Noradrenergic blockade and memory in patients with major depression and healthy participants

OBJECTIVE: Patients with major depressive disorder (MDD) often suffer from impaired declarative, episodic and working memory. Further, MDD is associated with alterations in the noradrenergic system. There is evidence that presynaptic α2 receptors that inhibit release of noradrenaline are upregulated in MDD. Results from our recent study demonstrated that increasing noradrenergic activity by blocking the α2 receptor with yohimbine leads to stronger memory consolidation in MDD patients. In the current study, we further examined the role of noradrenaline on memory in MDD by administering clonidine that activates presynaptic α2 receptors and thereby globally suppresses the noradrenergic output.

METHODS: In a placebo-controlled, within-subject crossover design, 20 patients with MDD and 20 healthy controls received either 0.15 mg of clonidine or placebo orally before memory testing. A word list paradigm (memory consolidation), an autobiographical memory test (retrieval) and a working memory test were applied. Salivary alpha-amylase and blood pressure were measured.

RESULTS: Across groups, clonidine decreased blood pressure and alpha-amylase. Clonidine impaired memory consolidation (word list learning) in depressed patients and controls. Memory retrieval and working memory were not affected by clonidine.

CONCLUSIONS: Reducing noradrenergic activity had a specific effect on memory consolidation in patients with MDD and healthy controls. The underlying mechanisms need further scrutiny.