Pathways by Which Inflammatory Cytokines Produce Neuropsychiatric Disturbance

In keeping with the observation that antidepressants mitigate emotional and behavioral symptoms resulting from immune system activation, significant evidence demonstrates that inflammatory cytokines affect neurotransmitters and neuroendocrine pathways that are regulated by currently available antidepressants and that have been implicated in the pathophysiology of depression and other stress-related neuropsychiatric disorders. It is increasingly recognized that these effects on the CNS and its outflow pathways may provide a physiological basis for the observation that immune activation frequently produces neuropsychiatric disturbance (Table 9-4).

TABLE 9-4. Potential mechanisms by which cytokines may influence behavior

Activation of corticotropin-releasing hormone pathways Alteration of monoamine metabolism Induction of the euthyroid sick syndrome

Disruption of glucocorticoid receptor signaling Alteration of regional brain activity Inhibition of relevant growth factors

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