The cholinergic neurotransmitter system has been implicated in mood disorders. Janowsky and colleagues (1973) demonstrated that increasing cholinergic activity with physostigmine rapidly shifted patients with bipolar disorder from symptoms of mania to symptoms of depression, and worsened symptoms of depression in patients with major depressive disorder. Given that patients with depression also experience cognitive difficulties, possibly as a result of cholinergic dysfunction, we designed a study to assess the effects of a cholinergic muscarinic blocker (scopolamine) on cognitive function and depression severity. After observing rapid antidepressant effects in a cohort of patients with depression, we designed a clinical trial to evaluate the effect of scopolamine on the severity of depression. Depression severity rapidly decreased following the administration of scopolamine. se same patients performed a working memory task with functional neuroimaging, where we found that baseline response in early visual processing areas when attending to face emotion correlated with the magnitude of subsequent clinical response to scopolamine. When attending to face identity, no correlation was observed. se findings suggest that baseline brain response when attending to face emotion may indicate the magnitude of cholinergic dysfunction in patients with depression, which may reflect the potential to respond to an anticholinergic antidepressant.
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