Background:　The　anterior　cingulate　cortex　(ACC)　plays　an　important　role　in　the　neuropathology　of　major　depressive　disorder　(MDD).　So　far,　the　effect　of　local　cortical　alteration　on　metabolites　in　multiple　subdivisions　of　ACC　has　not　been　studied.　We　aimed　to　investigate　structural　and　biochemical　changes　and　their　relationship　in　the　pregenual　ACC　(pgACC),　dorsal　ACC　(dACC)　in　MDD.　Methods:　We　obtained　magnetic　resonance　spectroscopy　(MRS)　in　two　investigated　regions　for　24　depressed　patients　and　matched　controls.　In　each　region,　cortical　thickness　(CTh)　was　calculated　within　a　template　mask　based　on　its　MRS　voxel.　We　investigated　neurotransmitter　concentrations　of　Glx,　N-acetyl　aspartate　(NAA),　and　myo-inositol　(m-lns)　in　two　investigated　regions,　as　well　as　their　relationships　with　CTh　in　depressed　individuals　and　healthy　controls.　Results:　Patients　showed　significantly　lower　cortical　thickness　in　dACC　compared　to　controls.　Glx　in　dACC　significantly　correlated　with　CTh　in　healthy　controls　but　not　MDD　patients,　while　NAA　and　CTh　in　dACC　significantly　correlated　in　both　groups.　A　marginal　decrease　of　Glx　in　pgACC　was　found　in　the　subgroup　of　more　severely　depressive　patients,　compared　to　the　mildly　depressed　patients.　Limitations:　Modest　sample　size　and　lack　of　episodes　of　depression　may　limit　the　generalizability　of　our　findings.　Conclusion:　Our　results　indicate　an　abolished　CTh-MRS　relation　in　dACC　associated　with　structural　decline　but　not　in　pgACC,　where　acute　MRS　alterations　prevailed.　Our　study　provides　the　first　evidence　of　a　neurochemical　basis　explaining　some　of　the　inter-individual　variability　in　CTh　in　MDD.　(C)　2014　Elsevier　B.V.　All　rights　reserved.