Trial Report Comorbidity and Sex Differences in Functional Disorders and Internalizing Disorders, 2024, Thomas

[Dolphin]

Free full text:
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4785891

Comorbidity and Sex Differences in Functional Disorders and Internalizing Disorders

26 Pages Posted: 11 Apr 2024

Nathaniel Thomas
affiliation not provided to SSRN

Nathan A. Gillespie
affiliation not provided to SSRN

Kenneth S. Kendler
Virginia Commonwealth University (VCU) - Virginia Institute for Psychiatric and Behavioral Genetics

Albertine J. Oldehinkel
affiliation not provided to SSRN

Judith G.M. Rosmalen
affiliation not provided to SSRN

Hanna M. van Loo
University of Groningen - Department of Psychiatry

Abstract

Objective:

Functional disorders (FDs) and internalizing disorders (IDs) are highly comorbid. In the current study we estimate comorbidity rates between FDs [fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS)]—and IDs—[major depressive disorder (MDD) and generalized anxiety disorder (GAD)] by leveraging self-reported diagnostic criteria to estimate comorbidity, sex differences, and the overrepresentation of particular combinations of diagnoses.

Method:

We analyzed data from 107,849 participants (mean age=49.3 (SD=13.0), 58.6% female) of the Lifelines Cohort Study. Lifelines is a prospective population-based cohort study in the northeast of the Netherlands. Current IDs and FDs were assessed according to diagnostic criteria between 2014-2017. We estimated tetrachoric correlations between diagnoses and tested for sex differences. Additionally, we estimated the ratio of observed-to-expected frequency for combinations of diagnoses.

Results:

FDs and IDs are highly comorbid (odds ratios: 3.2-12.6) with associations stronger among male participants. All three-, four-, and five-condition diagnoses were observed more frequently than expected by chance.

Conclusion:

High rates of comorbidity between FDs and IDs suggest shared risk factors. Studies that aim to explain sex differences and the overrepresentation of specific combinations of IDs and FDs will be an important contribution to understanding the etiology of these conditions.



Note:
Funding Declaration: This project was supported by NIMH grant R01MH125902. The Lifelines initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG), Groningen University and the Provinces in the North of the Netherlands (Drenthe, Friesland, Groningen). HvL was supported by a VENI grant from the Talent Program of the Netherlands Organization of Scientific Research (NWOZonMW 09150161810021).

Conflicts of Interest: None.

Ethical Approval: The Lifelines protocol has been approved by the UMCG Medical ethical committee under number 2007/152.

Highlights:

 Internalizing disorders and functional disorders are highly comorbid.

 Irritable bowel syndrome is not as closely related to internalizing disorders as
fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.

 The association between functional disorders and internalizing disorders is larger
in male participants.

 Combinations of functional disorders/internalizing disorders including three or
more conditions occur more frequently than expected by chance.

Suggested Citation:

Thomas, Nathaniel and Gillespie, Nathan A. and Kendler, Kenneth S. and Oldehinkel, Albertine J. and Rosmalen, Judith G.M. and van Loo, Hanna M., Comorbidity and Sex Differences in Functional Disorders and Internalizing Disorders. Available at SSRN: https://ssrn.com/abstract=4785891 or http://dx.doi.org/10.2139/ssrn.4785891

 

[Trish]

If the diagnoses are based on questionnaires, this is most likely to be about overlapping questions, not necessarily overlapping conditions.

 

[Hutan]

If anyone was in any doubt as to whether ME/CFS is regarded as a 'functional disorder', it is, (and it seems to be the latest name for hysteria; perhaps the BPS proponents think they have struck gold with a term that conceals what they are thinking so well)

Functional disorders (FDs) are characterized and diagnosed by the presence of somatic symptoms of unknown origin. Commonly diagnosed FDs include fibromyalgia (FM) with core symptom of musculoskeletal pain [1], myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with core symptoms of severe fatigue and post-exertional malaise [2], and irritable bowel syndrome (IBS) with core symptom of gastrointestinal problems [3]. FDs are common, costly, disabling, and highly comorbid [4,5].

If the diagnoses are based on questionnaires, this is most likely to be about overlapping questions, not necessarily overlapping conditions.

yes

Current MDD symptoms and GAD symptoms were assessed using the Mini- International Neuropsychiatric Interview (MINI) [27] as a computerized questionnaire at the research site. We assessed MDD symptoms in the past two weeks and GADsymptoms in the past 6 months.

Here is the MINI:
https://citeseerx.ist.psu.edu/docum...&doi=cd0609ea6d85ddaf335959cc96965f4fba452885
The instructions in that pdf include

Symptoms better accounted for by an organic cause or by the use of alcohol or drugs should not be coded positive in the M.I.N.I..

Here are the questions from the module assessing major depressive disorder:

A1:Have you been consistently depressed or down, most of the day, nearly every day, for the past two weeks ?
A2:In the past two weeks, have you been less interested in most things or less able to enjoy the things you used to enjoy most of the time ?

