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The cognitive correlates of major depressive disorder and administration of SSRI antidepressants
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Herzallah, Mohammad M.. The cognitive correlates of major depressive disorder and administration of SSRI antidepressants. Retrieved from https://doi.org/doi:10.7282/T38W3G5Q

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TitleThe cognitive correlates of major depressive disorder and administration of SSRI antidepressants
NameHerzallah, Mohammad M. (author); Paré, Denis (chair); Creese, Ian (co-chair); Delgado, Mauricio R. (internal member); Gluck, Mark A. (internal member); Myers, Catherine E. (internal member); Harmer, Catherine J. (outside member); Rutgers University; Graduate School - Newark
Date Created2015
Other Date2015-05 (degree)
SubjectBehavioral and Neural Sciences, Depression, Mental, Serotonin uptake inhibitors
Extent1 online resource (ix, 136 p. : ill.)
DescriptionA significant barrier to interpreting past studies of cognition in major depressive disorder (MDD) has been the inadequate dissociation of cognitive changes due to MDD from the side effects of antidepressants used to treat MDD such as Selective Serotonin Reuptake Inhibitors (SSRIs). The two most implicated brain regions in the pathophysiology of MDD are the basal ganglia (BG) and the hippocampus, which are also key areas for cognitive function. In this dissertation, we used cognitive assessment tools that selectively and sensitively evaluate BG and hippocampus function to tease apart the cognitive effects of MDD from those of SSRIs, and explore individual differences in cognitive function resulting from naturally occurring genetic variations. We studied two cognitive functions that have well-characterized neural bases informed by patient work and neuro-computational models: (1) Learning stimulus-response rules from positive and negative feedback, known to depend on the BG; and (2) Generalization of past stimulus-response learning to novel task demands and contexts, known to depend on the hippocampus. Investigating learning from positive and negative feedback revealed that MDD impaired learning from positive feedback in future SSRI-responders and non-responders, but spared learning from negative feedback only in SSRI-responders. SSRI administration, however, did not remediate the deficit in learning from positive feedback, but rather impaired learning from negative feedback in SSRI-responders, thereby bringing learning from positive and negative feedback into ‘balance’. Variations in dopamine levels reflected by naturally occurring genetic polymorphisms in the dopamine transporter gene modulated learning from positive feedback in both healthy and MDD states. Studying generalization of past learning revealed that MDD had no effect. However, SSRI-responders exhibited overgeneralization after SSRI administration. Overall, these findings define the cognitive profile of medication-naïve MDD and delineate the cognitive mechanism of action of SSRIs. Further, these results differentiate the cognitive profiles of SSRI responders and non-responders before and after treatment and highlight the cognitive effects of naturally occurring genetic variations. Clinical trials based on these findings could inform innovative individualized treatment protocols for MDD, guiding physician choices among antidepressants according to a patient’s individual cognitive and genetic profile upon initial diagnosis.
NotePh.D.
NoteIncludes bibliographical references
Noteby Mohammed M. Herzallah
Genretheses
Persistent URLhttps://doi.org/doi:10.7282/T38W3G5Q
Languageeng
CollectionGraduate School - Newark Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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