scholarly journals Neurodevelopmental Plasticity in Pre- and Postnatal Environmental Interactions: Implications for Psychiatric Disorders from an Evolutionary Perspective

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Young-A Lee ◽  
Yoshie Yamaguchi ◽  
Yukiori Goto
Keyword(s):  
Psychiatric Disorders ◽  
De Novo ◽  
Gene Mutations ◽  
Normal Subjects ◽  
Autism Spectrum ◽  
Biological Mechanisms ◽  
Behavioral Phenotypes ◽  
Environmental Interactions ◽  
De Novo Gene ◽  
Adverse Environmental Conditions

Psychiatric disorders are disadvantageous behavioral phenotypes in humans. Accordingly, a recent epidemiological study has reported decreased fecundity in patients with psychiatric disorders, such as schizophrenia and autism spectrum disorders. Moreover, the fecundity of the relatives of these patients is not exceedingly higher compared to the fecundity of the relatives of normal subjects. Collectively, the prevalence of psychiatric disorders among humans is expected to decrease over generations. Nevertheless, in reality, the prevalence rates of psychiatric disorders in humans either have been constant over a long period of time or have even increased more recently. Several attempts to explain this fact have been made using biological mechanisms, such as de novo gene mutations or variants, although none of these explanations is fully comprehensive. Here, we propose a hypothesis towards understanding the biological mechanisms of psychiatric disorders from evolutionary perspectives. This hypothesis considers that behavioral phenotypes associated with psychiatric disorders might have emerged in the evolution of organisms as a neurodevelopmental adaptation against adverse environmental conditions associated with stress.

Poster #T152 PHENOTYPIC FEATURES OF PATIENTS WITH SCHIZOPHRENIA CARRYING DE NOVO GENE MUTATIONS

2014 ◽  
Vol 153 ◽  
pp. S344
Author(s):  
Pierre J. Malherbe ◽  
J. Louis Roos ◽  
J Louw Roos ◽  
Maria Karayiorgou ◽  
René Ehlers
Keyword(s):  
De Novo ◽  
Gene Mutations ◽  
De Novo Gene ◽  
Phenotypic Features

scholarly journals Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Kyleen Luhrs ◽  
Tracey Ward ◽  
Caitlin M. Hudac ◽  
Jennifer Gerdts ◽  
Holly A. F. Stessman ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Copy Number ◽  
Depressive Disorders ◽  
De Novo ◽  
Familial Risk ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Genetic Etiology ◽  
Additive Contribution ◽  
Familial Risk Factors

The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD) with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n=62), de novo deletion copy number variations (DEL, n=74), de novo likely gene-disrupting mutations (LGDM, n=267), and children without a known genetic etiology (NON, n=2111). Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships.

scholarly journals Translational animal models of autism and neurodevelopmental disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 293-305 ◽  
Keyword(s):  
Mouse Models ◽  
De Novo ◽  
Single Gene ◽  
Neurodevelopmental Disorder ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Restricted Interests ◽  
Homologous Genes ◽  
Biological Outcomes

Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics.

scholarly journals De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia

2012 ◽  
Vol 44 (12) ◽  
pp. 1365-1369 ◽  
Author(s):  
Bin Xu ◽  
Iuliana Ionita-Laza ◽  
J Louw Roos ◽  
Braden Boone ◽  
Scarlet Woodrick ◽  
...  
Keyword(s):  
De Novo ◽  
Gene Mutations ◽  
De Novo Gene

scholarly journals Synaptic and brain-expressed gene sets relate to the shared genetic risk across five psychiatric disorders

2019 ◽  
Vol 50 (10) ◽  
pp. 1695-1705 ◽  
Author(s):  
Anke R. Hammerschlag ◽  
Christiaan A. de Leeuw ◽  
Christel M. Middeldorp ◽  
Tinca J. C. Polderman
Keyword(s):  
Gene Expression ◽  
Psychiatric Disorders ◽  
Expression Profiles ◽  
Autism Spectrum ◽  
Tissue Type ◽  
Specific Gene ◽  
Biological Mechanisms ◽  
Gene Sets ◽  
Independent Effects ◽  
Shared Risk

