Acute antidepressant drug administration and autobiographical memory recall: a functional magnetic resonance imaging study

Papadatou-Pastou M1, Miskowiak KW, Williams JM, Harmer CJ, Reinecke A

Exp Clin Psychopharmacol. 2012 Oct;20(5):364-72.


Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration of the antidepressant reboxetine on emotional autobiographical retrieval in healthy volunteers (14 men, 10 women). Functional magnetic resonance imaging was used in a double-blind between-groups investigation with reboxetine (4 mg) and placebo. Consistent with previous reports using lab-based stimuli, neural activation in the processing of positive versus negative memories was reduced following reboxetine compared with placebo in the left frontal lobe (extending into the insula) and the right superior temporal gyrus. This was paired with increased memory speed in volunteers given reboxetine versus placebo. The effect of reboxetine on emotional memory extends to recall of personally experienced events. Such effects may be relevant to the cognitive improvements found with recovery from depression and with the mechanism of action of contemporary antidepressant drugs.

Single dose antidepressant administration modulates the neural processing of self-referent personality trait words

Miskowiak K, Papadatou-Pastou M, Cowen PJ, Goodwin GM, Norbury R, Harmer CJ

Neuroimage. 2007 Sep 1;37(3):904-11.


Drugs which inhibit the re-uptake of monoamines in the brain are effective in the treatment of depression; however, the neuropsychological mechanisms which lead to the resolution of depressive symptomatology are unclear. Behavioral studies in healthy volunteers suggest that acute administration of the selective norepinephrine reuptake inhibitor reboxetine modulates emotional processing. The current study therefore explored the neural basis of this effect. A single dose of reboxetine (4 mg) or placebo was administered to 24 healthy volunteers in a double-blind between-group design. Neural responses during categorisation and recognition of self-referent personality trait words were assessed using event-related functional Magnetic Resonance Imaging (fMRI). Reboxetine had no effect on neuronal response during self-referent categorisation of positive or negative personality trait words. However, in a subsequent memory test, reboxetine reduced neuronal activation in a fronto-parietal network during correct recognition of positive target words vs. matched distractors. This was combined with increased speed to recognize positive vs. negative words compared to control subjects and suggests facilitated memory for positive self-referent material. These results support the hypothesis that antidepressants have early effects on the neural processing of emotional material which may be important in their therapeutic actions.