Central Institute of Mental Health

Mannheim, Germany

Central Institute of Mental Health

Mannheim, Germany
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Meyer-Lindenberg A.,Central Institute of Mental Health
NeuroImage | Year: 2012

I provide a brief and subjective view of where the field of imaging genetics is heading. After recapitulating early debates between imagers and geneticists revolving around the topic of candidate gene studies, I point out the importance of genome-wide significant, rare and common variants. I propose that the next stages will be dominated by large-scale multi-site studies that will enable the examination of rare-high penetrance variants and methodological developments that will be required to properly assess the effects of pleiotropy, epistasis, and gene-by environment interactions. The incorporation of new sources of biological information such as whole genome sequencing, proteomic, lipidomic and expression profiles and cellular models derived from induced pluripotent stem cells opens new vistas for imaging genetics in a translational enterprise that is ultimately hoped to improve and create therapeutic options for psychiatric disorders. © 2011 Elsevier Inc.

Kanske P.,Max Planck Institute for Human Cognitive and Brain Sciences | Kanske P.,Central Institute of Mental Health | Kotz S.A.,Max Planck Institute for Human Cognitive and Brain Sciences
Cerebral Cortex | Year: 2011

It has been hypothesized that processing of conflict is facilitated by emotion. Emotional stimuli signal significance in a situation. Thus, when an emotional stimulus is task relevant, more resources may be devoted to conflict processing to reduce the time that an organism is unable to act. In the present electroencephalography and functional magnetic resonance imaging (fMRI) studies, we employed a conflict task and manipulated the emotional content and prosody of auditory target stimuli. In line with our hypothesis, reaction times revealed faster conflict resolution for emotional stimuli. Early stages of event-related potential conflict processing were modulated by emotion as indexed in an enhanced frontocentral negativity at 420 ms. FMRI yielded conflict activation in the dorsal anterior cingulate cortex (dACC), a crucial part of the executive control network. The right ventral ACC (vACC) was activated for conflict processing in emotional stimuli, suggesting that it is additionally activated for conflict processing in emotional stimuli. The amygdala was also activated by emotion. Furthermore, emotion increased functional connectivity between the vACC and activity in the amygdala and the dACC. The results support the hypothesis that emotion speeds up conflict processing and suggest a new role for the vACC in processing conflict in particularly significant situations signaled by emotion. © 2011 The Author. Published by Oxford University Press. All rights reserved.

Trull T.J.,University of Missouri | Ebner-Priemer U.,Karlsruhe Institute of Technology | Ebner-Priemer U.,Central Institute of Mental Health
Annual Review of Clinical Psychology | Year: 2013

Ambulatory assessment (AA) covers a wide range of assessment methods to study people in their natural environment, including self-report, observational, and biological/physiological/behavioral. AA methods minimize retrospective biases while gathering ecologically valid data from patients' everyday life in real time or near real time. Here, we report on the major characteristics of AA, and we provide examples of applications of AA in clinical psychology (a) to investigate mechanisms and dynamics of symptoms, (b) to predict the future recurrence or onset of symptoms, (c) to monitor treatment effects, (d) to predict treatment success, (e) to prevent relapse, and (f) as interventions. In addition, we present and discuss the most pressing and compelling future AA applications: technological developments (the smartphone), improved ecological validity of laboratory results by combined lab-field studies, and investigating gene-environment interactions. We conclude with a discussion of acceptability, compliance, privacy, and ethical issues. Copyright © 2013 by Annual Reviews.

Zink C.F.,U.S. National Institutes of Health | Meyer-Lindenberg A.,Central Institute of Mental Health
Hormones and Behavior | Year: 2012

The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using "pharmacological fMRI" and "imaging genetics", respectively. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. © 2012.

Meyer-Lindenberg A.,Central Institute of Mental Health
Psychological Medicine | Year: 2010

For highly heritable brain disorders, such as schizophrenia and autism, investigating genetic effects on the level of neural systems seems an obvious approach. Nevertheless, the usefulness of the intermediate phenotypes (endo phenotypes) continues to be debated energetically. We argue that, while not all intermediate phenotypes are created equal, the hypothesis-driven investigation of the translational cascades linking genetic variation to disturbed behavior is a viable and important strategy that should not be supplanted by an exclusive focus on brainless, clinical/categorical phenotypes investigated in very large numbers of participants. © Cambridge University Press 2009.

