The LEARn model

An epigenetic explanation for idiopathic neurobiological diseases

Debomoy Lahiri, B. Maloney, N. H. Zawia

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Neurobiological disorders have diverse manifestations and symptomology. Neurodegenerative disorders, such as Alzheimer's disease, manifest late in life and are characterized by, among other symptoms, progressive loss of synaptic markers. Developmental disorders, such as autism spectrum, appear in childhood. Neuropsychiatric and affective disorders, such as schizophrenia and major depressive disorder, respectively, have broad ranges of age of onset and symptoms. However, all share uncertain etiologies, with opaque relationships between genes and environment. We propose a Latent Early-life Associated Regulation (LEARn) model, positing latent changes in expression of specific genes initially primed at the developmental stage of life. In this model, environmental agents epigenetically disturb gene regulation in a long-term manner, beginning at early developmental stages, but these perturbations might not have pathological results until significantly later in life. The LEARn model operates through the regulatory region (promoter) of the gene, specifically through changes in methylation and oxidation status within the promoter of specific genes. The LEARn model combines genetic and environmental risk factors in an epigenetic pathway to explain the etiology of the most common, that is, sporadic, forms of neurobiological disorders.

Original languageEnglish
Pages (from-to)992-1003
Number of pages12
JournalMolecular Psychiatry
Volume14
Issue number11
DOIs
StatePublished - Nov 2009

Fingerprint

Epigenomics
Genes
Nucleic Acid Regulatory Sequences
Genetic Models
Major Depressive Disorder
Autistic Disorder
Mood Disorders
Age of Onset
Neurodegenerative Diseases
Methylation
Schizophrenia
Alzheimer Disease
Gene Expression

Keywords

  • Brain disorders
  • Diet
  • Gene-environment interaction
  • Latency
  • Nutrition
  • Somatic epitype

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

The LEARn model : An epigenetic explanation for idiopathic neurobiological diseases. / Lahiri, Debomoy; Maloney, B.; Zawia, N. H.

In: Molecular Psychiatry, Vol. 14, No. 11, 11.2009, p. 992-1003.

Research output: Contribution to journalArticle

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