Mental Disorders in Danish Hospital Registers: A Review of Content and Possibilities for Epidemiological Research

Abstract

Background: The Danish national hospital registers are a rich source of data for psychiatric epidemiology. The potential to identify diagnosed mental disorders in the Danish population has resulted in a plethora of important research studies. However, no recent review of these research sources exists.

Objective: To review the content, data quality and epidemiological considerations regarding mental disorders in the Danish hospital registers.

Methods: We provide information on the setting, history, and data access regarding mental disorders in the Danish hospital registers (defined according to the International Classification of Diseases, Tenth Revision, F group Mental and behavioural disorder codes). We describe the registration of mental disorders over time in the Danish hospital registers, by providing counts of individuals diagnosed with mental disorders each year, by types of mental disorders, diagnosis, hospital contact, and contact unit. We also provide information on considerations when using these data sources, including data quality. For this, we searched PubMed to identify validation studies of coding of mental disorder diagnoses.

Results: Between 1969 and 2022, 1,136,280 individuals (10.7% of all individuals who resided in Denmark in this period) have been registered as having a mental disorder as a primary or secondary diagnosis in a psychiatric unit in Denmark at least once. The type of contact and unit diagnoses were made in varied by mental disorder type. The literature indicates that a large proportion of coded diagnoses in the Danish hospital registers of mental disorders were considered valid.

Conclusion: We provide an overview of the available data for investigating mental disorders in the Danish hospital registers. We raise awareness of the limitations researchers should be aware of when using this data and discuss their implications. Careful consideration should be given to these during study design and when reporting findings from register-based studies on diagnosed mental disorders.

Introduction

The hospital registers of Denmark – combined with a comprehensive population register – are a boon for epidemiology, providing rich data for psychiatric research.¹ The national datasets of routinely collected psychiatric data from hospital contacts can be combined with other administrative registers, survey data, and biological data (eg, biobanks and imaging studies). Based on these data, a profusion of papers has been published describing the epidemiology of mental disorders in Denmark and their associations with other factors, including sociodemographic variables, comorbidities, genetic factors, and mortality. Furthermore, register data can be used to supplement data in other kinds of research, providing detailed information on diagnoses in the participant’s history or during a follow-up period.²

Although the primary purpose of the hospital registers is to support administration and planning, Denmark has pioneered their use for research. Using the Danish hospital registers for psychiatric research provides a myriad of benefits. First, the entire Danish population is covered by the registries, providing the possibility to include all individuals, if relevant to a study. Second, prospectively collected routine data eliminate the possibility of recall bias and provide diagnosis dates for temporal ordering of disease onset. Additionally, data are available across the life course, with linkage to family members. This allows inclusion of both living and deceased Danish residents and enables transgenerational research,³ investigation of prenatal exposures, and conduct of sibling studies.⁴

The main aim of the current review is to describe how the Danish hospital registries, specifically the Danish National Patient Registry⁵ and the Danish Psychiatric Central Research Registry,⁶ can be used in psychiatric research. It summarizes important issues, including data quality, possible sources of bias, and potential linkage with other data sources, eg, the Danish National Prescription Registry⁷ and the Danish National Health Services Registry.⁸

Setting

The United Nations projects that Denmark’s population will have reached 5.99 million in 2025.⁹ All residents in Denmark are included in the Danish Civil Registration System, based on a unique personal identification number assigned at birth or upon immigration.¹⁰ When this register was established on April 2, 1968, due to the introduction of a new tax system, it included information from all persons legally living in the country at that time.

Residents of Denmark have free and equal access to health care, including mental health care, provided by the Danish National Health Service, organized into five regions.¹¹ Information about contacts with the Danish National Health Service is compiled in nationwide health registers, including the Danish hospital registers. All Danish registers use the same personal identification numbers, allowing accurate linkage between different data sources. Thus, hospital contact data can be used in conjunction with other administrative data, including data on vital statistics, socioeconomic status, comorbid disorders, and redeemed prescription medications. Additionally, data from sources other than administrative registers can be linked to hospital data. For example, a research group can provide Statistics Denmark with survey or clinical data for a subsample of the population. Given relevant consent by participants, Statistics Denmark can link this data to register data using a project-specific pseudonymisation key, which replaces personal identifiers with placeholder values, to ensure that no individuals can be identified. Examples of such external datasets include the national surveys “Hvordan har du det?”¹² (“How are you?” in Danish, also referred to as the Danish National Health Survey or Den Nationale Sundhedsprofil), a population-based national health survey on health, illness and well-being administered in the five Danish regions in 2010, 2013, 2017 and 2021 to collect data on health, well-being and sickness, including the Major Depression Inventory starting in 2017 in the Central Denmark Region; the iPSYCH Initiative for Integrative Psychiatric Research genetic sample,¹³ which examines genetic and risk factors in more than 130,000 individuals born in Denmark to investigate autism, attention deficit hyperactivity disorder, schizophrenia, bipolar disorder and depression;^14,15 and data from the Better Health in Late Life cohort, which is a cohort of 114,283 individuals between 50 and 65 years who have responded to a survey aimed at understanding multimorbidity after age 50 years.¹⁶ Additionally, it is also possible to link relatives within the registers, providing the potential for investigating mental disorders and their risk factors within families.

