Psychiatric disorder as a first manifestation of cancer: A 10-year population-based study

Transcription

1 Int. J. Cancer: 124, (2009) ' 2009 UICC Psychiatric disorder as a first manifestation of cancer: A 10-year population-based study Michael E. Benros 1 *, Thomas M. Laursen 1, Susanne O. Dalton 2 and Preben B. Mortensen 1 1 National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark 2 The Danish Cancer Society, The Institute of Cancer Epidemiology, Copenhagen, Denmark To investigate the possibility that psychiatric symptoms could be caused by a yet undetected cancer or be part of a paraneoplastic syndrome, nationwide population-based registers were linked including the Danish Psychiatric Central Register and the Danish Cancer Registry. Data were analysed as a cohort study using survival analysis techniques and incidence rate ratios (IRRs) were used as measures of relative risk. A total of 4,320,623 persons were followed in the 10-year period , resulting in 37,581,600 person-years at risk, 202,144 persons with a first-time psychiatric contact, and 208,995 persons diagnosed with cancer. During the first month after a first-time psychiatric contact, the incidence of all forms of cancer was elevated; IRR: 2.61 (95% CI, ). Particularly the incidence of brain tumours was elevated; IRR: (95% CI, ), but also the incidence of lung cancer; IRR: 2.98 (95% CI, ), and especially smallcell lung cancer; IRR: 6.13 (95% CI, ) was elevated. The elevated IRR for most cancers decreased towards unity within the first 3 months, except for brain tumours, for which the IRR remained significantly elevated during the first 9 months. One of every 63 patients above 50 years of age was diagnosed with malignant cancer within 1 year of first-time psychiatric contact. These results indicate an increased incidence of cancer, especially for brain tumours and small-cell lung cancer, in the first months after a first-time contact to a psychiatric hospital. Clinicians should be aware that first-onset psychiatric symptoms could be a sign of a yet undetected cancer. ' 2009 UICC Key words: cancer; paraneoplastic; register-based; neurology and psychiatry An increased risk for cancer has been observed in the first 1 2 years after admittance to a psychiatric hospital, especially for brain tumours. 1 3 In most studies, these first 1 2 years of followup were excluded because the aim was to study the long-term effects of psychiatric disorders and cancer risk. 1 6 We know that diagnostic delay in somatic diseases is a general problem for psychiatric patients. 7 To our knowledge, no largescale study has been conducted to establish the frequency of which patients with an undetected cancer are admitted to a psychiatric hospital instead of being treated for their cancer. Only a few studies have been conducted on patients with paraneoplastic symptoms before their cancers were detected, 8 11 and scientists in this field have recommended that further studies of this area should be conducted. 12 A paraneoplastic syndrome is most frequently observed in small-cell lung cancer (SCLC), but is also observed in a number of other cancer types. 10,12,13 We studied the occurrence of cancer in persons with newly diagnosed mental illness to investigate whether a group of patients exists in which the symptoms of the psychiatric disease are associated with a cancer or a paraneoplastic syndrome. We assumed that a cancer occurrence higher than what would be expected by chance shortly after a first hospitalisation with a mental disorder, would indicate that in these extra cases the psychiatric symptoms leading to treatment were likely to be caused by the yet undetected cancer. Material and methods Civil registration system Since 1968, the Danish Civil Registration System (CRS) has assigned an individual unique 10-digit registration number to all residents in Denmark, providing information on date of birth and gender of the person. The civil registration number (CPR number) is used as a personal identifier in all national registers, enabling accurate linkage between registers. 14 Danish psychiatric central register The Danish Psychiatric Central Register has been computerised since 1969, and currently includes data on approximately 450,000 persons and 1.6 million contacts, with a virtually complete coverage. This register contains data on all admissions to Danish psychiatric in-patient facilities, and as of January 1, 1995 registration of psychiatric out-patient activities has been included. 15 From 1994, the diagnostic system used was the Danish modification of the International Classification of Diseases, 10th Revision (ICD- 10). 