Aims: This study immunohistochemically examined the orbitofrontal cortex for three possible candidates in hypoxic/ischemic signaling: the cytokine transforming growth factor-β, the glucose transporter-1 and the neuron-specific oxygen-binding protein neuroglobin. Methods: Post-mortem tissue from 20 depressed and 20 non-depressed individuals was obtained and the expression of the three proteins was analyzed using image analysis software. Results: No significant changes were found in transforming growth factor-β or neuroglobin in the orbitofrontal cortex between depressed and non-depressed individuals. There was, however, a trend towards a reduction in glucose transporter-1 in the depressed group. Conclusions: This study does not clearly support the hypothesis that hypoxic/ischemic processes are behind the pathological deficits in the frontal-subcortical circuitry associated with depression and therefore does not provide evidence to support the 'vascular depression' hypothesis.