Routine primary care data for scientific research, quality of care programs and educational purposes: the Julius General Practitioners' Network (JGPN).

BACKGROUND: General Practitioners (GPs) in the Netherlands routinely register all patient contacts electronically. These records include longitudinally gathered clinical information of the patient contacts in coded data and free text. METHODS: Diagnoses are coded according to the International Coding of Primary Care (ICPC). Drug prescriptions are labelled with the Anatomical Therapeutic Chemical Classification (ATC), and letters of hospital specialists and paramedic health care professionals are linked or directly incorporated in the electronic medical files. A network of a large group of GPs collecting routine care data on an ongoing basis can be used for answering various research questions. RESULTS: The Julius General Practitioners' Network (JGPN) database consists of routine care data from over ten years of a dynamic cohort of around 370,000 individuals registered with the participating GPs from the city of Utrecht and its vicinity. Health care data are extracted anonymously every quartile of a year and these data are used by researchers. CONCLUSION: We describe the content and usability of our JGPN database, and how a wide variety of research questions could be answered, as illustrated with examples of published articles.

Economic Consequences and Potentially Preventable Costs Related to Osteoporosis in the Netherlands.

BACKGROUND: Osteoporosis often does not involve symptoms, and so the actual number of patients with osteoporosis is higher than the number of diagnosed individuals. This underdiagnosis results in a treatment gap. OBJECTIVES: To estimate the total health care resource use and costs related to osteoporosis in the Netherlands, explicitly including fractures, and to estimate the proportion of fracture costs that are linked to the treatment gap and might therefore be potentially preventable; to also formulate, on the basis of these findings, strategies to optimize osteoporosis care and treatment and reduce its related costs. METHODS: In this retrospective study, data of the Achmea Health Database representing 4.2 million Dutch inhabitants were used to investigate the economic consequence of osteoporosis in the Netherlands in 2010. Specific cohorts were created to identify osteoporosis-related fractures and their costs. Besides, costs of pharmaceutical treatment regarding osteoporosis were included. Using data from the literature, the treatment gap was estimated. Sensitivity analysis was performed on the base-case results. RESULTS: A total of 108,013 individuals with a history of fractures were included in this study. In this population, 59,193 patients were using anti-osteoporotic medication and 86,776 patients were using preventive supplements. A total number of 3,039 osteoporosis-related fractures occurred. The estimated total costs were €465 million. On the basis of data presented in the literature, the treatment gap in our study population was estimated to vary from 60% to 72%. CONCLUSIONS: The estimated total costs corrected for treatment gap were €1.15 to €1.64 billion. These results indicate room for improvement in the health care policy against osteoporosis.

Comparing episodes of antidepressants use with intermittent episodes of no use: A higher relative risk of suicide attempts but not of suicide at young age.

The Food and Drug Administration has issued a number of advisories regarding a possible causal link between antidepressants and suicide behaviour among young persons. We investigated the age dependency of (fatal) suicide attempts associated with antidepressants (N=232,561). By linking insurance claims with the death register of Statistics Netherlands (2002-2011), rates of (fatal) suicide attempts were estimated during antidepressant use and intermittent episodes without use. The age dependency of the relative risk of attempts and of suicide during episodes with compared with episodes without antidepressants was investigated by testing the {age × episode} interaction.The attempt rate during antidepressant use decreased with increasing age, concurrently with a decrease of the relative risk from 3.62 to 1.86 (p for interaction <0.001). This age dependency was found both at the early (<0.5 year) and at later stages after the first prescription (>5 years). No suicides were found among those aged <18 years, and no age dependency for the relative risk of suicide at ages ⩾ 18 was established (p>0.46). The association between antidepressants and suicide attempts at a young age does not necessarily point to a causal relationship, and, most importantly, did not translate to a similar age dependency for suicide.

Local Geographical Distribution of Acute Involuntary Psychiatric Admissions in Subdistricts In and Around Utrecht, the Netherlands.

