Medical Comorbidity in Women and Men with Schizophrenia
A Population-Based Controlled Study
Caroline P. Carney, MD, MSc,1,2,3,4Laura Jones, MSc,4Robert F. Woolson, PhD5
1Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA;2Department of Psychiatry, Indiana
University School of Medicine, Indianapolis, IN, USA;3Regenstrief Institute, Indianapolis, IN, USA;4Department of Epidemiology,
The University of Iowa College of Public Health, Iowa City, IA, USA;5Department of Biometry and Epidemiology,
Medical University of South Carolina, Charleston, SC, USA.
BACKGROUND: Persons with persistent mental illness are at risk for
failure to receive medical services. In order to deliver appropriate
preventive and primary care for this population, it is important to
determine which chronic medical conditions are most common.
OBJECTIVE: We examined chronic medical comorbidity in persons
with schizophrenia using validated methodologies.
DESIGN: Retrospective analysis of longitudinal administrative claims
data from Wellmark Blue Cross/Blue Shield of Iowa.
PARTICIPANTS: Subjects with schizophrenia or schizoaffective disor-
der (N=1,074), and controls (N=726,262) who filed at least 1 claim for
medical services, 1996 to 2001.
MEASUREMENTS: Case subjects had schizophrenia as the most clini-
cally predominant psychotic disorder, based on psychiatric hospitali-
zation, psychiatrist diagnoses, and outpatient care. Controls had no
claims for any psychiatric comorbidity. Using a modified version of the
Elixhauser Comorbidity Index, inpatient and outpatient claims were
used to determine the prevalence of 46 common medical conditions.
Odds ratios (ORs) were adjusted for age, gender, residence, and non-
mental health care utilization using logistic regression.
RESULTS: Subjects with schizophrenia were significantly more likely
to have 1 or more chronic conditions compared with controls. Adjusted
OR (95% confidence interval [CI]) were 2.62 (2.09 to 3.28) for hypothy-
roidism, 1.88 (1.51 to 2.32) for chronic obstructive pulmonary disease,
2.11 (1.36 to 3.28) for diabetes with complications, 7.54 (3.55 to 15.99)
for hepatitis C, 4.21 (3.25 to 5.44) for fluid/electrolyte disorders, and
2.77 (2.23 to 3.44) for nicotine abuse/dependence.
CONCLUSIONS: Schizophrenia is associated with substantial chronic
medical burden. Familiarity with conditions affecting persons with
schizophrenia may assist programs aimed at providing medical care
for the mentally ill.
KEY WORDS: chronic medical condition; schizophrenia; schizoaffec-
J GEN INTERN MED 2006; 21:1133–1137.
prevalence studies, studies reporting early or increased mor-
he co-occurrence of medical illness among persons with
schizophrenia has been addressed in epidemiological
tality, studies reporting an increased risk for HIV, studies
outlining barriers to health care delivery, and most recently
with regard to the association with the development of diabetes
mellitus.1–11Persons with schizophrenia may have fewer med-
ical visits, fewer documented medical problems, and be less
likely to receive a detailed physical examination.7Dixon et al.12
reported that subjects in the Schizophrenia Patient Outcomes
Research Team (PORT) most commonly self-reported problems
with eyesight, teeth, and high blood pressure. Among persons
in that sample, current medical problems independently
contributed to more severe psychosis and depression.12The
12-month prevalence of 8 medical disorders among Medicaid
beneficiaries with psychotic disorders and substance abuse
disorders was significantly elevated compared with benefici-
aries without these psychiatric disorders. Most recently, Sokal
et al.11reported that persons with schizophrenia had greater
odds of respiratory illnesses, even when controlling for smok-
ing. Medical illnesses among persons with schizophrenia also
tend to be more severe.11,12
These studies support earlier literature that a significant
medical burden exists for persons with schizophrenia. The
results are compelling, but the significance of the findings
may be restricted because of limitations in study design
including (1) small nonrepresentative samples, (2) patient
self-report of medical conditions, (3) cross-sectional chart
reviews, and (4) poorly defined criteria for chronic medical
conditions. Therefore, we conducted a population-based
study, spanning multiple years, and using criteria validated
for the detection of chronic medical conditions for adminis-
trative claims data. Research of this type lays the framework
for refining strategies for the prevention, screening, and treat-
ment of seriously mentally ill patients in primary care settings.
