Exploring the Comorbidity Between Mental Disorders and General Medical Conditions
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.
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.
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)