Atomoxetine and citalopram alter brain network organization in Parkinson’s disease

Publication: Brain Communications

Robin J Borchert, Timothy Rittman, Charlotte L Rae, Luca Passamonti, Simon P Jones, Deniz Vatansever, Patricia Vázquez Rodríguez, Zheng Ye, Cristina Nombela, Laura E Hughes, Trevor W Robbins, James B Rowe

6 September 2019


Parkinson’s disease has multiple detrimental effects on motor and cognitive systems in the brain. In contrast to motor deficits, cognitive impairments in Parkinson’s disease are usually not ameliorated, and can even be worsened, by dopaminergic treatments. Recent evidence has shown potential benefits from restoring other neurotransmitter deficits, including noradrenergic and serotonergic transmission.

The researchers studied global and regional brain network organization using task-free imaging (also known as resting-state), which minimizes performance confounds and the bias towards predetermined networks.

Thirty-three patients with idiopathic Parkinson’s disease were studied three times in a double-blinded, placebo-controlled counter-balanced crossover design, following placebo, 40 mg oral atomoxetine (selective noradrenaline reuptake inhibitor) or 30 mg oral citalopram (selective serotonin reuptake inhibitor).

In patients, atomoxetine improved fluency in proportion to plasma concentration, and improved response inhibition in proportion to increased hub Eigen centrality. Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering, modularity and path length increased in patients with milder forms of Parkinson’s disease, but decreased in patients with more advanced disease.

This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. The researchers propose that hub connectivity contributes to cognitive performance in Parkinson’s disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function.

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