Journal of affective disorders · 2026
Treatment-resistant depression is associated with reduced brain entropy.
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Lin Wei-Chen, Cheng Li-Kai, Su Tung-Ping, Chen Li-Fen, Tu Pei-Chi, Li Cheng-Ta, Bai Ya-Mei, Tsai Shih-Jen, Chen Mu-Hong
Аннотация
BACKGROUND: Brain entropy reflects the brain's functional complexity and encompasses both cognitive and affective processing. However, brain entropy remains to be systematically examined in patients with treatment-resistant depression (TRD).
METHODS: The study cohort comprised 48 adults with TRD and 38 healthy controls. All participants underwent resting-state functional magnetic resonance imaging. Sample entropy, an index of brain entropy, was calculated from blood oxygenation level-dependent time series for each of 166 regions of interest.
RESULTS: At an embedding dimension (m) of 1 and a tolerance (r) of 0.5, patients with TRD exhibited significantly lower entropy in the right angular gyrus, left cerebellar Crus II, and median raphe nucleus than did healthy controls. At r = 0.4, resting-state entropy was relatively broadly reduced in patients with TRD across the following regions: bilateral inferior frontal operculum; left gyrus rectus; right posterior orbitofrontal cortex; right angular gyrus; left inferior parietal cortex; bilateral cerebellar Crus II; cerebellar vermis lobules IV, V, VI, and VII; anterior cingulate cortex; thalamic nuclei; nucleus accumbens; ventral tegmental area; left red nucleus; and median raphe nucleus. These regions correspond to canonical large-scale networks, including the salience, default mode, reward, and cerebellar affective and motor networks, and involve thalamocortical and serotonergic pathways.
DISCUSSION: System-wide hypofunction, reflected by reduced entropy across large-scale networks, the cerebellum, and the median raphe nucleus, was associated with TRD.
METHODS: The study cohort comprised 48 adults with TRD and 38 healthy controls. All participants underwent resting-state functional magnetic resonance imaging. Sample entropy, an index of brain entropy, was calculated from blood oxygenation level-dependent time series for each of 166 regions of interest.
RESULTS: At an embedding dimension (m) of 1 and a tolerance (r) of 0.5, patients with TRD exhibited significantly lower entropy in the right angular gyrus, left cerebellar Crus II, and median raphe nucleus than did healthy controls. At r = 0.4, resting-state entropy was relatively broadly reduced in patients with TRD across the following regions: bilateral inferior frontal operculum; left gyrus rectus; right posterior orbitofrontal cortex; right angular gyrus; left inferior parietal cortex; bilateral cerebellar Crus II; cerebellar vermis lobules IV, V, VI, and VII; anterior cingulate cortex; thalamic nuclei; nucleus accumbens; ventral tegmental area; left red nucleus; and median raphe nucleus. These regions correspond to canonical large-scale networks, including the salience, default mode, reward, and cerebellar affective and motor networks, and involve thalamocortical and serotonergic pathways.
DISCUSSION: System-wide hypofunction, reflected by reduced entropy across large-scale networks, the cerebellum, and the median raphe nucleus, was associated with TRD.