Ever since Vogel's studies in the 1970s it has been known that acute sleep deprivation, particularly deprivation of REM sleep, produces a positive effect on people with . The extremely depressed person feels much better if he goes without REM sleep for a night or two. The suicidally depressed patient may forget the idea of suicide for a few hours or days if he is deprived of REM for a night or two. These basic observations have been confirmed many times since the 1970s (see the reading list below) but the question as to how REM deprivation helps depression has been left unanswered.

Despite the dramatic beneficial effects on serious depression we still have no idea as to why REM deprivation alleviates, at least temporarily, major depression. This is a very surprising fact. You would think that any clue or lead on what kinds of treatment work for major depression would be followed up on with major pushes in the research arena backed up by major funding streams from the National Institutes of Health. But the voices of depressed people, apparently, are not as loud as the voices of other health-related interest groups so funding for depression studies has never been adequate to the scale fo the problem.

A recent study, however, has managed to throw some fascinating light on the relations between acute sleep deprivation and alleviation of depression.



Gujar N, Yoo SS, Hu P, and Walker MP. of the Sleep and Neuroimaging Laboratory, Department of Psychology and Helen Wills Institute, University of California, Berkeley, Berkeley, California have recently reported (Gujar et al., Sleep deprivation amplifies reactivity of brain reward networks, biasing the appraisal of positive emotional experiences. J Neurosci. 2011 Mar 23;31(12):4466-74) that sleep deprivation amplifies reactivity throughout human mesolimbic reward brain networks in response to pleasure-evoking stimuli. In addition, this amplified reactivity was associated with a biased increase in the number of emotional stimuli judged as pleasant in the sleep-deprived group. Interestingly the degree of toward labeling incoming stimuli ‘positive' when in the sleep deprived state was correlated with activity in mesolimbic regions. In short, it appears that acute sleep deprivation increases reactivity in reward networks of the brain. The older neurobiological literature on REM deprivation in animals suggested that motivational and drive related states were heightened during after REM deprivation as animals seemed much more attuned to reinforcing and pleasureable stimuli. These facts led the older researchers to suggest that the normal function of REM was to dampen down pleasureable or motivational states or that REM functioned to re-tune catecholaminergic synapses throughout the brain. In any case both the older literature and the newer data suggest that REM specializes in handling negative motivational and appetitive states and thus it should not be surprising that REM deprivation has a potent if temporary effect. Nor should it be surprizing that REM indices are virtually always elevated in major depression. It seems that major depression is fueled at least in part by a kind of dis-inhibition of REM physiology.

Relevant articles



Agargun, M.Y., & Cartwright, R. (2003). REM sleep, dream variables and in depressed patients. Psychiatry Research, 119(1-2), 33-39.

Agargun, M. Y., Cilli, A. S., Kara, H., Tarhan, N., Kincir, F., & Oz, H. (1998). Repetitive frightening dreams and suicidal behavior in patients with major depression. Comprehensive Psychiatry, 39, 198-202.

Agargun , M. Y., Besiroglu, L., Cilli, A. S., Gulec, M., Aydin, A., Inci, R., et al. (2007). , suicide attempts, and melancholic features in patients with unipolar major depression. Journal of Affective Disorders, 98, 267-270.

American Association. (2000). (4th ed.). Washington, D.C.: American Psychiatric Association Press.

Antrobus, J.S. (1983). REM and NREM sleep reports: Comparison of word frequencies by cognitive classes. Psychophysiology, 20, 562-568.

Armitage, R. (2007). Sleep and circadian rhythms in mood disorders. Acta Psychiatrica Scandinavica, 115(s433), 104-115.

Balkin, T. J., Braun, A. R., Wesensten, N. J., Varga, P. B., Carson, R. E., Belenky, ., et al. (1999). Bi-directional changes in regional cerebral blood flow across the first 20 min of wakefulness. Sleep Research Online, 2(Suppl. 1), 6.

Baxter, L. R., Schwartz, J. M., Phelps, M. E., Mazziota, J. C., Guze, B. H., Selin, C. E., et al. (1989). Reduction of prefrontal cortex glucose metabolism common to three types of depression. Archives of General Psychiatry, 46, 243.

