Sleep deprivation in depression.

Sleep deprivation (SD) is a powerful antidepressant treatment that shows antidepressant responses within hours in 40-60% of depressed patients. In more than 80% of responders to SD, a relapse into depression occurred after the recovery night. In addition, it serves as an excellent tool to examine the neurobiological disturbance of depression and may profoundly contribute to the development of new specific and more rapidly acting antidepressants. The reason why SD works and relapses occur is still unclear. A key to solve this problem is to include the current knowledge about the neurobiological disturbance of depression in research, with a focus on neurobiological aspects of sleep and SD (sleep EEG, neuroendocrinology, neurochemistry and chronobiology). Based on findings from these different areas, different strategies to stabilize the antidepressant effect of SD have been applied. This article provides an overview of clinical and neurobiological responses related to SD in depression.

Pain sensitivity in major depression and its relationship to central serotoninergic function as reflected by the neuroendocrine response to clomipramine.

Several studies reported a decreased pain sensitivity in patients with depression, but the underlying neurobiological mechanisms of this phenomenon are unclear. While there is extensive evidence that the serotoninergic system plays a key role in pain modulation, especially in pain inhibitory mechanisms via descending pathways, as well as in the pathophysiology of depression, no study so far has examined its potential relevance in mediating the alteration of pain processing. The present study addresses the question of whether indices of serotoninergic dysfunction, as investigated by a neuroendrocine challenge paradigm, are related to pain sensitivity. Nineteen drug-free inpatients with unipolar major depression underwent a neuroendocrine challenge test by measuring cortisol and prolactin in response to intravenously administered clomipramine (12.5mg). Heat/cold pain thresholds, warmth/cold detection thresholds, measures of current pain complaints and mood were assessed the day before and three day after challenge procedure. When patients were classified in subgroups based on a median split of their cortisol response values, the low-responsive group showed significantly elevated heat pain thresholds and nearly significantly elevated cold pain thresholds compared to the high-responsive group. No such group differences were found with regard to somatosensory thresholds, measures of pain complaints and mood. Subgrouping on the basis of prolactin responsiveness did not reveal significant differences in any parameter. In summary, a decreased pain sensitivity was demonstrated in patients characterized by a reduced neuroendocrine responsiveness to clomipramine, suggesting an involvement of serotoninergic dysfunction underlying altered pain perception in depression.

Mid-term effects of serial sleep deprivation therapy implemented in cognitive-behavioral treatment on the neuroendocrine response to clomipramine in patients with major depression.

While data dealing with neurobiological effects of sleep deprivation (SD) are mainly restricted to the acute effects of a single night, only few studies have investigated mid-term effects after repeated SD. We therefore examined the clinical and hormonal characteristics of depressive patients before and after serial SD to determine potential sustained effects, focusing especially on serotoninergic functions. One tool to investigate serotoninergic dysfunction in depression is the use of serotoninergic agents to stimulate hormonal secretion, which is assumed to normalize during a clinically effective therapy. Eighteen drug-free inpatients with unipolar major depression received cognitive-behavioral treatment for three weeks and - according to a randomized control design - additional SD therapy (six nights of total SD within three weeks, separated by nights of recovery sleep) or no SD therapy (control group). Serotoninergic function was assessed by measuring cortisol and prolactin in response to intravenously administered clomipramine (12.5mg) before and after the treatment period. The post-treatment challenge test was performed three days after the last SD night. Apart from of a transient overnight improvement of mood induced by SD, both groups showed a comparable clinical course during the three-week treatment period. Compared to the control group, the SD-treated patients exhibited significantly decreased pre-stimulation cortisol levels and significantly increased cortisol responses to clomipramine, whereas no treatment effects were observed for prolactin. In conclusion, our findings suggest that the mid-term effects of serial SD therapy lead to a normalization of serotoninergic dysfunction, although an obvious impact on clinical symptoms was not detected.

Effects of total sleep deprivation in major depression: overnight improvement of mood is accompanied by increased pain sensitivity and augmented pain complaints.

OBJECTIVE: Major depressive disorder (MDD) is associated with more pain complaints and an altered pain perception. Studies regarding the longitudinal relationship between depressive symptoms and pain processing have rarely been performed and have produced inconsistent results. To clarify how short-term alleviation of depressive mood is linked to changes in pain processing, the effect of sleep deprivation (SD) on pain and somatosensory thresholds, pain complaints, and mood was investigated in MDD patients. METHODS: Nineteen drug-free inpatients with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, diagnosis of MDD were investigated for 3 weeks. All patients received cognitive-behavioral therapy and were randomized to obtain either additional SD therapy (six nights of total SD, separated by recovery sleep) or no SD therapy (control group). Heat/cold pain thresholds, warmth/cold thresholds, measures of current pain complaints, and mood were assessed the evening before and the morning after SD as well as before and after a normal night sleep in the control group. Long-term changes of depressive symptomatology were assessed by weekly mood ratings. RESULTS: Both treatment groups improved markedly in mood over the 3-week treatment period. SD regularly induced a moderate but statistically nonsignificant overnight improvement of mood, which was abolished by recovery sleep. Compared with the control condition, SD significantly decreased heat pain thresholds and nearly significantly cold pain thresholds; SD significantly augmented pain complaints the next morning. No such effects were observed for somatosensory thresholds. CONCLUSIONS: SD induced differential short-term effects on mood and pain, with the patients being less depressed but more pain vulnerable.