Depression Impairs Learning, whereas the Selective Serotonin Reuptake Inhibitor, Paroxetine, Impairs Generalization in Patients with Major Depressive Disorder
Date
2014-11-01
Authors
Herzallah, Mohammad M.
Moustafa, Ahmed A.
Natsheh, Joman Y.
Danoun, Omar A.
Simon, Jessica R.
Tayem, Yasin I.
Sehwail, Mahmud A.
Amleh, Ivona
Bannoura, Issam
Petrides, Georgios
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
To better understand how medication status and task demands affect cognition in Major
Depressive Disorder (MDD), we evaluated medication-naïve patients with MDD, medicated
patients with MDD receiving the Selective Serotonin Reuptake Inhibitors (SSRI) paroxetine, and
healthy controls. All three groups were administered a computer-based cognitive task with two
phases, an initial phase in which a sequence is learned through reward-based feedback (which our
prior studies suggest is striatal-dependent), followed by a generalization phase that involves a
change in the context where learned rules are to be applied (which our prior studies suggest is
hippocampal-region dependent). Medication-naïve MDD patients were slow to learn the initial
sequence but were normal on subsequent generalization of that learning. In contrast, medicated
patients learned the initial sequence normally, but were impaired at the generalization phase. We
argue that these data suggest (i) an MDD-related impairment in striatal-dependent sequence
learning which can be remediated by SSRIs and (ii) an SSRI-induced impairment in hippocampaldependent
generalization of past learning to novel contexts, not otherwise seen in the medicationnaïve
MDD group. Thus, SSRIs might have a beneficial effect on striatal function required for
sequence learning, but a detrimental effect on the hippocampus and other medial temporal lobe
structures critical for generalization.
Description
Keywords
Major Depressive Disorder , Selective Serotonin Reuptake Inhibitor (SSRI) , hippocampus , basal ganglia , reward , punishment , sequence learning , context-shift , generalization