TY  - JOUR
A1  - Kohl, S.
A1  - Gruendler, T. O. J.
A1  - Huys, D.
A1  - Sildatke, E.
A1  - Dembek, T. A.
A1  - Hellmich, M.
A1  - Vorderwulbecke, M.
A1  - Timmermann, L.
A1  - Ahmari, S. E.
A1  - Klosterkoetter, J.
A1  - Jessen, F.
A1  - Sturm, V.
A1  - Visser-Vandewalle, V.
A1  - Kuhn, J.
T1  - Effects of deep brain stimulation on prepulse inhibition in obsessive-compulsive disorder
JF  - Translational Psychiatry
N2  - Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200 ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr-OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation.
KW  - nucleus
KW  - serotonin
KW  - schizophrenia
KW  - dopamine
KW  - double-blind
KW  - psychiatric disorders
KW  - in vivo
KW  - acoustic startle
KW  - reflex
KW  - modulation
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-138300
VL  - 5
IS  - e675
ER  - 
TY  - JOUR
A1  - Klauke, Benedikt
A1  - Winter, Bernward
A1  - Gajewska, Agnes
A1  - Zwanzger, Peter
A1  - Reif, Andreas
A1  - Herrmann, Martin J.
A1  - Dlugos, Andrea
A1  - Warrings, Bodo
A1  - Jacob, Christian
A1  - Mühlberger, Andreas
A1  - Arolt, Volker
A1  - Pauli, Paul
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
T1  - Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma
JF  - PLoS One
N2  - The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.
KW  - COMT VAL(158)MET polymorphism
KW  - serotonin transporter gene
KW  - life events
KW  - community sample
KW  - acoustic startle
KW  - prepulse inhibition
KW  - panic disorder
KW  - caffeine-induced anxiety
KW  - fear-potentiated startle
KW  - posttraumatic-stress-disorder
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132184
VL  - 7
IS  - 6
ER  -