16 There are no private psychiatric in-patient facilities in Denmark, and all in- and out-patient treatment is provided free of charge, ensuring that all psychiatric admissions are represented in the register. Danish cancer registry The Danish Cancer Registry is a population-based registry, which has collected information on all individuals in Denmark with a diagnosis of cancer since Reporting of cancer was made mandatory by administrative order in Details of individual cases of cancer are available according to the Danish version of the ICD-7 for all years, and according to the International Classification of Diseases for Oncology (ICD-O) since Since 1978, ICD-O codes have been used to classify tumours, and the ICD-7 code is created from these automatically by a computerised conversion table. The morphology section of the ICD-O, second edition, has been in systematic use since This version of the ICD includes both malignant and benign brain tumours. The completeness and validity of the registry have been shown to be 95 98% by linkage to independent data from the Hospital Discharge Registry system, death certificates, and a pathology register. 17 Registration is made by personal evaluation of the mandatory reports, cross-checked against the Civil Registration System, updated, and combined with diagnosis made at autopsy. 18 Cancer diagnoses are registered by month and calendar year. Study population All 4,320,623 individuals born in Denmark who were alive on January 1, 1994 and with no cancer diagnosis or psychiatric hospital contacts prior to this date were identified. A total of 493,313 persons with a previous cancer diagnosis (except for nonmelanoma skin cancer), some 272,353 persons with a previous psychiatric hospital contacts, and additionally 29,193 persons with Grant sponsors: Stanley Medical Research Institute and Fabrikant Einar Willumsens Mindelegat. *Correspondence to: National Centre for Register-based Research, University of Aarhus, Taasingegade 1, 8000 Aarhus C, Denmark. Fax: Benros@ncrr.dk Received 26 September 2008; Accepted after revision 30 December 2008 DOI /ijc Published online 21 January 2009 in Wiley InterScience ( wiley.com). Publication of the International Union Against Cancer

2 2918 BENROS ET AL. both a previous cancer and a psychiatric admission were excluded from the analyses. Data were analysed as a cohort study, using survival analysis techniques. Poisson regression was used as an approximation to the Cox-regression. We used incidence rate ratios (IRRs) as the measure of relative risk. We chose to focus on adult onset of cancer and mental disorder and therefore the individual follow-up of each person began on the date of their fifteenth birthday or January 1, 1994, whichever came last. Persons were censored at the date of death, emigration, or December 31, 2003, whichever came first. The first-time psychiatric hospitalisation or contact was included in the analyses as a time-dependent exposure defined as the date of the first psychiatric in- or out-patient contact. The outcome was a cancer diagnosis defined as described below. Tests of significance and 95% confidence intervals (CIs) for the IRRs were based on log-likelihood tests. 19 Adjustment was made in all analyses for sex, age and calendar year. Assessment of cancer and psychiatric diagnosis Cancer sites of a priori interest included brain tumours (ICD-7 193), lung cancer (162), pancreas cancer (157), metastasis of all locations and unspecified sites with unknown primary cancer ( ). Further, we defined a group of cancers with suspected paraneoplastic effects, including breast cancer (ICD-7 170), kidney cancer (180), ovary cancer (175), testis cancer (178), gastrointestinal cancers ( ), haematological cancers ( ), thyroid cancer (194), and melanoma of the skin (190). Small-cell lung cancer (SCLC) was identified using the ICD-7 (162) code combined with morphology codes 80413, 80419, 80433, or All psychiatric diagnoses (F00-99) were categorized on the basis of the clinical ICD-10 main diagnosis. Psychiatric diagnoses of special interest were organic mental disorders (F00-09), psychotic disorders (F20-29), mood disorders (F30-39) and anxiety disorders (F40-F49). To ensure that the psychiatric diagnosis was actually established before the cancer diagnosis, we excluded the first month after the first psychiatric contact to rule out a possible overlap of diagnoses due to the different ways of recording the cancer disease (month and year only) and the hospital contact for psychiatric disorders (specific date). We validated the time intervals with the Hospital Discharge Register, 20 which contains the specific dates of the patient care pathway that led to the cancer