Exploring Comorbidity Within Mental Disorders Among a Danish National Population

Plana‐Ripoll, Oleguer; Pedersen, Carsten Bøcker; Holtz, Yan; Benros, Michael E.; Dalsgaard, Søren; Jonge, Peter de; Fan, Chun; Degenhardt, Louisa; Ganna, Andrea; Greve, Aja; Gunn, Jane; Iburg, Kim Moesgaard; Kessing, Lars Vedel; Lee, Brian K.; Lim, Carmen C W; Mors, Ole; Nordentoft, Merete; Prior, Anders; Roest, Annelieke M.; Saha, Sukanta; Schork, Andrew J.; Scott, James G.; Scott, Kate M.; Stedman, Terry; Sørensen, Holger J.; Werge, Thomas; Whiteford, Harvey; Laursen, Thomas Munk; Agerbo, Esben; Kessler, Ronald C.; Mortensen, Preben Bo; McGrath, John J.

doi:10.1001/jamapsychiatry.2018.3658

Cited by 446 publications

(395 citation statements)

References 28 publications

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“…There is very high comorbidity among the psychiatric cases in the iPSYCH cohort (Schork et al 2019b), and, for gastrointestinal infections, around 93% of the people who had gastrointestinal infections were also diagnosed with at least one other infection category from the previous section. It has been shown that individuals with one psychiatric diagnosis are more prone to getting another one, and this higher "comorbidity risk" can persist over time, as reported for a much larger Danish dataset (Plana-Ripoll et al 2019). We, therefore, adopted two approaches: in one approach, controls cannot have any psychiatric diagnosis or any infection category for their respective phenotype (super controls); for example, in the genome-wide association study (GWAS) for gastrointestinal infections, we excluded individuals who had other infection categories from being controls.…”

Section: Defining Cases and Controlsmentioning

confidence: 67%

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness

et al. 2020

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Gastrointestinal infections can be life threatening, but not much is known about the host's genetic contribution to susceptibility to gastrointestinal infections or the latter's association with psychiatric disorders. We utilized iPSYCH, a genotyped population-based sample of individuals born between 1981 and 2005 comprising 65,534 unrelated Danish individuals (45,889 diagnosed with mental disorders and 19,645 controls from a random population sample) in which all individuals were linked utilizing nationwide population-based registers to estimate the genetic contribution to susceptibility to gastrointestinal infections, identify genetic variants associated with gastrointestinal infections, and examine the link between gastrointestinal infections and psychiatric and neurodevelopmental disorders. The SNP heritability of susceptibility to gastrointestinal infections ranged from 3.7% to 6.4% on the liability scale. Significant correlations were found between gastrointestinal infections and the combined group of mental disorders (OR = 2.09; 95% CI: 1.82-2.4, P = 1.87 × 10 -25 ). Correlations with autism spectrum disorder, attention deficit hyperactivity disorder, and depression were also significant. We identified a genome-wide significant locus associated with susceptibility to gastrointestinal infections (OR = 1.13; 95% CI: 1.08-1.18, P = 2.9 × 10 -8 ), where the top SNP was an eQTL for the ABO gene. The risk allele was associated with reduced ABO expression, providing, for the first time, genetic evidence to support previous studies linking the O blood group to gastrointestinal infections. This study also highlights the importance of integrative work in genetics, psychiatry, infection, and epidemiology on the road to translational medicine.

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Section: Defining Cases and Controlsmentioning

confidence: 67%

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness

et al. 2020

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“…This literature has demonstrated a high degree of co‐occurrence between AUD and other mental disorders, with a particularly strong association between AUD/substance use disorders (SUDs) and other externalizing disorders (e.g., antisocial personality; see Kessler, for a review). From a clinical and public health perspective, the impact of comorbid conditions on individual outcomes is substantial (e.g., Cohen et al, ; Grant et al, ; Plana‐Ripoll et al, ), yet relatively little research has examined the severity of comorbid psychiatric disorders across psychopathology domains (e.g., externalizing, internalizing) with AUD. The ability to assess the extent to which the comorbid disorders (e.g., symptom count, severity) covary with AUD is limited given that most studies examining comorbidity rely on categorical representations of the disorders, consistent with the diagnostic systems that were in place at the time of the research (e.g., previous versions of the DSM).…”

