The role of neurotrophic factors in autism

Nickl‐Jockschat, Thomas; Michel, Tanja Maria

doi:10.1038/mp.2010.103

Cited by 84 publications

(61 citation statements)

References 180 publications

(197 reference statements)

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“…We focused our study on BDNF because it represents a particularly good candidate for early detection of psychiatric risk. BDNF has a well-established role in neurodevelopment and neuronal plasticity, and its deficiency has been linked to several psychiatric disorders that are associated with early-life adversity, including depression (34,36), schizophrenia (37), bipolar disorder (38), and autism (39). It seems likely that disrupted neural development and neural plasticity, associated with altered BDNF expression emerging in early life, could predispose an individual to behavioral deficits and multiple psychopathologies in adulthood (40).…”

Section: Discussionmentioning

confidence: 99%

DNA methylation of BDNF as a biomarker of early-life adversity

Kundaković

Gudsnuk

Herbstman

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

349

238

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Early-life adversity increases the risk for psychopathology in later life. The underlying mechanism(s) is unknown, but epigenetic variation represents a plausible candidate. Early-life exposures can disrupt epigenetic programming in the brain, with lasting consequences for gene expression and behavior. This evidence is primarily derived from animal studies, with limited study in humans due to inaccessibility of the target brain tissue. In humans, although there is evidence for DNA methylation changes in the peripheral blood of psychiatric patients, a fundamental question remains as to whether epigenetic markers in the blood can predict epigenetic changes occurring in the brain. We used in utero bisphenol A (BPA) exposure as a model environmental exposure shown to disrupt neurodevelopment and exert long-term effects on behavior in animals and humans. We show that prenatal BPA induces lasting DNA methylation changes in the transcriptionally relevant region of the Bdnf gene in the hippocampus and blood of BALB/c mice and that these changes are consistent with BDNF changes in the cord blood of humans exposed to high maternal BPA levels in utero. Our data suggest that BDNF DNA methylation in the blood may be used as a predictor of brain BDNF DNA methylation and gene expression as well as behavioral vulnerability induced by early-life environmental exposure. Because BDNF expression and DNA methylation are altered in several psychiatric disorders that are associated with early-life adversity, including depression, schizophrenia, bipolar disorder, and autism, BDNF DNA methylation in the blood may represent a novel biomarker for the early detection of psychopathology.epigenetics | biomarker | BDNF | bisphenol A | early life

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Section: Discussionmentioning

confidence: 99%

DNA methylation of BDNF as a biomarker of early-life adversity

Kundaković

Gudsnuk

Herbstman

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

349

238

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“…They can play a crucial role in the development and maintenance of the central nervous system and can influence the formation and elimination of neural connections (11,12). The potential role of NTFs in the pathophysiology of several psychiatric disorders such as bipolar disorders (13), depression (14), schizophrenia (10) as well as obsessive-compulsive disorders has been the focus of many studies (15,16).…”

Section: Introductionmentioning

confidence: 99%

“…Neurotrophic factors (NTFs) comprise a group of several protein superfamilies, which include neurotrophins (i.e., brain-derived neurotrophic factor [BDNF] and Neurotrophin-4 [NT-4]), neurokines (i.e., leukemia inhibitory factor [LIF]), insulin-like growth factors (i.e., IGF-1), and transforming growth factor-b (TGF-b) superfamilies (11). They can play a crucial role in the development and maintenance of the central nervous system and can influence the formation and elimination of neural connections (11,12).…”

Section: Introductionmentioning

confidence: 99%

Neonatal levels of neurotrophic factors and risk of autism spectrum disorders

Abdallah

Mortensen

Greaves‐Lord

et al. 2012

Acta Psychiatr Scand

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“…Multiple lines of evidence suggest a pathophysiological involvement of neurotrophic factors in ASD and, therefore, a potential role as biomarker candidates for these disorders [13]. Neurotrophic factors, which are involved in many processes in the CNS, play a critical role in the neurogenesis, differentiation, synaptic plasticity and long-term potentiation and are involved in learning, memory and attention [5,14].…”

Section: Introductionmentioning

confidence: 99%

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

et al. 2014

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Autism spectrum disorders (ASD) comprise neurodevelopmental disorders with clinical onset during the first years of life. The identification of peripheral biomarkers could significantly impact diagnosis and an individualized, early treatment. Although the aetiology of ASD remains poorly understood, there is increasing evidence that neurotrophins and their receptors represent a group of candidate genes for ASD pathophysiology and biomarker research. Total messenger RNA (mRNA) from whole blood was obtained from adolescents and adults diagnosed as ASD (n = 21) according to DSM-IV criteria and confirmed by the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) algorithms, as well as healthy controls (n = 10). The mRNA expression of neurotrophins (BDNF, NT3 and NT4) and their receptors (TrkA, TrkB and p75 (NTR) ) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, social cognition abilities of ASD patients and controls were determined according to three Theory of Mind (ToM) tests (Reading the Mind in the Eyes, Faux pas, and Happé stories). The NT3 and NT4 mRNA expression in the whole blood was significantly lower in ASD compared to healthy controls, while p75(NTR) was higher (P < 0.005). In addition, lower scores in three of the ToM tests were observed in ASD subjects compared to controls. A significant (P < 0.005) ToM impairment in Happé stories test was demonstrated in ASD. Nevertheless, no correlations were observed between neurotrophins and their receptors expressions and measures of ToM. Given their potential as peripheral blood-based biomarkers, NT3, NT4 and p75 (NTR) mRNA expression patterns may be useful tools for a more personalized diagnostics and therapy in ASD. Further investigations with larger numbers of samples are needed to verify these results.

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The role of neurotrophic factors in autism

Cited by 84 publications

References 180 publications

DNA methylation of BDNF as a biomarker of early-life adversity

DNA methylation of BDNF as a biomarker of early-life adversity

Neonatal levels of neurotrophic factors and risk of autism spectrum disorders

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

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