- Email: [email protected]
Cancer and mental illness
Cancer and Mental Illness Thomas
J. Craig and Shang
P. Lin
E RELATIONSHIP between mental illness and neoplastic disease has been the subject of controversy for decades.‘-;’ Early studies using proportionate mortality rates (i.e., the proportion of cancer deaths to total deaths in a given population) were interpreted as evidence that psychotic patients have a significantly lower rate of cancer than the general population.“-3 These studies have been extensively criticized on the grounds that since psychiatric patients tend to have increased mortality from a variety of causes (e.g., pneumonia) relative to the general population, if cancer mortality were more equal in incidence between patient and general population groups, the proportionate mortality data would spuriously suggest reduced cancer risk among patients.“-” Other reports using age specific or age adjusted mortality data, with three exceptions,‘-!’ have indicated an equal or slightly increased incidence of cancer mortality among psychiatric patients as compared to the general population.4-“.10-1”However, several of these studies have suggested that the relative risk of cancer is greater among female patients than among male patients, with male patients having relative risk equal to or less than the male general population.1 I-13.13In addition, a number of reports have commented that paranoid schizophrenics have an increased risk for cancer while other categories of schizophrenia are associated with reduced risk.‘sJ,5 To our knowledge, this hypothesis has not been further replicated. To complicate the picture, recent reports have raised the question of whether neuroleptic treatment might predispose to breast cancer through its dopamine blocking effect of raising serum prolactin.‘6,17 Virtually none of the studies examines cancer rates by age, sex. and diagnosis, however; thus there is little opportunity to identify more subtle trends. The present study, part of a larger study of mortality among psychiatric inpatients, provided the opportunity to investigate these issues in a relatively large sample. ‘I”
MATERIALS
AND METHODS
The study population consisted of all inpatients with diagnosis of schizophrenia or organic brain syndrome (OBS) aged 50 years or older, who were hospitalized at a large state hospital during the period l/l/72 to 1213 1177. The primary data for the present study are derived from a computerized data system which has been in operation at the hospital for more than a decade in conjunction with the Multi-State Information System (MSIS) of Rockland Research Institute. Information regarding admission to and discharge from the hospital are routinely collected along with demographic and diagnostic data. As part of a special mortality study, the causes of death for all inpatients dying during the study period were entered into the data system from their death certificates. The availability of this computerized system permitted the calculation of the exact number of days each
From
Thomas
Rocklund
lrrnd Rrsrurch Sciences Address
Research
J. Craig,
Institute.
Division, reprint
Institute.
M.P.H.:
Orungeburg. Research
Ortrngebrtrg,
Rockland reqrtests
@ 1981 by Grune
404
M.D.,
Research to Thomos
& Strutton.
Inc.
N. Y.; Shang Institute. J. Craig,
N. Y.
Ps~chicttrist.
Informution
Sciences
P. Lin. Ph.D.: Resenrch Orungeburg,
M.D.,
Division.
Rock-
Associute,
lnformution
Nut,
N. Y. 10956.
N. Y.
40 Woodbine
Road,
City.
0010-440X/8//2204-0009$01.00/0
Comprehensive
Psychiatry,
Vol. 22, No. 4 (July/August),
1981
CANCER AND MENTAL
patient
was an inpatient
mortality
rates
specitic
categories
patients permit
with
cancer
among
this length
patient
patients
assessment
The total
to exclude
of hospital
among
from
New
York
There
during
1973: the denominators by the New
the total
number
for
a total
each
the number
were the age-sex State
Health
In actual
specific
only
number
by
by 36s.
1973. was selected midyear
ot
contributed up a11 days
of age and sex specitic
estimated
practice,
by adding
in the study
to
and to
and dividing
of days contributed
age .(O and over during
was limited
on admission
of person-years
category
of 8703 person-years
the cancer
of stay. The total
were calculated age-sex
for
The study
mortality.
were
of these rates were the total number York
I year.
1 year length
to another.
State population.
The numerators
than
who were moribund on cancer
Person-years
numerators
to age, sex, and diagnostic
less than
resident
were
stay greater patients
The
according
with
category.
one age category
separately.
or death.
deaths
environment
patients
was a hospital
group. provided
to discharge
of all cancer
with a hospital
in each age-sex
patient
moved
was counted
admission
consisted
was 69. The denominators
inpatients each
405
of stay both
deaths occurred
deaths
which
from
of inpatients
more direct
tive cancer these
ILLNESS
in If a
to each category population. as a comparison deaths
recorded
1973 population.
both
Department.
