Normative modeling analysis reveals corpus callosum volume changes in early and mid-to-late first episode major depression

It has been widely accepted that major depressive disorder (MDD) impacts brain structures including the Corpus Callosum (CC). However, this assumption is based on scarce literature data involving small sample sizes. Furthermore, it is still unclear whether such CC volume changes may already be present at a first depressive episode.To further investigate this question, we compared 369 first-episode MDD patients (mean age = 35 years (sd = 12), 249 females; 283 early onset, 86 mid-to-late onset) from the open-source REST meta-MDD database closely matched for age and gender to 490 never-depressed individuals (mean age = 37 years (sd = 14); 309 females) using Z-scores obtained from normative neuroanatomical modeling to assess individual variability in CC (sub)volumes.Relative to the norms established by the healthy controls, first-episode MDD patients displayed CC volume (z-score) reductions in the entire CC (including the body), as did mid-to-late-onset first-episode MDD patients (age ≥ 45 y). In early-onset first-episode MDD patients (age ≤ 44 y), depression severity symptoms were related to volume increases in the entire CC, as well as the body and splenium.No data on depressive episode duration. Relatively small sample size for mid-to-late first-episode MDD patients.Our data revealed CC (sub)volume differences in early versus mid-to-late onset first episode MDD. Especially at early onset, depression severity may result in neural white matter activity as potential reaction to stress influences. Our results underline the importance of prompt clinical interventions at early onset MDD.