fatigue, mobility, pain and discomfort,sleep, work capacity), psychological health (bodily imageand appearance, negative feelings, positive feelings, selfesteem, spirituality, concentration), social relationships(personal relationships, social support, sexual activity),and environment (finances, physical safety, access tohealth services, home environment, opportunities to ac-quire new information, leisure activities, physical envi-ronment, transport). In addition, it also includes an itemeach on the overall QOL and general health.

The duration of untreated psychosis (DUP) wasdefined as the duration between the onset of psychoticsymptoms and the time that treatment was initiated.

2.4. Outcome assessment

Follow up assessments were scheduled for 6, 12, 18and 24months after their index hospitalization. Interviewswere conducted with the patient and best informant andmedical records were also reviewed at periodic intervalsafter the index hospitalisation. Clinical and symptomaticvariables were evaluated using PANSS, SUMD, and otherdata including number and total duration of rehospitalisa-tion following the index hospitalisation, the medicationdosage in daily chlorpromazine mg equivalents. Func-tional outcome was assessed using the GAF andWHOQOL-Bref scores. To improve the validity of theoutcome measures, ‘best estimate’ meetings were heldafter the completion of the 24-month follow up visit(Leckman et al., 1982) and involved the review of allassessments from index hospitalisation, follow upevaluations and available clinical records.

2.5. Statistical analysis

Data was analysed using the Statistical Package forSocial Sciences (SPSS)-PC version 11.0 (SPSS Inc,Chicago, Ill). Normality of quantitative data waschecked using the Kolmogorov–Smirnov 1-sampletest. Differences between groups were tested by t-testand Mann Whitney U-test for normal and non-normalcontinuous variables respectively and chi square test orFisher exact test for categorical variables wheneverappropriate. Correlations for normally distributed datawere made with linear regression (Pearson's r), and non-normally distributed data were correlated with a rank-method (Spearman's rs). The respective rating scoresassessed over time were subjected to repeated measure

Table 1Demographic and clinical characteristics of FES patients with (Group 1)and without (Group 2) physical comorbidity at baseline

Characteristic Group 1(N=31)

Group 2(N=111)

pvalue a

GenderMale 22 (71.0) 58 (52.3) 0.07Female 9 (29.0) 53 (47.7)

Age, mean (SD), years 28.1 (6.3) 27.9 (6.7) 0.88 b

EthnicityChinese 24 (77.4) 75 (67.5) 0.68Malay 6 (19.4) 29 (26.1)Indian 1 (3.2) 5 (4.5)Others 0 (0.0) 2 (.9)

Marital StatusSingle 24 (77.4) 76 (68.5) 0.46Married 5 (16.1) 26 (23.4)Separated/divorced 2 (6.5) 9 (8.1)

EducationLess than 10 years 19 (61.3) 62 (55.9) 0.83More than 10 years 12 (38.7) 49 (44.1)

EmploymentUnemployed 16 (51.6) 47 (42.3) 0.53Employed 15 (48.4) 64 (57.7)

Living arrangementsLives alone 0 (0.0) 5 (4.5) 0.59Lives with immediate family 30 (96.8) 105 (94.6)Lives with others 1 (3.2) 1 (0.9)

DUP, mean (SD), months 16.8 (24.7) 13.0 (19.4) 0.93b

Medication, CPZ eq, mg/day 101.5 (62.3) 135.6 (145.6) 0.46b

Abbreviation: DUP, duration of untreated psychosis; FES, first episodeschizophrenia.Data are presented as N (%) unless otherwise noted.a p values derived from χ2 test unless otherwise noted.b p values derived from Mann–Whitney test.

Table 2Physical comorbidity in patients with first episode schizophrenia(N=31, 100%) and their comparison with available populationprevalence rates

Medical or surgicalconditions

N (%) Available populationprevalence rate (%)

(1) Respiratory system 8 (5.60)Asthma 8 (5.60) 2.00–2.40 a

(2) Cardiovascular system 7 (4.93)Hypertension 5 (3.52) 0.40–2.20 b

Congenital heart disease 2 (1.41) 0.91c

(3) Endocrine system 6 (4.23)Hyperthyroidism 2 (1.41)Hypothyroidism 2 (1.41)Diabetes mellitus 2 (1.41) 0.20–0.70b

(4) Gastrointestinal system 5 (16.1)Known hepatitis B carrier 2 (1.41) 3.40–5.70 d

