Neuroscience Letters 483 (2010) 20–22 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Cerebrospinal fluid hypocretin-1 (orexin A) levels in mania compared to unipolar depression and healthy controls Frank M. Schmidt a , Matthias Brügel b , Jürgen Kratzsch b , Maria Strauß a , Christian Sander a , Petra Baum c , Joachim Thiery b , Ulrich Hegerl a , Peter Schönknecht a,∗ a Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany b Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Germany c Department of Neurology, University Hospital Leipzig, Germany article info Article history: Received 18 June 2010 Received in revised form 14 July 2010 Accepted 16 July 2010 Keywords: Hypocretin Mania Depression Vigilance Narcolepsy Locomotor activity abstract Background: Impairment of sleep–wake cycles and circadian rhythm are found in human narcolepsy which is characterized by deficiency of hypocretin (hcrt) or its receptors. A disturbed electroencephalog- raphy (EEG) based vigilance regulation is also found in affective disorders such as major depressive disorder (MDD) and mania. For the first time, in the present study hcrt levels were investigated in patients with a manic episode and compared with age-matched patients with MDD and controls. Meth- ods: 15 subjects were enrolled in the study after admission to hospital: 5 manic (mean YMRS 15.6 ± 2.9) and 5 age-matched patients with MDD (mean HDRS 11.6 ± 8.0), and 5 age-matched controls with- out any neurological or psychiatric disorder. Cerebrospinal fluid (CSF) hcrt levels were measured in all three groups using a fluorescence immunoassay (FIA). Results: Mean hcrt-1 level in manic patients (77.3 ± 20.7 pg/ml) did not differ significantly compared to patients with MDD (75.6 ± 15.7 pg/ml MDD) or controls (74.9 ± 19.3 pg/ml). Hcrt levels and severity of disease did not show a significant association. Conclusion: In the present study, for the first time hcrt-1 levels in manic patients were investigated but did not reveal significant differences neither compared to age-matched patients with MDD nor healthy controls without any psychiatric or neurological disorder. © 2010 Elsevier Ireland Ltd. All rights reserved. During the transition from alertness to sleep the brain under- goes different global functional states termed vigilance [8].A disturbed electroencephalography (EEG) based vigilance regula- tion can be found both in human narcolepsy and in affective disorders such as major depressive disorder (MDD) and mania. In those states, a reduction of total sleep duration and subjective sleep need, curtailed sleep, sleep latency reduction, shortened REM sleep latency, abrupt transitions from waking to relatively deep sleep are observed [21,25,9], and patients show untimely declines of vigi- lance stages in the early course of an EEG under resting-conditions with a subgroup presenting characteristics of micro-sleep in the first 19 s [23,24]. In narcolepsy, however, a loss of hypocretins (hcrt’s) 1 and 2 (orexin-A and B) or its receptors could be demonstrated [19,12,16]. Ancillary to the suprachiasmatic nucleus, site of circadian clock and rhythmicity [14,20], the hcrt’s work as mediators between activating and sleep-promoting regions. Loss of this regulating unit results in a flip–flop-pattern with direct contralateral inhi- ∗ Corresponding author. Tel.: +49 341 9724506; fax: +49 341 9724569. E-mail address: Peter.Schoenknecht@medizin.uni-leipzig.de (P. Schönknecht). bition of the activating aminergic and histaminergic site and the sleep-promoting ventrolateral preoptic region. This results in sudden switches between states of vigilance [10]. There- fore, hcrt’s are determined to be crucial for arousal, opposition of the sleep drive, sleep–wake transitions and cortical activity [10,18,15]. They also play a key role in sustained attention for the regulation of homeostasis [5], reward seeking and addic- tion [7,1] and induce an increase in locomotor activity whereas the release of hcrt itself can be triggered by locomotor activity [13,11,26,17]. Up to now, no study has examined hcrt’s in manic patients. In depression, only few but conflicting studies have examined lev- els of hcrt-1 descriptively in disorder of the spectrum of affective disorders, either lacking a homogenous group of MDD or healthy controls. In a sample of suicide attempters, Brundin et al. [2] found significantly reduced hcrt-1 levels in patients with major depressive disorder (MDD) compared to dysthymia and adjust- ment disorder. Levels of hcrt-1 were increased in suicidal patients with different psychiatric diagnoses in follow-up determination 1 year later [3]. Though sharing common pathogenetic features such as sleep disturbances and drop of EEG based vigilance states, CSF hcrt’s levels have never been investigated in patients with mania, 0304-3940/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2010.07.038