Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment

Papiol, Sergi; Arias, Bárbara; Gastó, Cristòbal; Gutiérrez, Blanca; Catalán, Rosa; Fañanás, Lourdes

doi:10.1016/j.jad.2007.02.017

Cited by 169 publications

(135 citation statements)

References 40 publications

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“…Especially when gene-environment interactions contribute to the pathophysiology of a distinct genetic marker, nonreplications of direct gene effects could occur because of low rates of childhood abuse exposure in the investigated samples (Gawlik et al, 2006;Papiol et al, 2007). Likewise, in our sample, no direct association between rs1360780 and depression was observed.…”

Section: Discussionmentioning

confidence: 60%

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Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population

Appel

Schwahn

Mahler

et al. 2011

Neuropsychopharmacol

215

151

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Childhood maltreatment and depressive disorders have both been associated with a dysregulation of the hypothalamic-pituitary-adrenal axis. The FKBP5 gene codes for a co-chaperone regulating the glucocorticoid-receptor sensitivity. Previous evidence suggests that subjects carrying the TT genotype of the FKBP5 gene single-nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to adverse effects of experimental stress. We therefore tested the hypothesis of an interaction of childhood abuse with rs1360780 in predicting adult depression. In all, 2157 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and Childhood Trauma Questionnaire. The DSM-IV diagnosis of major depressive disorder (MDD) was assessed by interview. Genotypes of rs1360780 were taken from the Affymetrix Human SNP Array 6.0. Significant interaction (p ¼ 0.006) of physical abuse with the TT genotype of rs1360780 was found increasing the BDI-II score to 17.4 (95% confidence interval (CI) ¼ 12.0-22.9) compared with 10.0 (8.2-11.7) in exposed CC/CT carriers. Likewise, the adjusted odds ratio for MDD in exposed TT carriers was 8.2 (95% CI ¼ 1.9-35.0) compared with 1.3 (0.8-2.3) in exposed subjects with CC/CT genotypes. Relative excess risk due to interaction (RERI) analyses confirmed a significant additive interaction effect (RERI ¼ 6.8; po0.05). In explorative analyses, the most severe degree of sexual and emotional abuse also yielded significant interaction effects (po0.05). This study revealed interactions between physical abuse and rs1360780 of the FKBP5 gene, confirming its role in the individual susceptibility to depression. Given the large effect sizes, rs1360780 could be included into prediction models for depression in individuals exposed to childhood abuse.

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Section: Discussionmentioning

confidence: 60%

“…In the STAR*D study, only the CT genotype but not the T allele was associated with depression in White non-Hispanics compared with controls (Lekman et al, 2008). In some clinical samples with smaller size no association was found (Gawlik et al, 2006;Papiol et al, 2007).…”

Section: Introductionmentioning

confidence: 90%

Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population

Appel

Schwahn

Mahler

et al. 2011

Neuropsychopharmacol

215

151

View full text Add to dashboard Cite

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“…CRF seems to enhance its own response to stress by increasing amount of CRFR1 in the CRF neural circuits within the PVN by an ultra short positive feedback loop as part of the functional adaptation of the HPA axis in response to stress. Indeed, a CRFR1 polymorphism is associated with an increased risk to present a seasonal pattern and an early onset of the first depressive episode, 49 indicating a possible causal role of this receptor in the pathogenesis of some aspects of depression. Moreover, CRFR1 seems to be involved in the antidepressant response to selective serotonin reuptake blocker.…”

Section: Crf Neurons and Crfr1 And Crfr2 Imbalancementioning

confidence: 99%

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

et al. 2008

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Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-b and tumor necrosis factor-a, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-a, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.

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“…FKBP5 activates glucocorticoid receptors and the hypothalamic-pituitary-adrenal axis, which regulate response to stress (Binder et al, 2004). Additionally, the corticotropin releasing hormone 1 (CRH1) variant is correlated with early onset of depressive symptoms (Papiol et al, 2007). CRH activates the HPA axis, thus supporting the role of the HPA axis in mediating depressive behavior.…”

Section: Genetic Predictors Of Depression and Antidepressant Responsementioning

confidence: 98%

Biological Alterations in Depression

Benton¹,

Wiltshire²

2011

Psychiatric Disorders - Trends and Developments

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Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment

Cited by 169 publications

References 40 publications

Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population

Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

Biological Alterations in Depression

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