Negative expectations in major depression: Association with brain structure and course of illness

J Affect Disord. 2026 Aug 21:122410. doi: 10.1016/j.jad.2026.122410. Online ahead of print.

ABSTRACT

BACKGROUND: Negative expectations towards the future are frequently observed in patients with major depressive disorder (MDD) and linked to less favourable outcomes like worse treatment response and suicidal behaviours. Despite clinical significance, the neurobiological underpinnings of negative expectations remain largely unexplored.

METHODS: This study compared structural MRI morphometric gray matter volume (SPM/CAT12) and two-year longitudinal clinical data between two groups of patients with DSM-IV-TR MDD (total N = 330), matched for age, sex, severity of depressive symptoms (HAMD), and global functioning (GAF scale), but differing in presence or absence of negative expectations assessed with the BDI-I item 2 „pessimism“.

RESULTS: In patients with negative expectations, the gray matter volume of the right middle frontal gyrus (rMFG) was increased compared to patients without negative expectations. Patients who expressed negative expectations at baseline had significantly longer duration of depressive episodes during the two-year follow up period. Average duration of subclinical depressive episodes was significantly predicted by the rMFG volume.

CONCLUSION: This study showed a correlation between negative expectations and brain structure, as well as with the course of illness. Clinically it sets the stage for future research into therapeutic interventions targeting patients‘ expectations as a potential modulator towards a more favourable outcome in MDD patients with negative expectations.

PMID:42628576 | DOI:10.1016/j.jad.2026.122410