RESULTS Age and sex specific mortality rates for all schizophrenic. paranoid schizophrenic, and OBS patients as well as the general population age SO and older are presented in Table I. Since cancer mortality among patients in the younger age groups was relatively unreliable due to small numbers. it was felt prudent to limit the present analysis to the age group over 50 years. Age specific mortality rates among male schizophrenics tend to parallel those in the general population until age 70-99, at which point patient rates drop while general population rates double. Male paranoid schizophrenics show a trend toward a reduction in age specific cancer mortality with age. However, the 5%59-yearold paranoid schizophrenics showed a rate three times that of the total schizophrenic group and general population. while OBS patients tended to parallel the total schizophrenic rates. In contrast. among women, rates for all schizophrenics exceeded those of the general population in all age groups although the general trends were similar. Paranoid schizophrenics again tended to have the highest rates among those under age 60 and comparatively lower rates thereafter. The OBS group paralleled the total schizophrenic and general population except for a substantial excess in the 60-69-year age group.
Table 1. Age and Sex Specific Cancer Mortality
Rate (per WOO*)
AgeGroup
Males Schizophrenia (total) Paranoid schizophrenia OBS General population Females Schizophrenia Paranoid schizophrenia 0% General population l
50-59
60-69
70-99
5.0 17.2 3.3
8.3 9.4 9.7 8.0
5.1 2.9 5.4 16.6
7.0 11.9 5.6 2.9
5.9 6.3 13.1 5.1
12.8 9.9 12.5 9.3
Per 1000 person years for patients; per 1000 persons for general population.
406
CRAIG AND LIN
DISCUSSION
The relationship between major psychiatric illness and neoplastic disorders has been an area of heated debate for decades. In a recent concise critique of a number of studies, FoY has shown that data based on proportionate mortality among psychotic patients have generally been interpreted as indicating a lower incidence of cancer among these patients than the general population. In contrast, studies of absolute mortality rates in patient and general populations have drawn the opposite conclusion. Fox clearly identifies the methodological flaws of the use of proportionate mortality data, chiefly the fact that death rates from a variety of causes differ markedly between inpatient and general population, thus rendering proportionate rates noncomparable. In conclusion, Fox tends to support the view that cancer rates are not systematically reduced among psychiatric patients and suggests that any observed discrepancies between patient and general population cancer rates may relate to selective environmental or admission factors operating on the hospitalized patients if not explainable by methodologic flaws. In addition to the flaws listed by Fox, these studies generally suffer from an absence of diagnostic differentiation (e.g.. “psychoses” are treated as a group) and failure to present age and sex specific absolute mortality rates. Despite this analysis, psychiatric investigators have long proposed a variety of hypotheses regarding a possible association between psychological factors and increased or decreased risk for development of cancer. These theories have included somatotype, personality types, specific dynamic issues, and the presence of specific affects, such as hopelessness.5*L8~‘9 In addition, despite the demonstrated weaknesses of the use of proportionate mortality rates, investigations using this methodology continue to be published.20 The present study examines age specific mortality rates for two substantially different patient groups (schizophrenia and OBS). Due to the relatively small sample of cancer deaths (48 schizophrenics and 21 OBS patients), detailed analyses as suggested by Fox,” were not possible. In 26.2% of the diagnosed cancer deaths, an autopsy was performed, a rate that is virtually identical to the rate for all causes of death in this study. This rate is comparable to some cited for other inpatient samples but lower than others?’ and is somewhat higher than the autopsy rate in the general population.22 While it is acknowledged that, in the absence of a 100% autopsy rate, some occult cancers may go unrecognized. it was felt that the similarity of autopsy rates with those in other studies and the general population would argue against any significant bias although the rate for both patient and general populations may be somewhat lower than would be found if all deaths were autopsied. In particular, Klotz”’ has noted the clinically “missed” rate of brain tumors in autopsied mental patients while Rothfeldz2 found two misdiagnosed cancers in a series of 100 autopsies of psychiatric patients. If any bias is introduced due to a lack of autopsies, it would probably tend to underestimate cancer mortality among psychiatric patients both because certain cancers (e.g., brain tumors) may be more prevalent in patients and because, as Rothfeld points out,22 psychiatric patients may be less cooperative with diagnostic study.
