The neurocircuitry of malaise, sleep disturbances, and arousal are hypothesized to involve both “within-system” changes in the mesocorticolimbic dopamine system for arousal and malaise, but also “between-system” changes in neurocircuits that are involved in malaise (CRF, norepinephrine, vasopressin, and hypocretin in the CeA and BNST) and sleep/arousal (hypocretin in the hypothalamus; Table 1). The gene discussed is HCRT; the disease is malaise.