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The neurotransmitter noradrenaline (NA) mediates arousal, attention and mood, and exerts antiinflammatory and neuroprotective effects. Alterations of monoamine signalling were reported in multiple sclerosis (MS) and psychiatric illness and may account for the high prevalence of comorbid depression and fatigue in MS patients. We assessed central noradrenaline transporter (NAT) availability using positron emission tomography (PET) and the NAT selective radiotracer S,S-[ 11 c] O-methylreboxetine in immunotherapy-naïve patients with relapsing-remitting MS (RRMS; n = 11) compared to healthy controls (HC; n = 12), and its association to lesion load, time since manifestation, the expanded disability status scale (EDSS), the fatigue scale Würzburger Erschöpfungsinventar bei MS (WEIMuS) and Beck Depression Inventory (BDI). We found NAT availability to be increased in the thalamus, amygdala, putamen and pons/midbrain of MS patients. No relation to clinical or psychometric variables was found. These first data indicate higher NAT availability in subcortical brain regions of immunotherapy-naïve RRMS patients. If these changes of noradrenergic neurotransmission predispose to psychiatric symptoms or associate with disease activity needs to be investigated in longitudinal studies or a larger sample which allows subgroup analyses. Abbreviations [ 11 C]MRB S,S-[ 11 C]O-methylreboxetine BDI Beck depression inventory BMI Body mass index BP ND Binding potential DMT Disease modifying therapy DRKS German clinical trials register DVR Distribution volume ratio EAE Experimental autoimmune encephalitis EDSS Expanded disability status scale FWHM Full-width at half maximum HC Healthy controls

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