Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer

Tabarés‐Seisdedos, Rafael; Rubenstein, John L.R.

doi:10.1038/mp.2009.2

Cited by 220 publications

(166 citation statements)

References 410 publications

(244 reference statements)

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“…miRNAs were shown to respond to various cellular stressors (Leung and Sharp, 2010) and are abundant in the nervous system, but research has mainly focused on neurons in the context of development and neurodegenerative disorders (Kim et al, 2007;Schaefer et al, 2007;Cuellar et al, 2008;Davis et al, 2008;De Pietri Tonelli et al, 2008;Dugas et al, 2010;Li and Jin, 2010;Zhao et al, 2010). It has been suggested that miRNAs play a role in psychiatric disorders such as schizophrenia and autism (Tabarés-Seisdedos and Rubenstein, 2009;Beveridge et al, 2010;Kim et al, 2010;Fénelon et al, 2011) and drug addiction Schaefer et al, 2010). Interestingly, miRNAs were recently implicated in the mechanism of action of antidepressants (Baudry et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

microRNA as Repressors of Stress-Induced Anxiety: The Case of Amygdalar miR-34

Haramati¹,

Navon²,

Issler³

et al. 2011

J. Neurosci.

228

178

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The etiology and pathophysiology of anxiety and mood disorders is linked to inappropriate regulation of the central stress response. To determine whether microRNAs have a functional role in the regulation of the stress response, we inactivated microRNA processing by a lentiviral-induced local ablation of the Dicer gene in the central amygdala (CeA) of adult mice. CeA Dicer ablation induced a robust increase in anxiety-like behavior, whereas manipulated neurons survive and appear to exhibit normal gross morphology in the time period examined. We also observed that acute stress in wild-type mice induced a differential expression profile of microRNAs in the amygdala. Bioinformatic analysis identified putative gene targets for these stress-responsive microRNAs, some of which are known to be associated with stress. One of the prominent stress-induced microRNAs found in this screen, miR-34c, was further confirmed to be upregulated after acute and chronic stressful challenge and downregulated in Dicer ablated cells. Lentivirally mediated overexpression of miR34c specifically within the adult CeA induced anxiolytic behavior after challenge. Of particular interest, one of the miR-34c targets is the stress-related corticotropin releasing factor receptor type 1 (CRFR1) mRNA, regulated via a single evolutionary conserved seed complementary site on its 3Ј UTR. Additional in vitro studies demonstrated that miR-34c reduces the responsiveness of cells to CRF in neuronal cells endogenously expressing CRFR1. Our results suggest a physiological role for microRNAs in regulating the central stress response and position them as potential targets for treatment of stress-related disorders.

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Section: Introductionmentioning

confidence: 99%

microRNA as Repressors of Stress-Induced Anxiety: The Case of Amygdalar miR-34

Haramati¹,

Navon²,

Issler³

et al. 2011

J. Neurosci.

228

178

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“…Chromosome 8p, from which at least seven miRNAs are transcribed, is an important area for neurodevelopmental disorders including autism and schizophrenia [10]. Patients with DiGeorge 22q11.2 deletion have a deficiency in DGCR8 (a key miRNA-processing gene) expression, resulting in decreased miR biosynthesis, imposing a 30-fold increased risk of schizophrenia [11].…”

Section: Microrna In Schizophreniamentioning

confidence: 99%

MicroRNA as Upcoming Biomarkers for Psychiatric Conditions

Narahari¹,

Hussain²,

Sreeram³

2017

Clin Depress

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Neural derived exosomes can be used as a diagnostic marker to screen various psychiatric conditions. These intravenously injected exosomes carry the potential to cross the blood brain barrier and deliver miRNA specifically to neurons, microglia, and oligodendrocytes in the brain, resulting in a specific gene knockdown. MicroRNAs have been identified as markers in depression where miR-16 has been found to be a negative regulator of the serotonin transporter (SERT) through computer analysis. Futhermore, where miR 134 levels in bipolar disorder have been discovered to be inversely correlated with severity of manic symptoms; manipulating expression or activity of miR-219 can prove as a therapeutic tool for schizophrenia. Despite these studies, the exact nature and extent of dysregulation of microRNAs in psychiatric disorders is yet to be determined. To realize the therapeutic potential of MiRNAs in greater depth; efficient, tissue-specific and nonimmunogenic delivery of exosomes must be developed.