diagnosis. All brain tumours that according to the Cancer Registry had been diagnosed within the first month after psychiatric admission/contact were diagnosed within a margin of 0 60 days after the date of the first psychiatric contact, reflecting the fact that the psychiatric contact had occurred at any time during the month before the cancer diagnosis, and that the cancer diagnosis was made at any time during the month of diagnosis. In this way, all brain tumours diagnosed within the second month after the psychiatric contact were diagnosed within a margin of days after the psychiatric contact. Results A total of 4,132 persons had a first-time psychiatric in- or outpatient contact from 1994 to 2003 with a subsequent first cancer diagnosis. Some 1,267 persons were diagnosed with cancer within the first year after their first-time psychiatric contact; of which some 145 persons had primary brain tumours. Table I shows an increased overall incidence rate ratio of cancer during the first 3 months after a first-time psychiatric contact. The incidence rate ratio of overall cancer was 2.61 (95% CI, ) during the first month when the reference group was cohort members without any previous cancer diagnosis. For brain tumours, the incidence rate ratio was increased almost 19-fold (IRR, 18.85; 95% CI, ), and the incidence rate ratios were also elevated for lung cancer (IRR, 2.98; 95% CI, ) and metastasing cancer (IRR, 2.81; 95% CI, ). The inci- TABLE I INCIDENCE RATE RATIOS (IRR) OF OVERALL AND SELECTED CANCER SITES, ADJUSTED FOR SEX, AGE, AND CALENDAR PERIOD, DENMARK, Metastasis Other cancers with Other cancers paraneoplastic potential 1 Small-cell lung cancer (SCLC) All cancers Brain tumour Lung cancer Total Total Total Total Total Total Total IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases Time since first psychiatric contact 1 month months months months months months , , The basic , , , , , , ,657 population (ref) 1 Includes cancers of the breast (ICD-7 170), kidney (180), ovary (175), testis (178), gastrointestinal ( ), haematological ( ), thyroid (194), and melanoma of the skin (190). 2 See definition in method section.

3 PSYCHIATRIC DISORDER AND CANCER 2919 TABLE II INCIDENCE RATE RATIOS (IRR) OF OVERALL AND SELECTED CANCER SITES STRATIFIED BY AGE GROUP, ADJUSTED FOR SEX, AGE, AND CALENDAR PERIOD, DENMARK, All cancers Brain tumour Lung cancer Total Total Total Time since first psychiatric contact IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases Age group years 1 month months months months months months year The basic population (ref) , , ,478 Age group years of age 1 month months months months months months year The basic population (ref) , , ,316 Age group month months months months months months year , The basic population (ref) , , ,089 1 See definition in method section. dence rate ratios for brain tumour remained significantly elevated during the first 9 months after the first-time psychiatric contact, whereas the incidence rate ratios for both lung cancer and metastasis were significantly elevated only during the first 2 months after a first-time psychiatric contact. Looking at the specific IRR of small-cell lung cancer (SCLC), we found that the incidence rate ratio was 6.13 (95% CI, ) during the first month after a first psychiatric contact. After 2 months, the incidence rate ratio of SCLC remained significantly elevated (IRR, 4.15; 95% CI, ), but no significant risk elevation was observed after that. For the combined group of other cancers with known paraneoplastic potential, the incidence rate ratio was significantly elevated only during the first month (IRR; 1.90; 95% CI, ) after which the incidence rate ratios were close to or even below unity. The same pattern occurred for the remaining group of cancers not previously suspected for paraneoplastic potential. In general, there were no differences when the analyses were separated by sex or calendar year. The only exception being pancreas cancer for which the incidence rate ratio was significantly elevated among women during the first month (n 5 7; IRR, 4.03; 95% CI, ) (data not shown). There were, however, too few cases of pancreas cancer in men to make any conclusions (n 5 2 during the first 3 months). When collapsing 4 6 months after first-time psychiatric contact, the incidence rate ratios for pancreas cancer were elevated (n 5 14; IRR, 1.80; 95% CI, ) and comparable for men and women. When stratified by age of first-time psychiatric contact the incidence rate ratios seem to be overall similarly increased by agegroup, type of cancer and time since first psychiatric contact, although a few exceptions are worth highlighting. In