Why ME/CFS might be norepinephrine-low but dopamine-normal
Catecholamines are a family of related brain chemicals: dopamine, norepinephrine, and epinephrine. If the body simply ran low on the raw material or a shared cofactor, you would expect the whole family to fall together.
That is not what a 2026 analysis found.
Using cerebrospinal fluid from people with ME/CFS and related conditions, Aregawi and colleagues built composite indices for the two main pathways. The norepinephrine pathway (norepinephrine plus its metabolites DHPG and MHPG) was significantly lower in post-infectious ME/CFS and in post-COVID patients with post-exertional malaise. The dopamine pathway (dopamine plus its metabolites DOPAC and HVA) was statistically indistinguishable from healthy controls (Aregawi et al. (2026)). Within the post-COVID group, only the subgroup with PEM was low.
Why selectivity matters. Norepinephrine is made from dopamine by an enzyme called dopamine-Ξ²-hydroxylase (DBH). DBH sits inside synaptic vesicles. But dopamine must first be pumped into the vesicle by a different protein, VMAT2, powered by an ATP-driven proton gradient; cytoplasmic dopamine never needs that transport step.
A shortage of energy at the vesicle would therefore impair the dopamine-to-norepinephrine conversion while leaving dopamine itself intact. That is one plausible mechanism β others include reduced DBH, altered reuptake, or cofactor loss β for the selective pattern observed. It is consistent with a disease built on an energy-supply problem; it is not proven.
The caveats. The study was small (n=16 in the ME/CFS arm), from a single centre, used a novel composite index, and has not been independently replicated. Physical deconditioning could lower norepinephrine without causing symptoms; that confound has not been eliminated. The selectivity is the most interesting part of the finding β and the part most in need of replication.