Preoperative limbic cortical thinning in mesial temporal lobe epilepsy surgical candidates is associated with pre-existing and de novo postoperative depression.
OBJECTIVE Depression is common in mesial temporal lobe epilepsy (mTLE), but its neuroanatomical basis-and overlap with major depressive disorder (MDD)-remains poorly defined. We investigated whether the cortical and subcortical alterations reported in MDD are also present in mTLE and leveraged the frequent occurrence of depression after epilepsy surgery to test whether such changes predate the onset of post-surgical depression. METHODS Eighty-nine mTLE patients scheduled for anterior temporal lobectomy were classified as never depressed (NoD, n = 42), depressed before surgical evaluation (PreD, n = 23), or developing de-novo depression after surgery (PostD, n = 22). Pre-operative 3 T MRI (1 mm T1, T2, FLAIR) was processed with FreeSurfer v6.3. Six frontotemporal-limbic regions showing the largest MDD effects in ENIGMA studies-orbitofrontal cortex, rostral anterior cingulate, insula, fusiform gyrus, hippocampus, posterior cingulate-were analyzed using a latent variable model. RESULTS Depression status significantly influenced combined morphology in both hemispheres (p < 0.05). Relative to NoD, both PreD and PostD groups showed reduced cortical thickness in the orbitofrontal cortex, fusiform gyrus, insula, and rostral anterior cingulate (Cohen's d = -0.04 to -0.14). Hippocampal volume and posterior cingulate thickness did not differ between groups. SIGNIFICANCE Four of the six frontotemporal regions showing the largest morphometric alterations in MDD also exhibit reduced cortical thickness in mTLE patients with past or future depression. This shared frontotemporal thinning pattern supports depression in mTLE as an expression of network pathology common to MDD, while residual regional differences may help explain the distinct phenotypic presentations of depression in these neuropsychiatric disorders. In PostD patients, these abnormalities were already present pre-operatively, consistent with a pre-existing vulnerability rather than a purely psychosocial reaction to surgery or epilepsy per se.