Mental Disorders in the Danish Hospital Registers

Diagnoses of mental disorders reside in the Danish National Patient Registry and the Danish Psychiatric Central Research Registry. Other registers and data sources contain additional information relevant to mental disorders and their treatment, eg, the Danish National Prescription Registry,^7,17 which maintains data on redeemed prescription medications, and the Danish National Health Service Registry,⁸ which maintains data on contacts and services provided by primary health care practitioners, including general practitioners, neurologists, geriatricians, private psychiatrists, and private psychologists. This review focuses on mental disorders diagnosed in hospital inpatient, outpatient, and emergency room settings. While it summarizes other sources of data on mental disorders, a full description of these sources is outside of the scope of the paper.

Comprehensive descriptions of the Danish National Patient Registry and the Danish Psychiatric Central Research Registry have been published by Schmidt et al⁵ and Mors et al,⁶ respectively. Briefly, these registers were established as two separate registers and merged in 1995 (Figure 1 provides the timeline of the registers).

Figure 1 Timeline of availability of mental disorder diagnosis data in the Danish hospital registers.

The Danish Psychiatric Central Research Registry (‘Det Psykiatriske Centrale Forskningsregister’)⁶ is an electronic register, containing information on patient contacts with psychiatric departments in Denmark. As described in detail by Mors et al,⁶ the systematic collection of nationwide clinical data on patients admitted to Danish psychiatric hospitals started in 1938, and the register was established in its current form in 1969 at the Department of Psychiatric Demography at Aarhus Psychiatric Hospital, Risskov. Since January 1, 1970, all psychiatric departments have been required to provide data to the Danish Psychiatric Central Research Registry. Thus, 1970 is the first year with complete and valid data. In addition to Danish nationwide data, the register has received data from the Faroe Islands since 1973 and from Greenland since 1979. Data collected during the 1938–1969 period, stored in the Danish State Archive, are of historical interest only.

As described by Schmidt et al,⁵ computerized Patient Administrative Systems were established in most non-psychiatric hospitals in Denmark in the early 1970s (here we use the term “non-psychiatric” to refer to all units except psychiatry and child and adolescent psychiatry; in Denmark, the former are usually referred to as “somatic” units). With guidance from the Danish Health and Medicines Authority, non-psychiatric data collection was standardized in 1977 when the Danish National Patient Registry was established. Initially, the Danish National Patient Registry (ie, ‘Landspatientregistret’ version 1 or ‘LPR1’) was a separate register limited to non-psychiatric departments. However, in 1995, the Danish Psychiatric Central Research Registry was encompassed within version 2 of the Danish National Patient Registry (‘LPR2’). A researcher wishing to work with data on psychiatric contacts, therefore, needs to obtain access to different registers depending on the time period of interest. Hospital contacts with psychiatric departments from 1969 to the end of 1994 are available within the Psychiatric Central Research Registry, while contacts with non-psychiatric departments are available from the Danish National Patient Registry starting in 1977. Although the Danish Psychiatric Central Research Registry was merged with the Danish National Patient Registry in 1995, the two sources of information (from psychiatric and non-psychiatric departments) continued to be available in independent registers until January–March 2019, when information from both psychiatric and non-psychiatric departments was combined in a single register—the Danish National Patient Registry—in its ‘LPR3’ version (Figure 1).

Registered data are available from the Danish Health Data Authority (‘Sundhedsdatastyrelsen’, or SDS) and Statistics Denmark. Table 1 shows some key datasets allowing researchers to identify mental disorder diagnoses and their dates. In order to differentiate between diagnoses made in psychiatric versus non-psychiatric departments within the Danish National Patient Registry version 3 (LPR3), it is necessary to identify the departments or units in which the diagnoses were made. Limiting to diagnoses made in ‘Psychiatry’ or ‘Child and Adolescent Psychiatry’ departments would likely mimic the former Danish Psychiatric Central Research Registry (1969–1994) or the psychiatric portion of the Danish National Patient Registry (1995–2019). Some psychiatric research studies have considered diagnoses made only within psychiatric departments,^18,19 while other studies have considered mental disorders diagnosed in both psychiatric and non-psychiatric departments.²⁰ Coding of diagnoses made in psychiatric departments (and potentially other selected departments, depending on the mental disorders of interest) would be expected to be more valid. We show below the number of individuals diagnosed with mental disorders in psychiatric versus other departments.

