Abstract : BACKGROUND: Analysis of cortical folding may provide insight into neurodevelopment deviations, which, in turn, can predispose to depression that responds particularly poorly to medications. We hypothesized that patients with treatment-resistant depression would exhibit measurable alterations in cortical folding. METHODS: We computed hemispheric global sulcal indices (g-SIs) in T(1)-weighted magnetic resonance images obtained from 76 patients and 70 healthy controls. We separately searched for anatomic deviations in patients with bipolar disorder (16 patients with treatment-resistant depression, 25 with euthymia) and unipolar depression (35 patients with treatment-resistant depression). RESULTS: Compared with healthy controls, both groups of patients with treatment-resistant depression exhibited reduced g-SIs: in the right hemisphere among patients with bipolar disorder and in both hemispheres among those with unipolar depression. Patients with euthymic bipolar disorder did not differ significantly from depressed patients or healthy controls. Among patients with bipolar disorder who were taking lithium, we found positive correlations between current lithium dose and g-SIs in both hemispheres. LIMITATIONS: We cannot estimate the extent to which the observed g-SI reductions are linked to treatment resistance and to what extent they are state-dependent. Furthermore, we cannot disentangle the impact of medications from that of the affective disorder. Finally, there is interindividual variation and overlap of g-SIs among patients and healthy controls that need to be considered when interpreting our results. CONCLUSION: Reduced global cortical folding surface appears to be characteristic of patients with treatment-resistant depression, either unipolar or bipolar. In patients with bipolar disorder, treatment with lithium may modify cortical folding surface.
