Evidence for IDO in depression is supported bystudies demonstrating that decreased levels of tryptophan and increased kyneurenin is associated with inflammation and depression.185 Increased IDO has also been positively correlated with depression, although a direct causal relationship has not been demonstrated. A recent study has now provided direct evidence that induction of IDO underlies the depressive behaviors caused by inflammation/activated immunologic conditions. This work was conducted using a bacterial immune activation model, Bacille Calmette-Guerin (BCM), which induces a long-lasting induction of interferon

and results in depressive behaviors in animal models.185,186 The results Inhibitors,research,lifescience,medical demonstrate that BCM-mediated immobility in the forced swim test is reversed by an IDO inhibitor, 1-methyltryptophan, and in mice that are deficient in IDO.185 In addition, BCM also increases the expression of a downstream enzyme, Inhibitors,research,lifescience,medical 3-hydroxyanthranilic acid oxygenase (3-HAO) that is involved in the synthesis of quinolinic acid. These studies indicate that an IDO inhibitor, and possibly an inhibitor of 3-HAO, could have efficacy for the treatment of depression and related mood disorders. Summary and future directions Significant advances have been made in characterizing the neuronal and glial damage, or structural Inhibitors,research,lifescience,medical alterations, at the cellular and anatomical levels in stress-related mood disorders and

other psychiatric illnesses, and in elucidating the molecular signaling MG132 proteasome pathways and mechanisms that underlie these changes. However, this work Inhibitors,research,lifescience,medical is still at a relatively early stage, and a more complete characterization of these complex alterations and signaling mechanisms will require extensive resources and time. Moreover, identification of genetic polymorphisms that impact these pathways and systems and that influence Inhibitors,research,lifescience,medical susceptibility or resilience to illness is a major area of research that will continue to develop and unfold. When ZD1839 combined with studies of environmental risk factors and lifetime history

of stress, this work will define and describe the mechanisms underlying individual variations of illness. Together, the results of this Brefeldin_A work can be used to formulate a comprehensive approach for the prevention and treatment of psychiatric illnesses. Changes in lifestyle and behavior can reduce stress and exposure to environmental factors that influence cellular risk and damage and prevent illness. These approaches, as well as behavioral interventions that enhance the activity and function of specific neural circuits, and thereby provide protection, can also be used once a person has become ill. Development of therapeutic agents that target neuroprotective mechanisms, combined with genetic information will ultimately provide tailored approaches for highly specific and efficacious treatments for depression and other illnesses.