Striatum-based circuitry of adolescent depression and anhedonia

Abstract

Objective: Striatum-based circuits have been implicated in both major depressive disorder (MDD) and anhedonia, a symptom that reflects deficits of reward processing. Yet adolescents with MDD often exhibit a wide range of anhedonia severity. Addressing this clinical phenomenon, we aimed to use intrinsic functional connectivity (iFC) to study striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity.

Method: A total of 21 psychotropic medication-free adolescents with MDD and 21 healthy controls (HC), group-matched for age and sex, underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxelwise maps indicating correlation strengths of spontaneous blood-oxygenation-level-dependent (BOLD) signals among 6 bilateral striatal seeds (dorsal caudate, ventral caudate, nucleus accumbens, dorsal-rostral putamen, dorsal-caudal putamen, ventral-rostral putamen) and the remaining brain regions were compared between groups. Relationships between striatal iFC and severity of MDD and anhedonia were examined in the MDD group. Analyses were corrected for multiple comparisons.

Results: Adolescents with MDD manifested increased iFC between all striatal regions bilaterally and the dorsomedial prefrontal cortex (dmPFC), as well as between the right ventral caudate and the anterior cingulate cortex (ACC). MDD severity was associated with iFC between the striatum and midline structures including the precuneus, posterior cingulate cortex, and dmPFC. However, distinct striatal iFC patterns involving the pregenual ACC, subgenual ACC, supplementary motor area, and supramarginal gyrus were associated with anhedonia severity.

Conclusions: Although MDD diagnosis and severity were related to striatal networks involving midline cortical structures, distinct circuits within the reward system were associated with anhedonia. Findings support the incorporation of both categorical and dimensional approaches in neuropsychiatric research.

Figure 1

Intrinsic functional connectivity (iFC) group comparison between adolescents with major depressive disorder (MDD) and healthy controls. Note: Maps showing regions with (left) increased iFC in MDD versus controls, and (right) increased iFC in controls versus MDD. Significant iFC with each seed is color coded, with regions functionally connected with more than 1 seed indicated in yellow. Display threshold: Z > 2.3.

Figure 2

Intrinsic functional connectivity (iFC) correlations with major depressive disorder (MDD) severity and associated plots. Note: Maps showing regions with iFC (left) positively correlated with MDD severity and (right) negatively correlated with MDD severity. Plots a–d below demonstrate these relationships. Display threshold: Z > 2.3. DC = dorsal caudate; dmPFC = dorsomedial prefrontal cortex; NAc = nucleus accumbens; PCC = posterior cingulate cortex; VRP = ventral rostral putamen.

Figure 3

Intrinsic functional connectivity (iFC) correlations with anhedonia scores and representative plots. Note: Maps showing regions with iFC (left) positively correlated with anhedonia severity and (right) negatively correlated with anhedonia severity. Plots a–d below demonstrate several of these relationships. Additional plots are available in Figure S4, available online. Display threshold: Z > 2.3. ACC = anterior cingulate cortex; DC = dorsal caudate; NAc = nucleus accumben; SMA = supplementary motor area; VC = ventral caudate.