Table 1 Relevant Datasets for Identifying Mental Disorders in the Danish Psychiatric Central Research Registry (DPCRR) and in the Danish National Patient Registry (DNPR)

In addition to the individual personal registration number, sex, and year of birth, the registers contain key data such as dates of admission and discharge, mode of admission (elective versus emergent), start and end of any outpatient treatment course or emergency room visit, all diagnoses (ie, primary and secondary diagnoses for each registered contact), and place of treatment including the specific department. The diagnosis codes are specified by clinicians at discharge. These include primary diagnosis (main reason for hospital contact) and secondary diagnoses (optional additional diagnoses related to the primary diagnosis).

Researchers need to consider several challenges affecting the quality of diagnostic coding. First, due to everyday time constraints, clinicians often only register the most important diagnosis (only a primary diagnosis is mandatory) with no specific additional codes. For example, for a condition like depression, they often use the “not otherwise specified” code, instead of subgrouping into moderate, severe, or severe with psychotic symptoms. Consistent with this challenge, hospital administrators primarily focus on diagnostic coding impacting reimbursement. This results from Denmark’s use of predefined reimbursement strategies, which reimburse hospitals a fixed amount for a specific diagnostic code, independent of complications, such as delirium. It is well known that the registered incidence of delirium is much lower than the expected/true incidence.²¹ In addition, even events such as self-harm and suicide attempts are often incorrectly coded.²² Another concern is that researchers sometimes fail to report whether they considered only primary diagnoses or both primary and secondary diagnoses of mental disorders identified from hospital registers. This is an important consideration when designing a register-based study. We provide below (section on “Number of individuals diagnosed with mental disorders in hospital registers”) an analysis of the impact of the two approaches.

During the evolution of the registers, two key changes occurred. First, from their inception up to and including 1993, diagnoses recorded in these registers were coded according to the International Classification of Diseases (ICD), Eighth Revision (ICD-8), which was introduced in Denmark in 1966.²³ From 1994 onwards, the Tenth Revision (ICD-10) has been used²⁴ (ICD-9 was never employed in Denmark). The switch from ICD-8 to ICD-10 represents a challenge for researchers for several reasons.²⁵ There are three times more diagnoses in ICD-10 than in ICD-8, and criteria-based definitions are used in ICD-10 in contrast with prototypic descriptions in ICD-8. In addition, the WHO has not published any data dictionaries to guide mapping between ICD-8 and ICD-10; although standard translations are available for most disorders.²⁶ Table 2 provides the mapping commonly used in Danish register-based research between ICD-10 categories and corresponding ICD-8 codes, together with a suggested possible earliest age of onset at which each mental disorder could be identified in the registers, as presented by Pedersen et al.¹⁹ A second change is that only inpatient contacts were registered prior to 1995, but from 1995 onwards, outpatient and emergency room contacts were also captured. A third consideration is that while public hospitals have been reporting to the Danish National Patient Registry since its inception, reporting became compulsory only in 2003 for private hospitals and private outpatient specialty clinics.⁵

Table 2 List of Types of Mental Disorders with Their Corresponding ICD-10 Codes, ICD-8 Equivalent Code, and Earliest Possible Age of Onset19

Data Access

In Denmark, access to individual-level data, including data in the Danish hospital registers, is regulated by Danish authorities, including the Danish Data Protection Agency (the independent authority in Denmark that oversees compliance with the data protection rules), the Danish Health Data Authority (which works with using data and creating digital coherence in the healthcare sector to improve health), the Ethical Committee (which ensures that research projects in the field of health are conducted in an ethically sound manner), and Statistics Denmark (which compiles and publishes Danish statistics). Approval to access the data relevant to a planned scientific research project can be granted to Danish research institutions and companies. Researchers at these institutions may then obtain the data. It is possible for international researchers to gain data access to register data if overseen by a Danish research institution with necessary approvals for data access. Data access is provided via a secured server, and researchers must adhere to strict rules regarding microdata (ie, information at the level of individuals).

Number of Individuals Diagnosed with Mental Disorders in Hospital Registers

To describe the registration of mental disorders over time in the Danish hospital registers, we provide counts of individuals diagnosed with mental disorders each year, according to specific types of mental disorders (broad categories from Table 2), type of diagnosis (primary or secondary), type of hospital contact (inpatient, outpatient, or emergency visit), and type of unit contacted (psychiatric or non-psychiatric). These counts are shown in Table 3. We define mental disorders according to ICD-10 F group codes (Mental and behavioural disorders). These include Organic, including symptomatic, mental disorders, which are sometimes excluded from the definition of mental disorders. The study was registered with the Danish Data Protection Agency at Aarhus University and approved by Statistics Denmark and the Danish Health Data Authority. According to Danish law, informed consent or ethical approval is not required for register-based studies in Denmark. All data were pseudonymized and not recognizable at an individual level and analyzed on the secured platform of Statistics Denmark.