AbstractBackgroundMounting evidence shows genetic overlap between multiple psychiatric disorders. However, the biological underpinnings of shared risk for psychiatric disorders are not yet fully uncovered. The identification of underlying biological mechanisms is crucial for the progress in the treatment of these disorders.MethodsWe applied gene-set analysis including 7372 gene sets, and 53 tissue-type specific gene-expression profiles to identify sets of genes that are involved in the etiology of multiple psychiatric disorders. We included genome-wide meta-association data of the five psychiatric disorders schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The total dataset contained 159 219 cases and 262 481 controls.ResultsWe identified 19 gene sets that were significantly associated with the five psychiatric disorders combined, of which we excluded five sets because their associations were likely driven by schizophrenia only. Conditional analyses showed independent effects of several gene sets that in particular relate to the synapse. In addition, we found independent effects of gene expression levels in the cerebellum and frontal cortex.ConclusionsWe obtained novel evidence for shared biological mechanisms that act across psychiatric disorders and we showed that several gene sets that have been related to individual disorders play a role in a broader range of psychiatric disorders.

De novo gene mutations in normal human memory B cells

Leukemia ◽  
2018 ◽  
Vol 33 (5) ◽  
pp. 1219-1230
Author(s):  
L. M. Slot ◽  
T. A. M. Wormhoudt ◽  
M. J. Kwakkenbos ◽  
K. Wagner ◽  
A. Ballering ◽  
...  
Keyword(s):  
B Cells ◽  
De Novo ◽  
Gene Mutations ◽  
Human Memory ◽  
Memory B Cells ◽  
De Novo Gene ◽  
Normal Human

scholarly journals Phenotypic features of patients with schizophrenia carrying de novo gene mutations: A pilot study

2015 ◽  
Vol 225 (1-2) ◽  
pp. 108-114 ◽  
Author(s):  
P.J. Malherbe ◽  
J.L. Roos ◽  
R. Ehlers ◽  
M. Karayiorgou ◽  
J.L. Roos
Keyword(s):  
Pilot Study ◽  
De Novo ◽  
Gene Mutations ◽  
De Novo Gene ◽  
Phenotypic Features

Age at fatherhood: heritability and associations with psychiatric disorders

2016 ◽  
Vol 46 (14) ◽  
pp. 2981-2988 ◽  
Author(s):  
E. M. Frans ◽  
P. Lichtenstein ◽  
C. M. Hultman ◽  
R. Kuja-Halkola
Keyword(s):  
Psychiatric Disorders ◽  
De Novo ◽  
Autism Spectrum ◽  
Genetic Component ◽  
Paternal Age ◽  
Genetic Liability ◽  
Healthy Men ◽  
Twin Model ◽  
Men 2 ◽  
Affected Sibling

BackgroundAdvancing paternal age has been linked to psychiatric disorders. These associations might be caused by the increased number of de novo mutations transmitted to offspring of older men. It has also been suggested that the associations are confounded by a genetic liability for psychiatric disorders in parents. The aim of this study was to indirectly test the confounding hypotheses by examining if there is a genetic component to advancing paternal age and if men with a genetic liability for psychiatric disorders have children at older ages.MethodWe examined the genetic component to advancing paternal age by utilizing the twin model in a cohort of male twins (N = 14 679). We also studied ages at childbirth in men with or without schizophrenia, bipolar disorder and/or autism spectrum disorder. Ages were examined in: (1) healthy men, (2) affected men, (3) healthy men with an affected sibling, (4) men with healthy spouses, (5) men with affected spouses, and (6) men with healthy spouses with an affected sibling.ResultsThe twin analyses showed that late fatherhood is under genetic influence (heritability = 0.33). However, affected men or men with affected spouses did not have children at older ages. The same was found for healthy individuals with affected siblings. Instead, these men were generally having children at younger ages.ConclusionAlthough there is a genetic component influencing late fatherhood, our data suggest that the associations are not explained by psychiatric disorders or a genetic liability for psychiatric disorders in the parent.

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