CANCER AND MENTAL
ILLNESS
407
While the reliability of hospital and death certificate diagnoses has been questioned, the agreement noted for neoplasms has generally been high (77%).2:L Cause of death was extracted from the patient’s official death certificate and coded according to the International Classification of Disease (ICD). eighth revision. The inclusion of three specific diagnostic groups was done with recognition of the limited reliability of clinical diagnosis. It was felt that the schizophrenic and organic diagnoses are sufficiently broad and different that a reasonable degree of reliability could be assumed. In addition, Babigian et al.,‘l found these to be the most reliable diagnostic categories over time (OBS 92%. schizophrenia 70%). The subgroup of paranoid schizophrenia may be somewhat more problematic as differentiated from the other schizophrenic categories but a recent unpublished medical audit from this hospital indicated a 92%’ rate of agreement between clinical and Diagnostic and Statistical Manual of Mental Disorders (DSM) III diagnoses for this subtype. Perhaps the major methodological weakness of the present study is the relatively small number of cancer deaths. However, almost half the studies cited by Perrin and Pierce: have equal or fewer cases. Nevertheless, because of small numbers, the rates reported in Table 1 must be regarded as suggestive rather than definitive. However, despite these limitations, these data raise important issues in the context of earlier studies which deserve further investigation in a larger sample. First of all. in only one instance (males aged 70-99) does the age specitic death rate among psychiatric patients fall substantially below that of the general population. Among men at younger ages, rates are comparable to the general population while female schizophrenics tend to have somewhat higher rates at all ages. Taken at face value, these findings support the results of studies of absolute mortality that cancer among psychiatric patients is at least as common as among the genera1 population. However, when examined in more detail, the data suggest more complex relationships among illness, age and cancer mortality. Thus. for both men and women under age 60. the cancer mortality rates for paranoid schizophrenics exceed those of all other groups. These rates are more than three times those in the corresponding genera1 population. At older ages, paranoid schizophrenic rates tend to be comparable to those of the general population groups except among males 70-99. While the small number of cases involved (there were 23 cancer deaths among paranoid schizophrenics) dictates considerable caution in interpretation of these findings, they are relevant in view of the earlier reports of increased cancer risk among this schizophrenic subtype. If such an excess can be replicated, it might suggest a pathogenic process specific to younger paranoid schizophrenics. In this regard, Chevens’ claimed that paranoid patients and manic depressives are particularly liable to malignant growths and cited White’s postulation of a “proliferative type of reaction” at both psychic and somatic levels. Freeman)” reported an increased proportionate mortality among paranoids and cycloids while Po11acp6 concluded that patients with paranoid trends tend to have endocrine hyperplasia and excessive tumor formation. Pert-in and Pierce’ also cite Moore’s report that 757~ of 87 cancer deaths in 700 psychiatric patients
408
CRAIG AND LIN
occurred in patients with paranoid trends. However, Perrin and Pierce tend to discount these suggestions because of methodological issues (proportionate mortality, increased autopsies among psychiatric patients) and because several studies showed that paranoid patients died at a later age than other patients. However, Scheflen;’ in a more methodologically rigorous study, found an increased cancer death rate in paranoid patients and suggested that the high incidence of mesomorphic body type in these patients, as reported by Kline,” might provide an explanation. The present findings document an increased cancer mortality rate among paranoid schizophrenics under age 60. The fact that this threefold excess occurred almost equally in men and women suggests that it is not related to such factors as neuroleptic use resulting in breast cancer.‘“,” In addition, if the earlier reports can be accepted as at least anecdotally corroborative, this finding seems to predate the use of most biologic treatments. Finally, as opposed to the speculations of Perrin and Pierce,” this excess is not explained by age since it is seen in younger patients only. In view of the earlier findings, the present data are suggestive and demand replication in a larger sample. While it is beyond the scope of this report to speculate on possible mechanisms, a variety of animal studies have linked deficiencies in the immune mechanism produced by shock or immunosuppressant endocrine activity (e.g., elevated steroid levels) to tumor production. 1)1Thus, neuroendocrinologic investigation of paranoid patients might offer a specific avenue to approach this etiologic question. Some support for this direction of investigation might be seen in the work of Kerr et al.,2X who reported an excess of neoplastic deaths among patients with affective disorders in view of recent evidence linking affective disorders to a variety of neuroendocrine abnormalities. The marked reduction in cancer mortality experienced by the elderly (70-99) male group differs from both female patient groups as well as the general population. The explanation for this deviation is not clear. Perhaps the most likely explanation would be that it is a chance variation. However, although the number of cases is too small for reliable analysis by specific cancer site, a more detailed examination of the data suggests a lower indicence of lung cancer mortality among the inpatient group as a whole when compared to the general population. Since lung cancer has been traditionally more common among men,2!’ the observed reduction in male rates may be associated with a reduced risk for lung cancer. Unfortunately, data regarding the prevalence of risk factors such as smoking in this population are not available. However, it is the authors’ anecdotal observation that psychiatric inpatients tend to smoke to a greater extent than their general population counterparts. Therefore. it is surprising to find a suggested lower risk for lung cancer in this population. As noted previously, this finding must be regarded with caution. However, the fact that this reduction is seen among both schizophrenic and OBS patients suggests that environmental factors may be operative. Also, the finding of a somewhat increased risk among women patients in other studies’1-13.i5 may be related to this divergence of mortality rates in the elderly. Clearly, this too is an area that requires further replication.
CANCER AND MENTAL
ILLNESS
409
The tinding of somewhat increased mortality rates at all ages for all categories of women patients also requires further investigation in the light of concerns regarding neuroleptic induced breast cancer. However. an argument against this possible mechanism is the fact that OBS patients (unpublished manuscript) who tend to be less likely to be receiving drugs than schizophrenics, have rates equal to or greater than the schizophrenic group. The present study replicates earlier findings that fail to support the contention that cancer is less common among psychiatric inpatients. However. a more detailed analysis suggests areas for future research, particularly with regard to a relatively increased cancer risk among younger paranoid schizophrenics and a reduced cancer rate among elderly male patients. CONCLUSION A study of cancer mortality among long-term psychiatric inpatients revealed age specific death rates similar to those found in the general population with two exceptions. Paranoid schizophrenics less than 60 years old had cancer death rates three times those of other patient groups and the general population while the cancer death rates among elderly male patients were substantially lower than those in the general population. The findings fail to support earliet contentions of reduced cancer mortality among the mentally ill. ACKNOWLEDGMENT The authors
wish to acknowledge
the assistance
of Mary
Herrmann
in manuscript
preparation.
