Studies for prevalence and causal relationship established that addressing comorbidities of mental illnesses with medical disease will be another revolution in psychiatry. Increasing number of evidence shows that there is a bidirectional connection between mood disorders and some medical diseases. Glucocorticoid/insulin signal mechanisms and immunoenflammatory effector systems are junction points that show pathophysiology between bipolar disorder and general medical situations susceptible to stress. A subgroup of mood disorder patients are under risk of developing obesity and diabetes. Their habits and life styles, genetic predisposition and treatment options are parameters that define this subgroup. Medical disease in adults had a significant relationship to adverse life experiences in childhood. This illustrates that adverse experiences in childhood are related to adult disease by two basic etiologic mechanisms: (1) conventional risk factors that actually are compensatory behaviors, attempts at self-help through the use of agents and foods; and (2) the effects of chronic stress.