Cognitive and Emotional Abnormalities in People with Systemic Lupus Erythematosus

140 Pages·2017·2.1 MB·English

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Dissertations, Theses, and Capstone Projects CUNY Graduate Center
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Philip Watson
Graduate Center, City University of New York
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Cognitive and Emotional Abnormalities in People with Systemic Lupus Erythematosus
by
Philip Watson

A dissertation submitted to the Graduate Faculty in Psychology, Clinical Psychology with
Emphasis in Neuropsychology Subprogram in partial fulfillment of the requirements for the
degree of Doctor of Philosophy, The City University of New York

2014
© 2014
Philip Watson
All Rights Reserved
This manuscript has been read and accepted for the
Graduate Faculty in Clinical Psychology in satisfaction of the
dissertation requirement for the degree of Doctor of Philosophy.

Justin Storbeck, Ph.D.

Date Chair of Examining Committee

Maureen O’Connor, Ph.D.

Date Executive Officer

Justin Storbeck, Ph.D.

Paul Mattis, Ph.D.

Jin Fan, Ph.D.

Supervisory Committee

THE CITY UNIVERSITY OF NEW YORK
iv
ABSTRACT

Cognitive and Emotional Abnormalities in People with Systemic Lupus Erythematosus
by
Philip Watson
Advisor: Justin Storbeck, Ph.D.
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder characterized by the
production of autoantibodies (ABs). Approximately 30-50% of patients produce ABs directed
against N-Methyl-D-aspartic acid receptors (NMDARs). Previous research with animals has
identified these ABs as being associated with amygdala damage and a deficit in fear
conditioning. People with SLE can have damage to the amygdala. This study aimed to determine
if emotional processing deficits occur in people with SLE and to associate such deficits, if they
exist, with anti-NMDAR AB presence, length of disease, cognition, and mood. Fifty-eight (11
AB+, 24 AB-, 23 healthy) women participated in tasks used to assess emotional facial
recognition, attention to emotional stimuli, and emotional learning, and underwent cognitive
testing, including measures of working memory, processing speed, executive functioning,
language, visuospatial processing, and memory. Lupus patients were slower than healthy
participants in identifying emotional faces, and measures of processing speed and executive
functioning proved to be significant predictors of recognition of emotional faces and speeded
reactions to emotional pictures. Thus, the results do not provide robust evidence for the existence
of emotional processing deficits in people with lupus. The results are discussed within the
context of the complex neuroanatomical system involved in cognition and affective processing.
Future studies aimed at identifying dysfunction in the cognitive-affective control network are
necessary to elucidate dysfunction in this patient group.
v
Table of Contents
ABSTRACT ................................................................................................................................... iv
LIST OF TABLES ....................................................................................................................... viii
LIST OF ILLUSTRATIONS ......................................................................................................... ix
INTRODUCTION .......................................................................................................................... 1
Clinical Presentation of SLE ....................................................................................................... 2
Neuropsychiatric SLE (NP-SLE) ............................................................................................. 4
Cognitive Function and SLE .................................................................................................... 5
Psychiatric Syndromes and SLE .............................................................................................. 9
Mechanisms for Disease ............................................................................................................ 12
Effects of Autoantibodies on Neuronal Tissue in SLE .......................................................... 12
Neuro-Anatomical Changes Associated with SLE ................................................................ 15
Behavioral Abnormalities Associated with SLE Pathology .................................................. 18
Emotional Processing, Cognitive Functions, and the Amygdala .............................................. 19
The Amygdala and Social Behavior....................................................................................... 27
Implications for People with SLE ............................................................................................. 28
Specific Aims ............................................................................................................................ 29
Aim 1. To determine if people with SLE have deficits in processing emotional stimuli. ..... 29
Aim 2. To determine the association between emotional processing and autoantibody
presence in people with SLE. ................................................................................................. 29
vi
Aim 3. To examine the influence of disease duration on emotional deficits in people with
SLE. ........................................................................................................................................ 30
Aim 4. To determine the relationship between emotional processing, cognitive functioning,
and affective symptoms in people with SLE. ......................................................................... 30
METHODS ................................................................................................................................... 31
Participants ................................................................................................................................ 31