REFERENCES I. Chevens
LCF:
The correlation
death with type of insanity. 57’.
of cause of
Dutch
2. Rudolf
G de M. Ashby
of cancer
in the
Wales.
J Ment
of
in a mental
psychotic
Psychiatry
5. Perrin GM, pects
of cancer.
and
hospital.
and Am
J
tumors in the insti-
65:145-155,
AMA
Arch
R: Om
Norsk
Psychosom
6. Fox BH: Cancer patients.
Med
as-
7. Peller mentally
201:9hh-968,
S. Stephenson
ill.
Public
CS:
Health
Psychiatr
12. lnnes
G.
psychiatric
Millar
patients.
13. Babigian
WM:
HM,
Cancer
Rep
BM.
Pederson
AM.
of death
among
suicide
psychiatric Arch
population
and
Gen Psychiatry
50:354--375.
in the
IS. Tokuhata state
56: 132-149.
Babigian
mental Health
In. Overall
HM:
attempters.
a general
Mortality
Med
among
J 15:143-148.
OdoroffCL:
of a population
14. Odegaard
Public
Patterns
among psychiatric Stand
Scot
a
popula-
34: 1155-I 161. 1977
GK.
17. Schyve
Stand Stehman
hospitals Prior
PM.
of breast Smithline
in
lY.SO-54.
lY.58
psychiatric
35:898-899.
IYX!
Mortality
of Michigan.
Rep 73:750-761. JE:
of the
27:353-3h7. VA:
ill-
lY69
0: The excess mortality
and the development Gen Psychiatry
The mortality
with psychiatric
1X:470-480.
insane. Acta Psychiatr
lY78
1941 X. Tefft
blandt
Laegenvillrshaban
B: Mortality
.Acta
experience
21:397-421.
death risk in hospitalized
Science
all
Stand
krefthyppigheten
Magasin
ness. Am J Psychiatry
mental
Psychiatr
1933
Rorsman
patients.
Acta
JR: of
lY70
1951
IR: Psychosomatic
IY.sY
tion.
hospitals.
population
I978
sinnssyke. II.
long-stay
I974
population.
Pierce
the
mental
Y4:771-7Ylt.
mortality
I949
4. Scheflen AE: Malignant Neurol
England
in
IO. Opsuhl
population.
I934
Analysis
106:185-189.
tutionalized
of
Sci 80:23-276, H:
of death
Psychiatry
hospitals
R. Dijk S. van Weerden-Dijkstra
57:3hl-3hX.
WR: The relative
in the general
mental
3. Josephy causes
Y. Girl Mortality
Sci 77:X-
1931
mortality and
J Ment
treatment
cancer.
Arch
1978 F. Meltzer
H\‘:
410
Neuroleptic-induced prolactin level elevation and breast cancer. Arch Gen Psychiatry 35: 1291-1301, 1978 18. Schmale Jr AH, Iker HP: The affect of hopelessness and the development of cancer. Psychosom Med 28:714-721. 1966 19. Bahnson CB. Kissen DM (eds): Psychophysiological aspects of cancer. Ann NY Acad Sci 125, 1966. 20. Achterberg J, Collerain I. Craig P: A possible relationship between cancer, mental retardation, and mental disorders. Sot Sci Med 12:135-139, 1978 21. Klotz M: Incidence of brain tumors in patients hospitalized for chronic mental disorders. Psychiatr Q 31:669-680, 1957 22. Rothfeld B: Comparison of autopsy and clinical diagnosis on psychiatric patients. Dis Nerv Syst 20:406-408, 1959 23. Gittelsohn A. Senning J: Studies on the reliability of vital and health records: I compari-
CRAIG AND LIN
son of cause of death and hospital record diagnoses. Am J Public Health 69:680-689. 1979 24. Babigian HM, Gardner EA. Miles HC, et al.: Diagnostic consistency and change in a followup study of 1215 patients. Am J Psychiatry 121:895-901, 1965 25. Freeman W: Biometrical studies in psychiatry. III The chances of death. Am J Psychiatry 85:425-442, 1928 26. Pollack OJ: Postmortem studies in mental patients. Frequent findings in paranoid state. Am J Clin Path 14:289-303, 1944 27. Kline NS, Tenney AM: Constitutional factors in the prognosis of schizophrenia. Am J. Psychiatry 107:434-441, 1950 28. Kerr TA, Shapiro K, Roth M: The relationship between premature death and affective disorders. Br J Psychiatry 115:1277-82, 1969 29. Seidman H. Silverberg BS, Bodden A: Probabilities of eventually developing and of dying of cancer. Cancer 28:33-46, 1978.