the age group years, the incidence rate ratio of overall cancer was elevated to 3.88 (95% CI, ) during the first month after a first-time psychiatric contact (Table II) whereas the respective incidence rate ratios were 3.11 (95% CI, ) in the years old and 2.33 (95% CI, ) in the above 65-years old (Table II). The incidence rate ratio for brain tumours were increased some 37-fold (IRR, 37.24; 95% CI, ) in the years old within the first month after first psychiatric contact (Table II) whereas the incidence rate ratio was 10-fold increased among the youngest (15 49 years old) for lung cancer within the first month compared with 2 3-fold increases in the age groups and 65 (Table II). When categorizing by presenting psychiatric symptom, the overall incidence of cancer was elevated to 1.97 (95% CI, ) during the first month after a first-time psychiatric contact with an organic brain disease (Table III). Also, the incidence rate ratio was 3.72 (95% CI, ) when the presenting psychiatric symptom was a mood disorder, where the excess incidence was confined to persons older than 50 years of age. Some age-differences in incidence rate ratios were further observed by presenting psychiatric symptom, with the incidence rate ratio for cancer within the first month after presenting with an organic mental disorder being 8.97 (95% CI, ; n 5 11) and 5.20 (95% CI, ; n 5 22) after a mood disorder in persons aged at time of first psychiatric contact (data not shown). Further, in the age group 65 years the incidence rate ratio was 3.77 (95% CI, ; n 5 18) in persons presenting with anxiety disorders after a first-time psychiatric contact (data not shown). The dominant types of brain tumours were meningiomas (44%) and gliomas (40%) during the first 9 months after a first-time psychiatric contact, where the incidence of brain tumours was significantly elevated. In comparison, meningiomas amounted to 26% and gliomas to 49% of total brain tumours diagnosed in the general population during the study period. The psychiatric diagnoses made before the detection of the brain tumour, were concentrated around organic mental disorders (F00 F09), a depressive episode (F32), anxiety disorders (F41) and reaction to stress, and adjustment disorders (F43). Almost half of the patients (49%), who within the first month after a first-time psychiatric contact were diagnosed with a brain tumour, had previously been diagnosed with an organic mental disorder (F00 F09). More specifically, these patients were diagnosed primarily with disorders in which evidence of brain-organic damage was a crite-

4 2920 BENROS ET AL. TABLE III INCIDENCE RATE RATIOS (IRR) OF OVERALL CANCER SITES IN PATIENTS, ADJUSTED FOR SEX, AGE, AND CALENDAR PERIOD, DENMARK, Psychiatric diagnosis and subsequent cancer incidence Time since first psychiatric contact F00 F09 Organic mental disorders F20 29 Psychotic disorders F30 F39 Mood disorders F40 49 Anxiety disorders Other diagnosis Total Total Total Total Total IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases IRR 95% CI Cases 1 month months months months months months year The basic population (ref) See definition in method section. rion (F06 F09), whereas diagnoses of dementia, amnestic syndrome, and delirium (F00 F05) were more prevalent in patients who had a longer delay in detection of the brain tumour. For patients with SCLC, the psychiatric diagnosis made within 1 year before the cancer diagnosis mainly included dementia (F01 F03), delirium (F05), depressive episodes (F32 F33), other anxiety disorders including panic disorder and generalised anxiety disorder (F41) and reaction to stress, and adjustment disorders (F43). During the study period 37,581,600 person-years were at risk, a total of 202,144 persons had a first-time psychiatric contact, and 208,995 persons were diagnosed with cancer, of which 7,452 (3.6%) persons had primary brain tumours. Above 50 years of age 68,922 persons had a first-time psychiatric contact and 181,235 persons were diagnosed with cancer, of which 5149 (2.8%) persons had primary brain tumours. In patients above 50 years of age, 1,093 cancers were diagnosed within 1 year after their first-time psychiatric contact; of which 113 (10%) would be primary brain tumours. Mood disorders (F30 39) were the first-time psychiatric contact in 18,018 patients above 50 years of age, and 336 cancers were diagnosed within 1 year. When looking specifically at the age span years of age, 22,688 persons were diagnosed with a first-time psychiatric contact and 59,222 persons with cancer. In total, 272 cancers were diagnosed within 1 year after their firsttime psychiatric contact; of which 45 (17%) were primary