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.
Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf & Schön Klinik Hamburg-Eilbek, Hamburg, Germany.
Anja
A
Kuffel
Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf & Schön Klinik Hamburg-Eilbek, Hamburg, Germany.
Sarah
S
Eikelmann
Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf & Schön Klinik Hamburg-Eilbek, Hamburg, Germany.
Kirsten
K
Terfehr
Department of Marketing, University of Siegen, Siegen, Germany.
Gunnar
G
Mau
Department of Psychiatry, Charité University Berlin, Campus Benjamin Franklin, Berlin, Germany.
Linn K
LK
Kuehl
Department of Psychiatry, Charité University Berlin, Campus Benjamin Franklin, Berlin, Germany.
Christian
C
Otte
Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf & Schön Klinik Hamburg-Eilbek, Hamburg, Germany.
Bernd
B
Löwe
Asklepios Fachklinikum Tiefenbrunn, Rosdorf, Germany.
Carsten
C
Spitzer
Department of Psychiatry, Charité University Berlin, Campus Benjamin Franklin, Berlin, Germany. Electronic address: katja.wingenfeld@charite.de.
Katja
K
Wingenfeld
D000284:Administration, Oral; D059331:Adrenergic Neurons / Q000187:drug effects* / Q000378:metabolism; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D004311:Double-Blind Method; D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055291:Salivary alpha-Amylases / Q000378:metabolism; D055815:Young Adult
D058647:Adrenergic alpha-2 Receptor Agonists; D055291:Salivary alpha-Amylases; D003000:Clonidine; D009638:Norepinephrine
Major depressive disorder; Memory consolidation and retrieval; Noradrenergic system; Working memory; α2 receptor agonist