We conducted a population-based controlled study using a
100% sample of Wellmark Blue Cross/Blue Shield of Iowa
administrative claims data from January 1, 1996 to December
31, 2001. These data are composed of inpatient and out-
patient claims submitted by all health care providers and
includes International Classification of Diseases (ICD-9)
Received for publication September 28, 2004
and in revised form February 5, 2005
Accepted for publication May 23, 2006
This research was supported by NIMH K08 MH01932-01A1 ‘‘Epide-
miology of Cancer and Mental Illness in Rural Areas’’ (Dr. Carney). The
authors thank Dr. Sheila Riggs of Wellmark Blue Cross Blue Shield of
Iowa and South Dakota for granting access to the data used in this
Address correspondence and requests for reprints to Dr. Carney:
Regenstrief Institute, 1050 Wishard Blvd, RG6, Indianapolis, IN 46202
diagnostic codes and Current Procedural Terminology Codes
The eligible study population included all subjects ages 18 to
64 who filed at least 1 claim for medical service during the
study period, 1996 to 2001. All subjects were residents of Iowa
and were classified as residing in a rural or urban county
based on the metropolitan statistical area definition.13The
basic medical insurance coverage was similar among subjects,
with only a small proportion (o10%) enrolled in a managed
The case population was composed of subjects diagnosed
with schizophrenia (ICD-9 295.0 to 295.3, 295.5 to 295.6,
295.8 to 295.9) or schizoaffective disorder (ICD-9 295.7) in the
inpatient or outpatient setting during 1996 to 2001. These
diagnoses will be described as schizophrenia throughout the
remainder of the text. Subjects were included provided that
schizophrenia was the most clinically predominant disorder,
regardless of whether other mental disorders (e.g., depression)
were also present. The most clinically predominant disorder
was determined by the number of claims for schizophrenia
based on the following criteria: (1) number of hospitalizations
for the given condition, and then (2) number of psychiatrist
visits for the condition, then (3) number of any other outpatient
claims for the condition. Subjects with claims for both schizo-
phrenia and bipolar disorder were included if schizophrenia
was more predominant than bipolar disorder.
The control population consisted of men and women who
had no mental disorder claims during 1996 to 2001.
The Elixhauser Comorbidity Index was used to assess medical
comorbidity using inpatient and outpatient claims data.14The
Elixhauser index was first used to describe chronic medical
conditions most commonly occurring in hospitalized persons.
As modified and validated by Klabunde, comorbid outpatient
conditions were also counted if the condition occurred either in
the inpatient setting or in 2 or more outpatient claims coded in
a period of no fewer than 30 days during 1996 to 2001.15This
time period was used to ensure that acute or miscoded out-
patient comorbidities were not included in the total comor-
bidity count. Twenty-six comorbidities were selected from the
Elixhauser Comorbidity index based on prevalence in the
general population and prior research on medical co-morbidity
in schizophrenia. Using the same methodology, we also exam-
ined twelve additional medical co-morbidities prevalent in the
adult population (stroke, ischemic heart disease, hyperlipide-
mia, pancreatitis, hepatitis C, other viral hepatitis, backache,
arthritis, asthma, accidents/injuries, benign prostatic hyper-
plasia, and headache), and 5 specific comorbidities unique to
women’s health care (cystitis, mammary dysplasia, endome-
triosis, inflammatory disease of the ovary, and disorders of
menstruation). Finally, we included nicotine, polysubstance,
and alcohol abuse/dependence conditions as comorbidities,
given the likelihood of these conditions to complicate the
course of underlying medical illness.
Demographic and clinical characteristics were analyzed using
w2tests for categorical variables and t tests for continuous
variables. Demographic variables included gender, age, urban
or rural residence, number of months eligible for medical care
as calculated from the first medical claim date to the last
medical claim date, and number of nonmental health care
visits. Membership files with actual dates of enrollment in
Blue Cross/Blue Shield were unavailable. Comorbidity was
further categorized as the presence of 0, 1, 2, 31 total condi-
tions described above.
