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
Background
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:
- 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.
- In patients with depressive episodes compared to control groups, the levels
of orexin in CSF are increased.
- The lability of vigilance regulation is associated with lower and the
rigidity of vigilance regulation is associated with higher levels of orexin in
CSF.
