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BACKGROUND: Alexithymia is a risk factor for major depressive disorder (MDD) and has been associated with diminished treatment response. Neuroimaging studies have revealed structural aberrations of the anterior cingulate cortex and the fusiform gyrus in healthy controls with high levels of alexithymia. The present study tried to corroborate and extend these results to patients with MDD compared with healthy controls. METHODS: We investigated the relationship between alexithymia, depression and grey matter volume in 63 patients with MDD (mean age ± standard deviation = 42.43 yr ± 11.91; 33 female) and 46 healthy controls (45.35 yr ± 8.37; 22 female). We assessed alexithymia using the Toronto Alexithymia Scale. We conducted an alexithymia × group analysis of covariance; we used a region-of-interest approach, including the fusiform gyrus and anterior cingulate cortex, and conducted whole brain analysis using voxelbased morphometry. RESULTS: Our analysis revealed a significant alexithymia × group interaction in the fusiform gyrus (left, pFWE = 0.031; right, pFWE = 0.010). Higher alexithymia scores were associated with decreased grey matter volume in patients with MDD (pFWE = 0.009), but with increased grey matter volume of the fusiform gyrus in healthy controls (pFWE = 0.044). We found no significant main effects in the region-of-interest analysis. LIMITATIONS: Owing to the naturalistic nature of our study, patients with MDD and healthy controls differed significantly in their alexithymia scores. CONCLUSION: Our results showed the fusiform gyrus as a correlate of alexithymia. We also found differences related to alexithymia between patients with MDD and healthy controls in the fusiform gyrus. Our study encourages research related to the transition from risk to MDD in people with alexithymia.