Translational Psychiatry - Serotonin versus catecholamine deficiency: behavioral and neural effects of experimental depletion in remitted depression

Despite immense efforts into development of new antidepressant drugs,
the increases of serotoninergic and catecholaminergic neurotransmission
have remained the two major pharmacodynamic principles of current drug
treatments for depression. Consequently, psychopathological or
biological markers that predict response to drugs that selectively
increase serotonin and/or catecholamine
neurotransmission hold the potential to optimize the prescriber’s
selection among currently available treatment options. The aim of this
study was to elucidate the differential symptomatology and
neurophysiology in response to reductions in serotonergic versus
catecholaminergic neurotransmission in subjects at high risk of
depression recurrence. Using identical neuroimaging procedures with [18F]
fluorodeoxyglucose positron emission tomography after tryptophan
depletion (TD) and catecholamine depletion (CD), subjects with remitted
depression were compared with healthy controls in a double-blind,
randomized, crossover design. Although TD induced significantly more
depressed mood, sadness and hopelessness than CD, CD induced more
inactivity, concentration difficulties, lassitude and somatic anxiety
than TD. CD specifically increased glucose metabolism in the bilateral
ventral striatum and decreased glucose metabolism in the bilateral
orbitofrontal cortex, whereas TD specifically increased metabolism in
the right prefrontal cortex and the posterior cingulate cortex. Although
we found direct associations between changes in brain metabolism and
induced depressive symptoms following CD, the relationship between
neural activity and symptoms was less clear after TD. In conclusion,
this study showed that serotonin and catecholamines have common and
differential roles in the pathophysiology of depression.

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