Depression impairs learning, whereas the selective serotonin reuptake inhibitor, paroxetine, impairs generalization in patients with major depressive disorder

Mohammad M. Herzallah, Ahmed A. Moustafa, Joman Y. Natsheh, Omar A. Danoun, Jessica R. Simon, Yasin I. Tayem, Mahmud A. Sehwail, Ivona Amleh, Issam Bannoura, Georgios Petrides, Catherine E. Myers, Mark A. Gluck

Research output: Contribution to journalArticle

17 Scopus citations

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 hippocampal-dependent generalization of past learning to novel contexts, not otherwise seen in the medication-naïve 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.

Original languageEnglish (US)
Pages (from-to)484-492
Number of pages9
JournalJournal of Affective Disorders
Volume151
Issue number2
DOIs
StatePublished - Nov 1 2013

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Psychiatry and Mental health

Keywords

  • Basal ganglia Sequence learning
  • Generalization
  • Hippocampus
  • Major depressive disorder
  • Selective serotonin reuptake inhibitor (SSRI)

Fingerprint Dive into the research topics of 'Depression impairs learning, whereas the selective serotonin reuptake inhibitor, paroxetine, impairs generalization in patients with major depressive disorder'. Together they form a unique fingerprint.

  • Cite this

    Herzallah, M. M., Moustafa, A. A., Natsheh, J. Y., Danoun, O. A., Simon, J. R., Tayem, Y. I., Sehwail, M. A., Amleh, I., Bannoura, I., Petrides, G., Myers, C. E., & Gluck, M. A. (2013). Depression impairs learning, whereas the selective serotonin reuptake inhibitor, paroxetine, impairs generalization in patients with major depressive disorder. Journal of Affective Disorders, 151(2), 484-492. https://doi.org/10.1016/j.jad.2013.06.030