brain tumours. From these numbers it can be seen that 1 of every 63 patients with a first-time psychiatric contact at the age above 50 was diagnosed with a cancer within 1 year, and 1 of every 610 patients were diagnosed with a primary brain tumour. For firsttime psychiatric contact with mood disorders, 1 of every 54 patients above 50 years of age was diagnosed with a cancer within 1 year. Discussion In our study, we found an increased incidence rate of cancer after a first-time psychiatric hospital admission or outpatient contact. During the first month, we observed an increased incidence rate of brain tumours being almost 19-times the expected, and the incidence rate of SCLC being 6 times as high as would be expected. For other cancers with paraneoplastic potential, the incidence rate ratio was also elevated significantly during the first month after a first-time psychiatric contact. The elevated incidence rate ratios for most cancers decreased to a non-significant level within the first 3 months, except for brain tumours, for which the incidence rate ratio remained significantly elevated during the first 9 months after the psychiatric in- or outpatient contact. We interpret our finding of a large excess cancer risk shortly after the first-time psychiatric contact as an indicator of cancer presenting primarily with psychiatric symptoms and being misinterpreted as a mental disorder. This misinterpretation may well be more widespread than suggested by our results because only psychiatric in- and out-patients were included in our study. Patients with onset of less severe psychiatric symptoms would either be untreated or receive treatment from their general practitioner, private practising psychiatrist or psychologist and were thus not included in this study. Furthermore, some subjects in our cohort might not yet have been diagnosed with cancer during the time of follow-up. If these subjects were identified and moved into our cohort, it would most likely have only strengthened the association between the conditions. We only studied the incidence rates of first primary cancers among persons with a first-time psychiatric in- or out-patient contact compared with the background population. Consequently, the risk estimates excluded an effect of persons with either a previous diagnosis of cancer or psychiatric disorder. It is not likely that the psychiatric disorder per se would cause the immediate peak of increased incidence of cancer in our study. We find that within months of the first-time psychiatric contact the risk have decreased towards unity and this is in line with other population-based studies not finding any long-term cancer risk for psychiatric patients 2,3,21 despite the fact that persons with mental disorders are at a higher risk for some forms of cancer probably due to a higher prevalence of for instance smoking and alcohol abuse. 22 The study took advantage of the population-based nationwide registers in Denmark. The strengths of this database are that all exposures were recorded independently of the outcome and that reporting was mandatory throughout the country during our study period. We included only results from the ICD-10 period, but the same pattern with a peak in cancer incidence within the first year after a first psychiatric contact also seemed to occur during the ICD-8 period, 2,3 making it likely that our findings represent an actual problem and not just a statistical coincidence. In contrary to previous studies in this field, we studied the incidence of psychiatric disorders as a first manifestation of cancer. Dalton et al. 2 found that the risk of cancer was increased for the first year after hospital admission for depression (SIR 1.19: 95% CI, ), with especially brain cancer (SIR 3.27: 95% CI, ) occurring more frequently than expected. These findings were then excluded, because the aim was to study the longterm effects of psychiatric disorders on cancer risk. Similar findings were observed for patients admitted with schizophrenia. 3 In a population based case-control study Carney et al. 1 found increased odds of primary central nervous system tumours in people with mental disorders in an insured population (women: OR, 2.12: 95% CI, ; men: OR, 2.09; 95% CI, ) and increased odds of respiratory system cancers (women: OR. 1.57: 95% CI, ; men: OR. 1.52: 95% CI ). Compared with the previous Danish studies during the ICD-8 period through 1993, 2,3 we updated and expanded the included psychiatric diagnoses and focused on the excluded period, the first year after the first psychiatric admission, to study the reverse causation with psychiatric symptoms due to a paraneoplastic phenomenon.