J. Craig and Shang
P. Lin
E RELATIONSHIP between mental illness and neoplastic disease has been the subject of controversy for decades.‘-;’ Early studies using proportionate mortality rates (i.e., the proportion of cancer deaths to total deaths in a given population) were interpreted as evidence that psychotic patients have a significantly lower rate of cancer than the general population.“-3 These studies have been extensively criticized on the grounds that since psychiatric patients tend to have increased mortality from a variety of causes (e.g., pneumonia) relative to the general population, if cancer mortality were more equal in incidence between patient and general population groups, the proportionate mortality data would spuriously suggest reduced cancer risk among patients.“-” Other reports using age specific or age adjusted mortality data, with three exceptions,‘-!’ have indicated an equal or slightly increased incidence of cancer mortality among psychiatric patients as compared to the general population.4-“.10-1”However, several of these studies have suggested that the relative risk of cancer is greater among female patients than among male patients, with male patients having relative risk equal to or less than the male general population.1 I-13.13In addition, a number of reports have commented that paranoid schizophrenics have an increased risk for cancer while other categories of schizophrenia are associated with reduced risk.‘sJ,5 To our knowledge, this hypothesis has not been further replicated. To complicate the picture, recent reports have raised the question of whether neuroleptic treatment might predispose to breast cancer through its dopamine blocking effect of raising serum prolactin.‘6,17 Virtually none of the studies examines cancer rates by age, sex. and diagnosis, however; thus there is little opportunity to identify more subtle trends. The present study, part of a larger study of mortality among psychiatric inpatients, provided the opportunity to investigate these issues in a relatively large sample. ‘I”
MATERIALS
AND METHODS
The study population consisted of all inpatients with diagnosis of schizophrenia or organic brain syndrome (OBS) aged 50 years or older, who were hospitalized at a large state hospital during the period l/l/72 to 1213 1177. The primary data for the present study are derived from a computerized data system which has been in operation at the hospital for more than a decade in conjunction with the Multi-State Information System (MSIS) of Rockland Research Institute. Information regarding admission to and discharge from the hospital are routinely collected along with demographic and diagnostic data. As part of a special mortality study, the causes of death for all inpatients dying during the study period were entered into the data system from their death certificates. The availability of this computerized system permitted the calculation of the exact number of days each
From
Thomas
Rocklund
lrrnd Rrsrurch Sciences Address
Research
J. Craig,
Institute.
Division, reprint
Institute.
M.P.H.:
Orungeburg. Research
Ortrngebrtrg,
Rockland reqrtests
@ 1981 by Grune
404
M.D.,
Research to Thomos
& Strutton.
Inc.
N. Y.; Shang Institute. J. Craig,
N. Y.
Ps~chicttrist.
Informution
Sciences
P. Lin. Ph.D.: Resenrch Orungeburg,
M.D.,
Division.
Rock-
Associute,
lnformution
Nut,
N. Y. 10956.
N. Y.
40 Woodbine
Road,
City.
0010-440X/8//2204-0009$01.00/0
Comprehensive
Psychiatry,
Vol. 22, No. 4 (July/August),
1981
CANCER AND MENTAL
patient
was an inpatient
mortality
rates
specitic
categories
patients permit
with
cancer
among
this length
patient
patients
assessment
The total
to exclude
of hospital
among
from
New
York
There
during
1973: the denominators by the New
the total
number
for
a total
each
the number
were the age-sex State
Health
In actual
specific
only
number
by
by 36s.
1973. was selected midyear
ot
contributed up a11 days
of age and sex specitic
estimated
practice,
by adding
in the study
to
and to
and dividing
of days contributed
age .(O and over during
was limited
on admission
of person-years
category
of 8703 person-years
the cancer
of stay. The total
were calculated age-sex
for
The study
mortality.
were
of these rates were the total number York
I year.
1 year length
to another.
State population.
The numerators
than
who were moribund on cancer
Person-years
numerators
to age, sex, and diagnostic
less than
resident
were
stay greater patients
The
according
with
category.
one age category
separately.
or death.
deaths
environment
patients
was a hospital
group. provided
to discharge
of all cancer
with a hospital
in each age-sex
patient
moved
was counted
admission
consisted
was 69. The denominators
inpatients each
405
of stay both
deaths occurred
deaths
which
from
of inpatients
more direct
tive cancer these
ILLNESS
in If a
to each category population. as a comparison deaths
recorded
1973 population.
both
Department.
RESULTS Age and sex specific mortality rates for all schizophrenic. paranoid schizophrenic, and OBS patients as well as the general population age SO and older are presented in Table I. Since cancer mortality among patients in the younger age groups was relatively unreliable due to small numbers. it was felt prudent to limit the present analysis to the age group over 50 years. Age specific mortality rates among male schizophrenics tend to parallel those in the general population until age 70-99, at which point patient rates drop while general population rates double. Male paranoid schizophrenics show a trend toward a reduction in age specific cancer mortality with age. However, the 5%59-yearold paranoid schizophrenics showed a rate three times that of the total schizophrenic group and general population. while OBS patients tended to parallel the total schizophrenic rates. In contrast. among women, rates for all schizophrenics exceeded those of the general population in all age groups although the general trends were similar. Paranoid schizophrenics again tended to have the highest rates among those under age 60 and comparatively lower rates thereafter. The OBS group paralleled the total schizophrenic and general population except for a substantial excess in the 60-69-year age group.
