Evidence for Linkage and Association of GABRB3 and GABRA5 to Panic Disorder

Hodges, Leslie C.; Fyer, Abby J.; Weissman, Myrna M.; Logue, Mark W.; Haghighi, Fatemeh; Evgrafov, Oleg V.; Rotondo, A; Knowles, James A.; Hamilton, Steven P.

doi:10.1038/npp.2014.92

Cited by 25 publications

(14 citation statements)

References 54 publications

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“…Further, meta-analyses reveal reduced cortical thickness in depressed patients within medial prefrontal and temporal regions 55 that show strong limbic cortico-striatal correlations within the current study. Our analyses additionally revealed genes implicated in ventral-striatal mediated behaviors, including OXT, GABRA3 , GABRA5 , GABRB1 , and GABRB3 , which have previously been linked to mesolimbic reward circuitry and risk for associated disorders 56 – 58 . Of note, 14% of the 505 AHBA limbic cortico-striatal genes have no established gene ontology annotation (count = 71), supporting the use of gene co-expression analyses as a tool for nominating genetic markers of behavior and mental illness.…”

Section: Discussionmentioning

confidence: 79%

Gene expression links functional networks across cortex and striatum

et al. 2018

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The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks. Network-associated expression is consistent across independent human datasets and evolutionarily conserved in non-human primates. Genes preferentially expressed within the limbic network (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and temporal pole) relate to risk for psychiatric illness, chloride channel complexes, and markers of somatostatin neurons. Somato/motor associated genes are enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses indicate that parallel cortico-striatal processing channels possess dissociable genetic signatures that recapitulate distributed functional networks, and nominate molecular mechanisms supporting cortico-striatal circuitry in health and disease.

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Section: Discussionmentioning

confidence: 79%

Gene expression links functional networks across cortex and striatum

et al. 2018

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“…This would account for the shared associations of each of these disorders with gamma-aminobutyric acid and endocannabanoid receptor physiology, 7 , 67 , 68 , 69 , 70 and the fact that benzodiazepines and exogenous cannabinoid use may be effective in aborting acute CVS attacks, 1 , 13 migraines, 70 seizures, 65 , 67 and panic attacks. 69 It would account for the utility of triptan medications in aborting migraines and CVS attacks. 1 , 18 , 55 It may also explain some reports of beneficial effects of nonsteroidal anti-inflammatory drugs in treating CVS.…”

Section: Introductionmentioning

confidence: 99%

The Cyclic Vomiting Syndrome Threshold: A Framework for Understanding Pathogenesis and Predicting Successful Treatments

Levinthal

2016

Clinical and Translational Gastroenterology

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Cyclic vomiting syndrome (CVS) is an uncommon, idiopathic disorder defined by recurrent, sudden-onset attacks of repetitive retching and vomiting that are separated by symptom-free intervals. CVS was long regarded as a disorder primarily experienced by children but is now known to present de novo in adulthood. Adult CVS has garnered more research attention over the past 20 years, and these efforts have identified some acute and prophylactic treatments for this disorder. However, CVS still lacks a unifying disease model, and this has hindered the development of new therapies. Here adult CVS is reframed as a neurogenic disorder, driven by various endophenotypic factors that shape patterns of activity within the neural circuits required for disease expression. The concept of the “CVS threshold” is put forth in parallel with exploring the remarkable similarity of adult CVS with features of chronic migraine, epilepsy, and panic disorder. Because of such shared neural mechanisms and overlapping endophenotypes, many therapies that have been developed for these other disorders could also be useful in managing CVS. This review seeks to achieve three primary aims: (1) to develop a comprehensive, explanatory framework for adult CVS pathogenesis, (2) to use this framework for identifying potentially novel therapies for CVS, and (3) to describe future research directions that are needed to move the field forward.

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“…The other genes in the distal chromosome 15q11.2‐q13 region include gamma aminobutyric acid (GABA) receptor subunits GABRB3, GABRA5 , and GABRG3 , which are not imprinted. Alterations in the GABAergic systems are associated with hunger (Turenius et al, ), anxiety (Hodges et al, ), OC symptoms, and addiction (Stephens, King, Lambert, Belelli, & Duka, ). While hypoactivity may contribute to obesity in PWS (Dhar et al, ), nearly 60% of our patients were reported to be hyperactive and perhaps this sheds some light on differences in metabolic phenotype in AS compared to PWS.…”

Section: Discussionmentioning

confidence: 99%

Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome

Carson

Bird

Childers

et al. 2019

Molec Gen & Gen Med

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Background Angelman Syndrome (AS) is a neurodevelopmental disorder with core features of intellectual disability, speech impairment, movement disorders, and a unique behavioral profile. Typically, AS results from absent maternal expression of UBE3A, but some individuals have imprinting defects in a portion of their cells. These individuals are mosaic for normal and defective UBE3A expression, resulting in mosaic AS (mAS) with a partial loss of gene expression. Methods This study aims to contrast the mAS phenotype to that of AS. Clinical characteristics of mAS were obtained from a parental survey of 22 mAS patients and from the Angelman Natural History study. These were contrasted with those of AS using historical data. Results Developmental delay was present in nearly all mAS patients, whereas the core features of AS were reported in less than 40%. While language and ability to manage activities of daily living were markedly improved over that expected in AS, mAS patients demonstrated a high incidence of behavioral challenges. Conclusion Clinical work‐up of an individual with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor should prompt methylation studies to rule out mAS. We expand the phenotypic spectrum of AS to include features that overlap with Prader‐Willi such as hyperphagia.

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Evidence for Linkage and Association of GABRB3 and GABRA5 to Panic Disorder

Cited by 25 publications

References 54 publications

Gene expression links functional networks across cortex and striatum

Gene expression links functional networks across cortex and striatum

The Cyclic Vomiting Syndrome Threshold: A Framework for Understanding Pathogenesis and Predicting Successful Treatments

Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome

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