Abstract
BACKGROUND: Several epidemiological studies and psychological models have suggested that major depressive disorder (MDD) with anhedonia is associated with suicidal ideation (SI). However, little is known about whether the functional network pattern and intrinsic topologically disrupted in patients with anhedonia are related to SI. METHODS: The resting-fMRI by applying network-based statistic (NBS) and graph-theory analyses was estimated in 273 patients with MDD (144 high anhedonia [HA], 129 low anhedonia [LA]) and 150 healthy controls. In addition, we quantified the SI scores of each patient. Finally, the mediation analysis assessed whether anhedonia symptoms could mediate the relationship between anhedonia-related network metrics and SI. RESULT: The NBS analysis demonstrated that individuals with HA have a single abnormally increased functional connectivity component in a frontal-limbic circuit (termed the "anhedonia-related network", including the frontal cortex, striatum, anterior cingulate cortex and amygdala). The graph-theory analysis demonstrated that the anhedonia-related network showed a significantly disrupted topological organization (lower gamma and lambda), which the small-world property trend randomized. Furthermore, the anhedonia symptoms could mediate the relationship between the anhedonia-related network metrics (the mean functional connectivity values, the area under the curves values of gamma and nodal local efficiency in nucleus accumbens) and SI. CONCLUSIONS: We found that disruption of the reward-related network in MDD leads to SI through anhedonia symptoms. These findings show the abnormal topological construction of functional brain network organization in anhedonia, shedding light on the neurological processes underlying SI in MDD patients with anhedonia symptoms.