Logistic regression was used to calculate odds ratios (ORs)
and 95% confidence intervals (CI) for each of the 46 comorbid-
ities examined. Odd ratios were adjusted for gender, age,
residence (rural vs urban), and nonmental health care utiliza-
tion. Odd ratio for comorbidities specific to 1 gender (e.g.,
benign prostatic hyperplasis, cystitis) were not adjusted for
gender. We adjusted for utilization by controlling for the num-
ber of known nonmental health encounters in order to take
into account potential differences in diagnostic patterns at-
tributed to contact with a provider during the time of observa-
tion from the first to the last known claim. All statistical tests
were 2 sided, with an a of 0.05. All analyses were performed
with SAS version 8.2.16Only adjusted findings are reported.
The Institutional Review Boards at Indiana University and
the University of Iowa approved this study.
Overall, 569 (53%) women and 505 (47%) men were identified
with schizophrenia. The mean age of the cases was 40.2 years
(SD, 11.9 years). Persons with schizophrenia had significantly
more months of follow-up, more overall health care visits, and
were only slightly more likely to live in urban settings than
controls, persons without schizophrenia (Table 1). Over 33% of
cases had 3 or more medical comorbidities, nearly 3 times
more than controls (33.2% vs 12.1%, respectively).
In the adjusted analyses, persons with schizophrenia had
increased ORs for conditions spanning nearly every organ
system, and markedly higher ORs for substance abuse and
dependence including alcohol 12.57 (95% CI 10.16 to 15.55),
nicotine 2.77 (2.33 to 3.44), and illicit substances 35.42 (28.35
to 44.27) (Table 2). Our findings confirm prior reports that
Table 1. Demographic Characteristics of Women and Men with
Schizophrenia Compared with Controls
Age, mean (SD)?
# Nonmental health care visits, mean
Length of follow-up (months), mean
Rural residence, n (%)
Women, n (%)
Number of comorbiditiesw
39.8 (24.6) 26.8 (23.8)
?Po.0001, based on the t-test.
wPo.0001, based on the w2statistic.
Carney et al., Medical Comorbidity in Schizophrenia
conditions related to tobacco use are more likely, including
peripheral vascular disease (OR 1.92, CI 1.01 to 3.65), stroke
(OR 2.11, 95% CI 1.22 to 3.65), chronic obstructive pulmonary
disease (OR 1.88, 95% CI 1.51 to 2.32), and asthma (OR 1.80,
95% CI 1.12 to 1.69). Although a higher percentage of persons
with schizophrenia had ischemic heart disease (2.3% vs 1.9%,
respectively) and hypertension (16.5% vs 9.2%, respectively)
than controls, the adjusted ORs for these conditions were not
Several conditions not previously reported were found to
occur at increased odds in this population. For instance, not
only do persons with schizophrenia have increased odds for
diabetes, they also have increased odds of complications
because of diabetes compared with controls (OR 2.11, 95%
CI 1.36 to 3.28). In addition, persons with schizophrenia have
increased odds of hypothyroidism (OR 2.62%, 95% CI 2.09 to
3.28), liver disease (OR 4.42%, 95% CI 2.47 to 7.89), and
pancreatitis (OR 4.00%, 95% CI 2.06 to 7.79) as well as
markedly increased odds of hepatitis C (OR 7.54%, 95% CI
3.55 to 15.99). However, these findings must be taken in the
context of the elevated odds of polysubstance and alcohol
abuse. Finally, renal failure (OR 2.94%, 95% CI 1.55 to 5.57)
and fluid and electrolyte disorders (OR 4.21%, 95% CI 3.25 to
5.44) also occurred at increased odds. Notable conditions not
occurring at increased odds in persons with schizophrenia
included hypertension, ischemic heart disease, hyperlipide-
mia, other hepatitis, and malignancies.