Section: Comorbidity Of Aud With Psychiatric Disordersmentioning

confidence: 99%

Psychiatric Comorbidity as a Function of Severity: DSM‐5 Alcohol Use Disorder and HiTOP Classification of Mental Disorders

Helle

Trull

Watts

et al. 2020

Alcoholism Clin & Exp Res

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Background Understanding the comorbidity of alcohol use disorder (AUD) and other psychiatric diagnoses has been a long‐standing interest of researchers and mental health professionals. Comorbidity is often examined via the diagnostic co‐occurrence of discrete, categorical diagnoses, which is incongruent with increasingly supported dimensional approaches of psychiatric classification and diagnosis, and for AUD more specifically. The present study examined associations between DSM‐5 AUD and psychiatric symptoms of other DSM‐IV and DSM‐5 disorders categorically, and dimensionally organized according to the Hierarchical Taxonomy of Psychopathology (HiTOP) spectra (e.g., Internalizing, Disinhibited Externalizing). Methods The comorbidity of AUD with other psychological disorders was examined in 2 independent nationally representative samples of past‐year drinkers via an initial examination in the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) Wave 2 and replicated in NESARC‐III. Results Analyses focusing on psychopathology symptom counts organized by spectra demonstrated that greater AUD severity was associated with a higher number of symptoms across HiTOP spectra. Traditional categorical analyses also demonstrated increasing prevalence as a monotonic function of DSM‐5 AUD severity gradients. Conclusions This study indicates that AUD and other psychiatric disorder comorbidity implies increased presence of multiple forms of psychopathology with a corresponding increased number of symptoms across hierarchical spectra. Greater AUD severity increases the likelihood of other psychopathology and, when present, “more severe” presentations. That is, on average, a given disorder (e.g., depression) is more severe when copresenting with an AUD, and increases in severity along with the AUD.

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“…Understanding the biological basis of sex differences in human disease, including neuropsychiatric disorders and traits, is critical for developing sex-informed diagnostics and therapeutics and realizing the promise of precision medicine [4]. Moreover, genetic variants with sex-differentiated effects across multiple traits may influence patterns of comorbidity for neuropsychiatric disorders and related behavioral traits, suggesting the need for cross-disorder genetic analyses to be evaluated in the context of sex-specific effects [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Examining sex-differentiated genetic effects across neuropsychiatric and behavioral traits

Martin

Khramtsova

Goleva

et al. 2020

Preprint

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Background:The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations across these traits, we tested for a sex-differentiated genetic architecture within and between traits. Methods:Using genome-wide association study (GWAS) summary statistics for 20 neuropsychiatric and behavioral traits, we tested for differences in SNP-based heritability (h 2 ) and genetic correlation (rg<1) between sexes. For each trait, we computed z-scores from sex-stratified GWAS regression coefficients and identified genes with sex-differentiated effects. We calculated Pearson correlation coefficients between z-scores for each trait pair, to assess whether specific pairs share variants with sex-differentiated effects. Finally, we tested for sex differences in between-trait genetic correlations.Results: With current sample sizes (and power), we found no significant, consistent sex differences in SNP-based h 2 . Between-sex, within-trait genetic correlations were consistently high, although significantly less than 1 for educational attainment and risk-taking behavior. We identified genome-wide significant genes with sex-differentiated effects for eight traits. Several trait pairs shared sex-differentiated effects. The top 0.1% of genes with sex-differentiated effects across traits overlapped with neuron-and synapse-related gene sets. Most between-trait genetic correlation estimates were similar across sex, with several exceptions (e.g. educational attainment & risk-taking behavior). Conclusions: Sex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic, requiring large sample sizes. Genes with sex-differentiated effects are enriched for neuron-related gene sets. This work motivates further investigation of genetic, as well as environmental, influences on sex differences.

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Exploring Comorbidity Within Mental Disorders Among a Danish National Population

Cited by 446 publications

References 28 publications

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness

Psychiatric Comorbidity as a Function of Severity: DSM‐5 Alcohol Use Disorder and HiTOP Classification of Mental Disorders

Examining sex-differentiated genetic effects across neuropsychiatric and behavioral traits

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