Measures .................................................................................................................................... 33
Emotional recognition ............................................................................................................ 33
Emotionally modulated attention ........................................................................................... 34
Emotional Learning ................................................................................................................ 35
Neuropsychological Testing ................................................................................................... 37
Anti-NMDAR Autoantibody.................................................................................................. 40
Mood Assessments ................................................................................................................. 41
Procedure ................................................................................................................................... 41
Screening ................................................................................................................................ 41
Testing .................................................................................................................................... 41
RESULTS ..................................................................................................................................... 43
Aim 1. To determine if people with SLE have deficits in processing emotional stimuli. ......... 43
Aim 2. To determine the association between emotional processing and autoantibody presence
in people with SLE. ................................................................................................................... 46
vii
Aim 3. To examine the influence of disease duration on emotional processing deficits in
people with SLE. ....................................................................................................................... 49
Aim 4. To determine the relationship between emotional processing, cognitive functioning,
and affective symptoms in people with SLE. ............................................................................ 53
DISCUSSION ............................................................................................................................... 57
Group Differences in Emotional Processing ............................................................................. 57
The Effect of Anti-NMDAR AB on Emotional Processing ...................................................... 59
The Role of Disease Duration ................................................................................................... 61
The Influence of Cognitive Functioning and Mood on Emotional Processing ......................... 62
Neurobiological Implications .................................................................................................... 63
Treatment Implications .............................................................................................................. 65
Limitations of the Present Study ............................................................................................... 66
Future Directions ....................................................................................................................... 68
Conclusion ................................................................................................................................. 69
TABLES AND FIGURES ............................................................................................................ 71
APPENDIX ................................................................................................................................... 99
REFERENCES ........................................................................................................................... 100
viii
LIST OF TABLES
Table 1. Neuropsychiatric Syndromes in SLE; page 71.
Table 2. Summary of cognitive performance of NP-SLE patients, SLE patients, and healthy
controls in previously published work; 72.
Table 3. Demographic information of healthy controls and anti-NMDAR AB negative and
positive lupus patients; page 75.
Table 4. Summary of results for Aim 1; page76.
Table 5. Summary of results for Aim 2; page 77.
Table 6. Summary of results for Aim 3; page78.
Table 7. Summary of results for Aim 4; page 79.
Table 8. Comparison of neuropsychological performance between healthy controls and anti-
NMDAR AB negative and positive lupus patients; page 80.
Table 9. Factor loadings of the components of the factor analysis used in creating composite
scores for the neuropsychological measures; page 81.
ix
LIST OF ILLUSTRATIONS
Figure 1. Shrunken amygdala neurons following immunization with anti-NMDAR antibodies;
page 82.
Figure 2. Mice immunized with MAP-Peptide to imitate SLE showed an impairment in
emotional learning when compared to mice immunized with MAP-Core; page 83.
Figure 3. Cortical connections of the amygdala; page 84.
Figure 4. Mean percent of accurate responses in identifying neutral and emotional faces in
healthy controls and participants with lupus; page85.
Figure 5. Mean reaction time differences in milliseconds between healthy controls and
participants with lupus when identifying neutral and emotional faces; page 86.
Figure 6. Mean reaction time in milliseconds between healthy controls and lupus patients for all
emotional and neutral face types; page 87.
Figure 7. Mean log reaction time differences between healthy controls and lupus patients in
responding to neutral and emotional targets; page 88
Figure 8. The physiological responses (eye blink response (A) and skin conductance response
(B)) are presented for benign and unconditioned stimulus trials during a fear-conditioning task;
page 89.
Figure 9. Mean percent of accurate responses in identifying neutral and emotional faces for AB-
and AB+ lupus patients; page 91.