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Vigilance regulation and level of orexin at episodes of mania and episodes of depression

​Research staff

PD Dr. P. Schönknecht, S. Olbrich, C. Sander, E. Arendt, Dr. med. M. Strauß, Dr. M. Adamaszek, Prof. Dr. U. Hegerl

Cooperation partner


Patients with psychiatric disorders differ in the dynamic of their vigilance regulation. With the electroencephalogram (EEG) different EEG-vigilance-levels can be distinguished at the transition from active wakefulness to the beginning of light sleep. Under resting conditions with eyes closed, the spontaneous transition between these stages can be observed, whereas there are clear differences subject to diagnosis and states of disease: During depressive episodes, a stabile A-stadium without physiological declines in vigilance in the first 10 minutes of examination can often be observed in terms of a rigid regulation type. But patients with manic syndromes often show already after a few seconds a change (vigilance declines) in B-stadia in terms of a labile regulation, which is combined with the occurence of sleep spindles. The neurobiological mechanisms of this dysfunction in vigilance regulation are not clear until now.

Newer findings pointed to the influence of paracrin mechanisms on vigilance regulation, especially there is an influence of the hypothalamic hormones hypokretin 1 and hypokretin 2 (orexine). Orexin receptores are placed in the im limbic system, the frontobasal cortices and the medullary tegmentum.
"In narcolepsy, a disorder that is characterized by a lability of vigilance regulation, significant lower levels of orexin in liquor cerebrospinalis (CSF) compared to a control group were measured in a multi centric study. The relation between narkolepsy and orexine could be documented in animal models: in a labrador breed of dog with autosomal-recessive narcolepsy a deletion of the receptor gene for hypocretin 2 was developed. In an animal model of knock-out-mice for hypocretin 2 narkolepsy-related symptomes occured. If a role of orexin in the pathomechanism of depressive and manic syndromes could be detected, this would have far-ranging consequences for the development of new therapy strategies (f.e. psychostimulants in manic episodes).

Objective target

In the actual project the following hypotheses are to be tested:

  1. In patients with manic episodes compared to control groups, lower levels of orexin in CSF could be found. This hypothesis is based on the assumption that a reduction of the orexin-mediated aminergic activation leads to a dysfunctional regulation of the sleep-wake-cylce.
  2. In patients with depressive episodes compared to control groups, the levels of orexin in CSF are increased.
  3. The lability of vigilance regulation is associated with lower and the rigidity of vigilance regulation is associated with higher levels of orexin in CSF.
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