title: Depression impairs learning, whereas the selective serotonin reuptake inhibitor, paroxetine, impairs generalization in patients with major depressive disorder.
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.
authors: Al-Quds Cognitive Neuroscience Lab, Faculty of Medicine, Al-Quds University, Abu Dis, Palestinian Territories; Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA. Electronic address: mohammad.m.herzallah@gmail.com.
authors: Mohammad M
authors: MM
authors: Herzallah
authors: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA; Department of Veterans Affairs, New Jersey Health Care System, East Orange, NJ, USA; School of Psychology, University of Western Sydney, Sydney, NSW, Australia.
authors: Ahmed A
authors: AA
authors: Moustafa
authors: Al-Quds Cognitive Neuroscience Lab, Faculty of Medicine, Al-Quds University, Abu Dis, Palestinian Territories; Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA.
authors: Joman Y
authors: JY
authors: Natsheh
authors: Al-Quds Cognitive Neuroscience Lab, Faculty of Medicine, Al-Quds University, Abu Dis, Palestinian Territories.
authors: Omar A
authors: OA
authors: Danoun
authors: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA.
authors: Jessica R
authors: JR
authors: Simon
authors: Al-Quds Cognitive Neuroscience Lab, Faculty of Medicine, Al-Quds University, Abu Dis, Palestinian Territories.
authors: Yasin I
authors: YI
authors: Tayem
authors: Al-Quds Cognitive Neuroscience Lab, Faculty of Medicine, Al-Quds University, Abu Dis, Palestinian Territories.
authors: Mahmud A
authors: MA
authors: Sehwail
authors: Al-Quds Cognitive Neuroscience Lab, Faculty of Medicine, Al-Quds University, Abu Dis, Palestinian Territories.
authors: Ivona
authors: I
authors: Amleh
authors: Al-Quds Cognitive Neuroscience Lab, Faculty of Medicine, Al-Quds University, Abu Dis, Palestinian Territories.
authors: Issam
authors: I
authors: Bannoura
authors: The Zucker Hillside Hospital North Shore-LIJ Health System, Hofstra North Shore-LIJ School of Medicine, New York, USA.
authors: Georgios
authors: G
authors: Petrides
authors: Department of Veterans Affairs, New Jersey Health Care System, East Orange, NJ, USA; Department of Neurology and Neurosciences, New Jersey Medical School/UMDNJ, Newark, NJ, USA; Department of Psychology, Rutgers University, Newark, NJ, USA.
authors: Catherine E
authors: CE
authors: Myers
authors: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA.
authors: Mark A
authors: MA
authors: Gluck
mesh_terms: D000293:Adolescent; D000328:Adult; D003071:Cognition / Q000187:drug effects; D003865:Major Depressive Disorder / Q000150:complications* / Q000188:drug therapy; D005260:Female; D005793:Generalization, Psychological / Q000187:drug effects*; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Basal ganglia; Generalization; Hippocampus; Major depressive disorder; Selective serotonin reuptake inhibitor (SSRI); Sequence learning
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