Exploring the Comorbidity Between Mental Disorders and General Medical Conditions

Mental disorders have been shown to be associated with a number of general medical conditions (also referred to as somatic or physical conditions). The investigators aim to undertake a comprehensive study of comorbidity among those with treated mental disorders, by using high-quality Danish registers to provide age- and sex-specific pairwise estimates between the ten groups of mental disorders and nine groups of general medical conditions.

The investigators will examine the association between all 90 possible pairs of prior mental disorders and later GMC categories using the Danish national registers. Depending on whether individuals are diagnosed with a specific mental disorder, the investigators will estimate the risk of receiving a later diagnosis within a specific GMC category, between the start of follow-up (January 1, 2000) or at the earliest age at which a person might develop the mental disorder, whichever comes later. Follow-up will be terminated at onset of the GMC, death, emigration from Denmark, or December 31, 2016, whichever came first. Additionally for dyslipidemia, follow-up will be ended if a diagnosis of ischemic heart disease was received. A "wash-out" period will be employed in the five years before follow-up started (1995-1999), to identify and exclude prevalent cases from the analysis. Individuals with the GMC of interest before the observation period will be considered prevalent cases and excluded from the analyses (i.e. prevalent cases were "washed-out"). When estimating the risk of a specific GMC, the investigators will consider all individuals to be exposed or unexposed to the each mental disorder depending on whether a diagnosis is received before the end of follow-up. Persons will be considered unexposed to a mental disorder until the date of the first diagnosis, and exposed thereafter.

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Key information

Conditions

Organic, Including Symptomatic, Mental Disorders Acquired Immunodeficiency Syndrome Allergy Anemia Arrhythmias, Cardiac Arthritis Atrial Fibrillation Autoimmune Diseases Autoimmune Diseases of the Nervous System Basal Ganglia Diseases Behavior Behavioural Disorder Blood-Borne Infections Bone Diseases Bone Diseases, Metabolic Brain Diseases Cancer Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Chemically-Induced Disorders Chronic Disease Chronic Gastritis Chronic Kidney Diseases Chronic Liver Disease Chronic Pulmonary Disease Communicable Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Connective Tissue Disorder Crystal Arthropathies Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Diabetes Mellitus Digestive System Diseases Disease Attributes Disorder of Psychological Development Disorders of Adult Personality and Behavior Diverticular Disease of Large Intestine Dyslipidemias Ear Diseases Eating Disorder Endocrine System Diseases Epilepsy Eye Diseases Feeding and Eating Disorders Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastroenteritis Gastrointestinal Diseases Genetic Diseases, Inborn Genital Diseases Genital Diseases, Male Glucose Metabolism Disorders Gout HIV Infections HIV/AIDS Headache Disorders Headache Disorders, Primary Hearing Disorders Heart Diseases Heart Failure Hematologic Diseases Hemic and Lymphatic Diseases Hypersensitivity Hypertension Immune System Diseases Immunologic Deficiency Syndromes Infections Inflammatory Bowel Diseases Intellectual Disability Intestinal Diseases Ischemic Heart Disease Joint Diseases Kidney Diseases Lentivirus Infections Lipid Metabolism Disorders Male Urogenital Diseases Mental Disorders Mental Retardation Metabolic Diseases Metabolism, Inborn Errors Migraine Migraine Disorders Mood Disorders Mood [Affective] Disorders Movement Disorders Multiple Sclerosis Musculoskeletal Diseases Myocardial Ischemia Neoplasms Nervous System Diseases Neurobehavioral Manifestations Neurodegenerative Diseases Neurodevelopmental Disorders Neurologic Manifestations Neuropathy Neurotic, Stress-related and Somatoform Disorders Nutritional and Metabolic Diseases Osteoporosis Otorhinolaryngologic Diseases Pain Parkinson Disease Parkinsonian Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms Peripheral Occlusive Disease Prostate Disorders Prostatic Diseases Purine-Pyrimidine Metabolism, Inborn Errors RNA Virus Infections Renal Insufficiency Renal Insufficiency, Chronic Retroviridae Infections Rheumatic Diseases Schizophrenia Schizophrenia Spectrum and Other Psychotic Disorders Sensation Disorders Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Signs and Symptoms Signs and Symptoms, Digestive Skin and Connective Tissue Diseases Slow Virus Diseases Somatoform Disorders Stroke Substance Use Substance-Related Disorders Synucleinopathies Thyroid Diseases Thyroid Disorder Urogenital Diseases Urologic Diseases Vascular Diseases Virus Diseases Vision Disorders

Age range

1 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

The investigators will analyse data from all individuals born in Denmark between 1900-2015 and who resided there between 2000-2016; giving a study size of over 5.5 million people. The National Patient Register, Cause of Death Register and National Prescription Registry of Denmark will all be used as sources of information about the mental disorders and general medical conditions (GMC) of interest. These are considered to be of high quality and validity.

The rate of diagnosis with a specific GMC group between those exposed and unexposed to each of ten mental disorders will be examined using hazard ratios (HRs) and 95% confidence intervals (CI), using Cox proportional hazards models with age as the underlying time scale. The following models will be run to provide all persons and sex-specific estimates, considering exposure to each mental disorder and whether the association differs depending on the time since onset of the mental disorder (lagged HRs):

Model A: adjusted for sex and birth date which, in combination with underlying age in the models, adjusts also for calendar time

Model B: additionally adjust for mental disorder comorbidity with onset before, but not after, the mental disorder of interest

Finally, cumulative incidence proportions of diagnosis with a GMC after being diagnosed with a mental disorder will be estimated. This will provide absolute risks of developing a GMC after a specific time, given a previous diagnosis of a mental disorder. To compare cumulative incidence proportions among people diagnosed with a mental disorder to those among people without a diagnosis, a matched reference group will be generated for each mental disorder. For every index person with the mental disorder, up to five age- and sex-matched individuals (who had not received a diagnosis of the relevant mental disorder by the age the index person was diagnosed) will be randomly selected. Cumulative incidence proportions will be generated for each reference group. All analyses will be performed on the secured platform of Statistics Denmark STATA/MP version 15.1 (Stata Corporation, College Station, Texas, USA).

An interactive webpage will be developed to visualize all results from this study. The Danish Data Protection Agency and the Danish Health Data Authority approved this study.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Born in Denmark between 1900-2015
Resided in Denmark during the study period (2000-2016)

Exclusion criteria

Excluded from analyses for each specific GMC, if considered a prevalent case of that GMC (i.e. ascertained to have a diagnosis for the GMC during the washout period of 1995-1999)