Table 3 Number of Patients Registered as Having a Primary or Secondary Diagnosis of a Mental Disorder or a Primary Diagnosis of a Mental Disorder in Denmark According to Broad Disease Categories During 1970–2022 (ICD-8 and ICD-10 Codes are Provided in Table 2)

A total of 10,552,670 individuals resided in Denmark between January 1, 1969, and December 31, 2022. Among them, 1,136,280 (10.7%) have been registered as having a mental disorder (ICD-8 codes 290–315 or ICD-10 codes F00-F99) as a primary or secondary diagnosis in a psychiatric unit in Denmark at least once between 1969 and 2022. Among these individuals, 564,381 (49.7% of those diagnosed with a mental disorder) had at least one inpatient contact, 787,629 (69.3%) had at least one outpatient clinic contact, and 301,144 (26.5%) had at least one emergency contact. The number of individuals who had contacts as both inpatient and outpatient during the study period was 269,463 (23.7%). The exclusion of individuals diagnosed before age 1 (the earliest age of onset for any mental disorder)¹⁹ led to the exclusion of 0.07% of those diagnosed. The number of individuals registered as having a mental disorder from 1969 to 2022 (when treatment in non-psychiatric units was also considered) increased to 1,752,199 (16.6% of the population residing in Denmark during this period). Of those diagnosed, 1,091,825 (62.3%) had an inpatient contact, 1,077,114 (61.4%) an outpatient contact, and 426,110 (24.3%) an emergency contact. The number of individuals who had contacts as both inpatient and outpatient during the study period was 502,049 (28.7%).

Table 3 shows the number of patients registered with a diagnosis of a mental disorder, by type of mental disorder and unit of contact (psychiatric units or all types of hospital units, with psychiatric units nested within all hospital units) from 1969 to 2022. The highest number of patients received a diagnosis of “Neurotic, stress-related, and somatoform disorders”, which were diagnosed in 611,763 patients in all hospital units. Of these, 78.6% were diagnosed in psychiatric units. The least common mental disorder group was “Eating disorders”, diagnosed in 41,105 patients; 86.7% of these were seen in psychiatric units. The mental disorders for which the largest proportion of patients were seen in psychiatric units were “Specific personality disorders” (95.6%) and “Pervasive developmental disorders” (95.5%). In contrast, only 42.2% of “Mental and behavioural disorders due to psychoactive substance use” were diagnosed in psychiatric departments. Using primary diagnoses only, researchers can identify 99.6% of individuals diagnosed in psychiatric units, but only 76.0% of those diagnosed in either psychiatric or non-psychiatric units (Table 3).

Several important trends in the number of individuals with contacts related to a mental disorder diagnosis have been observed over time. Figure 2a shows the percentage of individuals with a hospital contact linked to a diagnosed mental disorder in a psychiatric unit within inpatient, outpatient clinic and emergency settings for each year, by sex. During the period 1969 to 2022, the number of unique individuals diagnosed with a mental disorder in inpatient settings remained relatively stable. In general, a larger percentage of females than males were hospitalized in a psychiatric unit each year until 2009, when both females and males had similar percentages of inpatient contacts. After inclusion of outpatient settings in the registers in 1995, the number of unique individuals diagnosed with a mental disorder in outpatient settings increased sharply from 1995 to 2017. For emergency setting contacts, which were also introduced in 1995, the number of individuals increased until 2014, followed by a decline. Although more females than males were diagnosed in outpatient and emergency settings, trends over time were similar for both sexes. The percentage of outpatient and emergency contacts was lower in 2020 than in 2019, which could be due to the COVID-19 pandemic. However, a decrease was also seen from 2018 to 2019, before the start of the pandemic and its restrictions. This could be related to the change to version 3 of the hospital register. The same estimates are shown in Figure 2b, but for both sexes combined and by unit type (psychiatric unit or any hospital unit). In general, diagnoses made in psychiatric units follow a pattern similar to those made in any unit. However, the number of individuals diagnosed each year during an inpatient contact in any unit increased slightly after the mid-1990s until 2012–2014, after which a decrease was observed. This was not seen for diagnoses in inpatient psychiatric units, which remained flat.

Figure 2 The annual percentage of individuals with a hospital contact linked to a diagnosed mental disorder in Denmark within inpatient, outpatient and emergency settings, 1969–2022. (a) shows the percentage of females and males diagnosed in psychiatric units, while (b) shows the percentage of individuals diagnosed in psychiatric units or all hospital units. Data on non-psychiatric units have been available since 1977 in the Danish National Patient Registry. Note: The graphs show the number of individuals with a hospital contact for a mental disorder each year, not the number of first-time diagnoses, as a percentage of the total number of people registered in Denmark. Most psychiatric diagnoses (eg, schizophrenia, bipolar disorder) cannot be made in an emergency room setting but may be based on previously diagnosed disorders.

