Genetic basis of anxiety-like behaviour: a critical review

Clément, Yan; Calatayud, François; Belzung, Catherine

doi:10.1016/s0361-9230(01)00637-2

Cited by 142 publications

(83 citation statements)

References 227 publications

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“…[3][4][5][6][7][8][9] Nevertheless, the genes and molecular pathways involved remain largely unknown, and this is an important limitation to the development of more efficient therapeutic methods.…”

Section: Introductionmentioning

confidence: 99%

Expression of α-synuclein is increased in the hippocampus of rats with high levels of innate anxiety

et al. 2008

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A genomic region neighboring the a-synuclein gene, on rat chromosome 4, has been associated with anxiety-and alcohol-related behaviors in different rat strains. In this study, we have investigated potential molecular and physiological links between a-synuclein and the behavioral differences observed between Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rats, a genetic model of anxiety. As expected, LEW rats appeared more fearful than SHR rats in three anxiety models: open field, elevated plus maze and light/dark box. Moreover, LEW rats displayed a higher preference for alcohol and consumed higher quantities of alcohol than SHR rats. a-Synuclein mRNA and protein concentrations were higher in the hippocampus, but not the hypothalamus of LEW rats. This result inversely correlated with differences in dopamine turnover in the hippocampus of LEW and SHR rats, supporting the hypothesis that a-synuclein is important in the downregulation of dopamine neurotransmission. A novel single nucleotide polymorphism was identified in the 3 0 -untranslated region (3 0 -UTR) of the asynuclein cDNA between these two rat strains. Plasmid constructs based on the LEW 3 0 -UTR sequence displayed increased expression of a reporter gene in transiently transfected PC12 cells, in accordance with in-vivo findings, suggesting that this nucleotide exchange might participate in the differential expression of a-synuclein between LEW and SHR rats. These results are consistent with a novel role for a-synuclein in modulating rat anxiety-like behaviors, possibly through dopaminergic mechanisms. Since the behavioral and genetic differences between these two strains are the product of independent evolutionary histories, the possibility that polymorphisms in the a-synuclein gene may be associated with vulnerability to anxiety-related disorders in humans requires further investigation.

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Section: Introductionmentioning

confidence: 99%

Expression of α-synuclein is increased in the hippocampus of rats with high levels of innate anxiety

et al. 2008

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“…There is ample scientific evidence that genetic factors and environmental factors interact in a complex fashion (Clement et al, 2002). More systematic research is needed to build up clear evidence about the mere effects of genetic background and environmental factors as well as their interplay in the development of pathological anxiety.…”

Section: Definition Of Pathological Anxietymentioning

confidence: 99%

Pathological anxiety in animals

Ohl

Arndt

Staay

2008

The Veterinary Journal

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Selective breeding programmes in domestic and laboratory animals generally focus on physiological and/or anatomical characteristics. However, selection may have an (unintended) impact on other characteristics and may lead to dysfunctional behaviour that can affect biological functioning and, as a consequence, compromise welfare and quality of life. In this review it is proposed that various behavioural dysfunctions in animals are due to pathological anxiety. Although several approaches have been undertaken to specify the diagnostic criteria of pathological anxiety as a behavioural disorder in animals, the causal aetiology largely remains unknown. This is mainly due to the fact that integrated concepts, combining the behavioural syndrome and (neuro-) physiological processes, are widely lacking. Moreover, even the term anxiety itself represents a poorly defined concept or category. A definition is suggested and the potential causes of pathological anxiety are explored with a plea for developing adequate diagnostic tools and therapies to fight pathological anxiety in animals based on insight from scientific research.

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“…2 Animal models, although limited in their ability to comprehend human complexities, are an invaluable tool in the research of markers for psychiatric disorders in general, and PTSD in particular. A good PTSD animal model of clinical conditions, should fulfill four criteria: 3,4 etiological, face, construct and predictive validity. Unlike many other mental disorders, the diagnostic criteria for PTSD specify an etiological factor, which is an exposure to a lifethreatening, traumatic event.…”

Section: Introductionmentioning

confidence: 99%

“…23 Among all the unconditioned stressors, the predator stress seems to be the most potent stressor, since its effects on fear/anxiety potentiation can last for 3 weeks. 13 In addition to behavioral models which utilize different components of environmental stimuli, many researchers use genetic models such as inbred strains, selected lines, linkage studies and gene targeting techniques (reviewed in Clement et al 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Biological alterations may underline the onset and persistence of PTSD symptoms. 4,25,26 Such alterations are likely to be associated with differential gene transcription and may last long term after the exposure to the triggering event. The long-term alterations are likely to be associated with the PTSD state, while alterations that fade with time are more likely to represent the response to the acute stressful event.…”

Section: Introductionmentioning

confidence: 99%

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WFS1 gene as a putative biomarker for development of post-traumatic syndrome in an animal model

et al. 2007

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Post-traumatic stress disorder (PTSD) is an anxiety disorder that may develop after the experiencing or witnessing of a life-threatening event. PTSD is defined by the coexistence of three clusters of symptoms: re-experiencing, avoidance and hyperarousal, which persist for at least 1 month in survivors of the event (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Using an established model of PTSD, we addressed the well-accepted clinical finding that only a minority (about 20%) of the individuals exposed to a traumatic event develop PTSD. Moreover, we followed individual rat behavior for up to a month, and then treated the PTSD-like animals with citalopram. Our data demonstrate high face (20% of rats exposed to a reminder of the stressor develop symptoms characteristic of PTSD) and predictive (response to citalopram) validities. Based on these validities we identified alterations in the Wolframin gene in the CA1 and amygdala regions, specifically in exposed PTSD-like rats, which were normalized after treatment with citalopram. We suggest the Wolframin gene as a putative biomarker for PTSD. Since Wolframin gene undergoes alternative splicing and has polymorphism in the population, it may serve a future marker for identification of the vulnerable population exposed to a traumatic event.

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Genetic basis of anxiety-like behaviour: a critical review

Cited by 142 publications

References 227 publications

Expression of α-synuclein is increased in the hippocampus of rats with high levels of innate anxiety

Expression of α-synuclein is increased in the hippocampus of rats with high levels of innate anxiety

Pathological anxiety in animals

WFS1 gene as a putative biomarker for development of post-traumatic syndrome in an animal model

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