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Prof. Dr. Andreas Meyer-Lindenberg

Translational neurogenetics of psychiatric disorders

Many severe psychiatric disorders and complex behaviours are highly heritable. We investigate genetic variation associated with risk for disorders such as schizophrenia, depression and autism and behavioural phenomena such as attachment or impulsive violence in a translational approach, with an emphasis on multimodal neuroimaging to identify neural systems mediating genetic risk. The ultimate goal is the construction of a neural risk architecture of the studied target behaviour as guide for the discovery and evaluation of novel treatment strategies.

We are focusing on these major aspects

  1. Neurogenetic risk mechanisms of depression and anxiety
    We study the impact on genetic risk on neural function and cognition using multimodal neuroimaging. A recent focus of that work is the investigation of epistatic interactions, relating multiple genetic variants to neural phenotypes, and the study of neural mechanisms predictive of therapeutic response and course in a longitudinal perspective.
  2. Neural mechanisms of complex social behaviours under genetic control
    Many aspects of social behaviour are highly heritable, are key components of severe psychiatric disorders that are themselves heritable, and are essential for reproductive fitness. Consequently, we have launched a program to investigate genetic contributions to the human social brain.
  3. Genetic modulation of neural plasticity
    The goal of this project is to identify the functional correlates, neurochemical mechanisms and the impact of genomic variation on experimentally induced prefrontal cortical plasticity in the human.
(a) Neural mechanisms of hypersociability in WS (Meyer-Lindenberg et al., 2005a). Amygdala activation for socially relevant face stimuli (top row) and less relevant scene stimuli (bottom row) stimuli, rendered on normal coronal MRI. First column: normal controls (NC), Second column: participants with WS (WS). Subjects with WS show decreased activation to social fear stimuli, but increased signalling to non-social stimuli, mirroring their anxiety profile.
(b) Neural circuits for amygdala regulation and social function under genetic control impacted in WS (Meyer- Lindenberg et al., 2006a): both orbitofrontal cortex (OFC) and cingulate interact with amygdala in healthy controls, but OFC is disconnected in WS.
(c) structure (left) and functional connectivity (right) affected by genetic variation in 5-HTTLPR (Callicott et al., 2005). Carriers of the short allele show relative volume reductions in subgenual cingulate and amygdala, and reduced connectivity of amygdala to subgenual cingulate, delineating a feedback circuit for fear extinction and social cognition.
(d) structural (left, using voxel-based morphometry) and functional results (right, during an emotional faces matching task) show an impact of genetic variation in MAO-A on amygdala, cingulate and orbitofrontal volume and function (Meyer-Lindenberg et al., 2006c). Volume is relatively reduced in carriers of the low expression allele implicated in risk for impulsive violence. Amygdala activation is increased, while activation of regulatory cingulate and orbitofrontal regions is decreased.
(e) the prosocial hormone oxytocin modulates amygdala activation in healthy humans (Kirsch et al., 2005). Stimuli and display as in (a). Top: placebo, Bottom: oxytocin.

Selection of recent publications

  1. Oettl LL, Ravi N, Schneider M, Scheller MF, Schneider P, Mitre M, et al. Oxytocin Enhances Social Recognition by Modulating Cortical Control of Early Olfactory Processing. Neuron. 2016;90(3):609-21.
  2. Millan MJ, Andrieux A, Bartzokis G, Cadenhead K, Dazzan P, Fusar-Poli P, et al. Altering the course of schizophrenia: progress and perspectives. Nat Rev Drug Discov. 2016.
  3. Loth E, Spooren W, Ham LM, Isaac MB, Auriche-Benichou C, Banaschewski T, et al. Identification and validation of biomarkers for autism spectrum disorders. Nat Rev Drug Discov. 2016;15(1):70-3.
  4. Inta D, Lang UE, Borgwardt S, Meyer-Lindenberg A, Gass P. Adult neurogenesis in the human striatum: possible implications for psychiatric disorders. Mol Psychiatry. 2016;21(4):446-7.
  5. Holz N, Boecker R, Buchmann AF, Blomeyer D, Baumeister S, Hohmann S, et al. Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression. Cereb Cortex. 2016;26(3):904-14.
  6. Franke B, Stein JL, Ripke S, Anttila V, Hibar DP, van Hulzen KJ, et al. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nat Neurosci. 2016;19(3):420-31.
  7. Cao H, Bertolino A, Walter H, Schneider M, Schafer A, Taurisano P, et al. Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia. JAMA Psychiatry. 2016.
  8. Tost H, Champagne FA, Meyer-Lindenberg A. Environmental influence in the brain, human welfare and mental health. Nat Neurosci. 2015;18(10):1421-31.
  9. Hibar DP, Stein JL, Renteria ME, Arias-Vasquez A, Desrivieres S, Jahanshad N, et al. Common genetic variants influence human subcortical brain structures. Nature. 2015;520(7546):224-9.
  10. Stefansson H, Meyer-Lindenberg A, Steinberg S, Magnusdottir B, Morgen K, Arnarsdottir S, et al. CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature. 2014;505(7483):361-6.

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