Diagnosis-independent contribution of low-grade inflammation to cortical atrophy across psychiatric disorders

Brain Behav Immun. 2026 May 1:106792. doi: 10.1016/j.bbi.2026.106792. Online ahead of print.

ABSTRACT

BACKGROUND: Peripheral low-grade inflammation has been implicated in the pathophysiology of various psychiatric disorders and has been associated with cortical brain structural alterations. However, it remains unclear whether inflammation-related cortical atrophy is disorder-specific or reflects shared, diagnosis-independent vulnerability across psychiatric conditions.

METHODS: We investigated cross-sectional and longitudinal associations between baseline high-sensitivity C-reactive protein (hs-CRP) and cortical thickness in participants from the Marburg Affective Disorders Cohort Study (MACS). The baseline sample comprised 683 patients (524 with major depressive disorder [MDD], 82 with bipolar disorder [BD], 77 with schizophrenia [SCZ]) and 620 healthy controls (HC) (59.9% female). After two years, follow-up data were available for 163 patients (125 MDD, 18 BD, 20 SCZ) and 184 HC (57.3% female). Serum hs-CRP levels were measured in all participants, and cortical thickness was assessed using structural MRI with FreeSurfer parcellation. Models were adjusted for age, sex, BMI, site, and diagnosis, with multiple comparisons corrected using the false discovery rate.

RESULTS: Higher baseline hs-CRP was significantly associated with reduced cortical thickness in the left paracentral lobule at baseline (β = -0.029; p _FDR = 0.017) and with cortical thinning over time in the left fusiform gyrus (β = -0.014; p _FDR = 0.038) in longitudinal analyses. No significant interaction effects were found for age, sex, diagnosis, or smoking status.

CONCLUSIONS AND RELEVANCE: Peripheral low-grade inflammation was associated with progressive cortical thinning across diagnostic groups, supporting a diagnosis-independent neurobiological mechanism, that is not specific to any psychiatric disorder, highlighting peripheral inflammation as potential target for preventive and therapeutic strategies in psychiatric care.

PMID:42070700 | DOI:10.1016/j.bbi.2026.106792