BACKGROUND: Acute involuntary psychiatric admissions (AIPA) tend to be applied more often in urban areas. OBJECTIVE: The current study aims to describe AIPA prevalence differences between the subdistricts in an urban area, and to identify which district characteristics are associated with a higher AIPA district density. METHODS: Information was collected on consecutive AIPAs over a 64-month period (2005-2010) in 49 subdistricts in and around the city of Utrecht, the Netherlands, including 1098 AIPAs. District characteristics included several demographic and economical factors and health care characteristics such as number of sheltered living facilities. RESULTS: The AIPA density (mean 4.4/10,000 inhabitants/y) was four to five times higher in the most urbanized subdistrict (around 12) compared to the suburban subdistricts (2.5-3). On the district level, the main correlates with AIPA density per district were unemployment rate and small household size. Other correlates were percentage of non-Western immigrants and number of facilities of sheltered living. CONCLUSIONS: The considerable AIPA density variation between subdistricts in this urban environment reflects that people who are prone to psychiatric admissions live in economically less prosperous environments. Impaired social networks and economic concerns may also contribute to an environment representing social defeat, increased demoralization, or social fragmentation.

Frequent Use of Antibiotics Is Associated with Colorectal Cancer Risk: Results of a Nested Case-Control Study.

BACKGROUND: Microbiotical dysbiosis induced by a Western diet seems to be associated with an increased risk of developing colorectal cancer (CRC). Few other factors with an effect on the colonic microbiota and their association with CRC have been evaluated. AIM: We investigated whether the use of antibiotics is associated with CRC risk. METHODS: Data on the use of antibiotics and comedication were extracted from a health insurance database for subjects with a diagnostic-related group for CRC between 2006 and 2011 and four age- and sex-matched controls. Antibiotic use was categorized according to the number of prescriptions during a 5-year follow-up period (1-6 years prior to CRC). Multivariable conditional binary logistic regression analysis was used to estimate odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for different levels of use. RESULTS: A total of 4029 cases (47 % male, mean age at diagnosis 71 ± 11 years) and 15,988 controls were included. Antibiotics had been prescribed to 2630 (65.3 %) cases and 10,234 (64.0 %) controls (p = 0.13). An increasing use of antibiotics was associated with an increasing risk of CRC [multivariable OR for high (≥8 prescriptions) vs. no prescriptions: 1.26, 95 % CI 1.11-1.44, p-trend <0.01]. For each increase of 5 prescriptions, the OR for CRC was 1.05 (95 % CI 1.01-1.09). CONCLUSION: We found an association between the use of antibiotics, especially when used frequently, and the risk of developing CRC. Further studies are needed to establish under which conditions the use of antibiotics increases the risk of developing CRC.

Effectiveness of pharmacotherapy in behavioural therapeutic smoking cessation programmes.

BACKGROUND: In 2011, pharmacotherapy as a part of smoking cessation treatment was reimbursed through the basic health insurance in the Netherlands. We examine the (cost)-effectiveness of pharmacotherapy added to behavioural therapy. METHODS: An observational study was conducted using data from the suppliers of the smoking cessation programmes together with information on costs from health insurance company Achmea. National suppliers, general practitioners and healthcare centres offered four different programmes. (i) Behavioural support (=therapy); (ii) Behavioural support combined with nicotine replacement therapy (NRT); (iii) Behavioural support combined with smoking cessation aids (=medication) (SCA); (iv) Behavioural support combined with NRT and SCA. The primary independent variable was the programme type, and the primary outcome was whether someone quitted smoking. To examine the effectiveness of the different programmes logistic regression and logistic multilevel analyses were performed. Bootstrapping was used to evaluate cost-effectiveness. RESULTS: The results indicate that behavioural support combined with SCA has more quitters than the reference programme of behavioural support alone, and it also seems the most cost-effective programme for general practitioners and healthcare centres. Behavioural therapy combined with NRT had also more quitters, although the difference with the reference programme was smaller. CONCLUSION: Behavioural support combined with SCA seems the most successful programme. However, as we performed an observational study, firm conclusions about the differences in effectiveness between the programme types cannot be made. Future research should consider the type of smoker (smoking history, amount of cigarettes per day).

Constipation-related direct medical costs in 16 887 patients newly diagnosed with chronic constipation.