Table 1. Age and Sex Specific Cancer Mortality
Rate (per WOO*)
AgeGroup
Males Schizophrenia (total) Paranoid schizophrenia OBS General population Females Schizophrenia Paranoid schizophrenia 0% General population l
50-59
60-69
70-99
5.0 17.2 3.3
8.3 9.4 9.7 8.0
5.1 2.9 5.4 16.6
7.0 11.9 5.6 2.9
5.9 6.3 13.1 5.1
12.8 9.9 12.5 9.3
Per 1000 person years for patients; per 1000 persons for general population.
406
CRAIG AND LIN
DISCUSSION
The relationship between major psychiatric illness and neoplastic disorders has been an area of heated debate for decades. In a recent concise critique of a number of studies, FoY has shown that data based on proportionate mortality among psychotic patients have generally been interpreted as indicating a lower incidence of cancer among these patients than the general population. In contrast, studies of absolute mortality rates in patient and general populations have drawn the opposite conclusion. Fox clearly identifies the methodological flaws of the use of proportionate mortality data, chiefly the fact that death rates from a variety of causes differ markedly between inpatient and general population, thus rendering proportionate rates noncomparable. In conclusion, Fox tends to support the view that cancer rates are not systematically reduced among psychiatric patients and suggests that any observed discrepancies between patient and general population cancer rates may relate to selective environmental or admission factors operating on the hospitalized patients if not explainable by methodologic flaws. In addition to the flaws listed by Fox, these studies generally suffer from an absence of diagnostic differentiation (e.g.. “psychoses” are treated as a group) and failure to present age and sex specific absolute mortality rates. Despite this analysis, psychiatric investigators have long proposed a variety of hypotheses regarding a possible association between psychological factors and increased or decreased risk for development of cancer. These theories have included somatotype, personality types, specific dynamic issues, and the presence of specific affects, such as hopelessness.5*L8~‘9 In addition, despite the demonstrated weaknesses of the use of proportionate mortality rates, investigations using this methodology continue to be published.20 The present study examines age specific mortality rates for two substantially different patient groups (schizophrenia and OBS). Due to the relatively small sample of cancer deaths (48 schizophrenics and 21 OBS patients), detailed analyses as suggested by Fox,” were not possible. In 26.2% of the diagnosed cancer deaths, an autopsy was performed, a rate that is virtually identical to the rate for all causes of death in this study. This rate is comparable to some cited for other inpatient samples but lower than others?’ and is somewhat higher than the autopsy rate in the general population.22 While it is acknowledged that, in the absence of a 100% autopsy rate, some occult cancers may go unrecognized. it was felt that the similarity of autopsy rates with those in other studies and the general population would argue against any significant bias although the rate for both patient and general populations may be somewhat lower than would be found if all deaths were autopsied. In particular, Klotz”’ has noted the clinically “missed” rate of brain tumors in autopsied mental patients while Rothfeldz2 found two misdiagnosed cancers in a series of 100 autopsies of psychiatric patients. If any bias is introduced due to a lack of autopsies, it would probably tend to underestimate cancer mortality among psychiatric patients both because certain cancers (e.g., brain tumors) may be more prevalent in patients and because, as Rothfeld points out,22 psychiatric patients may be less cooperative with diagnostic study.
