Altered Cerebral Perfusion in Executive, Affective, and Motor Networks During Adolescent Depression

Abstract

Objective While 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 for 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 25 medication-naive adolescents (ages 13–17 years) diagnosed with major depressive disorder (MDD) and 26 well-matched controls 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<0.05, corrected). Hyperperfusion was also observed within the subcallosal cingulate, putamen, and fusiform gyrus (p<0.05, 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<0.05, 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.

Baseline brain perfusion and brain structure in patients with major depression: a multimodal magnetic resonance imaging study

“…Inference of meaningful local group differences was based on a correction for multiple comparisons at the cluster level, using an uncorrected height threshold of p < 0.005 together with an extent threshold of p < 0.05. 33 All analyses were inclusively masked by a statistical parametric map comprising voxels with positive rCBF values that were significantly (p < 0.05) different from zero when averaged across both groups of patients and controls.…”

“…To achieve this significance we used an uncorrected height threshold of p < 0.005 together with an extent threshold of p < 0.05. 33 …”

“…57 Decreased rCBF in the PHC in the acute phase of the illness is consistent with reported lower mean medial temporal lobe blood flow in adolescent depression. 33 Perfusion deficits of medial temporal lobe structures may partly explain cognitive deficits, particularly mnemonic and executive functions, in patients with MDD. [58][59][60][61] Higher striatal perfusion revealed in our sample might be part of the overall increased activity/ responsiveness of limbic structures according to currently hypothesized MDD models.…”

“…Nonmedi cated patients may present prefrontal hypoperfusion when measured with ASL. 33,36 Major depressive disorder has been repeatedly associated with brain volume change. 19,20,21,[22][23][24] Volume reduction of the ACC, as found in our medicated patient subsample, is a robust finding in patients with MDD.…”

“…Third, in patients with MDD we explored the association between rCBF and clinical features, such as the severity of depressive symptoms and the duration of illness, including the number of depressive episodes. Based on cerebral perfusion data in adolescent, 33 adult [34][35][36] and late-life depression 37 and on PET findings reporting metabolic changes in patients with MDD, we predicted that patients would exhibit abnormal lateral prefrontal, anterior cingulate and medial temporal rCBF compared with controls. Given that regions exhibiting abnormal neural activity and aberrant brain volume in patients with MDD may spatially overlap, we expected that correction for brain atrophy would also affect rCBF data.…”