Our results are consistent with those from prior studies:
persons with schizophrenia have significant increased medical
comorbidity for conditions related to modifiable behaviors
(e.g., chronic obstructive pulmonary disease), as well as con-
Table 2. Prevalence and Adjusted Odds Ratios for Medical Conditions in Women and Men with Schizophrenia Compared with Controls
n (%) OR (95% CI)w
Cases (N=1,074) Controls?(N=726,262)
Ischemic heart disease
Congestive heart failure
Peripheral vascular disorder
Other neurological disorders
Diabetes w/out complications
Fluid and electrolyte disorders
Accidents and injuries
Inflammatory disease of ovary
Disorders of menstruation
0.99 (0.81 to 1.20)
0.86 (0.56 to 1.31)
0.86 (0.69 to 1.06)
2.38 (1.42 to 4.01)
1.92 (1.37 to 2.70)
1.92 (1.01 to 3.65)
2.11 (1.22 to 3.65)
6.66 (3.64 to 12.18)
9.67 (7.66 to 12.21)
1.37 (1.12 to 1.69)
1.88 (1.51 to 2.32)
1.80 (1.34 to 2.42)
1.62 (1.23 to 2.14)
2.11 (1.36 to 3.28)
2.62 (2.09 to 3.28)
2.73 (2.01 to 3.71)
3.96 (1.26 to 12.45)
2.94 (1.55 to 5.57)
4.21 (3.25 to 5.44)
4.42 (2.47 to 7.89)
4.00 (2.06 to 7.79)
7 (0.7)492 (0.1)7.54 (3.55 to 15.99)
48 (4.5) 9,164 (1.3)1.90 (1.38 to 2.62)
54 (5.0) 15,939 (2.2)1.40 (1.04 to 1.89)
358 (33.3) 145,431 (20.0) 1.19 (1.03 to 1.37)
2.30 (1.01 to 5.22)
1.52 (1.05 to 2.22)
1.50 (1.12 to 2.00)
12.57 (10.16 to 15.55)
2.77 (2.23 to 3.44)
35.42 (28.35 to 44.27)
?Other comorbidities with nonsignificant odds ratios not listed in Table 2 include valvular disease, pulmonary circulation disorders, peptic ulcer disease,
AIDS, lymphoma, metastatic cancer, nonmetastatic cancer, rheumatoid arthritis, coagulopathy, blood loss anemia, other hepatitis, backache, benign
prostatic hyperplasia, mammary dysplasia, endometriosis.
wAdjusted for age, gender (except gender-specific comorbidities), residence (rural/urban), and number of nonmental health care visits.
Carney et al., Medical Comorbidity in Schizophrenia
ditions that may influence the course of mental symptoms
(e.g., hypothyroidism). We add to prior studies by identifying
increased risk for conditions not previously reported, such as
deficiency anemias, hypothyroidism, neurological disorders,
and fluid and electrolyte conditions. It is possible that such
conditions were diagnosed in this insured population because
subjects had greater financial access to physician and diag-
nostic services than the uninsured or underinsured who have
previously been studied. It is also noteworthy that the ORs for
ischemic heart disease and hypertension were not elevated,
given the increased odds for nicotine abuse. We speculate that
this is likely because of underdiagnosis of these conditions in
Finally, compared with controls without mental illness,
persons with schizophrenia were more likely to have a greater
number of conditions spanning several disease categories
including cardiovascular, pulmonary, neurological, and endo-
crine diseases. One-third of this young population (average age
40 years) had 3 or more chronic comorbidities, and only 29% of
persons with schizophrenia compared with 54% of controls
had no claims for comorbidities.
