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Molecular and translational psychiatry - Projekte

Molecular Genetics of psychiatrically-relevant phenotypes

​In this project we analyze the molecular genetics of psychiatrically-relevant (endo)phenotypes. We utilize genome-wide association analyses, complemented with candidate gene approaches. The analyzed phenotypes comprise electroencephalographic data, such as evoked potentials and resting EEG, sleep-wake behavior, and psychometric scales.

Cooperation partners:
ENIGMA Group, Dr. Philippe Jawinski, Prof. Dr. Markus Scholz, Dr. Holger Kirsten

ESF-NWG 102P6 and FUNCTION 4 and 5 in the frame of the LIFE project

Recent selected publications:

Jawinski P, Kirsten H, Sander C, Spada J, Ulke C, Huang J, Burkhardt R, Scholz M, Hensch T & Hegerl U (2018). Human brain arousal in the resting state: A genome-wide association study. Molecular Psychiatry Apr 27 [Epub ahead of print].

Jawinski P, Tegelkamp S, Sander C, Hantzsch M, Huang J, Mauche N, Scholz M, Spada J, Ulke C, Burkhardt R, Reif A, Hegerl U & Hensch T (2016). Time to wake up: No impact of COMT Val158Met gene variation on circadian preferences, arousal regulation and sleep. Chronobiol Int 33: 893-905.

Spada J, Scholz M, Kirsten H, Hensch T, Horn K, Jawinski P, Ulke C, Burkhardt R, Wirkner K, Loeffler M, Hegerl U & Sander C (2016). Genome-wide association analysis of actigraphic sleep phenotypes in the LIFE Adult Study. J Sleep Res 25: 690-701.

Jawinski P, Sander C, Mauche N, Spada J, Huang J, Schmidt A, Hantzsch M, Burkhardt R, Scholz M, Hegerl U & Hensch T (2015). Brain Arousal Regulation in Carriers of Bipolar Disorder Risk Alleles. Neuropsychobiology 72: 65-73.

Personality and Psychopathology

​Fundamental temperamental dimensions provide a dimensional framework for both normal personality and psychopathology. In the current project, we analyze biological correlates of subclinical affectivity and affective personality traits, and how such personality traits are associated with psychopathology and psychiatrically-relevant behavior, such as sleep-wake behavior.

Recent selected publications:

Hensch T, Wozniak D, Spada J, Sander C, Ulke C, Wittekind D, Thiery J, Löffler M, Jawinski P, Hegerl U (in press). Vulnerability to Bipolar Disorder is linked to Sleep and Sleepiness. Translational Psychiatry

Hensch T & Strobel A (in Druck). Die differentiellpsychologische Perspektive in der Klinischen Psychologie. In HU Wittchen & J Hoyer (Hrsg.), Klinische Psychologie und Psychotherapie. Heidelberg: Springer.

CNS-arousal in psychiatric disorders

​Arousal fundamentally impacts normal and abnormal behavior and 'arousal and regulatory systems' has been implemented as one of the basic domains of the Research Domain Criteria (RDoC) project of the National Institute of Mental Health (NIMH). Symptoms of hypersomnia and insomnia are highly prevalent in the normal population, and in neurological and psychiatric disorders they are especially pronounced and occur across different disease categories, such as insomnia, affective disorders and ADHD. In these diseases, arousal dysregulation has been suggested to play a pathogenetic role (Geissler, Romanos, Hegerl & Hensch, 2014; Hegerl, Sander & Hensch, 2016).
In this project we analyze brain arousal and its temporal dynamics in psychiatric disorders, such as uni- and bipolar depression and (hypo)mania, and whether arousal and its regulation may predict treatment response.

Note: Special Issue "CNS-Arousal—Transdiagnostic Relevance and Therapeutic Implications" in Brain Sciences is now open for submission.

Recent selected publications:

Ulke C, Wittekind DA, Spada J, Franik K, Jawinski P, Hensch T, Hegerl U. Brain arousal regulation in SSRI-medicated patients with major depression. J Psychiatr  Res. 2019 Jan;108:34-39. doi: 10.1016/j.jpsychires.2018.11.003. Epub 2018 Nov 3.

Ulke C, Tenke CE, Kayser J, Sander C, Böttger D, Wong LYX, Alvarenga JE, Fava M, McGrath PJ, Deldin PJ, Mcinnis MG, Trivedi MH, Weissman MM, Pizzagalli DA, Hegerl U, Bruder GE. Resting EEG Measures of Brain Arousal in a Multisite Study of Major Depression. Clin EEG Neurosci. 2019 Jan;50(1):3-12.

Ulke C, Sander C, Jawinski P, Mauche N, Huang J, Spada J, Wittekind D, Mergl R, Luck T, Riedel-Heller S, Hensch T, Hegerl U. Sleep disturbances and upregulation of brain arousal during daytime in depressed versus non-depressed elderly subjects. World J Biol Psychiatry. 2017 Dec;18(8):633-640.