Figure 3 displays the percentage of individuals with a hospital diagnosis linked to each type of mental disorder, by sex. For most mental disorder types, the general trend in the percentage of unique individuals diagnosed in each setting is similar for males and females; however, the magnitude differs according to sex, with some disorders more common in males (eg, Mental and behavioral disorders due to psychoactive substance use, and Schizophrenia and related disorders) and others more common in females (eg, Organic, including symptomatic, mental disorders and Mood disorders). Interestingly, the yearly percentage of inpatient contacts due to schizophrenia and related disorders was similar in males and females until 1993–1994, followed by a decline for both sexes, but more pronounced in females. This decline coincides with the transition from LPR1 to LPR2 and the implementation of ICD-10 in Denmark, indicating that the equivalency of ICD-8 and ICD-10 codes might be imprecise for some disorders.²⁶

Figure 3 The annual percentage of individuals with a hospital contact linked to a mental disorder diagnosis, by mental disorder type in a psychiatric unit within inpatient, outpatient, and emergency settings, 1969–2022. Note: The graphs show the number of individuals with a hospital contact for each mental disorder each year, not the number of first-time diagnoses, as a percentage of the total number of people registered in Denmark. Most psychiatric diagnoses (eg, schizophrenia, bipolar disorder) cannot be made in an emergency room setting but may be based on previously diagnosed disorders.

Trends in contacts related to diagnoses of each type of mental disorder in psychiatric units versus all hospital units are shown in Figure 4. The percentage of individuals receiving a diagnosis of most mental disorder types (exceptions being Pervasive developmental disorders and Behavioral and emotional disorders with onset usually occurring in childhood and adolescence) decreased since the late 2010s, driven by the decrease in outpatient diagnoses. Other notable trends include the aforementioned drop in the percentage of individuals diagnosed with schizophrenia spectrum disorders in inpatient settings in 1994; and a decrease in individuals diagnosed with personality disorders in inpatient settings in the 1980s. Additionally, there was a relatively large increase in individuals diagnosed with intellectual disabilities in 1999. While this followed the general trend, it was a particularly sharp increase. Another noteworthy pattern is that the percentage of individuals diagnosed with mental and behavioral disorders due to psychoactive substance use in inpatient settings was larger than the number diagnosed in outpatient settings, indicating that substance use disorders diagnosed in non-psychiatric units might be different in nature from those diagnosed in psychiatric units.

Figure 4 The annual percentage of individuals with a hospital contact linked to a diagnosed mental disorder either in a psychiatric unit or in any hospital unit, within inpatient, outpatient and emergency settings, 1969–2022, by mental disorder type. Data on non-psychiatric units have been available since 1977 from the Danish National Patient Registry. Note: The graphs show the number of individuals with a hospital contact for each mental disorder each year, not the number of first-time diagnoses, as a percentage of the total number of people registered in Denmark. Most psychiatric diagnoses (eg, schizophrenia, bipolar disorder) cannot be made in an emergency room setting but may be based on previously diagnosed disorders.

Considerations for Psychiatric Research Using the Danish Hospital Registers

Data Quality

Using the terms (validity OR reliability) AND (register OR registry OR database OR databases) AND (Danish[Title/Abstract] OR Denmark[Title/Abstract]) AND (psychiatr*), we searched PubMed on 29 September 2023 to find studies that considered the validity of mental disorder diagnoses in the Danish hospital registers. A summary of the results can be found in Table 4. Studies covered disorders within the following ICD-10 groups: F00-F09 (Organic, including symptomatic mental disorders); F20-F29 (Schizophrenia, schizotypal, and delusional disorders); F30-F39 (Mood disorders); F40-F48 (Neurotic, stress-related, and somatoform disorders); F80-F89 (Disorders of psychological development); and F90-F98 (Behavioural and emotional disorders with onset usually occurring in childhood and adolescence). In general, the literature indicated that a large proportion of coded diagnoses in the Danish hospital registers of mental disorders were considered valid (indicated by the proportion of confirmed diagnoses upon review of patient records). Some studies showed that validity varied according to specific disorder types or other factors. The lowest validity was observed for schizophrenia/schizophrenia-related disorders by Loffler et al.²⁷ Their study considered validity using ICD-8 codes in patients diagnosed in 1976. However, more recent studies of the validity of schizophrenia diagnoses in the DPCRR,^28,29 during a period when only ICD-10 codes were used, reported that 88.8%–89.7% of diagnoses could be confirmed. Furthermore, it is reassuring that for schizophrenia, diagnostic stability (ie, whether patients keep the schizophrenia diagnosis over time) in the registers is very similar to that found in clinical studies.^30,31

Table 4 Summary of Studies That Considered the Validity of Psychiatric Diagnoses in the Danish Psychiatric Central Research Registry (DPCRR) or the National Patient Registry (DNPR)

While the evidence suggests good validity for several mental disorders with the Danish hospital registers, it should be considered that not all mental disorders have been included in validation studies and those that have been carried out cover limited periods.