If you answered yes to either of those questions (and I think almost by definition, people with ME/CFS would have to answer 'yes' to A2, you proceed to seven questions. These are:

A3: Over the past two weeks, when you felt depressed and/or uninterested :

• Was your appetite decreased or increased nearly every day or did your weight decrease or increase without trying intentionally ? (i.e., ± 5 % of body weightor±3,5kgor±8lbs.,fora70kg/120lbs.personinamonth)
  IF YES TO EITHER, CODE YES
• Did you have trouble sleeping nearly every night (difficulty falling asleep, waking up in the middle of the night, early morning wakening, or sleeping excessively) ?
• Did you talk or move more slowly than normal or were you fidgety, restless or having trouble sitting still, almost every day?
• Did you feel worthless or guilty, almost every day?
• Did you repeatedly consider hurting yourself, feel suicidal, or wish that you were dead ?
• Did you feel tired or without energy, almost every day?
• Did you have difficulty concentrating or making decisions, almost every day?

If you answered yes to just one of A1 or A2, you need to answer yes to 4 of those seven A3 questions in order to be diagnosed with MDD. If you answered yes to both A1 and A2, you just need to answer yes to 3 of those seven questions to be diagnosed with MDD.

I think many people with ME/CFS who are not clinically depressed could answer yes to A2, and answer yes to 4 of the A3 questions for a particular 2 week period with a lot of PEM (trouble sleeping, talking or moving more slowly, feeling without energy, difficulty concentrating or making decisions). All of those responses could be due to their illness. Someone with gut issues could easily have problems with appetite or weight loss too.

So, it really comes down to whether the investigators properly instructed the participants about not ticking the box if the issue is due to an 'organic cause', and if the person believes that they have an 'organic illness'.

Basically, this is junk science

 

[Hutan]

Criteria for ME/CFS is Fukuda.

The overall prevalence rates of MDD, GAD, FM, ME/CFS, and IBS were 2.7%, 5.3%, 5.9%, 2.8%, and 5.1% respectively.

Conflicts of interest/Competing interests: Nathaniel S. Thomas, Nathan A. Gillespie, Kenneth S. Kendler, Albertine J. Oldehinkel, Judith G.M. Rosmalen and Hanna M. van Loo declare that they have no conflicts of interest

sure

Funding: This project was supported by NIMH grant R01MH125902. ..

That's the USA NIH's National Institute of Mental Health. It has been giving the Virginia Commonwealth University around USD600,000 per year for the last three years for work on "AN INTEGRATIVE APPROACH TO THE ETIOLOGY OF INTERNALIZING DISORDERS IN THE LIFELINES COHORT"
https://taggs.hhs.gov/Detail/AwardDetail?arg_AwardNum=R01MH125902&arg_ProgOfficeCode=134

 

[Hutan]

One of the authors, selected pretty much at random
Kenneth S Kendler
https://www.niaaa.nih.gov/biography-dr-kenneth-kendler

Dr. Kenneth Kendler is a world-renowned expert on the genetics of psychiatric and substance abuse disorders.

He uses various strategies, including linkage analysis, candidate gene association analysis, and genome wide association to unravel the genetic mysteries of schizophrenia, alcohol abuse, major depression, and nicotine dependence.

Specifically, he has investigated why some people’s genetics make them less able to cope with adversity, and therefore more vulnerable to psychiatric illness and/or addiction than people with a different genetic makeup. His work is making it possible to identify the specific genetic variants that may be responsible for these differences in vulnerabilities. In addition, Dr. Kendler has helped develop critical statistical and developmental models to explain how specific genetic and environmental factors contribute to psychiatric and alcohol problems.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684780/

At the time of writing, Kendler is the second most highly cited psychiatric researcher in the world.

Conclusion from this Thomas paper:

Overlapping symptoms, familial aggregation, and shared genetic variance between IDs and FDs [13,45,55] are important considerations in future studies that explore combined diagnoses.

Roll on the GWAS's from this team. What a nightmare.

 

[Jonathan Edwards]

Interesting that they have shared genetic variance when so far we have no genetic data for ME/CFS!!

 

[dave30th]

Kendler is the co-chief editor of Psychological Medicine—or was when I wrote to them. The other is a British BPS guy and colleague of the PACE folks. Enough said.

 

[rvallee]

If the diagnoses are based on questionnaires, this is most likely to be about overlapping questions, not necessarily overlapping conditions.

A common complaint from MDs is that they can't tell the difference. Which is normal, without tests to validate, they usually can't tell the difference between most diseases anyway. And really the people behind this research should think of that and the worst part of this is that they likely did and saw nothing wrong with it anyway.

 

[Dolphin]

It has just been published here:
https://www.sciencedirect.com/science/article/abs/pii/S0163834324001671