Major Depressive Disorder (MOD) is one of the most prevalent psychiatric problems faced by U.S. adults. Although MOD appears to be highly heritable, genetic association studies for this disorder have been variable and equivocal. Identifying intermediate phenotypes may be crucial for advancing our understanding of MDD. Neurobiological models suggest that genetic variants of the serotonin transporter (5-HTTLPR) play a crucial role within a widely distributed and interconnected system of cortical and subcortical pathways that regulate processing of emotion cues. Some researchers have speculated that serotonergic polymorphisms increase the risk for and maintenance of affective disorders by contributing to altered processing of emotional stimuli. Our primary aim is to use a state-of-the-art eye tracking paradigm to examine whether polymorphisms of the 5-HTTLPR are associated with biased processing of dysphoric emotion cues among adults with MDD. Further, we will also examine whether short 5-HTTLPR allele carriers with no current or past psychopathology also display similar processing biases of dysphoric emotion cues when induced into a transient dysphoric mood. Secondary aims will examine 5-HTTLPR genotype effects for other emotion cue processing biases, such as over-identifying sadness in emotionally ambiguous stimuli, difficulty disengaging attention from dysphoric information, and self-reported tendencies to ruminate about emotional information.
Our final aim i s to investigate two other genetic polymorphisms (i.e., Catechol-O-methyltransferase [COMT] and tryptophan hydroxylase 2 [TPH2]) that have been associated with increased risk for MDD, impact the function of the corticolimbic emotion circuits, and have a relatively high minor allele frequency. This translational study should thus help to elucidate the mechanisms by which three common genetic polymorphisms contribute to the expression of a critical phenotype in MDD. Thus, the proposed study should advance our knowledge of the etiological and maintenance processes for MDD and provide specific direction for the design of treatment programs for this serious psychiatric problem. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH076897-02
Application #
7497977
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Kozak, Michael J
Project Start
2007-09-19
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$265,478
Indirect Cost
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Wells, Tony T; Judah, Matt R; Ellis, Alissa J et al. (2015) Inhibition of Attention for Affective Material: Contributions by HOMER1 Gene Variation. Psychol Neurosci 8:495-508
Wells, Tony T; Vanderlind, W Michael; Selby, Edward A et al. (2014) Childhood abuse and vulnerability to depression: cognitive scars in otherwise healthy young adults. Cogn Emot 28:821-33
Pearson, Rahel; McGeary, John E; Beevers, Christopher G (2014) Association between serotonin cumulative genetic score and the Behavioral Approach System (BAS): Moderation by early life environment. Pers Individ Dif 70:140-144
Wells, Tony T; Clerkin, Elise M; Ellis, Alissa J et al. (2014) Effect of antidepressant medication use on emotional information processing in major depression. Am J Psychiatry 171:195-200
Vanderlind, W Michael; Beevers, Christopher G; Sherman, Stephanie M et al. (2014) Sleep and sadness: exploring the relation among sleep, cognitive control, and depressive symptoms in young adults. Sleep Med 15:144-9
Disner, Seth G; McGeary, John E; Wells, Tony T et al. (2014) 5-HTTLPR, HTR1A, and HTR2A cumulative genetic score interacts with mood reactivity to predict mood-congruent gaze bias. Cogn Affect Behav Neurosci 14:1259-70
Bredemeier, Keith; Beevers, Christopher G; McGeary, John E (2014) Serotonin transporter and BDNF polymorphisms interact to predict trait worry. Anxiety Stress Coping 27:712-21
Wells, Tony T; Beevers, Christopher G; Knopik, Valerie S et al. (2013) Dopamine D4 receptor gene variation is associated with context-dependent attention for emotion stimuli. Int J Neuropsychopharmacol 16:525-34
Beevers, Christopher G; Worthy, Darrell A; Gorlick, Marissa A et al. (2013) Influence of depression symptoms on history-independent reward and punishment processing. Psychiatry Res 207:53-60
Clasen, Peter C; Wells, Tony T; Ellis, Alissa J et al. (2013) Attentional biases and the persistence of sad mood in major depressive disorder. J Abnorm Psychol 122:74-85

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