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The cognitive correlates of major depressive disorder and administration of SSRI antidepressants

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TitleInfo
Title
The cognitive correlates of major depressive disorder and administration of SSRI antidepressants
Name (type = personal)
NamePart (type = family)
Herzallah
NamePart (type = given)
Mohammad M.
NamePart (type = date)
1985-
DisplayForm
Mohammad M. Herzallah
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Paré
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Denis
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Denis Paré
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Advisory Committee
Role
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chair
Name (type = personal)
NamePart (type = family)
Creese
NamePart (type = given)
Ian
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Ian Creese
Affiliation
Advisory Committee
Role
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co-chair
Name (type = personal)
NamePart (type = family)
Delgado
NamePart (type = given)
Mauricio R.
DisplayForm
Mauricio R. Delgado
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Gluck
NamePart (type = given)
Mark A.
DisplayForm
Mark A. Gluck
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Myers
NamePart (type = given)
Catherine E.
DisplayForm
Catherine E. Myers
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Harmer
NamePart (type = given)
Catherine J.
DisplayForm
Catherine J. Harmer
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - Newark
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
Genre (authority = ExL-Esploro)
ETD doctoral
OriginInfo
DateCreated (qualifier = exact)
2015
DateOther (qualifier = exact); (type = degree)
2015-05
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2015
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
A 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.
Subject (authority = RUETD)
Topic
Neuroscience
Subject (authority = ETD-LCSH)
Topic
Depression, Mental
Subject (authority = ETD-LCSH)
Topic
Serotonin uptake inhibitors
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - Newark Electronic Theses and Dissertations
Identifier (type = local)
rucore10002600001
Identifier
ETD_6488
Identifier (type = doi)
doi:10.7282/T38W3G5Q
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (ix, 136 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Mohammed M. Herzallah
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Herzallah
GivenName
Mohammad
MiddleName
M.
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-05-01 00:03:30
AssociatedEntity
Name
Mohammad Herzallah
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - Newark
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2015-11-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after November 30th, 2015.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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ETD
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windows xp
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