TY - JOUR
T1 - Depression impairs learning, whereas the selective serotonin reuptake inhibitor, paroxetine, impairs generalization in patients with major depressive disorder
AU - Herzallah, Mohammad M.
AU - Moustafa, Ahmed A.
AU - Natsheh, Joman Y.
AU - Danoun, Omar A.
AU - Simon, Jessica R.
AU - Tayem, Yasin I.
AU - Sehwail, Mahmud A.
AU - Amleh, Ivona
AU - Bannoura, Issam
AU - Petrides, Georgios
AU - Myers, Catherine E.
AU - Gluck, Mark A.
PY - 2013
Y1 - 2013
N2 - To better understand how medication status and task demands affect cognition in major depressive disorder (MDD), we evaluated medication-naive 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-naive 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 hippocampal-dependent generalization of past learning to novel contexts, not otherwise seen in the medication-naive 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 is critical for generalization.
AB - To better understand how medication status and task demands affect cognition in major depressive disorder (MDD), we evaluated medication-naive 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-naive 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 hippocampal-dependent generalization of past learning to novel contexts, not otherwise seen in the medication-naive 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 is critical for generalization.
UR - http://handle.uws.edu.au:8081/1959.7/533556
U2 - 10.1016/j.jad.2013.06.030
DO - 10.1016/j.jad.2013.06.030
M3 - Article
SN - 0165-0327
VL - 151
SP - 484
EP - 492
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
IS - 2
ER -