Borbély, A. A., & Wirz-Justice, A. (1982) Sleep, sleep deprivation and depression, a hypothesis derived from model of sleep regulation. Human Neurobiology, 1, 205-210.

Born, J., & Wagner, U. (2004). consolidation during sleep: Role of cortisol feedback. Annals of the New York Academy of Sciences, 1032, 198-201.

Botvinick , M. M. (2008). Hierarchical models of behavior and prefrontal function. Trends in Cognitive Sciences, 12, 298-311.

Brabbins, C. J., Dewey, M. E., Copeland, J. R. M., Davidson, I. A., McWilliam, C., Saunders, P., et al. (1993). in the elderly: Prevalence, differences and relationships with morbidity and mortality. International Journal of Geriatric Psychiatry, 8, 473-480.

Bradley, B.P., Mogg, K. & Williams, R. (1995). Implicit and explicit memory for emotion-congruent information in depression and . Behaviour Research and , 33, 755-770.

Braun, A. R., Balkin, T. J., Wesenstein, N. J., Varga, M., Baldwin, P., Selbie, S., et al. (1997). Regional cerebral blood flow throughout the sleep-wake cycle. Brain, 120, 1173-1197.

Brody, A. L., Saxena, S., Silverman, D. H. S., Alborzian, S., Fairbanks, L. A., Maidment, K. M., et al. (1999). Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine. Psychiatry Research: Neuroimaging, 91,127-139.

Cantero, J. L., Atienza, M., Stickgold, R., Kahana, M. J., Madsen, J. R., & Kocsis, B. (2003). Sleep-dependent theta oscillations in the human hippocampus and neocortex. Journal of Neuroscience, 23, 10897-10903.

Carragher, N., Adamson, G., Bunting, B., & McCann, S. (2009). Subtypes of depression in a nationally representative sample. Journal of Affective Disorders, 113, 88-99.

Cartwright, R. (1992). Masochism in and its relation to depression. Dreaming, 2, 79- 84.

Cartwright, R., Luten, A., Young, M., Mercer, P., & Bears, M. (1998) Role of REM sleep and dream affect in overnight mood regulation: A study of normal volunteers. Psychiatry Research, 81, 1-8.

Crawford, J. R., & Henry, J. D. (2004). The positive and negative affect schedule (PANAS): Construct validity, measurement properties and normative data in a large non-clinical sample. British Journal of Clinical Psychology, 43(Pt 3), 245-265.

Dang-Vu, T. T., Desseilles, M., Laureys, S., Degueldre, C., Perrin, F., Phillips, C., et al. (2005). Cerebral correlates of delta waves during non-REM sleep revisited. NeuroImage, 28, 14-21.

Davidson, R. J. (2002). Anxiety and affective style: Role of prefrontal cortex and amygdala. Biological Psychiatry,51, 29-37.

Dekker, J., Koelen, J. A., Peen, J., Schoevers, R. A., & Gijsbers-van Wijk, C. (2007). Gender differences in clinical features of depressed outpatients: Preliminary evidence for subtyping of depression? Women and Health, 46(4), 19-38.

Delorme, A., & Makeig, S. (2004). EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics. Journal of Neuroscience Methods, 134, 9-21.

DeRubeis, R. J., Siegle, G. J., & Hollon, S. D. (2008). Cognitive therapy versus medication for depression: Treatment outcomes and neural mechanisms. Nature Reviews Neuroscience , 9, 788-796.

Dew, M. A., Hoch, C. C., Buysse, D. J., Monk, T. H., Begley, A. E., Houck, P. R., et al. (2003). Healthy older adults' sleep predicts all-cause mortality at 4 to 19 years of follow-up. Psychosomatic Medicine, 65(1), 63-73.

Domhoff, G.W. (1996). Finding meaning in dreams: A quantitative approach. New York: Plenum Press.

Domhoff, G.W. (2003). The scientific study of dreams: Neural networks, cognitive development, and content analysis. Washington D.C.: American Psychological Association.

