Variations in FKBP5 and BDNF genes are suggestively associated with depression in a Swedish population-based cohort

Lavebratt, Catharina; Åberg, Elin; Sjöholm, Louise K.; Forsell, Yvonne

doi:10.1016/j.jad.2010.02.113

Cited by 132 publications

(103 citation statements)

References 57 publications

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“…Similarly, elevated glucocorticoid levels have been associated with larger amygdala volumes (Buss et al 2012;Lupien et al 2011). Considering a heightened amygdala response and a larger volume as possible endophenotypes for stress-related disorders, the present findings are in line with previous reports suggesting an important role of the FKBP5 T allele in mood disorders (Appel et al 2011;Binder et al 2004;Lavebratt et al 2010;Lekman et al 2008;Zobel et al 2010) and PTSD (Binder et al 2008).…”

Section: Discussionsupporting

confidence: 92%

“…Indeed, T homozygotes were found to exhibit elevated cortisol levels during recovery after stress (Ising et al 2008). In line with this, rs1360780 has been associated with psychopathology such as mood disorders (Binder et al 2004;Lavebratt et al 2010;Lekman et al 2008;Zobel et al 2010) and suicidality (Brent et al 2010). Moreover, this SNP has been shown to interact with childhood abuse in predicting PTSD symptoms (Binder et al 2008) and susceptibility to depression (Appel et al 2011), with an increased risk in the TT genotype following childhood abuse.…”

Section: Introductionmentioning

confidence: 76%

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Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

et al. 2014

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Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective selfreport (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. Abstract Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stresssensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxelbased morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective selfreport (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-env...

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 76%

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

et al. 2014

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“…The rs1360780 T allele was identified as the risk allele by three studies, the rs9470080 T allele by two studies, and the rs3800373 C allele by one study (Zannas and Binder 2014). Some studies did not take into account FKBP5 environment interactions and three studies found that the rs1360780 T allele was associated with increased risk of depression (Lekman et al 2008;Lavebratt et al 2010;Szczepankiewicz et al 2014), two studies found an effect of rs4713916 (Zobel et al 2010;Szczepankiewicz et al 2014), and non-replicated findings were reported for rs9470080, rs9296158 (Szczepankiewicz et al 2014) and rs3800373 (Zobel et al 2010).…”

Section: Genetic Polymorphismsmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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“…In all, 16 studies explored the interaction between childhood adversity and BDNF in depression, 4 reported a significant effect [73,74,76,77] and 5 showed partial support for this interaction [65][66][67][68]78] (see Table 3). For instance, rather than investigating child adversity as one overarching construct, Aguilera and colleagues [66] focused on different types and only found a significant interaction between child sexual abuse and BDNF.…”

Section: Childhood Adversitymentioning

confidence: 99%

Interaction between stress and the BDNF Val66Met polymorphism in depression: A systematic review and meta-analysis

Hosang¹,

Shiles²,

McGuffin³

et al. 2014

Comprehensive Psychiatry

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Background: Major depression is a disabling psychiatric illness with complex origins. Life stress (childhood adversity and recent stressful events) is a robust risk factor for depression. The relationship between life stress and Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has received much attention. The aim of the present work was to review and conduct a meta-analysis on the results from published studies examining this interaction. Methods: A literature search was conducted using PsychINFO and PubMed databases until 22 November 2013. A total of 22 studies with a pooled total of 14,233 participants met the inclusion criteria, the results of which were combined and a meta-analysis performed using the Liptak-Stouffer z-score method. Results: The results suggest that the Met allele of BDNF Val66Met significantly moderates the relationship between life stress and depression (P = 0.03). When the studies were stratified by type of environmental stressor, the evidence was stronger for an interaction with stressful life events (P = 0.01) and weaker for interaction of BDNF Val66Met with childhood adversity (P = 0.051). Conclusions:The interaction between BDNF and life stress in depression is stronger for stressful life events rather than childhood adversity. Methodological limitations of existing studies include poor measurement of life stress.

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Variations in FKBP5 and BDNF genes are suggestively associated with depression in a Swedish population-based cohort

Cited by 132 publications

References 57 publications

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Interaction between stress and the BDNF Val66Met polymorphism in depression: A systematic review and meta-analysis

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