5 PSYCHIATRIC DISORDER AND CANCER 2921 To our knowledge, our study is the largest investigation of this issue with more than 37 million person-years at risk. Further, our study describes the strongest associations with the excess risk of cancer primarily occurring during the first months after psychiatric contact indicating possible initial misdiagnosis and/or diagnostic delay due to symptoms mimicking psychiatric disease. During the period with increased incidence rate of brain tumours, meningiomas amounted to a seemingly larger proportion (44%) of the diagnosed brain tumour cases, than otherwise seen in the general population (26%). This could indicate that meningiomas, which tend to be slow growing tumours, are the type of brain tumour most likely to be misinterpreted as a mental disorder. Slowly growing tumours, such as meningiomas, may produce psychiatric symptoms with minimal neurologic signs, posing greater diagnostic difficulty. 23 Our finding of a higher percentage of meningiomas among psychiatric patients correlates with the tendency of previous findings. Also in previous findings, brain tumours with psychiatric symptoms tended to be more common among the elderly. 24 Meningiomas can be successfully treated by neurosurgery, thus early diagnosis is obviously important. Our study looked at primary brain tumours and if also brain metastases could have been included as a valid category, it would markedly increase the number of tumours present in the brain, because metastases to the brain are more common than primary brain tumours. It has been proposed that patients with psychiatric disorders may be at greater risk for delay in diagnosis or treatment of malignancy. 25 Although our findings certainly seem to confirm this in the sense that patients are referred to a psychiatric hospital setting with symptoms that are likely to be caused by an undetected cancer, our finding of the declining incidence rate ratio over the first few months after the first psychiatric admission or contact could suggest that most of these patients are eventually being referred to more relevant treatment, after they have entered the psychiatric system. Further, organic aetiology (ICD F00-09) was suspected or detected early on in a considerable part of cases by a psychiatrist. The large excess cancer incidence shortly after the first-time psychiatric contact could be seen as an indicator of psychiatric symptoms being misinterpreted especially by the general practitioner. In the Danish health care service all citizens are assigned a general practitioner. The general practitioners act as gatekeepers with regard to hospital treatment and treatment by specialists. 26 We have no information about the duration of doctors delay, when for instance a general practitioner misinterprets psychiatric symptoms caused by a yet undetected cancer. It is likely that the increased cancer incidence during the first months after a first-time psychiatric contact might be due to an increased detection rate during admission to hospital of cancers that might otherwise have not been diagnosed or have been delayed in diagnosis. The diagnosis of other cancers with paraneoplastic potential had similarly elevated incidence as other cancers, suggesting that a first-time psychiatric contact could also lead to a concurrent cancer diagnosis, identified through contact with a hospital. However, the specific findings of a particularly increased risk for brain and lung cancers with known paraneoplastic psychiatric symptoms do, however, indicate that our findings cannot be entirely explained by surveillance bias. Behavioural alterations in cancer patients may represent a sickness syndrome, which includes symptoms that overlap with those seen in major depression. 27 Sickness/depressive symptoms respond to antidepressant therapy irrespective of putative aetiology. 28 This indicates that the symptoms of a yet undetected cancer may respond to treatment with antidepressants, and that this therefore may delay the detection and treatment of an underlying cancer. The incidence of overall cancer was increased four-times the first month after a first-time psychiatric contact with mood disorders (F30-39) in persons older than 50 years of age. The study seems to confirm previous findings in smaller studies that psychiatric symptoms can be the first symptom of a malignant cancer, and that paraneoplastic symptoms are often present before the detection of a cancer. 10,29 Several causal mechanisms may be involved in the link between cancer and psychiatric symptoms. The psychiatric symptoms could be caused by direct pressure of a brain tumour or metastases, immunological reactions, ectopic hormone production, or even hypoperfusion. 10,13,24,30,31 The 6-fold increased incidence rate ratio of SCLC during the first month supports the hypothesis that especially SCLC can cause paraneoplastic psychiatric symptoms. 