BACKGROUND: Chronic constipation is a common condition, but the exact impact on healthcare budgets in Western Europe is poorly documented. OBJECTIVES: The aim of this study was to (a) investigate chronic constipation-related direct medical costs in patients with newly diagnosed chronic constipation and (b) study differences in costs according to natural history. PATIENTS AND METHODS: We identified 16 887 patients newly diagnosed with chronic constipation in a Dutch health insurance database (∼1.3 million patients) in 2006-2009. Individuals with chronic constipation were selected on the basis of chronic laxative use (≥90 days/year) and diagnostic related groups for chronic constipation. On the basis of the episodes of laxative use and diagnostic related groups, individuals were categorized as having persistent, episodic, and nonrecurrent disease. Unadjusted costs for laxatives and hospital care for chronic constipation and constipation-related comorbidities were assessed and compared between patients with nonrecurrent, episodic, and persistent disease. Factors associated with costs were identified using Cox regression analyses. RESULTS: The mean total chronic constipation-related direct medical costs in the first year after diagnosis were &OV0556;310±845 and consisted of laxatives (45%) and hospital care for chronic constipation (26%) as well as constipation-related comorbidities (29%). Costs were highest in patients with persistent disease (&OV0556;367±882) compared with patients with episodic (&OV0556;292±808) and nonrecurrent (&OV0556;263±613) disease (P<0.01). Male sex was associated with higher costs, whereas increasing age, diabetes, and use of opioids were associated with lower costs. CONCLUSION: Pharmacy costs and hospital care costs for chronic constipation-related comorbidities were the largest cost drivers for total constipation-related direct medical costs in patients with newly diagnosed chronic constipation. Direct medical costs differed according to patient characteristics.

Neighborhood ethnic density and psychotic disorders among ethnic minority groups in Utrecht City.

PURPOSE: Recent studies have shown increased incidence of non-affective psychotic disorders (NAPD) among ethnic minorities compared to the native population, but not, or less so, in areas with a high own-group proportion. The aim is to investigate this ethnic density effect in Utrecht and whether this effect is due to higher rates of NAPD among Dutch persons in areas with high minority proportions. We also explore the geographical scale at which this effect occurs and the influence of social drift prior to NAPD. METHODS: NAPD cases in the Psychiatric Case Registry Middle Netherlands (N = 2,064) and living in Utrecht during 2000-2009 were analyzed in a Poisson model in relation to both individual-level and district- vs. neighborhood-level characteristics. RESULTS: With increasing minority density, especially of the neighborhood, the rate ratios of NAPD significantly decreased among both non-Western (from 2.36 to 1.24) and Western immigrants (from 1.63 to 1.01), in comparison with Dutch persons. This was partly explained by higher rates of NAPD among Dutch persons in areas with high minority density. But there was also a trend to lower NAPD rates among non-Western minorities in these areas (P = 0.074).This trend was significant among Surinamese/Antilleans (P = 0.001) and Moroccans aged 18-30 years (P = 0.046). Among the Dutch, a social drift to minority-dense neighborhoods prior to NAPD registration was found. CONCLUSIONS: Our findings support the beneficial association with own-group presence at the smaller scale neighborhood level. Findings show also that this association is more pronounced in immigrant vs. native comparisons and is not found within all ethnic groups.

Effect of aging on healthcare costs of inflammatory bowel disease: a glimpse into the future.

BACKGROUND: Population aging is expected to result in a substantial additional burden on healthcare resources in the near future. We aimed to assess the current and future impact of aging on direct healthcare costs (DHC) attributed to inflammatory bowel disease (IBD). METHODS: Patients with IBD from a Dutch multicenter cohort filled out 3-monthly questionnaires for 2 years. Elderly (≥60 yr) and younger patients (18-60 yr) IBD were analyzed for differences in 3-monthly DHC, productivity losses, and out-of-pocket costs. Prevalence rates were obtained from a health insurance database. Estimates of annual DHC and prevalence rates were applied to the total Dutch adult population in 2011 and then projected to 2040, using predicted changes in population demography, prices, and volume. RESULTS: IBD-attributable DHC were lower in elderly than in younger patients with IBD with respect to 3-monthly DHC (&OV0556;359 versus &OV0556;978, P < 0.01), productivity losses (&OV0556;108 versus &OV0556;456, P < 0.01), and out-of-pocket costs (&OV0556;40 versus &OV0556;57, P < 0.01). Between 2011 and 2040, the percentage of elderly IBD patients in the Netherlands has been projected to rise from 24% to 35%. Between 2011 and 2040, DHC of the total IBD population in the Netherlands are projected to increase from &OV0556;161 to &OV0556;661 million. Population aging accounted for 1% of this increase, next to rising prices (29%), and volume growth (70%). CONCLUSIONS: Population aging has a negligible effect on IBD-attributable DHC of the IBD population in the near future, because the average costs incurred by elderly patients with IBD are considerably lower than those incurred by younger patients with IBD.

