Dynamics of the systemic inflammatory response surrounding stressors and the association with neuropsychiatric and somatic outcomes 2026 Berlot et al

[Andy]

Highlights​

• Inflammatory response is associated with vulnerability to stress-related conditions.
• Inflammation around stressors was associated with reduced risk of adverse outcomes.
• More favourable outcomes were observed in dynamic than static immune profiles.
• Dynamic inflammation predicted less anxiety, mood, pain, and somatic outcomes.
• Immune adaptability may support resilience to adverse events and chronic stressors.

Abstract​

Acute and chronic stressors contribute to neuropsychiatric disorders. However, the role of inflammatory dynamics around stress exposure remains unclear. Using TriNetX, an international electronic health records database, we examined how systemic inflammatory activity and its temporal dynamics relate to risk of mental illness and somatic symptoms.

We compared 44,904 individuals with records of accidents and leukocytosis in the surrounding period with matched individuals with normal leukocyte counts, and performed analogous comparisons for socioeconomic and psychosocial stressors in cohorts of 100,855 individuals with leukocytosis and matched controls. To contrast dynamic with static inflammatory responses, we compared cohorts exhibiting leukocyte count changes with those maintaining persistently normal or elevated counts around stressor exposure. Incidence of psychiatric and somatic symptom diagnoses were evaluated within two years of the stressor.

Following acute stressors, leukocytosis (compared with normal leukocyte counts) was associated with lower rates of anxiety disorders (Odds Ratio 0.88, 95% Confidence Interval 0.83–0.93), depression (0.92, 0.86–0.98), cognitive symptoms (0.86, 0.81–0.92) and several somatic symptoms, with similar reductions in anxiety (0.92, 0.88–0.95) and depression (0.92, 0.89–0.96) observed after chronic stressors. A dynamic inflammatory response was associated with the most favourable outcomes, with lower rates of anxiety, depression, cognitive difficulties, fatigue, and pain-related symptoms compared to persistently lower or higher inflammation, and lower rates of functional neurological disorder compared to low inflammation.

Our findings suggest that patterns of inflammatory response to stressors are associated with diverse mental health and somatic outcomes, with transient immune activation showing a more favourable outcome profile.

Open access

 

[Andy]

From the supplementary data file.

2. Definition of outcomes of interest

The following variables of interest were identified among mental health/interface conditions, each encoded as a dichotomous variable:

1) Anxiety disorders, encoded as Other anxiety disorders (F41)
2) Depression/depressive episode, encoded as Depressive episode (F32) or Major depressive disorder, recurrent (F33)
3) Post-traumatic stress disorder (PTSD) (F43.1) for acute stressors; or Adjustment disorders (F43.2) for chronic stressors
4) Functional neurological disorder (FND), encoded as Conversion disorder with motor symptom of deficit (F44.4), Conversion disorder with seizures or convulsions (F44.5), Conversion disorder with sensory symptom or deficit (F44.6), Conversion disorder with mixed symptom presentation (F44.7), Other dissociative and conversion disorders (F44.89), or Dissociative and conversion disorder, unspecified (F44.9)
5) Somatoform disorders (F45)
6) Sleep disorders, encoded as Sleep disorders not due to a substance or known physiological condition (F51)
7) Cognitive symptoms, encoded as Other symptoms and signs involving cognitive functions and awareness (R41.8)

 

[Andy]

Among conditions and symptoms associated with pain, somatic symptoms and fatigue, the following outcomes were of interest (each encoded as a dichotomous variable):

8) Headache (R51)
9) Unspecified chest pain, encoded as Chest pain, unspecified (R07.9)
10) Unspecified abdominal pain (R10.9)
11) Low back pain (M54.5)
12) Fibromyalgia (M79.7)
13) Breathing abnormalities, encoded as Abnormalities of breathing (R06)
14) Palpitations (R00.2)
15) Irritable bowel syndrome (K58)
16) Pruritus, encoded as Pruritus, unspecified (L29.9)
17) Malaise and fatigue (R53)

 

[Sean]

4) Functional neurological disorder (FND), encoded as Conversion disorder with motor symptom of deficit (F44.4), Conversion disorder with seizures or convulsions (F44.5), Conversion disorder with sensory symptom or deficit (F44.6), Conversion disorder with mixed symptom presentation (F44.7), Other dissociative and conversion disorders (F44.89), or Dissociative and conversion disorder, unspecified (F44.9)​

That is, a wastebasket for dumping everything medicine doesn't yet have an explanation for.