on the CNS. Immune cells respond to signals from the CNS. Communication between neuroendocrine and immune system Glucocorticoids and catecholamines influence immune cells. Hypothalamic Pituitary Adrenal axis releases the needed hormones to support the immune system. Activity of the immune system is correlated with neurochemical/neuroendocrine activity of brain cells. Connections between glucocorticoids and immune system Anti-inflammatory hormones that enhance the organism's response to a stressor. Prevent the overreaction of the body's own defense system. Overactivation of glucocorticoid receptors can lead to health risks. Regulators of the immune system. Affect cell growth, proliferation and differentiation. Cause immunosuppression which can lead to an extended amount of time fighting off infections. High basal levels of cortisol are associated with a higher risk of infection. Suppress cell adhesion, antigen presentation, chemotaxis and cytotoxicity. Increase apoptosis. Corticotropin-releasing hormone (CRH) Release of corticotropin-releasing hormone (CRH) from the hypothalamus is influenced by stress. CRH is a major regulator of the HPA axis/stress axis. CRH Regulates secretion of Adrenocorticotropic hormone (ACTH). CRH is widely distributed in the brain and periphery CRH also regulates the actions of the Autonomic nervous system ANS and immune system. Furthermore, stressors that enhance the release of CRH suppress the function of the immune system; conversely, stressors that depress CRH release potentiate immunity. Central mediated since peripheral administration of CRH antagonist does not affect immunosuppression. HPA axis/stress axis responds consistently to stressors that are new, unpredictable and that have low-perceived control. As cortisol reaches an appropriate level in response to the stressor, it deregulates the activity of the hippocampus, hypothalamus, and pituitary gland which results in less production of cortisol. Relationships between prefrontal cortex activation and cellular senescence Psychological stress is regulated by the prefrontal cortex (PFC) The PFC modulates vagal activity Prefrontally modulated and vagally mediated cholinergic input to the spleen reduces inflammatory responses Pharmaceutical advances Glutamate agonists, cytokine inhibitors, vanilloid-receptor agonists, catecholamine modulators, ion-channel blockers, anticonvulsants, GABA agonists (including opioids and cannabinoids), COX inhibitors, acetylcholine modulators, melatonin analogs (such as Ramelton), adenosine receptor antagonists and several miscellaneous drugs (including biologics like Passiflora edulis) are being studied for their psychoneuroimmunological effects. For example, SSRIs, SNRIs and tricyclic antidepressants acting on serotonin, norepinephrine, dopamine and cannabinoid receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of IFN-gamma and IL-10, as well as TNF-alpha and IL-6 through a psychoneuroimmunological process. Antidepressants have also been shown to suppress