Peptic ulcer disease 3 (2.11)(5) Others 5 (16.1)Glucose-6-phosphate

dehydrogenase deficiency1 (0.70) 1.62 e

Retinal detachment 1 (0.70) 0.011 f

Salivary tumour 1 (0.70)Eczema 2 (1.41) 2.00 g

Total 31 (21.83%)

a Females, 2.0% and males, 2.4%, reference Ng (1999).b Reference Ministry of Health (2001).c Reference Tan et al. (2005).d Hepatitis B surface antigen (HBsAg) prevalence, females, 3.4%

and males, 5.7%, reference Goh (1997).e Reference Joseph et al. (1999).f Reference Wong et al. (1999).g Reference Tay et al. (1999).

85K. Sim et al. / Schizophrenia Research 88 (2006) 82–89

analysis of variance, using diagnosis (FES patients withand without physical comorbidity) as between-groupfactor and the different rating scores over time as withingroup factors. Significant interactions (group versustime) were then explored with post-hoc change scoreanalyses. A p-valueb0.05 (2-tailed) was taken to indi-cate statistical significance.

3. Results

3.1. Demographic and clinical characteristics

Table 1 compares the basic demographic and clinicalcharacteristics of FES patients with and without medical

comorbidity. Of the 142 patients, physical comorbiditywas present in 21.8% (n=31) of the patients: 16.9%(n=24) had co-existing medical illnesses, 4.2% (n=6)had co-existing surgical illnesses and 0.7% (n=1) hadboth at baseline. The medical or surgical conditionswere related to the respiratory, cardiovascular, endocrineand other bodily systems (Table 2). There were nosignificant baseline differences between those patientswith and without physical comorbidity, in terms of age,gender, ethnicity, marital status, employment status,education, DUP, PANSS, GAF, WHOQOL-Bref scores(Tables 1 and 3).

3.2. Longitudinal outcomes

Over time, significant rating score changes betweenthe 2 groups with and without physical comorbidityinvolved insight scores in terms of awareness ofconsequences of mental illness (F 3.79, p=0.007) andawareness of effects of medications (F 4.07, p=0.005),PANSS total (F 48.18, pb0.001) and general psycho-pathology (F 34.09, pb0.001) subscale scores, QOL in

Table 3Comparison of baseline SUMD, PANSS, GAF, WHOQOL-Brefscores in FES patients with (Group 1) and without physicalcomorbidity (Group 2)

Characteristic a Group 1(N=31)

Group 2(N=111)

pvalue b

SUMD (current awareness) c

Mental disorder 2.3±0.7 2.6±0.6 0.16Social consequences 2.3±0.6 2.5±0.7 0.23Treatment efficacy 2.3±0.9 2.2±0.8 0.63

PANSSTotal score 67.4±16.5 68.2±18.8 0.80Positive symptom 20.0±7.1 19.1±5.9 0.59Negative symptom 13.0±7.3 15.4±8.5 0.33General symptom 33.9±7.9 33.8±9.3 0.81

GAF 39.0±12.4 43.1±14.4 0.26

WHOQOL-Bref d

Physical health 46.9±18.9 52.4±13.5 0.06Psychological health 55.0±22.1 54.9±16.2 0.86Environment 55.8±22.8 58.4±17.8 0.67Social relationships 49.3±18.1 44.0±18.6 0.21

Abbreviations: SUMD, Scale to Assess Unawareness of MentalDisorders; PANSS, Positive and Negative Symptoms Scale; GAF,Global Assessment of Functioning; WHOQOL-Bref, World HealthOrganization Quality of Life-Bref Scale, ADL, activities of dailyliving; FES, first episode schizophrenia.a Values reported as mean±SD.b p values derived from Mann–Whitney test.c Lower scores indicate better insight.d Lower scores indicate poorer QOL, and included scores for the

four domains, overall quality of life, total score and also indicatingwhich sub-items within each of the four domains were statisticallysignificant in and of themselves.

86 K. Sim et al. / Schizophrenia Research 88 (2006) 82–89

the physical (F 16.81, p=0.001) subdomain as well asglobal assessment of functioning (F 30.27, pb0.001)rating scores. Inclusion of PANSS scores as a covariatein the repeated measurement analyses for insight, GAF,WHOQOL-Bref scores did not change the mainfindings. There was no significant group versus timeinteraction in antipsychotic dosages in daily chlorprom-azine mg equivalents (F 1.60, p=0.18) between FESpatients with and without physical comorbidity.

