28/06/2025
π Clues from the Edge of Science
Exploring early hypotheses and emerging evidence in ADHD and autism β not established facts, but possible new directions in science.
Each post in this series takes a closer look at ideas still under investigation β intriguing, thought-provoking, and worth watching.
π§ Neuroinflammation and ADHD: A Possible Link?
When we think of ADHD, we often think of attention, impulsivity, or dopamine β not the immune system. But a growing body of early research is exploring something less obvious: neuroinflammation.
Neuroinflammation isnβt always harmful β in fact, it plays a critical role in brain health. Immune cells like microglia and astrocytes help maintain and repair the brain, support neuroplasticity, and guide synaptic pruning. This physiological neuroinflammation is part of normal brain function, especially during development.
But when this system becomes dysregulated, it may turn maladaptive. In this altered state, neuroinflammation can affect brain function in subtle but potentially important ways.
π¬ What do we know so far?
Emerging research has reported elevated levels of inflammatory molecules β such as IL-6, TNF-Ξ±, and CRP β in children and adults with ADHD. These cytokines can interact with neurons and glial cells, potentially influencing how neural networks and brain chemistry function.
In animal models, maternal immune activation (i.e., immune system stimulation during pregnancy) has been shown to affect offspring brain development and behaviour in ways that resemble ADHD phenotypes β including changes in activity, attention, and impulsivity.
π§ͺ One of the Possible Mechanisms
Several mechanisms have been proposed to explain how neuroinflammation might interact with ADHD. One of these hypotheses is that neuroinflammation alters neurotransmitter systems already implicated in ADHD β particularly dopamine, glutamate, and noradrenaline. For instance:
IL-6 can reduce dopamine synthesis and availability by lowering the availability of tyrosine hydroxylase, the key enzyme involved in dopamine production.
Chronic inflammation may disrupt the glutamateβGABA balance, which is critical for cognitive stability and attention.
Pro-inflammatory cytokines like TNF-Ξ± may interfere with dopamine transporter (DAT) and vesicular storage, altering dopamine signalling efficiency.
Microglial activation can increase extracellular glutamate and impair its uptake, contributing to excitotoxicity and further neurotransmitter imbalance.
So while inflammation may not cause ADHD, in some individuals it may modulate systems already involved in attention and self-regulation, adding a new layer to our understanding of how ADHD might work β at least in some cases.
This line of research is still young, and findings remain preliminary. But it opens an exciting new frontier in the biology of neurodevelopment.
https://cambridgeadhdclinic.com/adhd-neuroinflammation-link/
π For those of you who want to go further, see:
Oades, R. D., Dauvermann, M. R., Schimmelmann, B. G., Schwarz, M. J., & Myint, A. M. (2010). Attention-deficit hyperactivity disorder (ADHD) and glial integrity: An exploration of associations of cytokines and kynurenine metabolites with symptoms and attention. Behavioral and Brain Functions, 6(1), 32.
Corominas-Roso, M., Ramos-Quiroga, J. A., Palomar, G., CatalΓ‘n, R., Rigau-Ratera, E., & Casas, M. (2017). Cortisol and inflammatory biomarkers in adults with attention-deficit hyperactivity disorder. Neuropsychobiology, 75(3), 159β168.
Donfrancesco, R., Nativio, P., Balia, C., Villa, M. P., & Andriola, E. (2023). Alterations in striatal architecture and biochemical marker levels in an animal model of ADHD: Focus on proinflammatory cytokines. Biomedicines, 11(6), 1556.
Reed, M. D., Yim, Y. S., Wimmer, R. D., Kim, T. K., Tooke, K. I., Pace, B. T., ... & Huh, J. R. (2020). IL-17a promotes sociability in mouse models of neurodevelopmental disorders. Nature, 577(7789), 249β253.