Wittekind DA, Spada J, Gross A, Hensch T, Jawinski P, Ulke C, Sander C, Hegerl U. Early report on brain arousal regulation in manic vs depressive episodes in bipolar disorder. Bipolar Disord. 2016 Sep;18(6):502-510.

Hegerl U, Sander C, Hensch T (2016). Arousal regulation in affective disorders. In: T Frodl (Hrsg.) Systems Neuroscience in Depression (p. 341 - 370) Elsevier Verlag.

Geissler J, Romanos M, Hegerl U & Hensch T (2014). Hyperactivity and sensation seeking as autoregulatory attempts to stabilize brain arousal in ADHD and mania? ADHD Attention Deficit and Hyperactivity Disorders 6, 159-173.

Hegerl U & Hensch T (2014). The vigilance regulation model of affective disorders and ADHD. Neuroscience & Biobehavioral Reviews 44, 45-57.

Validity and reliability of the VIGALL

​Whereas earlier versions of the Vigilance Algorithm Leipzig (VIGALL) have already been validated via simultaneous EEG-PET and EEG-MRI as well as autonomic parameters, the current project contributes data to the recent algorithm's reliability and validity. This is done applying arousal-sensitive evoked potentials, performance (such as reaction times), and indicators of autonomic arousal (heart rate and skin conductance level). In addition, associations of arousal as assessed by VIGALL with subjective ratings, such as habitual sleepiness, are analyzed.
Recent selected publications:
Huang J and Hensch T, (equally contributing first authors), Ulke C, Sander C, Spada J, Jawinski P & Hegerl U (2017). Evoked potentials and behavioral performance during different states of brain arousal. BMC Neurosci 18: 21.

Jawinski P and Kittel J, (equally contributing first authors), Sander C, Huang J, Spada J, Ulke C, Wirkner K, Hensch T & Hegerl U (2017). Recorded and Reported Sleepiness: The Association Between Brain Arousal in Resting State and Subjective Daytime Sleepiness. Sleep 40.

Ulke C and Huang J (equally contributing first authors), Schwabedal JTC, Surova G, Mergl R & Hensch T (2017). Coupling and dynamics of cortical and autonomic signals are linked to central inhibition during the wake-sleep transition. Scientific Reports 7: 11804.

Huang J, Sander C, Jawinski P, Ulke C, Spada J, Hegerl U & Hensch T (2015). Test-retest reliability of brain arousal regulation as assessed with VIGALL 2.0. Neuropsychiatric Electrophysiology 1: 1-13.

Micro- & macrostructural brain changes in mood disorders

Macrostructure, tissue integrity and connectivity of the hypothalamus in mood disorders

Among the neuronal networks structurally and functionally afflicted in uni- and bipolar disorders the limbic-prefrontal network deserves special interest. One of its components, the hypothalamus not only relates the somatic symptomatology characterizing depressive episodes (e. g. insomnia and loss of appetite and libido). It also regulates the hypothalamus-pituitary-adrenal axis which represents a biological structure by which stress may cause pathological brain changes. The hypothalamus is therefore potentially crucial to unraveling the structural and functional changes found in mood disorders. Hard to capture with regular imaging techniques little is known about its in vivo structure, though. Drawing on the improvements of high-field MRI and diffusion-weighted MRI we are now able to investigate its macro- and microstructure and its network connections.

Cooperation partners:

Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Department of Neuropsychology A. Anwander, Department of Neurophysics S. Geyer, R. Trampel

Selected Publications: 

Schindler S, Schmidt L, Stroske M, Storch M, Anwander A, Trampel R, Strauss M, Hegerl U, Geyer S & Schonknecht P (2019) Hypothalamus enlargement in mood disorders. Acta Psychiatr Scand 139: 56-67.

Wolff J, Schindler S, Lucas C, Binninger AS, Weinrich L, Schreiber J, Hegerl U, Moller HE, Leitzke M, Geyer S & Schonknecht P (2018) A semi-automated algorithm for hypothalamus volumetry in 3 Tesla magnetic resonance images. Psychiatry Res Neuroimaging 277: 45-51.

Schindler S, Schreiber J, Bazin PL, Trampel R, Anwander A, Geyer S & Schonknecht P (2017) Intensity standardisation of 7T MR images for intensity-based segmentation of the human hypothalamus. PLoS ONE 12: e0173344.

Schmidt FM, Schindler S, Adamidis M, Strauss M, Trankner A, Trampel R, Walter M, Hegerl U, Turner R, Geyer S & Schonknecht P (2017) Habenula volume increases with disease severity in unmedicated major depressive disorder as revealed by 7T MRI. Eur Arch Psychiatry Clin Neurosci 267: 107-115.

Schindler S, Schonknecht P, Schmidt L, Anwander A, Strauss M, Trampel R, Bazin PL, Moller HE, Hegerl U, Turner R & Geyer S (2013) Development and evaluation of an algorithm for the computer-assisted segmentation of the human hypothalamus on 7-Tesla magnetic resonance images. PLoS ONE 8: e66394.

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