Potential Challenges for Epidemiological Research

While the Danish hospital registers provide huge benefits to research, there are also potential issues with register data, which, depending on a study’s design and research question, can lead to selection bias, information bias or confounding. The Danish Civil Registration System includes everyone living in Denmark regardless of whether they have been in contact with the health care system. If a study selects its population via the Civil Registration System (regardless of diagnoses), selection bias should be minimal. Conversely, the Danish hospital registers capture nationwide data on people who have contact with the hospital system, including on clinical diagnoses made for mental disorders in psychiatric and non-psychiatric departments. Thus, patients treated by private psychiatrists or psychologists, pedagogical psychological counselling services, in some forensic psychiatry settings, or in the primary sector would not be registered in the Danish hospital registers. This means mental disorder diagnoses in the Danish hospital registers are skewed to the more severe end of the spectrum, ie, those requiring hospitalizations or outpatient clinic visits. Thus, patients seen in other settings would be misclassified as not having a mental disorder in a register-based research study using Danish hospital register diagnoses. Therefore, if a study uses the hospital registers to define their population (as an example, a study of outcomes in patients with depression that identifies those with depression in the hospital registers), there will be selection of only people who received a diagnosis, which could introduce bias depending on the specific research question. However, if register data are used to identify mental disorder diagnoses as an exposure or outcome, the same misclassification could introduce information bias, rather than selection bias. The extent to which misclassification can introduce bias (regardless of whether it is information or selection bias) will vary by disorder of interest. For severe disorders like schizophrenia or bipolar disorder, all diagnosed patients can be identified through the hospital registers as they can only be diagnosed in secondary psychiatric hospital settings (cases which never receive a diagnosis will still be missed); but misclassification can be present in other forms eg diagnostic uncertainty in the early stages of the clinical process.³⁰ However, for less severe cases of eg, depression and anxiety, it is likely a larger proportion will not be identifiable in the registers. A recent study⁴¹ estimated that only 14.5% of persons who screened positive for depression in a survey and 16.5% of those with a prescription for an antidepressant were in contact with a psychiatric department with a diagnosis of major depressive disorder. Alternatively, if these patients do receive treatment within secondary care after an initial diagnosis, their diagnosis would be registered in the Danish hospital registers; however, their initial Danish hospital register diagnosis (which is normally used as a proxy for date of onset in register-based studies, despite the likely lag between actual onset and clinical diagnosis) would be later than the date when they originally received a diagnosis. While the time to diagnosis is not possible to investigate in registers, as it is not possible to identify onset, research from other fields provides evidence. For example, a systematic review of duration of untreated eating disorders, indicated a delay of between 30 and 67 months, depending on eating disorder type.⁴² Therefore, researchers using the Danish hospital registers as the only source of information to identify mental disorders should transparently report how the study population is defined and that they define mental disorders using diagnoses made during hospital contacts. When reporting prevalence or incidence rates, they should be explicit that these relate to mental disorder diagnoses made within the hospital setting, rather than all mental disorder patients. This is particularly pertinent when considering disorders like depression and anxiety, which are commonly treated in primary care. The hospital registers can be supplemented with additional data, eg, from the Danish National Prescription Registry⁷ and Danish National Health Service Registry (as discussed below);⁸ however, these resources can also introduce misclassification due to the lack of specificity of pharmaceutical therapies for mental disorders⁴³ and the lack of diagnostic codes in the Danish National Health Service Registry.⁸ Further, if researchers have access to other data sources containing a subsample of the population, additional analyses could include quantitative bias analysis or inverse probability weights, to help identify and quantify potential biases.

When using the registers, it is important to be aware of clinical trends that may impact registration. For example, Danish health authorities required for several years that antidepressant treatment for individuals below age 25 years be initiated by a psychiatrist rather than a general practitioner. The result was that many young patients were seen in secondary hospital settings and hence registered with a mental disorder diagnosis, leading to an “artificial” increase in this age group. Another example is the rapid increase in ADHD cases during recent years, which are often diagnosed in private settings (eg, private psychiatrists or psychologists) rather than in the hospital setting, where their diagnoses would be captured in the Danish registers. This is echoed by the increase in prescriptions for central nervous system stimulants used in the treatment of ADHD, which have doubled in the past 5 years.⁴⁴

Finally, as the Danish hospital registers contain data collected during clinical contacts, primarily for administrative purposes and reimbursement, rather than for research purposes, the data do not provide researchers with an opportunity to specify confounders relevant to the associations of interest, for example, adverse childhood experiences, which are important risk factors for mental disorders⁴⁵ and are challenging to conceptualize using register data. It may be possible to identify confounding variables from other registers (eg, variables related to socioeconomic status from the Integrated Database for Labour Market Research), but researchers will not be able to specify how these are conceptualized. Alternatively, additional relevant confounders could be identified in surveys, which can be linked to registers. However, surveys are carried out using smaller samples of the population and can potentially not be representative. Other important clinical data and considerations (eg, symptoms, clinical interpretation, individual course, compliance) relevant to the diagnoses and treatment are also not available in the registers.