Primary non-variceal upper gastrointestinal bleeding in NSAID and low-dose aspirin users: development and validation of risk scores for either medication in two large Dutch cohorts.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose acetylsalicylic acid (ASA) have several adverse gastrointestinal (GI) effects, including upper GI bleeding. We aimed to develop a simple risk score to identify high risk NSAID and ASA users for primary upper GI bleeding. METHODS: Using data from two large anonymized health insurance databases, we defined a development and validation cohort with NSAID and ASA users which were followed-up for the occurrence of a primary upper GI bleeding. Cox regression analyses identified risk factors which were combined into simple risk scores. C-statistics were used to evaluate the discriminative ability of these scores in a validation cohort. RESULTS: In total, 421 cases of upper GI bleeding were identified in the initial cohort of 784,263 NSAID users (incidence rate 54.2 per 10,000 person-years), while 1,295 cases of upper GI bleeding were identified in 235,531 ASA users (incidence rate 37.9 per 10,000 person-years). The risk of upper GI bleeding increased with a higher risk score, which for NSAID users included age, male gender, anemia and concomitant use of ASA or anticoagulants. For ASA users, age, anemia, diabetes and concomitant use of other antiplatelet drugs or anticoagulants were included in the risk score. The C-statistics in the validation cohort were 0.68 and 0.63 or NSAID and ASA users, respectively. CONCLUSION: Risk factors for primary upper GI bleeding are to a large extent similar for NSAID and ASA users. Using a risk score based on these risk factors, patients at the highest risk can be identified with moderate accuracy.

Mortality and psychiatric disorders among public mental health care clients in Utrecht: a register-based cohort study.

BACKGROUND: Different studies have shown similar or even lower mortality among homeless persons with compared to homeless persons without a severe mental disorder. AIMS: To clarify the association between presence of a psychiatric diagnosis and mortality among the socially marginalized. METHODS: The Public Mental health care (PMHc) is a legal task of the municipal authority aiming at prevention and intervention in case of (imminent) homelessness among persons with a serious shortage of self-sufficiency. The data of PMHc clients (N=6,724) and personally matched controls (N=66,247) were linked to the registries of Statistics Netherlands and analysed in a Cox model. RESULTS: The increased mortality among PMHc clients, compared to the general population (HR=2.99, 95%-CI: 2.63-3.41), was associated with a broad range of death causes. Clients with a record linkage to the Psychiatric Case Registry Middle Netherlands ('PMHc+') had an increased risk of suicide (HR=2.63, 0.99-7.02, P=0.052), but a lower risk of natural death causes (HR=0.71, 0.54-0.92, P=0.011), compared to clients without this record linkage ('PMHc-'). Compared to controls, however, 'PMHc-' clients experienced substantially increased risks of suicide (HR=3.63, 1.42-9.26, P=0.007) and death associated with mental and behavioural disorders (ICD-10 Ch.V) (HR=7.85, 3.54-17.43, P<0.001). CONCLUSION: Psychiatric services may deliver an important contribution to the prevention of premature natural death among the socially marginalized. KEYPHRASES: The earlier observed lower mortality among vulnerably housed and homeless persons with a psychiatric diagnosis compared to vulnerably housed and homeless persons without a psychiatric diagnosis appears to be due to a significantly lower risk of natural causes of death. Compared to controls from the general population, vulnerably housed and homeless persons without registered diagnosis at a local psychiatric service have a significantly increased mortality associated both with natural death causes and with suicide and death due to mental and behavioural disorders. Services for mental health care may deliver an important contribution to the prevention of premature death due to somatic disorders among the socially marginalized.

Cause-specific mortality among patients with psychosis: disentangling the effects of age and illness duration.

BACKGROUND: There is a large mortality gap between patients with a nonaffective psychotic disorder and those in the general population, is associated with both natural and nonnatural death causes. OBJECTIVE: This study aims to assess whether mortality risks vary for different causes of death according to the duration since diagnosis and age in a large sample of patients with nonaffective psychotic disorder. METHODS: Data of patients with nonaffective psychotic disorder (n = 12,580) from 3 Dutch psychiatric registers were linked to the cause of death register of Statistics Netherlands and compared with personally matched controls (n = 124,143) from the population register. Death rates were analyzed by duration since the date of the registered diagnosis of the (matched) patient and their age using a Poisson model. RESULTS: Among patients, the rates of all-cause death decreased with longer illness duration. This was explained by lower suicide rates. For example, among those between 40 and 60 years of age, the rate ratios (RR) of suicide during 2-5 and > 5 years were 0.52 and 0.46 (p = 0.002), respectively, when compared with the early years after diagnosis. Compared with controls, patients experienced higher rates of natural death causes during all stages and in all age categories, rate ratios 2.35-5.04; p < 0.001-0.025. There was no increase in these rate ratios with increasing duration or increasing age for patients when compared with controls. CONCLUSIONS: The high risk of natural death causes among patients with nonaffective psychotic disorder is already present at a comparatively young age. This suggests caution in blaming antipsychotics or the accumulating effects of adverse lifestyle factors for premature death. It is better to proactively monitor and treat somatic problems from the earliest disease stages onward.

