Depression Impairs Learning, whereas the Selective Serotonin Reuptake Inhibitor, Paroxetine, Impairs Generalization in Patients with Major Depressive Disorder 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 Myers, Catherine E. Gluck, Mark A. 2018-09-29T08:53:00Z 2018-09-29T08:53:00Z 2014-11-01
dc.description.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. en_US
dc.description.sponsorship We would like to thank Al-Quds Cognitive Neuroscience Lab students: Salam Abdellatif, Dana Deeb, Aya Imam, Issa Isaac, Hussain Khdour, Jeries Kort and Mohammad Taha for their excellent technical assistance. Research reported in this publication was supported by the National Institutes of Health Award R21MH095656 from the Fogarty International Center and the National Institute of Mental Health to MAG, the Palestinian American Research Center (PARC), as well as generous donations from Saad N. Mouasher, Daryl Kulok, Dr. Samih Darwazah and Stewart and Lois Gross. en_US
dc.identifier.issn 0165-0327
dc.language.iso en_US en_US
dc.publisher Elsevier en_US
dc.subject Major Depressive Disorder en_US
dc.subject Selective Serotonin Reuptake Inhibitor (SSRI) en_US
dc.subject hippocampus en_US
dc.subject basal ganglia en_US
dc.subject reward en_US
dc.subject punishment en_US
dc.subject sequence learning en_US
dc.subject context-shift en_US
dc.subject generalization en_US
dc.title Depression Impairs Learning, whereas the Selective Serotonin Reuptake Inhibitor, Paroxetine, Impairs Generalization in Patients with Major Depressive Disorder en_US
dc.type Article en_US
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