TY  - JOUR
A1  - Ziegler, Georg C.
A1  - Ehlis, Ann-Christine
A1  - Weber, Heike
A1  - Vitale, Maria Rosaria
A1  - Zöller, Johanna E. M.
A1  - Ku, Hsing-Ping
A1  - Schiele, Miriam A.
A1  - Kürbitz, Laura I.
A1  - Romanos, Marcel
A1  - Pauli, Paul
A1  - Kalisch, Raffael
A1  - Zwanzger, Peter
A1  - Domschke, Katharina
A1  - Fallgatter, Andreas J.
A1  - Reif, Andreas
A1  - Lesch, Klaus-Peter
T1  - A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD
JF  - Genes
N2  - The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
KW  - ADHD
KW  - CDH13
KW  - neurodevelopment
KW  - executive functions
KW  - working memory
KW  - Big Five
KW  - agreeableness
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245220
SN  - 2073-4425
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Kuhn, Manuel
A1  - Scharfenort, Robert
A1  - Schümann, Dirk
A1  - Schiele, Miriam A.
A1  - Münsterkötter, Anna L.
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
A1  - Haaker, Jan
A1  - Kalisch, Raffael
A1  - Pauli, Paul
A1  - Reif, Andreas
A1  - Romanos, Marcel
A1  - Zwanzger, Peter
A1  - Lonsdorf, Tina B.
T1  - Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament
JF  - Social Cognitive and Affective Neuroscience
N2  - Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.
KW  - VBM
KW  - childhood maltreatment
KW  - adversity
KW  - stressful life events
KW  - mismatch
KW  - allostatic load
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189645
VL  - 11
IS  - 4
ER  - 
TY  - JOUR
A1  - Gottschalk, Michael G.
A1  - Richter, Jan
A1  - Ziegler, Christiane
A1  - Schiele, Miriam A.
A1  - Mann, Julia
A1  - Geiger, Maximilian J.
A1  - Schartner, Christoph
A1  - Homola, György A.
A1  - Alpers, Georg W.
A1  - Büchel, Christian
A1  - Fehm, Lydia
A1  - Fydrich, Thomas
A1  - Gerlach, Alexander L.
A1  - Gloster, Andrew T.
A1  - Helbig-Lang, Sylvia
A1  - Kalisch, Raffael
A1  - Kircher, Tilo
A1  - Lang, Thomas
A1  - Lonsdorf, Tina B.
A1  - Pané-Farré, Christiane A.
A1  - Ströhle, Andreas
A1  - Weber, Heike
A1  - Zwanzger, Peter
A1  - Arolt, Volker
A1  - Romanos, Marcel
A1  - Wittchen, Hans-Ulrich
A1  - Hamm, Alfons
A1  - Pauli, Paul
A1  - Reif, Andreas
A1  - Deckert, Jürgen
A1  - Neufang, Susanne
A1  - Höfler, Michael
A1  - Domschke, Katharina
T1  - Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes
JF  - Translational Psychiatry
N2  - Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.
KW  - human behaviour
KW  - molecular neuroscience
KW  - personalized medicine
KW  - predictive markers
KW  - psychiatric disorders
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227479
VL  - 9
ER  -