3.2.1. Clinical outcomesCompared to baseline measurements, patients with

physical comorbidity had greater reduction of theirSUMD scores in terms of awareness of consequences ofmental illness at 12 (−20.61% versus −3.11%, z=−2.06,p=0.04) months and awareness of effects of treatment at12 (−18.47% versus 3.42%, z=−2.68, p=0.007) and 18(−26.62% versus −2.05%, z=−2.89, p=0.004) monthsrespectively, indicating better insight into their psychoticillness. At 24 months, patients with physical comorbidity

had greater reduction in their PANSS total (−53.21%versus −41.68%, z=−2.67, p=0.008) and generalpsychopathology subscale (−48.11% versus 37.22%,z=−2.17, p=0.03) scores, suggesting better improvementin their psychopathology compared to patients withoutphysical comorbidity. There was no significant differencein the total number and duration of hospitalizationbetween the two groups of FES patients with and withoutphysical comorbidity over time.

3.2.2. Functional outcomesCompared with baseline scores, patients with phys-

ical comorbidity had less reduction in their WHOQOLscores in the physical health domain at 12 (−47.06%versus −54.46%, z=−2.14, p=0.032) and 18 (−47.60%versus −64.08%, z=−2.37, p=0.018) months andgreater increase in the GAF scores at 18 (115.78%versus 67.83%, z=−1.99, p=0.047) and 24 (131.64%versus 76.84%, z=−1.98, p=0.048) months, indicatingbetter subjective rating of QOL and objective measure oftheir global psychosocial functioning prospectively.

4. Discussion

This study highlighted that physical comorbidity wasnot uncommon amongst patients admittedwith FES.Overtime, patients with physical comorbidity showed signif-icant improvements in their level of awareness of theconsequences of their mental illness, effects of treatmentas well as psychopathology, observer rated global func-tioning and self rated QOL, thus disproving our hypo-thesis that patients with physical comorbidity had poorersymptomatic and functional outcomes. This is, to the bestof our knowledge, the first study documenting the rates ofphysical comorbidity and their longitudinal impact onclinical and functional outcomes in patients with firstbreak schizophrenia.

Of note, the baseline prevalence rates of physicalillnesses such as diabetes (1.4%) and hypertension (3.5%)found in our patients with FES were higher than reportedrates of comparable age groups within the generalpopulation (diabetes mellitus: 0.2% for age group 18–24 years old, 0.7% for age group 25–44 years old; hy-pertension: 0.4% for age group 18–24 years old, 2.2% forage group 25–44 years old), based on data from theNational Health Surveillance Survey (Ministry of Health,2001). The prevalence rates of physical illnesses in ourstudy were substantial but however, lower than those ofearlier reports (Koranyi, 1979; Koran et al., 1989), whichcould be partly accounted by patient age differencesbetween studies. For example, Koranyi (1979) investi-gated medical illnesses in psychiatric patients (including

87K. Sim et al. / Schizophrenia Research 88 (2006) 82–89

patients with schizophrenia) between the ages of 15–91 years old (mean age of 33.1 years for males and33.9 years for females), and found that up to 43% of thepatients suffered from ‘major medical illnesses’, with apreponderance in the older patients (mean age of36.3 years for males and 37.9 years for females withphysical illnesses). Our findings of common, reportedmedical conditions involving the various bodily systemswithin our patients were consistent with that found in aprevious Schizophrenia Patient Outcomes Research Team(PORT) study (Dixon et al., 1999), although not withinpatients with first episode illness. In the study by Dixon etal. (1999), self reported rates of physical illnesses wereevaluated in 719 patients and the majority of patientsreported at least one physical condition, with cardiovas-cular, respiratory and endocrine conditions being reportedby 49%, 21% and 15% respectively of the study cohort.The presence of these physical illnesses in our youngercohort of patients experiencing their first break psychoticillness, behooves clinicians to be attentive to its possibleoccurrence within this group of individuals which wouldwarrant early attention and referral to other medical orsurgical specialties for further management, wheneverindicated.

