Major depressive disorders are associated with distinct changes in sleeping and waking brain activity. Sleep in depressives is characterized by increased rapid-eye-movement (REM) sleep, shortened REM latency, as well as decreased slow-wave sleep and sleep efficiency. During wakefulness depressives show decreased activation of the left prefrontal cortex (PFC) when compared to the right. Changes in sleep architeckture and asymmetries in waking PFC activity may be related since PFC asymmetries also persist during sleep. Indeed recent positron emission tomography (PET) studies suggest that under normal cirecumstances actrivationh of the left PFC inhibits activity in the amygdala, a structure actively involved in processing negative emotions and anatomically positioned to modulate both REM sleep and arousal. Thus in expression, decreased left PFC activation mazy release the amygdala from left PFC inhibition, resulting in increased REM sleep expression. Increased amygdala actiovation may also decrease slow-wave sleep and sleep efficiency by raising arousal levels. These hypotheses will be tested using two complementary approaches. In the firsz, sleep measures will be correlated with patterns of PFC activation asymmetry and amygdala activation using a combination of EEG and PET imaging techniques in depressives. In the second, the effect of lesioning either the left or right PFC on sleep will be investigated in rhesus monkeys. Ultimately, a greater understanding of the mechanisms involved in abnormal sleep in depression promises to provide insight into the etiology and treatment of depression.