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“…58 A growing number of studies have revealed mutations common to autism, attention-deficit/ hyperactivity disorder, and schizophrenia. [17][18][19][20] The only nonpsychiatric comorbidities associated with subgroup 3 were asthma and cardiac dysrhythmia. * Known…”

Section: Subgroupmentioning

confidence: 99%

“…For example, there exist mutations common to ASD, attentiondeficit/hyperactivity disorder, and schizophrenia. [17][18][19][20] Mutations responsible for Rett syndrome 21 and Fragile X 22 carry a much higher risk of ASD and epilepsy. The association between peripartum infections and ASD is also well-documented.…”

mentioning

confidence: 99%

Comorbidity Clusters in Autism Spectrum Disorders: An Electronic Health Record Time-Series Analysis

2013

PEDIATRICS

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WHAT'S KNOWN ON THIS SUBJECT: Individuals with autism spectrum disorders have a higher comorbidity burden than the general pediatric population, including higher rates of seizures, psychiatric illness, and gastrointestinal disorders. WHAT THIS STUDY ADDS:Comorbidities do not occur evenly. Our clustering analysis reveals subgroups characterized by seizure, psychiatric disorders, and complex multisystem disorders including auditory and gastrointestinal disorders. Correlations between seizure, psychiatric disorders, and gastrointestinal disorders are validated on a sample from a second hospital. abstract OBJECTIVE: The distinct trajectories of patients with autism spectrum disorders (ASDs) have not been extensively studied, particularly regarding clinical manifestations beyond the neurobehavioral criteria from the Diagnostic and Statistical Manual of Mental Disorders. The objective of this study was to investigate the patterns of cooccurrence of medical comorbidities in ASDs.METHODS: International Classification of Diseases, Ninth Revision codes from patients aged at least 15 years and a diagnosis of ASD were obtained from electronic medical records. These codes were aggregated by using phenotype-wide association studies categories and processed into 1350-dimensional vectors describing the counts of the most common categories in 6-month blocks between the ages of 0 to 15. Hierarchical clustering was used to identify subgroups with distinct courses.RESULTS: Four subgroups were identified. The first was characterized by seizures (n = 120, subgroup prevalence 77.5%). The second (n = 197) was characterized by multisystem disorders including gastrointestinal disorders (prevalence 24.3%) and auditory disorders and infections (prevalence 87.8%), and the third was characterized by psychiatric disorders (n = 212, prevalence 33.0%). The last group (n = 4316) could not be further resolved. The prevalence of psychiatric disorders was uncorrelated with seizure activity (P = .17), but a significant correlation existed between gastrointestinal disorders and seizures (P , .001). The correlation results were replicated by using a second sample of 496 individuals from a different geographic region.CONCLUSIONS: Three distinct patterns of medical trajectories were identified by unsupervised clustering of electronic health record diagnoses. These may point to distinct etiologies with different genetic and environmental contributions. Additional clinical and molecular characterizations will be required to further delineate these subgroups.

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Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer

Cited by 220 publications

References 410 publications

microRNA as Repressors of Stress-Induced Anxiety: The Case of Amygdalar miR-34

microRNA as Repressors of Stress-Induced Anxiety: The Case of Amygdalar miR-34

MicroRNA as Upcoming Biomarkers for Psychiatric Conditions

Comorbidity Clusters in Autism Spectrum Disorders: An Electronic Health Record Time-Series Analysis

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