CANCER AND MENTAL
ILLNESS
407
While the reliability of hospital and death certificate diagnoses has been questioned, the agreement noted for neoplasms has generally been high (77%).2:L Cause of death was extracted from the patient’s official death certificate and coded according to the International Classification of Disease (ICD). eighth revision. The inclusion of three specific diagnostic groups was done with recognition of the limited reliability of clinical diagnosis. It was felt that the schizophrenic and organic diagnoses are sufficiently broad and different that a reasonable degree of reliability could be assumed. In addition, Babigian et al.,‘l found these to be the most reliable diagnostic categories over time (OBS 92%. schizophrenia 70%). The subgroup of paranoid schizophrenia may be somewhat more problematic as differentiated from the other schizophrenic categories but a recent unpublished medical audit from this hospital indicated a 92%’ rate of agreement between clinical and Diagnostic and Statistical Manual of Mental Disorders (DSM) III diagnoses for this subtype. Perhaps the major methodological weakness of the present study is the relatively small number of cancer deaths. However, almost half the studies cited by Perrin and Pierce: have equal or fewer cases. Nevertheless, because of small numbers, the rates reported in Table 1 must be regarded as suggestive rather than definitive. However, despite these limitations, these data raise important issues in the context of earlier studies which deserve further investigation in a larger sample. First of all. in only one instance (males aged 70-99) does the age specitic death rate among psychiatric patients fall substantially below that of the general population. Among men at younger ages, rates are comparable to the general population while female schizophrenics tend to have somewhat higher rates at all ages. Taken at face value, these findings support the results of studies of absolute mortality that cancer among psychiatric patients is at least as common as among the genera1 population. However, when examined in more detail, the data suggest more complex relationships among illness, age and cancer mortality. Thus. for both men and women under age 60. the cancer mortality rates for paranoid schizophrenics exceed those of all other groups. These rates are more than three times those in the corresponding genera1 population. At older ages, paranoid schizophrenic rates tend to be comparable to those of the general population groups except among males 70-99. While the small number of cases involved (there were 23 cancer deaths among paranoid schizophrenics) dictates considerable caution in interpretation of these findings, they are relevant in view of the earlier reports of increased cancer risk among this schizophrenic subtype. If such an excess can be replicated, it might suggest a pathogenic process specific to younger paranoid schizophrenics. In this regard, Chevens’ claimed that paranoid patients and manic depressives are particularly liable to malignant growths and cited White’s postulation of a “proliferative type of reaction” at both psychic and somatic levels. Freeman)” reported an increased proportionate mortality among paranoids and cycloids while Po11acp6 concluded that patients with paranoid trends tend to have endocrine hyperplasia and excessive tumor formation. Pert-in and Pierce’ also cite Moore’s report that 757~ of 87 cancer deaths in 700 psychiatric patients
408
CRAIG AND LIN
occurred in patients with paranoid trends. However, Perrin and Pierce tend to discount these suggestions because of methodological issues (proportionate mortality, increased autopsies among psychiatric patients) and because several studies showed that paranoid patients died at a later age than other patients. However, Scheflen;’ in a more methodologically rigorous study, found an increased cancer death rate in paranoid patients and suggested that the high incidence of mesomorphic body type in these patients, as reported by Kline,” might provide an explanation. The present findings document an increased cancer mortality rate among paranoid schizophrenics under age 60. The fact that this threefold excess occurred almost equally in men and women suggests that it is not related to such factors as neuroleptic use resulting in breast cancer.‘“,” In addition, if the earlier reports can be accepted as at least anecdotally corroborative, this finding seems to predate the use of most biologic treatments. Finally, as opposed to the speculations of Perrin and Pierce,” this excess is not explained by age since it is seen in younger patients only. In view of the earlier findings, the present data are suggestive and demand replication in a larger sample. While it is beyond the scope of this report to speculate on possible mechanisms, a variety of animal studies have linked deficiencies in the immune mechanism produced by shock or immunosuppressant endocrine activity (e.g., elevated steroid levels) to tumor production. 1)1Thus, neuroendocrinologic investigation of paranoid patients might offer a specific avenue to approach this etiologic question. Some support for this direction of investigation might be seen in the work of Kerr et al.,2X who reported an excess of neoplastic deaths among patients with affective disorders in view of recent evidence linking affective disorders to a variety of neuroendocrine abnormalities. The marked reduction in cancer mortality experienced by the elderly (70-99) male group differs from both female patient groups as well as the general population. The explanation for this deviation is not clear. Perhaps the most likely explanation would be that it is a chance variation. However, although the number of cases is too small for reliable analysis by specific cancer site, a more detailed examination of the data suggests a lower indicence of lung cancer mortality among the inpatient group as a whole when compared to the general population. Since lung cancer has been traditionally more common among men,2!’ the observed reduction in male rates may be associated with a reduced risk for lung cancer. Unfortunately, data regarding the prevalence of risk factors such as smoking in this population are not available. However, it is the authors’ anecdotal observation that psychiatric inpatients tend to smoke to a greater extent than their general population counterparts. Therefore. it is surprising to find a suggested lower risk for lung cancer in this population. As noted previously, this finding must be regarded with caution. However, the fact that this reduction is seen among both schizophrenic and OBS patients suggests that environmental factors may be operative. Also, the finding of a somewhat increased risk among women patients in other studies’1-13.i5 may be related to this divergence of mortality rates in the elderly. Clearly, this too is an area that requires further replication.
CANCER AND MENTAL
ILLNESS
409
The tinding of somewhat increased mortality rates at all ages for all categories of women patients also requires further investigation in the light of concerns regarding neuroleptic induced breast cancer. However. an argument against this possible mechanism is the fact that OBS patients (unpublished manuscript) who tend to be less likely to be receiving drugs than schizophrenics, have rates equal to or greater than the schizophrenic group. The present study replicates earlier findings that fail to support the contention that cancer is less common among psychiatric inpatients. However. a more detailed analysis suggests areas for future research, particularly with regard to a relatively increased cancer risk among younger paranoid schizophrenics and a reduced cancer rate among elderly male patients. CONCLUSION A study of cancer mortality among long-term psychiatric inpatients revealed age specific death rates similar to those found in the general population with two exceptions. Paranoid schizophrenics less than 60 years old had cancer death rates three times those of other patient groups and the general population while the cancer death rates among elderly male patients were substantially lower than those in the general population. The findings fail to support earliet contentions of reduced cancer mortality among the mentally ill. ACKNOWLEDGMENT The authors
wish to acknowledge
the assistance
of Mary
Herrmann
in manuscript
preparation.
