Functional and Morphological Markers of Adolescent-Onset Depression Open Access

Denker, Alexander (Fall 2017)

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Adolescence is a time of dramatic physical, behavioral, social, mental, and brain changes. Adolescence is also a period of psychiatric vulnerability. The likelihood of a depressive episode increases dramatically post-puberty. Moreover, as suicide is one of the leading causes of death among youth, the study of depression in adolescent populations is of great public health and scientific concern. As part of a larger investigation of mechanisms and treatment of depression in adolescents, the present study aimed to address two primary questions: 1) Are there differences in white matter connectivity between regions implicated in reward processing and mood in patients diagnosed with major depressive disorder (MDD) and controls? 2) Are there different patterns of neural activity involved in reward anticipation and feedback in patients and controls? We employed diffusion tensor imaging (DTI) and functional MRI in combination with behavioral inventory data from the Beck Depression Inventory (BDI) and the Behavioral Activation for Depression Scale (BADS) to address these questions. We found a trend approaching significance for greater functional anisotropy (FA), an indicator of tract integrity, in a tract connecting the right anterior insula and the right nucleus accumbens (NAcc) in patients versus controls. The relationship between group and FA in this tract was further indicated by significant positive relationships between FA and BDI scores and between FA and the avoidance/rumination subscale of the BADS questionnaire. Using the Monetary Incentive Delay Task, we found main effects of bilateral activation of the NAcc during reward anticipation and right NAcc activation in response to reward gain feedback. Furthermore, significant relationships between bilateral NAcc activation during reward anticipation and BDI scores as well as between bilateral NAcc and BADS avoidance/rumination scores were present. Our study contributes to the understanding of the morphological markers and functional mechanisms of depression in adolescence and may have implications for the evaluation of treatment.   

Table of Contents


Studying the neural markers of reward-based decisions in adolescents. 2

Using the Monetary Incentive Delay (MID) task to probe the neural mechanisms of reward anticipation. 4

Contributions of this study. 8


Overview.. 8

Participants. 9

Imaging Acquisition. 10

fMRI Analyses. 10

DTI Analyses. 10

Self-Report Questionnaires. 10

Monetary Incentive Delay Task. 11


DTI 12

MID Feedback and Anticipation Findings. 13


Limitations. 17

Future Directions. 18

Figure 1. Examples of MID “no change” and “loss” trials. 22

Figure 2. Partial regression of FA x Group. 23

Figure 3. Partial regression of Beck’s Depression Inventory Total Scores x FA. 24

Figure 4. Partial regression of BADS Total Score x FA. 25

Figure 5. Partial regression of BADS avoidance/rumination subscale x FA. 26

Figure 6. Partial regression of right NAcc activation for the MID won>lost feedback contrast x FA. 27

Figure 7. Whole brain map of MID win>neutral anticipation activity. 28

Figure 8. Whole brain map of MID won>lost feedback activity. 29

Figure 9. Anterior insula-nucleus accumbens tract (REDACTED FOR UPLOAD TO EMORY ETD) 30


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