Association between FKBP5 and CRHR1 genes with suicidal behavior: A systematic review

Cruz-Cano, Eduardo De la

doi:10.1016/j.bbr.2016.09.032

Cited by 24 publications

(17 citation statements)

References 77 publications

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“…The most common of those are related to acute or chronic exposure to stress, such as most neuropsychiatric disorders, mostly due to FKBP51’s stress inducibility and possibly to its key role in controlling GR function. With different degrees of involvement, FKBP51 has been previously associated with substance abuse [ 166 , 167 ], autism [ 168 ], bipolar disorder [ 169 , 170 ], depression [ 12 , 116 ], schizophrenia [ 171 ], post-traumatic stress disorder (PTSD) [ 172 , 173 ], suicide [ 174 ], attention-deficit/hyperactivity disorder [ 175 ], anxiety [ 176 ], and the effects of early trauma and stress in general [ 177 , 178 , 179 ].…”

Section: Functions Of Fkbp51mentioning

confidence: 99%

The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease

Fries

Gassen

Rein

2017

IJMS

126

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Among the chaperones and co-chaperones regulating the glucocorticoid receptor (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across different disciplines. This review provides an update on the role of the different co-chaperones of Hsp70 and Hsp90 in the regulation of GR function. The development leading to the focus on FKBP51 is outlined. Further, a survey of the vast literature on the mechanism and function of FKBP51 is provided. This includes its structure and biochemical function, its regulation on different levels—transcription, post-transcription, and post-translation—and its function in signaling pathways. The evidence portraying FKBP51 as a scaffolding protein organizing protein complexes rather than a chaperone contributing to the folding of individual proteins is collated. Finally, FKBP51’s involvement in physiology and disease is outlined, and the promising efforts in developing drugs targeting FKBP51 are discussed.

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Section: Functions Of Fkbp51mentioning

confidence: 99%

The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease

Fries

Gassen

Rein

2017

IJMS

126

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“…Corticotropin releasing hormone binding protein (CRHBP), FK506-binding protein 51 (FKBP5) and glucocorticoid receptor gene (NR3C1) promoters were significantly hypermethylated in depressed patients with largest effects in patients with severe suicidal ideation ( Roy et al, 2017 ). Even genetic studies point to significant associations between FKBP5 and CRHR1 genes and a high rate of attempted suicide ( De la Cruz-Cano, 2017 ) and some genetic studies have reported that CRHBP and FKBP5 genes interact with childhood trauma to increase the risk for suicidal behavior ( Roy et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents

et al. 2018

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The aim of this study, comprising 88 suicide attempters, was to identify hypothalamic-pituitary-adrenal (HPA) -axis coupled CpG-sites showing methylation shifts linked to severity of the suicide attempt. Candidate methylation loci were further investigated as risk loci for a general psychiatric risk score in two cohorts of adolescents (cohort 1 and 2). The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. Subjects were stratified into high-risk and low-risk groups based on the severity of the suicidal behavior. We included CpG sites located within 2000 basepairs away from transcriptional start site of the following HPA-axis coupled genes: corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FK506-binding protein 51 (FKBP5) and the glucocorticoid receptor (NR3C1). The methylation state of two corticotropin releasing hormone (CRH)-associated CpG sites were significantly hypomethylated in the high-risk group of suicide attempters (n = 31) (cg19035496 and cg23409074) (p < 0.001). Adolescent cohort 1 and 2 consisted of 129 and 93 subjects, respectively, and were stratified by the in silico generated DAWBA measurements of a general psychiatric risk score into high-risk group (>~50% risk) or controls. In adolescent cohort 2, cg19035496 was hypermethylated in subjects with a high general psychiatric risk score. Our results show epigenetic changes in the CRH gene related to severity of suicide attempt in adults and a general psychiatric risk score in adolescents.

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“…Umwelt-Interaktionen aus dem Bereich der HPA-Achse (5) wie FKBP5 mit Kindheitstraumata (14,44,45) eher stabil. Es bleibt abzuwarten, ob sich diese Interaktionen replizieren lassen.…”

Section: Fazitunclassified

Aspekte der Genetik, Epigenetik und Gen-Umwelt-Interaktion bei suizidalem Verhalten

Giegling¹,

Rujescu²

2017

Nervenheilkunde

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ZusammenfassungSuizidalem Verhalten liegt ein komplexes Zusammenspiel von vielen Faktoren zugrunde. Es wirken unterschiedliche Risiken zusammen, wie psychiatrische Erkrankungen, Persönlichkeitsparameter (z. B. Aggression, Impulsivität, Neurotizismus), schwere Kindheitstraumata, chronische Erkrankungen, soziale Faktoren (z. B. Arbeitslosigkeit, fehlendes soziales Netz, traumatische Lebensereignisse), kognitive Flexibilität sowie neurobiologische und genetische Faktoren. Dabei fungieren die letzteren im Sinne prädisponierender Risikofaktoren in Wechselwirkung mit Umweltfaktoren. Im Folgenden sollen die konsistentesten genetischen Befunde zusammengefasst werden. Insbesondere wird auf die familiäre Häufung suizidalen Verhaltens sowie auf die geschätzte Heritabilität von ca. 40–55% eingegangen. Darüber hinaus werden Kandidatengenstudien insbesondere aus dem Feld des serotonergen Systems vorgestellt, neuere genomweite Assoziationsstudien diskutiert sowie Gen-Umwelt-Analysen und epigenetische Ansätze beleuchtet.

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Association between FKBP5 and CRHR1 genes with suicidal behavior: A systematic review

Cited by 24 publications

References 77 publications

The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease

The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease

Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents

Aspekte der Genetik, Epigenetik und Gen-Umwelt-Interaktion bei suizidalem Verhalten

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