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. 2014 Feb:155:65-74.
doi: 10.1016/j.jad.2013.10.025. Epub 2013 Oct 25.

Functional connectivity of negative emotional processing in adolescent depression

Tiffany C Ho  1 , Guang Yang  1 , Jing Wu  1 , Pete Cassey  1 , Scott D Brown  1 , Napoleon Hoang  1 , Melanie Chan  1 , Colm G Connolly  1 , Eva Henje-Blom  1 , Larissa G Duncan  1 , Margaret A Chesney  1 , Martin P Paulus  1 , Jeffrey E Max  1 , Ronak Patel  1 , Alan N Simmons  1 , Tony T Yang  2
Affiliations

Functional connectivity of negative emotional processing in adolescent depression

Tiffany C Ho et al. J Affect Disord. 2014 Feb.

Abstract

Background: The subgenual anterior cingulate cortex (sgACC) and its connected circuitry have been heavily implicated in emotional functioning in adolescent-onset major depressive disorder (MDD). While several recent studies have examined sgACC functional connectivity (FC) in depressed youth at rest, no studies to date have investigated sgACC FC in adolescent depression during negative emotional processing.

Methods: Nineteen medication-naïve adolescents with MDD and 19 matched healthy controls (HCL) performed an implicit fear facial affect recognition task during functional magnetic resonance imaging (fMRI). We defined seeds in bilateral sgACC and assessed FC using the psychophysiological interaction method. We also applied cognitive behavioral modeling to estimate group differences in perceptual sensitivity in this task. Finally, we correlated connectivity strength with clinical data and perceptual sensitivity.

Results: Depressed adolescents showed increased sgACC-amygdala FC and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus FC compared to HCL (p<0.05, corrected). Among the MDD, sgACC-precuneus FC negatively correlated with depression severity (p<0.05, corrected). Lastly, MDD adolescents exhibited poorer perceptual sensitivity in the task than HCL, and individual differences in perceptual sensitivity significantly correlated with sgACC FC and depression scores (p<0.05, corrected).

Limitations: Subjects were clinically homogenous, possibly limiting generalizability of the findings.

Conclusions: Adolescent depression is associated with biased processing of negative stimuli that may be driven by sgACC dysregulation and may possibly lead to an imbalance among intrinsic functional brain networks. This work also establishes the use of combining neuroimaging and cognitive behavioral modeling methods to investigate cognitive and neural differences between psychiatric and healthy populations.

Keywords: Adolescent depression; Functional connectivity; Functional magnetic resonance imaging; Linear ballistic accumulator model; Psychophysiological interaction; Subgenual anterior cingulate cortex.

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Conflict of interest statement

Conflicts of interest:

Dr. Tiffany Ho reports no biomedical financial interests or potential conflicts of interest.

Mr. Guang Yang reports no biomedical financial or potential conflicts of interest.

Mr. Jing Wu reports no biomedical financial interests or potential conflicts of interest.

Mr. Pete Cassey reports no biomedical financial interests or potential conflicts of interest.

Dr. Scott Brown sits on the editorial board of the Journal of Mathematical Psychology.

Mr. Napoleon Hoang works as an assistant editor at Elsevier.

Ms. Melanie Chan reports no biomedical financial interests or potential conflicts of interest.

Dr. Colm Connolly reports no biomedical financial interests or potential conflicts of interest.

Dr. Eva Henje-Blom receives grant or research support from the Swedish Research Council, the Swedish Society of Medicine, and the Swedish American Association.

Dr. Larissa Duncan receives grant or research support from the National Institutes of Health.

Dr. Margaret Chesney receives grant or research support from the National Institutes of Health.

Dr. Martin Paulus receives grant or research support from the National Institutes of Health.

Dr. Jeffrey Max receives grant or research support from the National Institutes of Health. He also provides expert testimony in cases of traumatic brain injury on an ad hoc basis for plaintiffs and defendants on a more or less equal ratio. This activity constitutes approximately 5% of his professional activities.

Mr. Ronak Patel reports no biomedical financial interests or potential conflicts of interest.

Dr. Alan Simmons receives grant or research support from the Veterans Affairs and the Center of Excellence in Stress and Mental Health.

Dr. Tony Yang reports no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1
Figure 1. Implicit fear facial affective recognition paradigm
60 facial trials and 12 baseline trials (crosshair fixation) were presented in pseudorandom order. Facial stimuli displayed one of three fear levels: FearStrong (FS, 1 00%), FearModerate (FM; 50%), and FearNeutral (FN; 0%) and were presented twice at each level of the fear intensities (a). Each trial lasted 3000 ms, with an inter-trial interval (ITI) randomly varying according to a Poisson distribution (mean ITI=2000 ms). For each facial trial, subjects were asked to indicate the gender of the face (male or female) by pushing one of two buttons on a button box. These choices were displayed in boxed text on the bottom left and right corners but will disappear once a response is made (b). See Behavioral task and stimuli under Methods for more details.
Figure 2
Figure 2. Group differences in LBA parameters
Each panel shows the posterior predictive distribution of the magnitude (μ) of the difference between the MDD and HCL groups for each parameter of the LBA model. Positive differences indicate larger parameter estimates for the MDD group, while negative differences indicate smaller parameter estimates for the MDD group. A distribution peaking at zero (denoted by the red line at x=0) indicates no difference between groups for that parameter. Odds ratios (ORs) indicating amount of evidence in favor of a difference are reported beneath each panel. See Figure S5 for posterior predictive distributions of the precision (σ) of the estimated group difference for each LBA hyper-parameter. To see posterior predictive distributions of each parameter for MDD and HCL separately, please see Figure S4.
Figure 3
Figure 3. Group differences in functional connectivity
We employed a psychophysiological interaction (PPI) method of functional connectivity, with bilateral subgenual anterior cingulate cortex (sgACC) defined as seeds and FearStrong-FearNeutral as the condition of interest. This analysis revealed the following clusters with significantly differently functional connectivity with sgACC in MDD relative to HCL (orange=increased, blue=decreased): All coordinates are in Talairach space and results are overlaid over a standardized Talairach template. Significance of each cluster is p<0.05 (see Controlling for multiple comparisons under Methods for more details).
See this image and copyright information in PMC

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