The impact of medical comorbidity in schizophrenia is
significant because medical comorbidity affects quality of life
and delivery of psychiatric and medical services. Dixon et al.
reported that not only did persons with clinically diagnosed
schizophrenia sampled from a variety of community and treat-
ment settings have at least 1 medical problem, these persons
also had worse perceived physical health status, more psycho-
sis, more depression, and a greater likelihood of suicide
attempt. Medical comorbidity can either cause or exacerbate
the psychotic illness.17Because medical conditions may go
unrecognized in this population, it is possible that unrecog-
nized medical conditions contribute to prolonged hospitaliza-
tions and treatment failure.17–20
Primary care and behavioral health providers dealing with
apparent exacerbations of mental illness in their patients with
schizophrenia may need to consider whether symptoms are
being driven by undiagnosed medical conditions. Unfortu-
nately, failure to treat medical conditions in persons with
schizophrenia is a common problem,17–19,21and these pa-
tients are more likely to report substantial barriers to care
including economic barriers and delays in seeking care.10
Even among insured persons with mental disorders, risks for
delaying care or not receiving needed care are substantial.22
Reasons include failure of psychiatric providers to ask about
medical issues and patient inability to identify primary care
provider by name.23Recognition of treatment barriers has led
to calls for integration of physical and mental health treatment
services,12,22,24–28and integrated services have been success-
fully demonstrated in inpatient settings, outpatient clinics,
detoxification units, and smoking cessation programs.28–31
Furthermore, primary care providers may play an essen-
tial role in providing care to persons with schizophrenia, and
may be first in line to assess medical conditions, especially in
homeless shelters, walk-in clinics, or emergency treatment
venues. Our results may guide the evaluation of persons with
schizophrenia. For instance, the high rates of alcohol and
polysubstance abuse increase the likelihood that presenting
signs and symptoms of worsening psychosis may be related to
substance intoxication, withdrawal, or medical conditions
(e.g., hypothyroidism, congestive heart failure, diabetes).
These findings also indicate that systems of care for primary
and secondary prevention are important, especially for condi-
tions related to smoking and infection.
Our study has several important strengths. Unlike stu-
dies conducted in a single hospital or clinic setting, our study
analyzed a large population-based sample of adults. The data
represent practice patterns of a diverse group of physicians in
a wide geographical area. Because these subjects were com-
mercially insured, the findings represent a population rarely
studied, the commercially insured chronically mentally ill. We
examined 6 years of claims data, with a follow-up period of
approximately 40 months for subjects with schizophrenia. The
use of rigorous case-finding methodology further ensures
specificity of the schizophrenia-spectrum diagnoses and the
generalizability of these finding to other men and women
having schizophrenia. The use of the Klabunde comorbidity
measure also ensures that the medical conditions are likely to
The limitations of this work should also be considered.
First, this study included insured adults from Iowa, a racially
homogeneous state. These results are generalizable to simi-
larly insured populations but may not apply to racial and
ethnic minorities and the uninsured. Second, limitations in-
herent to the analysis of claims data may have affected our
results. Subjects who did not visit health care providers during
the study period are not represented and could have only been
captured if enrollment data were available. Thus, the ‘‘true’’
rates of comorbidity may be different from those reported.
Physician failure to bill for services or failure to code medical
diagnoses may have resulted in lower than expected rates of
comorbidity. We have no reason to suspect that this differen-
tially affected either the cases or controls. However, physician
failure to provide needed medical assessments of persons with
schizophrenia may have resulted in lower rates of claims for
specific medical diagnoses. Subjects with multiple insurers
may also have resulted in lower than expected rates of service
receipt represented in these data. Differences because of dis-
parate length of follow-up were controlled for in the adjusted
analyses. Yet, it is possible that persons with schizophrenia
had longer follow-up times for fear of losing health benefits.22
Finally, we had limited access to data regarding tobacco use,
and risk for some conditions may be changed if tobacco use
were entered into statistical models. However, logistic models
controlling for smoking did not change the elevated risk for
respiratory conditions in the Sokal et al.11study.
In summary, this research contributes to the growing
literature on medical and psychiatric comorbidity by describ-
ing a commercially insured population of men and women with
schizophrenia compared with contemporaries without admin-
istrative claims for mental illness. Using rigorous methodol-
ogy, we confirmed the findings of prior studies (e.g., increased
comorbid diabetes) and extended these studies by identifying
other comorbid medical conditions (e.g., hypothyroidism, ane-
mia) in persons with schizophrenia. Our findings support
the development and dissemination of coordinated medical
and psychiatric systems of care, especially those directed at
detection and the primary and secondary prevention of these
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Carney et al., Medical Comorbidity in Schizophrenia