Drevets, W. C. (2007). Orbitofrontal cortex function and structure in depression. Annuals of the New York Academy of Sciences,1121,499-527.

Drevets, W. C., Price, J. L., Bardgett, M. E., Reich, T., Todd, R. D., & Raichle, M. E. (2002). Glucose metabolism in the amygdala in depression: Relationship to diagnostic subtype and plasma cortisol levels. Pharmacology Biology & Behavior, 71, 431-447.

Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., et al. (1997). Subgenual prefrontal cortex abnormalities in mood disorders. Nature, 386, 824-827.

Drevets, W. C., Marcus, E., & Raichle, M D. (1992). Neuroanatomical circuits in depression: Implications for treatment mechanisms. Bulletin, 28, 261-274.

Ebert, D., Feistel, H., & Barocka, A. (1991). Effects of sleep deprivation on the limbic system and the frontal lobes in affective disorders: A study with Tc-99m-HMPAO SPECT. Psychiatry Reasearch: NeuroImaging, 40, 247-251.

Ebert, D., Feistel, H., Barocka, A. & Kaschka, W. (1994a). Increased limbic blood flow and total sleep deprivation in major depression with melancholia, Psychiatry Research: Neuroimaging, 55, 101-109.

Ebert, D., Feistel, H., Kaschka, W., Barocka, A, & Pirner, A. (1994b). Single photon emission computerized tomography assessment of cerebral D2 receptor blockade in depression before and after sleep deprivation--Preliminary results, Biological Psychiatry, 35, 880-885.

Ellman, S. J., Spielman, A. J., Luck, D., Steiner, S. S., & Halperin, R. (1991). REM deprivation: A review. In S. L. Ellman & J. S. Antrobus (Eds.), The mind in sleep: Psychology and psychophysiology (pp. 327-376). New York: John Wiley.

Giedke, H., & Schwarzler, F. (2002). Therapeutic use of sleep deprivation in depression. Sleep Medicine Reviews, 6, 361-377.

Giles, D. E., Roffwarg, H. P., Schlesser, M. A., & Rush, A. J. (1986). Which endogenous depressive symptoms relate to REM latency reduction? Biological Psychiatry, 21, 473-482.

Gillin. J. C., Buchsbaum, M., Wu, J., Clark, C. & Bunney, W. (2001). Sleep deprivations as a model experimental antidepressant treatment: Findings from function brain imaging. Depression and Anxiety, 14, 37-49.

Goodwin, G. M., Austin, M-. P., Dougall, N., Ross, M., Murray, C., O'Carroll, R. E., et al. (1993). State changes in brain activity shown by the uptake of 99mTc-Exametazime with single photon emission tomography in major depression before and after treatment. Journal of Affective Disorders, 29, 243-253.

Gottesman, C., & Gottesman, I. (2007). The neurobiological characteristics of (REM) sleep are candidate endophenotypes of depression, , mental retardation and . Progress in Neurobiology, 81,237-250.

Hu, P., Stylos-Allan, M., & Walker, M. P. (2006). Sleep facilitates consolidation of emotionally arousing declarative memory. Psychological Science, 10, 891-898.

Kripke, D.F. (2003). Sleep and mortality. Psychosom Medicine, 65(1), 74.

Kupfer, D. J., & Foster, G. (1972). Interval between onset of sleep and rapid-eye-movement sleep as an indicator of depression, Lancet, 2, 684-686.

Maquet, P., & Franck, G. (1997). REM sleep and amygdala. Molecular Psychiatry, 2(3), 195-196.

Maquet, P., Peters, J. M., Aerts, J., Delfiore, G., Degueldre, C., Luxen, A., & Franck, G. (1996). Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature, 383, 163-166.

Maquet, P., & Phillips, C. (1999). Rapid eye movement sleep: Cerebral metabolism to functional brain mapping. In S. Inoue (Ed.), Rapid eye movement sleep (pp. 276-285). New York: Marcel Dekker.

Maquet, P., Ruby, P., Maudoux, A., Albouy, G., Sterpenich, V., Dang-Vu, T., et al. (2005). Human during REM sleep and the activity profile within frontal and parietal cortices: A reappraisal of functional neuroimaging data. Progress in Brain Research, 150, 219-227.

