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Levinson S.C.,Max Planck Institute for Psycholinguistics | Levinson S.C.,Donders Institute for Brain
Trends in Cognitive Sciences | Year: 2016

Most language usage is interactive, involving rapid turn-taking. The turn-taking system has a number of striking properties: turns are short and responses are remarkably rapid, but turns are of varying length and often of very complex construction such that the underlying cognitive processing is highly compressed. Although neglected in cognitive science, the system has deep implications for language processing and acquisition that are only now becoming clear. Appearing earlier in ontogeny than linguistic competence, it is also found across all the major primate clades. This suggests a possible phylogenetic continuity, which may provide key insights into language evolution. © 2015 Elsevier Ltd.

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder with hyperactivity as one of the hallmarks. Aberrant dopamine signaling is thought to be a major theme in ADHD, but how this relates to the vast majority of ADHD candidate genes is illusive. Here we report a Drosophila dopamine-related locomotor endophenotype that is shared by pan-neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not found in control models and could be ameliorated by methylphenidate, validating its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can be further exploited in high throughput to characterize the growing number of candidate genes. It represents an equally useful outcome measure for testing chemical compounds to define novel treatment options.Molecular Psychiatry advance online publication, 12 May 2015; doi:10.1038/mp.2015.55. © 2015 Macmillan Publishers Limited

Homberg J.R.,Donders Institute for Brain
Brain Research | Year: 2012

There is high consensus that stress-related disorders like depression are shaped by nature × nurture interactions. However, the complexity appears larger than envisaged and nature × nurture research is progressing too slowly. An important reason is that mainstream research is focussing on the idea that a combination of genotypic stress-sensitivity and stress exposure inevitably leads to maladaptive stress-coping responses, and thereby stress-related disorders. However, stress-coping responses can also be adaptive and adhere to the expected norm. Here I elaborate the 'environment' mismatch hypothesis proposed by Mathias Schmidt (Psychoneuroendocrinology, 36, 330-338, 2011) to the stress-coping (mis)match (SCM) hypothesis postulating that stress-coping responses-as programmed by nature × age-dependent nurture interactions-are adaptive when they match current stress conditions, but maladaptive when they mismatch current stress conditions. For instance, acquisition of an active stress-coping response during nurture may lead to the programmed release of active coping responses in current life. This is adaptive when current stress is escapable, but maladaptive when current stress is inescapable, leading to agitation. A model par example for nature × nurture interactions is the serotonin transporter promoter polymorphism, which will be discussed in the framework of the SCM hypothesis. The potential role of the prefrontal-amygdala circuit and the therapeutic implications of the SCM hypothesis will also be discussed. © 2011 Elsevier B.V.

Muller C.P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Homberg J.R.,Donders Institute for Brain
Behavioural Brain Research | Year: 2015

The use of psychoactive drugs is a wide spread behaviour in human societies. The systematic use of a drug requires the establishment of different drug use-associated behaviours which need to be learned and controlled. However, controlled drug use may develop into compulsive drug use and addiction, a major psychiatric disorder with severe consequences for the individual and society. Here we review the role of the serotonergic (5-HT) system in the establishment of drug use-associated behaviours on the one hand and the transition and maintenance of addiction on the other hand for the drugs: cocaine, amphetamine, methamphetamine, MDMA (ecstasy), morphine/heroin, cannabis, alcohol, and nicotine. Results show a crucial, but distinct involvement of the 5-HT system in both processes with considerable overlap between psychostimulant and opioidergic drugs and alcohol. A new functional model suggests specific adaptations in the 5-HT system, which coincide with the establishment of controlled drug use-associated behaviours. These serotonergic adaptations render the nervous system susceptible to the transition to compulsive drug use behaviours and often overlap with genetic risk factors for addiction. Altogether we suggest a new trajectory by which serotonergic neuroadaptations induced by first drug exposure pave the way for the establishment of addiction. © 2014 Elsevier B.V.

Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

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