Inflammation, Anxiety, and Stress in Attention-Deficit/Hyperactivity Disorder
Luigi Francesco Saccaro, Zoé Schilliger, Nader Ali Perroud, Camille Piguet · 2021 · 102 citationsRead the paper
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and serious neurodevelopmental disorder characterized by symptoms of inattention and/or hyperactivity/impulsivity. Chronic and childhood stress is involved in ADHD development, and ADHD is highly comorbid with anxiety. Similarly, inflammatory diseases and a pro-inflammatory state have been associated with ADHD. However, while several works have studied the relationship between peripheral inflammation and stress in affective disorders such as depression or bipolar disorder, fewer have explored this association in ADHD. In this narrative review we synthetize evidence showing an interplay between stress, anxiety, and immune dysregulation in ADHD, and we discuss the implications of a potential disrupted neuroendocrine stress response in ADHD. Moreover, we highlight confounding factors and limitations of existing studies on this topic and critically debate multidirectional hypotheses that either suggest inflammation, stress, or anxiety as a cause in ADHD pathophysiology or inflammation as a consequence of this disease. Untangling these relationships will have diagnostic, therapeutic and prognostic implications for ADHD patients.
What the full text shows
Theory or simulation- Childhood trauma is associated with ADHD onset and persistence; a significant portion of children exposed to trauma exhibit ADHD symptoms. — 20% to 50% of children (Children exposed to childhood trauma)
- Genetic traits associated with higher BMI increase the risk of ADHD, potentially mediated by increased peripheral inflammation (CRP). (55,374 ADHD patients from the Psychiatric Genomics Consortium)
- Anxiety patients exhibit moderately higher concentrations of pro-inflammatory markers (IL1-β, IL6, and TNF-alpha) compared to healthy controls. (Meta-analysis of 1,077 anxiety disorder patients)
- Anxiety severity is associated with alterations in both immune and HPA axis indexes. (2,789 patients with depression or anxiety)
- Setup
- Review of cross-sectional observational studies, systematic reviews, meta-analyses, and original articles.
- How
- Narrative review synthesizing existing literature and evidence on the interplay between stress, anxiety, and immune dysregulation in ADHD.
- Limitations
- Narrative review rather than a systematic review · Excluded related disorders like autism spectrum disorder or depression · Directional causality between inflammation, stress, and ADHD remains undetermined
Summarized by Gemma 4 from the open-access full text · 12 Oct 2026. Read it