title: Interneuron epigenomes during the critical period of cortical plasticity: Implications for schizophrenia.
abstract: Schizophrenia, a major psychiatric disorder defined by delusions and hallucinations, among other symptoms, often with onset in early adulthood, is potentially associated with molecular and cellular alterations in parvalbumin-expressing fast spiking interneurons and other constituents of the cortical inhibitory GABAergic circuitry. The underlying mechanisms, including the role of disease-associated risk factors operating in adolescence such as drug abuse and social stressors, remain incompletely understood. Here, we summarize emerging findings from animal models, highlighting the ability of parvalbuminergic interneurons (PVI) to induce, during the juvenile period, long-term plastic changes in prefrontal and visual cortex, thereby altering perception, cognition and behavior in the adult. Of note, molecular alterations in PVI from subjects with schizophrenia, including downregulated expression of a subset of GABAergic genes, have also been found in juvenile stress models of the disorder. Some of the transcriptional alterations observed in schizophrenia postmortem brain could be linked to changes in the epigenetic architecture of GABAergic gene promoters, including dysregulated DNA methylation, histone modification patterns and disruption of promoter-enhancer interactions at site of chromosomal loop formations. Therefore, we predict that, in the not-to-distant future, PVI- and other cell-type specific epigenomic mappings in the animal model and human brain will provide novel insights into the pathophysiology of schizophrenia and related psychotic diseases, including the role of cortical GABAergic circuitry in shaping long-term plasticity and cognitive function of the cerebral cortex.
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, United States; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, United States; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, United States. Electronic address: Hirofumi.Morishita@mssm.edu.
authors: Hirofumi
authors: H
authors: Morishita
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Marija
authors: M
authors: Kundakovic
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Lucy
authors: L
authors: Bicks
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Amanda
authors: A
authors: Mitchell
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, United States; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, United States; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, United States. Electronic address: Schahram.akbarian@mssm.edu.
authors: Schahram
authors: S
authors: Akbarian
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000254:growth & development* / Q000503:physiopathology; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D059330:GABAergic Neurons / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D009473:Neuronal Plasticity; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000254:growth & development / Q000503:physiopathology; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D013997:Time Factors; D014793:Visual Cortex / Q000254:growth & development / Q000503:physiopathology
chemical_list: D010320:Parvalbumins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: Cortical plasticity; Critical period; Epigenome; Parvalbuminergic interneuron; Schizophrenia