Treatment-resistant depression is associated with reduced brain entropy

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).

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.

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.

System-wide hypofunction, reflected by reduced entropy across large-scale networks, the cerebellum, and the median raphe nucleus, was associated with TRD.