Gebicke-Haerter P.J.,Central Institute of Mental Health
Pharmacopsychiatry | Year: 2012

Investigations on gene variants as milestones in the development of schizophrenia have not fulfilled the enormous, initial expectations. Neither candidate gene approaches trying to associate single genes with the disorder, nor genome-wide association studies (GWAS), that have been welcomed more recently with great enthusiasm, could end the general disappointment associated with these strategies. Owing to very large numbers of samples and most advanced sequencing technologies, some variants have been found but their effects, even in combination are very small. In summary, most of the tentative heritability of schizophrenia remains unexplained. More hope to find mechanisms connecting genes with the disorder lies in analyses of the epigenome with technologies developed during the last 10 or 15 years and undergoing more and more refinement recently. Although investigations on interactions between DNA methylation patterns and histone modifications will probably be the greatest challenge in molecular genetics for the next decades, they appear to be the most promising approaches on complex brain disorders that typically show a high dependence on environmental factors. © Georg Thieme Verlag KG Stuttgart · New York.

Schredl M.,Central Institute of Mental Health | Reinhard I.,Central Institute of Mental Health
Sleep Medicine Reviews | Year: 2011

Many studies have reported gender differences in nightmare frequency. In order to study this difference systematically, data from 111 independent studies have been included in the meta-analysis reported here. Overall, estimated effect sizes regarding the gender difference in nightmare frequency differed significantly from zero in three age groups of healthy persons (adolescents, young adults, and middle-aged adults), whereas for children and older persons no substantial gender difference in nightmare frequency could be demonstrated. There are several candidate variables like dream recall frequency, depression, childhood trauma, and insomnia which might explain this gender difference because these variables are related to nightmare frequency and show stable gender differences themselves. Systematic research studying the effect of these variables on the gender difference in nightmare frequency, though, is still lacking. In the present study it was found that women tend to report nightmares more often than men but this gender difference was not found in children and older persons. Starting with adolescence, the gender difference narrowed with increasing age. In addition, studies with binary coded items showed a markedly smaller effect size for the gender difference in nightmare frequency compared to the studies using multiple categories in a rating scale. How nightmares were defined did not affect the gender difference. In the analyses of all studies and also in the analysis for the children alone the data source (children vs. parents) turned out to be the most influential variable on the gender difference (reporting, age). Other results are also presented. Investigating factors explaining the gender difference in nightmare frequency might be helpful in deepening the understanding regarding nightmare etiology and possibly gender differences in other mental disorders like depression or posttraumatic stress disorder. © 2010 Elsevier Ltd.

Schredl M.,Central Institute of Mental Health
International Review of Neurobiology | Year: 2010

Dreams have been studied from different perspectives: psychoanalysis, academic psychology, and neurosciences. After presenting the definition of dreaming and the methodological tools of dream research, the major findings regarding the phenomenology of dreaming and the factors influencing dream content are briefly reviewed. The so-called continuity hypothesis stating that dreams reflect waking-life experiences is supported by studies investigating the dreams of psychiatric patients and patients with sleep disorders, i.e., their daytime symptoms and problems are reflected in their dreams. Dreams also have an effect on subsequent waking life, e.g., on daytime mood and creativity. The question about the functions of dreaming is still unanswered and open to future research. © 2010 Elsevier Inc.

Mier D.,Central Institute of Mental Health | Kirsch P.,Central Institute of Mental Health | Meyer-Lindenberg A.,Central Institute of Mental Health
Molecular Psychiatry | Year: 2010

Genetic variation in catechol-O-methyltransferase (COMT), encoding an enzyme critical for prefrontal dopamine flux, has been studied extensively using both behavioral and neuroimaging methods. In behavior, pleiotropic action of a functional Val158Met (rs4680) polymorphism on executive cognition and emotional stability has been described and proposed to be of evolutionary significance (the warrior/worrier hypothesis). We conducted a meta-analysis of all available neuroimaging studies of rs4680 to investigate the evidence for a neural substrate of this behavioral pleiotropy. We show significant association between the COMT genotype and prefrontal activation, with large (d=0.73) effect size without evidence for publication bias. Strong and opposing effects were found for executive cognition paradigms (favoring Met allele carriers) and emotional paradigms (favoring Val), providing meta-analytical evidence for a neural substrate for the pleiotropic behavioral effects of COMT genetic variation and validating the use of intermediate phenotypes as a method to bridge between genes and behavior. © 2010 Macmillan Publishers Limited All rights reserved.

Meyer-Lindenberg A.,Central Institute of Mental Health
Dialogues in Clinical Neuroscience | Year: 2010

Recent years have seen an explosive growth of interest in the application of imaging genetics to understand neurogenetic mechanisms of schizophrenia. Imaging genetics applies structural and functional neuroimaging to study subjects carrying genetic risk variants that relate to a psychiatric disorder. We review selected aspects of this literature, starting with a widely studied candidate gene-the catechol-0-methyltransferase gene (COMT)-discussing other candidate genes in the dopaminergic system, and then discussing variants with genome-wide support. In future perspectives, approaches to characterize epistatic effects, the identification of new risk genes through forward-genetic approaches using imaging phenotypes, and the study of rare structural variants are considered. © 2010 LLS SAS.

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