Morbidity and doctor characteristics only partly explain the substantial healthcare expenditures of frequent attenders: a record linkage study between patient data and reimbursements data.

BACKGROUND: Frequently attending patients to primary care (FA) are likely to cost more in primary care than their non-frequently attending counterparts. But how much is spent on specialist care of FAs? We describe the healthcare expenditures of frequently attending patients during 1, 2 or 3 years and test the hypothesis that additional costs can be explained by FAs' combined morbidity and primary care physicians' characteristics. METHODS: Record linkage study. Pseudonymised clinical data from the medical records of 16 531 patients from 39 general practices were linked to healthcare insurer's reimbursements data. Main outcome measures were all reimbursed primary and specialist healthcare costs between 2007 and 2009. Multilevel linear regression analysis was used to quantify the effects of the different durations of frequent attendance on three-year total healthcare expenditures in primary and specialist care, while adjusting for age, sex, morbidities and for primary care physicians characteristics. Primary care physicians' characteristics were collected through administrative data and a questionnaire. RESULTS: Unadjusted mean 3-year expenditures were 5044 and 15 824 Euros for non-FAs and three-year-FAs, respectively. After adjustment for all other included confounders, costs both in primary and specialist care remained substantially higher and increased with longer duration of frequent attendance. As compared to non-FAs, adjusted mean expenditures were 1723 and 5293 Euros higher for one-year and three-year FAs, respectively. CONCLUSIONS: FAs of primary care give rise to substantial costs not only in primary, but also in specialist care that cannot be explained by their multimorbidity. Primary care physicians' working styles appear not to explain these excess costs. The mechanisms behind this excess expenditure remain to be elucidated.

Infection load as a predisposing factor for somatoform disorders: evidence from a Dutch General Practice Registry.

OBJECTIVE: Somatoform disorders (SDs) are characterized by chronic multiple functional somatic (FS) symptoms. It has been suggested that infections may be triggers for FS symptoms to occur, pointing to the immune system as a pathogenic factor in their development. The current study aimed to compare the prevalence of infections (i.e., infection load) in the history of patients with SDs with that of matched controls. METHODS: Samples (n = 185) were identified in the Psychiatric Case Register Middle Netherlands and the Julius General Practitioners Network. Patients with an SD diagnosis in the Psychiatric Case Register Middle Netherlands were compared with matched persons without somatoform complaints (controls) on their infection load in two periods before the date of the psychiatric diagnosis or a matched date for the controls (i.e., the total period for which data were available and a 3-year period). Infection load was defined as the total number of infections documented in the Julius General Practitioners Network. RESULTS: Patients with SD had significantly more infections than did controls in both periods (total period: mean [standard error] = 0.87 [0.10] versus 0.51 [0.06], z = -3.08, p = .002; 3-year period: 3.44 [0.47] versus 2.15 [0.50], z = -2.91, p = .004). CONCLUSIONS: Results show that patients with SD have a higher infection load preceding their diagnosis as compared with matched controls, implicating that infection load may indeed predispose for developing FS symptoms. These findings emphasize the importance of further research on immunological mechanisms in FS symptoms. Limitations of the study are discussed.

Cancer mortality in patients with psychiatric diagnoses: a higher hazard of cancer death does not lead to a higher cumulative risk of dying from cancer.

PURPOSE: Both increased as well as decreased cancer mortality among psychiatric patients has been reported, but competing death causes were not included in the analyses. This study aims to investigate whether observed cancer mortality in patients with psychiatric disorders might be biased by competing death causes. METHOD: In this retrospective cohort study on data from the Psychiatric Case Register Middle Netherlands linked to the death register of Statistics Netherlands, the risk of cancer death among patients with schizophrenia (N = 4,590), bipolar disorder (N = 2,077), depression (N = 15,130) and their matched controls (N = 87,405) was analyzed using a competing risk model. RESULTS: Compared to controls, higher hazards of cancer death were found in patients with schizophrenia (HR = 1.61, 95 % CI 1.26-2.06), bipolar disorder (HR = 1.20, 95 % CI 0.81-1.79) and depression (HR = 1.26, 95 % CI 1.10-1.44). However, the HRs of death due to suicide and other death causes were more elevated. Consequently, among those who died, the 12-year cumulative risk of cancer death was significantly lower. CONCLUSIONS: Our analysis shows that, compared to the general population, psychiatric patients are at higher risk of dying from cancer, provided that they survive the much more elevated risks of suicide and other death causes.

