Altered cerebral perfusion in executive, affective, and motor networks during adolescent depression

Abstract

Objective: Although substantial literature has reported regional cerebral blood flow (rCBF) abnormalities in adults with depression, these studies commonly necessitated the injection of radioisotopes into subjects. The recent development of arterial spin labeling (ASL), however, allows noninvasive measurements of rCBF. Currently, no published ASL studies have examined cerebral perfusion in adolescents with depression. Thus, the aim of the present study was to examine baseline cerebral perfusion in adolescent depression using a newly developed ASL technique: pseudocontinuous arterial spin labeling (PCASL).

Method: A total of 25 medication-naive adolescents (13-17 years of age) diagnosed with major depressive disorder (MDD) and 26 well-matched control subjects underwent functional magnetic resonance imaging. Baseline rCBF was measured via a novel PCASL method that optimizes tagging efficiency.

Results: Voxel-based whole brain analyses revealed significant frontal, limbic, paralimbic, and cingulate hypoperfusion in the group with depression (p < .05, corrected). Hyperperfusion was also observed within the subcallosal cingulate, putamen, and fusiform gyrus (p < .05, corrected). Similarly, region-of-interest analyses revealed amygdalar and insular hypoperfusion in the group with depression, as well as hyperperfusion in the putamen and superior insula (p < .05, corrected).

Conclusions: Adolescents with depression and healthy adolescents appear to differ on rCBF in executive, affective, and motor networks. Dysfunction in these regions may contribute to the cognitive, emotional, and psychomotor symptoms commonly present in adolescent depression. These findings point to possible biomarkers for adolescent depression that could inform early interventions and treatments, and establishes a methodology for using PCASL to noninvasively measure rCBF in clinical and healthy adolescent populations.

Keywords: cerebral blood flow; functional magnetic resonance imaging (fMRI); major depressive disorder (MDD); pseudocontinuous arterial spin labeling (PCASL).

Figure 1

A graphical depiction of the prescans and pseudocontinuous arterial spin labeling (PCASL) scan in the optimized PCASL method. Note: See Image Acquisition under Method for more details). A series of time of flight (TOF) images were acquired to generate a high-resolution view of the main feeding arteries to the brain. The coordinates of the tagging plane and feeding arteries are then saved into a configuration file (Figure 1A). The spatial coordinates of the feeding arteries from the TOF scan are used to image the vascular territories via vessel-encoded arterial spin labeling (ASL) (Figure 1B). Lastly, up to 2 multiphase PCASL (MP-PCASL) scans are used to estimate phase tracking errors in each of the territory masks acquired from the vascular territorial imaging scan (Figure 1C). Note that the first MP-PCASL scan is used to measure the uncorrected phase errors while the second MP-PCASL scan is to verify that the errors are minimized after modulating the radiofrequency phase and in-plane gradients to the PCASL pulse train. If the phase tracking errors from the first MP-PCASL scan are less than 20°, then the second MP-PCASL scan is skipped (Figure 1C). The optimized global radio frequency phase and in-plane gradients determined by the MP-PCASL scan(s) are then applied to the tagging module for the PCASL scan (Figure 1D). LCA=left carotid artery; RCA=right carotid artery; VA=vertebral artery. From Shin et al. Pseudocontinuous arterial spin labeling with optimized tagging efficiency. Magnetic resonance in medicine. Oct 2012;68(4):1135-1144. Reprinted with permission from John Wiley and Sons.

Figure 2

The voxel-based whole brain analysis revealed 12 clusters with significantly different regional cerebral blood flow (rCBF) levels in major depressive disorder (MDD) compared with healthy controls (HCL) (orange=increased, blue=decreased). Note: Eight clusters revealed significantly lower mean rCBF in the MDD compared to the HCL group: bilateral parahippocampal gyri/insula, right inferior frontal/dorsolateral prefrontal cortex (Brodmann area [BA] 44/45 and BA46), right anterior cingulate cortex, right middle occipital gyrus, left inferior temporal gyrus, and bilateral cerebellum. Four clusters revealed significantly higher mean rCBF in the MDD compared to HCL group: right subcallosal cingulate, right putamen, and bilateral fusiform gyrus. All locations are reported in Talairach coordinates (see Results and Table 1 for more details). Results are overlaid on a standardized Talairach template. Significance of each cluster is p<0.05 (see Whole Brain Analysis under Method for more details). L=left; R=right.

Figure 3

The region-of-interets (ROI) analysis revealed 5 clusters with significantly different regional cerebral blood flow (rCBF) levels in major depressive disorder (MDD) compared with healthy controls (HCL) (orange=increased, blue=decreased). Note: Three clusters with significantly lower rCBF levels in MDD compared with HCL: right amygdala (top row) and bilateral insula (middle row). Two clusters revealed significantly higher rCBF levels in MDD compared with HCL: right superior insula (Brodmann Area [BA] 13; middle row) and right putamen/lentiform nucleus (bottom row). All locations are reported in Talairach coordinates (see Results and Table 2 for more details). Results are overlaid on a standardized Talairach template. Significance of each cluster is p<0.05 (see Region-of-Interest Analysis under Method for more details). L=left; R=right.