In terms of psychopathology, the lower PANSS totaland general psychopathology scores over time indicatedless severe symptomatology in patients with physicalcomorbidity compared to those without. This is incontrast with previous theories suggesting that medicalillnesses may worsen the symptoms of psychoticillnesses (Dixon et al., 1999; Lyketsos et al., 2002),which could be mediated by higher activity of thehormonal stress system (Corcoran et al., 2003). Thebetter insight as indicated by the greater level ofawareness of mental illness, its consequences and theneed for treatment found in FES patients with physicalcomorbidity is crucial as the psychotic illness canadversely affect insight, with the potential to impactnegatively on the compliance with psychotropic med-ications as well as drugs taken for other medicalconditions (Kamali et al., 2006). Poor adherence withtreatment could result in deleterious consequences suchas poorer control of the physical conditions and relapseof psychiatric illness requiring hospitalization (Ucok etal., 2006). In this regard, the longitudinal trend towardsimprovement of insight in patients with physicalcomorbidity, denotes opportunities for patient educationabout the nature of both the psychiatric and physicalillness as well as collaborative discussion of relevanttreatment plans. Indeed, disease specific knowledge hasbeen associated with lower barriers towards treatmentcare plans and can improve the management of the

physical comorbidities in these individuals (Dickersonet al., 2005).

The higher level of QOL especially in the physicalhealth domain found in our patients with physicalcomorbidity is in contrast to the findings of Dixon et al.(1999) who reported lower perceived physical as well asmental health status in their study group with medicalcomorbidity. However, the better subjective QOL wasconsistent with the objective GAF scores in this studywhich showed a greater increase at 18 and 24 monthswithin patients with physical comorbidity. The prospec-tive finding of a greater subjective sense of well-being inthis study may be related to the better improvement ininsight over time which can potentially result in less useof denial as a way of coping and better understandingand handling of their physical illnesses in these FESpatients. This is supported by recent findings of a greatersense of emotional well-being being associated withawareness into the need for treatment (Hasson-Ohayonet al., 2006). Furthermore, better insight can indepen-dently and positively affect attitudes towards treatment(Day et al., 2005) with associated better outcome interms of greater subjective QOL (Hofer et al., 2004).

Several explanations for the better clinical andfunctional outcomes are possible in our patients withphysical comorbidity. First, patients with physicalcomorbidity may be more familiar with the healthservices, have better understanding of the healthcaresystem as well as healthcare access, and are betteraccustomed to taking medications (Goldman, 1999).Second, the better insight in these individuals into theconsequences of their mental illness and effects oftreatment could have contributed to a greater willing-ness to accept their illnesses, better compliance withtreatment (both psychiatric and medical) and improvedprospective outcomes (Kamali et al., 2006; Schwartz etal., 1997). Third, the early attendance to the physicalillness during their first episode of psychotic illnesscould have led to better control and coping and whichalso involved their psychiatric treatment, with conse-quent positive impact on the functional outcomes(Lobban et al., 2004). Fourth, patients with physicalcomorbidity may delineate specific subgroups ofpatients with varying prognosis (including those withmore favourable prognosis), and who are biologicallydifferent. In this regard, the complex genetic andenvironmental determinants of different medical ill-nesses may also interact with those which underlie thepsychotic illnesses such as schizophrenia over time(Josiassen and Schindler, 1996; Nasrallah, 2003).

Limitations of the study included first, its smallsample size and hence we are not able to evaluate the

88 K. Sim et al. / Schizophrenia Research 88 (2006) 82–89

differential impact of the different physical comorbid-ities on the psychotic illness. Second, we only includedinpatients with FES, thus disallowing the results to begeneralisable to all cases of FES including those who arenot admitted to a psychiatric facility. Third, the length offollow up is limited to 24 months and the clinicaloutcomes of these patients over a longer period of timeremain unknown. Fourth, we only evaluated FESpatients within the age group between 18–40 yearsold, hence precluding generalisability of findings toindividuals who fall outside the age inclusion criteria.

In conclusion, physical comorbidity was not infre-quently found in FES patients who are not confoundedby the effects of treatment or chronicity of illness.Clinicians need to be aware of its presence which maynot necessarily be associated with worse clinical andfunctional longitudinal outcomes. Instead, early identi-fication of these medical problems can potentiallyimprove the overall physical and psychological statusof these patients. This requires an integrated, co-ordinated and comprehensive approach to foster thera-peutic rapport, treatment adherence and careful moni-toring of not only the psychiatric illnesses, but also thephysical conditions of these individuals over time.

Acknowledgements

This study was supported by a National HealthcareGroup Research Grant (K.S.) (STP/02003).

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