Data-driven subtypes of internalizing and functional somatic symptoms: A hybrid mixture modeling approach 2026 Saini et al

[Andy]

Highlights​

• Internalizing and functional disorders are highly comorbid.
• We identified six data-driven subgroups: Healthy, Pain, Tension/Pain, Anxiety, Cognition/Fatigue, Depression.
• Fatigue, sleep problems, and concentration difficulty were endorsed across all subgroups.
• Comorbidity may partly arise from transdiagnostic symptoms lowering the diagnostic threshold of multiple disorders.

Abstract​

Background​

The mechanisms underlying the high comorbidity between internalizing disorders (IDs) and functional disorders (FDs) remain unclear. This study aimed to identify data-driven subgroups of major depressive disorder (MDD), generalized anxiety disorder (GAD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS) symptoms in the general population, capturing shared symptom patterns while accounting for variation in symptom severity.

Method​

We analyzed cross-sectional data from 72,919 adults in the Dutch Lifelines Cohort Study, randomly divided into training and validation subsets. Twenty-seven ID and FD criteria symptoms were examined using mixed-measurement item response theory models in the training set, with the optimal model validated in the validation set. Class characteristics were assessed through associations with risk factors, ID/FD diagnosis and comorbidity patterns.

Results​

Six classes best described the data: Healthy (57.5%), Pain (13.8%), Tension/Pain (9.1%), Anxiety (9.0%), Cognition/Fatigue (6.4%), and Depression (4.3%). All classes showed a combination of ID and FD symptoms, with the Cognition/Fatigue and Depression classes being most mixed, and the Pain and Anxiety classes most domain-specific. Transdiagnostic symptoms were highly endorsed across all classes. ID–FD comorbidity was highest in the Cognition/Fatigue and Depression classes, with the Depression class showing the greatest functional impairment.

Conclusions​

The identified classes comprised mixed symptoms from multiple disorders, rather than disorder-specific profiles. ID-FD comorbidity may partly result from non-specific defining symptoms lowering the threshold for fulfilling criteria for multiple disorders. Symptom-level evaluation can help identify more homogenous and clinically relevant subgroups. Longitudinal research is needed to clarify underlying mechanisms.

Open access

 

[rvallee]

Trying to make sense of this, and as best as I can tell, they tried to make the case that "functional disorders" are mostly mood/affective/"internalizing" disorders, didn't, and try to find excuses for why it's not entirely wrong.

Class 2 (‘Pain’, 13.8%) was mainly defined by ME/CFS and FM pain symptoms, with near zero endorsement of ID symptoms (<0.08)

Etiologically, non-specific symptoms may arise from multiple mechanisms rather than a single pathway, resulting in their high endorsement across disorders. Moreover, their endorsement may reflect different underlying processes depending on the clinical context and can complicate diagnosis. For example, somatic MDD symptoms, such as fatigue and sleep disturbances, may reflect pain rather than emotional distress in individuals with FM, allowing them to meet MDD thresholds despite endorsing few core depressive features. Similarly, ME/CFS pain symptoms frequently co-occur in FM, potentially contributing to higher FM prevalence across classes, whereas sore throat and tender lymph nodes are rarely endorsed and are weak indicators of ME/CFS [10], [76]. These findings indicate that some disorder-defining symptoms (e.g., fatigue and headaches) capture general malaise rather than disorder-specific pathology [10].

Yes, lots of symptoms are common across diagnoses, even more so the most common symptoms, and if you ask overlapping questions you will get overlapping answers. This is why most WebMD searches include cancer as a possibility. Except they're doing their best not to get it:

Further research is necessary to understand ID-FD comorbidity.

"When you fail, just try again", I guess. It's allowed. They're allowed to just try again and again to prove the belief they so desperately hold, and just because they can't doesn't mean it's wrong, as far as they're concerned.

Longitudinal studies are needed to examine how shared vulnerabilities develop and contribute to comorbidity

Not only that, they want to try for longer, because stagnation is the goal. As long as this thing doesn't move, it just stays in place, providing excuses for systemic failure.

Future longitudinal studies should assess class stability and identify predictors of ID-FD comorbidity.

Many more studies. Infinite studies. The goal is to "study", not to learn anything.

The whole framing of 'endorsing' is weird. They mean symptoms being reported, but prefer to frame it oddly for some reason. I guess that "functional" symptoms can't be reported, like real symptoms, merely endorsed. Or whatever. ¯\_(ツ)_/¯

So mostly they poorly replicated similar diagnostic criteria, using mostly the same criteria, debunked their assumption, but still prefer the model to reality, because the model is everything, the model is dead, long live the model, ALL HAIL THE MODEL.

 

[SNT Gatchaman]

The whole framing of 'endorsing' is weird.

See this discussion on r/med from last year. There's some amusement to be found in the replies.

 

[Utsikt]

Reminds me of «do you concur?» from Catch Me If You Can..

 

[rvallee]

See this discussion on r/med from last year. There's some amusement to be found in the replies.

That discussion did not clarify what is looking a lot like a dog whistle that can sometimes be used one way, but so inconsistently that it can't be relied on as actually meaning that. It doesn't have to be, but is usually accusatory and meant to diminish the value of the report.

For sure it looks like it can have a valid distinction, "patient told me" vs "I asked the patient and they concurred" ), but in this context it doesn't really make sense since they are only doing unprompted asking from a list.