Psychotropic drug use in patients with various chronic somatic diseases

Background and Objectives: To reveal insight into prevalence and incidence of psychotropic drug use in patients with various chronic somatic diseases and into time differences between incidence of the somatic disease and start of psychotropic drug use. Methods: A cohort study was performed using the Agis Health Database from 2002 to 2005. Patients with one or more of nine frequently occurring chronic somatic diseases were selected (N = 140,983). The non-exposed group (N = 417,486) was composed of patients without any of these nine diseases. For the somatic disease prescribed drugs were used as a proxy-indicator. Prevalences and incidences of psychotropic drug use were calculated as well as mean time between the incidence of the somatic disease and release date of the psychotropic drug. Results: Prevalence of antidepressant drugs and benzodiazepines was increased among patients with somatic diseases, with odds ratios of respectively 1.83 (95%CI 1.80-1.87) and 2.31 (95%CI 2.27-2.35). In the first year after incidence of the somatic disease, mean duration in time to start of psychotropic drug use was significantly shorter compared to patients without somatic disease. Conclusions: Physicians should be aware of the high prevalence and earlier onset of psychotropic drug use in all patients with chronic somatic diseases (AU)

Psychosis and suicide risk by ethnic origin and history of migration in the Netherlands.

BACKGROUND: There is an increased incidence of non-affective psychotic disorders (NAPD) among first- and second-generation migrants in Europe. The purpose of this population-based study was to compare the risk of suicide in Dutch natives and immigrants with or without NAPD. METHODS: Cases of NAPD (n=12 580) from three Dutch psychiatric registers were linked to the cause of death register of Statistics Netherlands and were compared to matched controls (n=244 792) from the population register, who had no such diagnosis. Hazard ratios (HRs) of suicide were estimated and adjusted for age and gender by Cox regression analysis. RESULTS: The presence of NAPD was strongly associated with suicide risk in each ethnic group. However, for all ethnic minority groups the HRs were somewhat lower than among Dutch natives, for whom the HR was 23.4 (95%-CI; 18.5-29.7). A closer examination revealed that suicide risk was influenced by the history of migration. While the risk for immigrants of the first generation, diagnosed with NAPD, was significantly lower than that for native Dutch patients (HR=0.45; 95%-CI: 0.28-0.73), the risk for those of the second generation was more similar to that for the Dutch (HR=0.85; 95%-CI: 0.51-1.40) (P value of history of migration=0.005). CONCLUSION: Immigrants diagnosed with NAPD of the first generation appear to be protected against suicide, whereas this protection is waning among those of the second generation. This is the first study worldwide on suicide in migrants with NAPD and the first study of suicide in patients with NAPD in the Netherlands.

Familial clustering of schizophrenia, bipolar disorder, and major depressive disorder.

PURPOSE: To investigate familial clustering of schizophrenia, bipolar disorder, and major depressive disorder. METHODS: Combining data from a psychiatric case registry and Statistics Netherlands provided information on 4,673 affected probands and 18,692 matched population controls. RESULTS: Probands with schizophrenia had relative risks (RRs) for having a sibling with schizophrenia of 3.77 (95% confidence interval (CI): 2.60-5.46) and with bipolar disorder of 1.79 (95% CI: 0.64-4.96) as compared with a reference proband. Probands affected with bipolar disorder have an RR of 6.51 (95% CI: 2.60-16.29) for having a sibling with bipolar disorder and of 1.71 (95% CI: 0.71-4.14) for having a sibling with schizophrenia as compared with a reference proband. Probands affected with major depressive disorder also have increased risk for having a sibling with schizophrenia (RR: 2.04, 95% CI: 1.54-2.72) as compared with a reference proband, which was similar to the risk for having a sibling with major depressive disorder (RR: 1.91, 95% CI: 1.63-2.24) or bipolar disorder (RR: 2.06, 95% CI: 1.18-3.60). CONCLUSION: Our findings suggest, as previous studies have, that risk across schizophrenia and bipolar disorder is considerably lower (twofold) than within diagnostic entities, whereas for major depressive disorder risk is similar within and across diagnostic entities.