Identification of Mental Disorders Prior to the Establishment of the Register

Since data on mental disorders became available in 1969 at the earliest, we do not have lifetime diagnostic information for individuals born before this date. If researchers aim to identify prevalent cases of mental disorders using the Danish hospital registers, they will misclassify cases that were diagnosed prior to 1969, ie, prior to establishment of the registers. An example is Person A in Figure 5, a prevalent case prior to 1969, who is not recognized as such in the registers. Further, if researchers aim to identify incident cases, they risk misclassifying prevalent cases as incident cases for individuals with a hospital-based diagnosis of a mental disorder prior to 1969. Person B in Figure 5 provides an example, as the diagnosis received prior to 1969 would not be captured, and the diagnosis received in the 1980s would appear to be an incident case. These issues are also relevant to the addition of outpatient and emergency visits to the Danish hospital registers in 1995. Individuals with mental disorders diagnosed during outpatient or emergency visits between 1969 and 1994 do not appear in the registers (unless they also received a diagnosis as an inpatient). Despite receiving a mental disorder diagnosis during an outpatient contact in the early 1990s, Person C in Figure 5 would not be included as a case in the registers until 2000, on receipt of a second outpatient diagnosis.

Figure 5 Examples of misclassification due to the lack of data prior to the establishment of the register.

Left truncation poses a concern, particularly for data collected during the early years of the Danish hospital registers. Employing a washout period (a period commencing in the years after inception of a register but prior to the start of follow-up) will help researchers identify prevalent cases and minimize their misclassification as incident cases. In a recent study based on Danish registers, we showed that the lifetime cumulative incidence of mental disorders based on 2010–2021 data was estimated to be 49% for females and 45% for males without use of a washout period. The cumulative incidence decreased to 40% and 37%, respectively, when pre-2010 data were used to identify prevalent cases.⁴⁶

Temporal Health Trends

Incidence rates of mental disorders have been previously reported as increasing since the 1970s, with the age of onset shifting downward.⁴⁷ While several factors may play into these observed trends, administrative changes in the registers and changes over time in diagnostic practice and focus on disorders have a role. Specific changes include political reforms (in the 1970s and 1980s), the shift from ICD-8 to ICD-10 codes in 1994, and the addition of outpatient and emergency contacts to the Danish hospital registers in 1995. A change in diagnostic criteria is expected again soon, with the introduction of ICD-11; this is likely to once more impact observed trends. One example of a disorder whose registration has increased over time is bipolar disorder. While bipolar disorder type 2 does not have a specific diagnostic code, clinicians’ heightened awareness of this condition may underlie the general increase in bipolar disorder diagnoses in the registers.⁴³ Additionally, some specific trends have been observed, including an increase in schizotypal disorders restricted to the Capital Region of Denmark between 2000 and 2018.³⁰ Time trends in healthcare contacts might also depend on capacity in the healthcare sector, clinical trends, and both calendar time and birth cohort.⁴⁸ Researchers pooling individuals diagnosed over a long period should consider that patient characteristics (eg, age of onset, distribution of comorbid conditions, or polygenic burden for mental disorders) might have changed over time.

Generalizability of Findings from the Danish Registers

Findings from these registers can be used to generate hypotheses that can be investigated further, including in other countries and with other data sources. Additionally, the register data can be used to replicate other studies and investigate whether findings are similar in a different population or included in multi-cohort studies to see if the same results are obtained across cohorts. However, it should be recognized that the generalizability of the findings from Danish register-based studies could be limited, particularly with regard to countries with different healthcare systems and different socioeconomic profiles.

Linkage of Other Key Sources of Data on Mental Disorders

As mentioned above, the unique personal identification number assigned to all Danish residents allows Danish hospital registers to be linked with other data sources.