REFERENCES I. Chevens
LCF:
The correlation
death with type of insanity. 57’.
of cause of
Dutch
2. Rudolf
G de M. Ashby
of cancer
in the
Wales.
J Ment
of
in a mental
psychotic
Psychiatry
5. Perrin GM, pects
of cancer.
and
hospital.
and Am
J
tumors in the insti-
65:145-155,
AMA
Arch
R: Om
Norsk
Psychosom
6. Fox BH: Cancer patients.
Med
as-
7. Peller mentally
201:9hh-968,
S. Stephenson
ill.
Public
CS:
Health
Psychiatr
12. lnnes
G.
psychiatric
Millar
patients.
13. Babigian
WM:
HM,
Cancer
Rep
BM.
Pederson
AM.
of death
among
suicide
psychiatric Arch
population
and
Gen Psychiatry
50:354--375.
in the
IS. Tokuhata state
56: 132-149.
Babigian
mental Health
In. Overall
HM:
attempters.
a general
Mortality
Med
among
J 15:143-148.
OdoroffCL:
of a population
14. Odegaard
Public
Patterns
among psychiatric Stand
Scot
a
popula-
34: 1155-I 161. 1977
GK.
17. Schyve
Stand Stehman
hospitals Prior
PM.
of breast Smithline
in
lY.SO-54.
lY.58
psychiatric
35:898-899.
IYX!
Mortality
of Michigan.
Rep 73:750-761. JE:
of the
27:353-3h7. VA:
ill-
lY69
0: The excess mortality
and the development Gen Psychiatry
The mortality
with psychiatric
1X:470-480.
insane. Acta Psychiatr
lY78
1941 X. Tefft
blandt
Laegenvillrshaban
B: Mortality
.Acta
experience
21:397-421.
death risk in hospitalized
Science
all
Stand
krefthyppigheten
Magasin
ness. Am J Psychiatry
mental
Psychiatr
1933
Rorsman
patients.
Acta
JR: of
lY70
1951
IR: Psychosomatic
IY.sY
tion.
hospitals.
population
I978
sinnssyke. II.
long-stay
I974
population.
Pierce
the
mental
Y4:771-7Ylt.
mortality
I949
4. Scheflen AE: Malignant Neurol
England
in
IO. Opsuhl
population.
I934
Analysis
106:185-189.
tutionalized
of
Sci 80:23-276, H:
of death
Psychiatry
hospitals
R. Dijk S. van Weerden-Dijkstra
57:3hl-3hX.
WR: The relative
in the general
mental
3. Josephy causes
Y. Girl Mortality
Sci 77:X-
1931
mortality and
J Ment
treatment
cancer.
Arch
1978 F. Meltzer
H\‘:
410
Neuroleptic-induced prolactin level elevation and breast cancer. Arch Gen Psychiatry 35: 1291-1301, 1978 18. Schmale Jr AH, Iker HP: The affect of hopelessness and the development of cancer. Psychosom Med 28:714-721. 1966 19. Bahnson CB. Kissen DM (eds): Psychophysiological aspects of cancer. Ann NY Acad Sci 125, 1966. 20. Achterberg J, Collerain I. Craig P: A possible relationship between cancer, mental retardation, and mental disorders. Sot Sci Med 12:135-139, 1978 21. Klotz M: Incidence of brain tumors in patients hospitalized for chronic mental disorders. Psychiatr Q 31:669-680, 1957 22. Rothfeld B: Comparison of autopsy and clinical diagnosis on psychiatric patients. Dis Nerv Syst 20:406-408, 1959 23. Gittelsohn A. Senning J: Studies on the reliability of vital and health records: I compari-
CRAIG AND LIN
son of cause of death and hospital record diagnoses. Am J Public Health 69:680-689. 1979 24. Babigian HM, Gardner EA. Miles HC, et al.: Diagnostic consistency and change in a followup study of 1215 patients. Am J Psychiatry 121:895-901, 1965 25. Freeman W: Biometrical studies in psychiatry. III The chances of death. Am J Psychiatry 85:425-442, 1928 26. Pollack OJ: Postmortem studies in mental patients. Frequent findings in paranoid state. Am J Clin Path 14:289-303, 1944 27. Kline NS, Tenney AM: Constitutional factors in the prognosis of schizophrenia. Am J. Psychiatry 107:434-441, 1950 28. Kerr TA, Shapiro K, Roth M: The relationship between premature death and affective disorders. Br J Psychiatry 115:1277-82, 1969 29. Seidman H. Silverberg BS, Bodden A: Probabilities of eventually developing and of dying of cancer. Cancer 28:33-46, 1978.