Nishida, M., Pearsall, J. Buckner, R. L., & Walker, M. P. (2008). REM sleep, prefrontal theta, and the consolidation of human emotional memory. Cerebral Cortex.

Nofzinger, E. A. (2005). Neuroimaging and sleep medicine. Sleep Medicine Reviews, 9, 157-172.

Nofzinger, E. A. (2008). Functional neuroimaging of sleep disorders. Current Pharmaceutical Design, 14(32), 3417-3429.

Nofzinger, E. A., Berman, S., Fasiczka, A., Miewald, J. M., Meltzer, C. C., Price, J. C., et al. (2001). Effects of bupropion SR on anterior paralimbic function during waking and REM sleep in depression: Preliminary findings using. Psychiatry Research, 106(2), 95-111.

Nofzinger, E. A., Buysse, D. J., Germain, A., Carter, C., Luna, B., Price, J. C., et al. (2004). Increased activation of anterior paralimbic and executive cortex from waking to rapid eye movement sleep in depression. Archives of General Psychiatry, 61(7),695-702.

Nofzinger, E. A., Mintun, M. A., Wiseman, M. B., Kupfer, D. J., & Moore, R.Y. (1997). Forebrain activation in REM sleep: An FDG PET study. Brain Research, 770, 192-201.

Nofzinger, E. A., Nichols, T. E., Meltzer, C. C., Price, J., Steppe, D. A., Miewald, J. M., et al. (1999). Changes in forebrain function from waking to REM sleep in depression preliminary analyses of (18F) FDG PET studies. Psychiatry Research, 91(2), 59-78.

Tsuno, N, Besset, A., & Ritchie, K. (2005). Sleep and depression. Journal of Clinical Psychiatry, 66, 1254-1269.

Van Moffaert, M. M. M. P. (1994). Sleep disorders and depression: the ‘chicken and egg' situation. Journal of Psycosomatic Research, 38(Suppl. 1), 9-13.

Vogel, G. W. (1975). A review of REM sleep deprivation. Archives of General Psychiatry, 32, 749-761.

Vogel, G. W., Thurmond, A., Gibbons, P., Sloan, K., & Walker, M. (1975). REM sleep reduction effects on depression syndromes. Archives of General Psychiatry, 32, 765-777.

Volk, S. A., Kaerndler, S. H., Hertel, A., Maul, F. D., Manoocheri, R., Weber, R., et al. (1997). Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow? Psychiatry Research: NeuroImaging, 75(2), 67-74.

Volk, S., A., Kaendler, S. H., Weber, R., Georgi, K., Maul, R. Hertel, A., et al. (1992). Evaluation of the effect of total sleep deprivation on cerebral blood flow using single photon emission computerized tomography. Acta Neurologica Scandinavica, 86, 473-483.

Winokur, A., Gary, K. A., Rodner, S., Rae-Red, C., Fernando, A. T., & Szuba, M. P. (2001). Depression, sleep physiology, and antidepressant drugs. Depression and Anxiety, 14(1), 19-28.

Wu, J. C., Buchsbaum, M., & Bunney, W. E. (2001). Clinical neurochemical implications of sleep deprivation's effects on the anterior cingulate of depressed responders. Neuropharmacology, 25, S74-S78.

Wu, J. C., Buchsbaum, M. S., Gillin, J. C., Tang, C., Cadwell, S., Wiegand, M., et al. (1999). Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex. American Journal of Psychiatry, 156, 1149-1158.

Wu, J. C., Gillin, G. C., Buchsbaum, M. S., Hershey, R. & Johnson, J. C. (1992). Effects of sleep deprivation on brain metabolism of depressed patients. American Journal of Psychiatry, 149, 538-543.

Wu, J. C., Gillin, J. C., Buchsbaum, M. S., Schachat, C., Darnall, L. A., Keator, D. B., et al. (2008). Sleep deprivation PET correlations of Hamilton symptom improvement ratings with changes in relative glucose metabolism in patients with depression. Journal of Affective Disorders, 107, 181-186.