13 Many patients with paraneoplastic syndromes produce antibodies that react with both the nervous system and tumour antigens. 32,33 However, our study cannot provide any evidence regarding these or other causal mechanisms. Older age groups have an increased incidence of cancer and other somatic illness, which should be considered in the evaluation of patients with new-onset psychiatric symptoms, especially those older than 50 years. The general mortality for psychiatric patients is proven to be greater than that of the basic population. 34,35 Therefore better diagnostic work-ups for patients with first-onset psychiatric symptoms may lead to earlier detection of cancer and other somatic diseases causing the psychiatric symptoms. In line with this, it has been recommended that psychiatric disorder with onset after the age of 50 is an indication for CT or MR brain imaging It has also been suggested that older patients, particularly if smokers, should be examined for anti-hu antibodies, which might indicate that the tumour is probably SCLC. 10,12 There is evidence that treatment of the underlying tumour may lead to a better outcome of paraneoplastic symptoms, and psychiatric paraneoplastic symptoms have been observed to resolve completely after resection of the cancer. 10,12,24,38 40 So even if treatment of the cancer does not prolong the patient s lifespan, it would still improve the quality of life. The IRR of cancer is similar when looking at persons older or younger than 50 years, but when stratified into multiple age groups the highest risk is concentrated around the age span years of age where the IRR of all cancers were increased almost 4-fold and the IRR of brain tumours were increased 37 times. Because cancer incidence is higher with increasing age, the absolute risk is not higher than in older persons with a first-time psychiatric contact. If we were to screen all patients in Denmark above 50 years of age with a first-time psychiatric contact, we would have to screen 6,892 persons per year. If we presume that by screening all patients at first-time contact, we would find the cancers otherwise detected within 1 year; 1 of every 63 patients screened would have a malignant cancer, and 1 of 610 screened would have a primary brain tumour. If only screening patients with mood disorders (F30-39), 1 of every 54 patients screened would have a malignant cancer. In addition to this a thorough check-up program would probably also reveal many other somatic diseases, and we might even have made a conservative prediction by only including tumours otherwise detected within 1 year after first-time psychiatric contact. However, all cancers, diagnosed within the first year after a first-time psychiatric contact for persons older than 50 years, accounted for 0.6% of the total number of cancers diagnosed in people born in Denmark, and less than 2.2% of all brain tumours diagnosed were diagnosed within the first year after a first-time psychiatric contact. We do not believe that this allows us to conclude that screening of all psychiatric first-contact patients, or subgroups of them, with, e.g., neuroimaging or other examination techniques, is unwarranted. There may be other benefits of such a procedure as well as negative consequences, and a formal analysis of costs and benefits was beyond the scope of our study. Nonetheless, we do believe that our data suggest the need for such careful assessments before any recommendations for or against screening can be made. In summary, we have shown an increased incidence rate ratio for cancer in the months after a first-time psychiatric in- or outpatient contact. This was especially the case for brain tumours with an almost 19-fold increased incidence rate ratio during the first month. But also the incidence rates of SCLC were increased

6 2922 BENROS ET AL. 6-fold during the first month, indicating that certain cancers might mimic psychiatric disorders. These findings might generalise to the wider range of less severe psychiatric disorders that mostly would be treated by the general practitioner and therefore not included in this study. Clinicians should be aware that in patients, particularly older patients with first-onset psychiatric disorders, the psychiatric symptoms could be a sign of a yet undetected cancer. Acknowledgements This study was approved by the Danish Data Protection Agency. Michael Eriksen Benros received a personal grant from Fabrikant Einar Willumsens Mindelegat. All researchers had full independence from funders and there was no conflict of interest. M.E. Benros and T.M. Laursen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analyses. 1. Carney CP, Woolson RF, Jones L, Noyes R, Jr, Doebbeling BN. 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