Human brain is a complex system with dynamic responses. Intercommunication of brain regions to perform a real world task results into unique functional models based on activation of brain regions and strength of their interconnectivity. The functional models may be studied under the categories of anatomical, effective and functional connectivity. Variability of these models under same conditions signifies pathophysiology of a psychotic disease. Functional model of an abnormal brain has a different physiological connectivity pattern as compared to a normal one. Identification of these abnormalities may have useful implications for clinical diagnosis and prognosis. It may also be helpful in prediction of treatment response of an antidepressant. This paper provides description of functional models for pathophysiology of major depressive disorder (MDD) using functional magnetic resonance imaging (fMRI). © 2012 IEEE.