AbstractIntroductionDifferential diagnosis between bipolar and unipolar mood disorder is therapeutically critical but remains clinically difficult. Neurophysiological measures, if validly demonstrated, can greatly enhance current clinical practices. We have examined differential performances of near‐infrared spectroscopy (NIRS) during cognitive tasks among euthymic bipolar and unipolar subjects and healthy controls.MethodsFourteen remitted patients with bipolar disorder and 39 remitted patients with major depression along with 24 healthy controls were administered a verbal fluency task and their prefrontal activation was measured with NIRS. The time courses of oxygenated hemoglobin concentration in the bilateral prefrontal cortices were averaged to yield two indices of cortical activation: area under the curve (AUC) and weighted center (WC).ResultsThe AUC was significantly different among the three groups, with both bipolar and unipolar subjects showing significantly smaller AUC than healthy controls (P = 0.01 and P < 0.001). The WC was also significantly different among the three groups, but this time with unipolar patients showing significantly smaller WC than bipolar or healthy controls (P = 0.023 and P = 0.008). The discriminant function combining AUC and WC had a sensitivity of 0.71 (95%CI: 0.42 to 0.86) and a specificity of 0.46 (0.30 to 0.60) to differentially diagnose euthymic bipolar from unipolar patients.DiscussionGiven the current promising findings, a more rigorous study of NIRS with a larger number of untreated patients with bipolar and unipolar patients is warranted.