First, Danish hospital register data can be linked to other registers. The Danish National Prescription Registry⁷ can provide information on prescriptions for psychotropic medications. A recent study estimated that 77% of males and 83% of females in Denmark will be diagnosed with a mental disorder or will be prescribed a psychotropic medication at some point in their lives.⁴⁹ However, the lack of specificity in antidepressants, anxiolytics, antipsychotics, and stimulants means they cannot be universally used as proxies for mental disorders. Thus, these estimates might not reflect the actual prevalence of mental health conditions in society. Additionally, medication use can be considered an exposure in itself, ie, if a researcher is interested in investigating a mental disorder as a risk factor, it could be difficult to separate out whether observed associations are due to medication use or due to the mental disorder being treated. Furthermore, indications for prescribed medications in the Danish National Prescription Registry were only introduced in 2004. While the data has been more complete since 2006, general practitioners do not receive compensation for registering indications and thus might be less likely to do so. While indications can help to identify a more well-defined group (eg, indication of “depression” for an antidepressant prescription), the data is still limited by low specificity (data are not validated and many clinicians only register broad categories, such as “mental disorder”), lack of subgrouping (the type and severity of the disorder is not registered), and, most importantly, confounding by indication (antidepressants are prescribed for anxiety, obsessive-compulsive disorder, stress-related conditions, pain, etc.).⁵⁰

Data from the National Health Services Registry could be used to complement the hospital registers in identifying mental disorders.⁸ However, these data are collected for reimbursement purposes and do not include diagnoses or test results. Still, they provide an indication of services provided by general practitioners (talk therapy sessions or psychometric tests) or sessions with private psychologists or psychiatrists. While the Cause of Death Register⁵¹ can provide information on deaths from mental disorders, such disorders are not commonly listed as causes of death. However, deaths from suicide are an indicator of mental distress or depressive disorders, and these deaths, together with those listing a mental disorder as the underlying cause of death, have been used by researchers in combination with mental disorder diagnoses to define these disorders.^52,53 Importantly, some disorder-specific registers and databases have been established to register the quality of diagnostic evaluation, treatment, and care of patients, including the Danish Schizophrenia Registry,⁵⁴ the Danish Dementia Registry,⁵⁵ and the Danish Depression Database.⁵⁶

Second, Danish hospital registers can also be linked to cohorts with more detailed information (eg, from clinical settings) and survey data. After permission is granted, researchers access the data on the secure servers of Statistics Denmark (or the Danish National Health Authority), in which personal identification numbers are pseudonymised. Statistics Denmark employees can apply the same pseudonymisation to cohort and survey data by means of personal identification numbers and then upload the data to the servers, allowing this data to be used together with registry data. As mentioned above, noteworthy examples include genetic data from the iPSYCH project,¹³ the nationally representative Hvordan har du det? survey,¹² and the Better Health in Late Life cohort.¹⁶ For example, the iPSYCH cohort was created by selecting all those identified as having a diagnosis of schizophrenia, bipolar disorder, affective disorder, autism and attention-deficit/hyperactivity disorder diagnosed until December 31, 2015, within the Danish hospital registers and a random sample of the entire Danish population. This cohort has been used in numerous studies, linking register data with genetic data (not available in the administrative registers) to provide insights into the development and progression of mental disorders.^57,58 Combining registers with survey data, “Hvordan har du det?” has allowed researchers to investigate self-reported stress and outcomes of multimorbidity and mortality.⁵⁹

Other Nordic countries are also recognized for their nationwide health registers and their research potential. In Finland, data on mental disorder diagnoses made in hospitals can be obtained from the Hospital Discharge Register from 1967 to 1993 and the Care Register for Health Care from 1994 onwards. Additionally, primary care diagnoses are available in the Register of Primary Healthcare Visits from 2011 onwards. Similarly, in Sweden, mental disorder diagnoses made in inpatient settings are available in the National Patient Register since 1969, but data linkage across national registers is only possible since 1984, when these were recorded using personal identification numbers. Since 2001, outpatient data are also included. In Norway, diagnoses made within public mental health-care services have been collected in the National Patient Registry since 2001 for adults and 2003 for children and adolescents; data linkage has been possible since 2008. Since 2017, data from primary care contacts have been available in the Norwegian Registry for Primary Health Care. Researchers have used these similar, rich resources to conduct multinational studies, allowing comparison of findings.

Conclusions

The Danish hospital registers have provided information for a large number of research studies in the field of psychiatric epidemiology. The registers make it possible to identify individuals with mental disorders diagnosed within hospital settings with high validity and minimal selection. However, researchers should be aware of limitations, including the representativeness of mental disorder cases, changes in mental disorder registration over time, specific clinical issues that may affect the data, and the availability of a number of registers.

Acknowledgments

Oleguer Plana Ripoll has received funding from the Lundbeck Foundation (Fellowship no. R345-2020-1588) and Independent Research Fund Denmark (grants nos. 1030-00085B and 2066-00009B). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclosure

Dr Ole Köhler-Forsberg reports personal fees from Lundbeck Pharma A/S and WCG Clinical Services, outside the submitted work. Professor Henrik Toft Sørensen reports funding for other studies in the form of institutional research grants to (and administered by) Aarhus University. None of these studies have any relation to the present study. The authors report no other conflicts of interest in this work.

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