Vol 6 n° 1 - Predictors of Response to Treatment in Neuropsychiatry
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7 8 Posters & images in neuroscience Spectral EEG sleep profiles as a tool for prediction of clinical response to antidepressant treatment Sleep and depression Two qualitatively different brain states characterize nor- mal human sleep: non–rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM sleep is further subdivided into four stages: stage 1 is the light- est and stage 4 the deepest. Stages 3 and 4 are often defined as d sleep or slow-wave sleep (SWS) due to the occurrence of slow (0.5-3.5 Hz) “delta” waves. REM sleep  (also  called  paradoxical  sleep)  alternates  with NREM throughout the night in recurrent NREM-REM cycles of about 90 min. Sleep-wake regulation is classi- cally viewed as resulting from the interaction of two reg- ulating processes (homeostatic [S] and circadian [C]).1 In this model, the propensity to sleep or be awake at any given time is a consequence of a sleep debt (Process S) and its interaction with signals coming from the circa- dian  clock  located  in  the  suprachiasmatic  nucleus (Process C). In 1982, Borbely and Wirz-Justice2 suggested that the characteristic sleep disturbances of major depressive patients reflect a homeostatic Process S deficiency, ie, a failure to accumulate SWS pressure during the daytime, leading to sleep initiation and maintenance difficulties, and early emergence of REM sleep. Indeed, character- istic  sleep  EEG  changes  such  lengthening  of  sleep latency, sleep disruption, and disturbances in REM sleep organization have been consistently identified in depres- sive illness.3 Spectral analysis of NREM sleep in major depressed patients has shown lower d activity (power spectra in the d wave) in NREM sleep4-6 and decreased d incidence particularly in the first non-REM period, 7 supporting the “Process S” deficiency hypothesis. Using spectral  analysis  of  the  sleep-onset  period, we  have recently brought support to this hypothesis: we found that homeostatic sleep regulation processes are partially maintained  in  primary  insomniacs, but  not  in  major depressed patients with insomnia.8 Sleep EEG and antidepressant response Some studies have shown that the clinical response to various antidepressant therapies could be predicted by sleep electroencephalography (EEG) parameters. For instance,   the   amount   of   REM   sleep   suppression observed after the first dose of antidepressant may pre- dict ultimate clinical response.9,10 REM rebound follow- ing antidepressant withdrawal was also found predictive of antidepressant response. Kupfer et al11 demonstrated that the antidepressant response to two consecutive days of pulse loading of clomipramine followed by placebo was  positively  correlated  with  the  amount  of  REM rebound. Similarly, Gillin et al9 noted that patients who improved during treatment with amitriptyline exhibit a clear REM sleep rebound during withdrawal, whereas patients with no improvement show no such REM sleep rebound. Induction of cytokine synthesis and fever has been shown to suppress REM sleep and improve mood in patients with major depression.12 Finally, some studies showed that increased REM activity (ie, more rapid eye movements  occurring  during  REM  sleep)  identify depressive patients who do not respond to psychother- apy and may warrant somatic treatment.13,14 The results of some studies cast doubt on the value of REM  suppression  as  a  predictor  of  antidepressant response. For instance, data suggest that effective long- term pharmacotherapy of recurrent major depression with imipramine15 or nortriptyline16 is associated with Copyright © 2004 LLS SAS. All rights reserved