Exploring depression through brain morphology and inflammation

Major depressive disorder (MDD) is one of the leading causes of disability worldwide [1]. Behind this single diagnosis lies a heterogeneous condition: two patients under the same diagnosis can differ in symptoms, biology, and treatment response. Are we treating one disorder, or several biologically distinct forms under a single name? Evidence suggests that a subgroup of patients with MDD shows elevated inflammatory biomarkers, alongside anhedonia, neurovegetative symptoms, and reduced antidepressant responsiveness [2].

I would like to share findings from 176 hospitalized adults with MDD. We examined whether two blood markers — C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) — relate to depression in terms of clinical features and brain morphology.

Using literature-based cut-offs (CRP > 3.0 mg/L [3], NLR > 3.53 [4]), approximately one-third of patients fell into the high-inflammation group. CRP was associated with suicide attempt and suicidal plan after adjustment for age, sex, and BMI, and correlated with clinical severity. NLR showed no significant clinical associations. Voxel-based morphometry revealed regionally distinct gray matter correlates: CRP with temporal, occipital, and parietal differences; NLR with thalamic and superior temporal differences.

Taken together, these exploratory findings contribute to understanding the biological heterogeneity of depression. Identifying clinically meaningful subgroups and guiding personalized approaches are central aims in the field. These results align with recent proposals to introduce inflammation as a formal specifier for MDD in the future DSM-6 [3].

[1] World Health Organization, 2025[2] Penninx et al., 2025. Lancet Reg. Health Eur[3] Jha et al., 2025. JAMA Psychiatry[4] Forget et al., 2017. BMC Res. Notes