Pleiotropic genes in psychiatry: Calcium channels and the stress-related FKBP5 gene in antidepressant resistance

Fabbri, Chiara; Corponi, Filippo; Albani, Diego; Forloni, Gianluigi; Schruers, Koen; Kasper, Siegfried; Kautzky, Alexander; Zohar, Joseph; Souery, Daniel; Montgomery, Stuart; Cristalli, Carlotta Pia; Mantovani, Vilma; Mendlewicz, Julien; Serretti, Alessandro

doi:10.1016/j.pnpbp.2017.10.005

Cited by 36 publications

(46 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data evidenced different outcomes (remission and response) for anxiety-related symptoms (HARS) and mania-related symptoms (YMRS). Unfortunately, we were not able to fully replicate the results obtained for depressive symptoms in a previous work by our group [38]. It has to be noted, though, that we previously investigated a major depressive disorder sample, which presents some differences compared to BPD.…”

Section: Discussioncontrasting

confidence: 72%

See 1 more Smart Citation

FKBP5 Gene Variants May Modulate Depressive Features in Bipolar Disorder

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background: Previous evidence suggested the possible association of FK506 binding protein 5 (FKBP5) gene variants in bipolar disorder (BPD). Objective: Given the need of refinement of the findings obtained in large but poorly phenotyped samples, this study investigated the possible role of variants within FKBP5 in a small but deeply phenotyped BPD sample. Methods: A sample (N = 131) of bipolar patients were investigated with 10 polymorphisms within the FKBP5 gene. A control sample (N = 65) was also used for the analyses. Treatment response and remission of symptoms were evaluated using of the Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Young Mania Rating Scale (YMRS). The same analyses were also performed on the depressive subsample of BPD (D.BPD). Results: rs3800373 was associated with disorder risk in the depressive BPD subsample with the G allele being more frequent in subjects with a D.BPD phenotype. This was the only association that survived statistical correction. Conclusions: rs3800373 FKBP5 may increase the risk of developing predominantly depressed BPD, probably through the creation of an enhancer consensus sequence in the 3′UTR of the gene, thus potentially increasing its expression. This finding seems to be partially supported by literature data, which evidenced increased levels of FKBP5 in psychiatric subjects.

show abstract

Section: Discussioncontrasting

confidence: 72%

“…The choice of the single-nucleotide polymorphisms (SNPs) was performed through a literature review of the data available on FKBP5 and its correlation with psychiatric disorders [31, 37, 38]. The list of SNPs was further enriched to guarantee its maximum possible coverage of the gene.…”

Section: Methodsmentioning

confidence: 99%

FKBP5 Gene Variants May Modulate Depressive Features in Bipolar Disorder

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Some studies have already tested this approach, despite convincing independent replication is lacking. [79][80][81] The improvement in our statistical analysis methods and in genotyping technologies will both contribute to the evolution of pharmacogenomics in the next years. For example, the cost of genotyping has shown more than an exponential decrease after 2007 and the cost for sequencing a human genome dropped from $95.263.072 in 2001 to $1.121 in 2017.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics and Depression: A Critical Perspective

Corponi

Fabbri

Serretti

2019

Psychiatry Investig

Self Cite

View full text Add to dashboard Cite

Depression leads the higher personal and socio-economical burden within psychiatric disorders. Despite the fact that over 40 antidepressants (ADs) are available, suboptimal response still poses a major challenge and is thought to be partially a result of genetic variation. Pharmacogenetics studies the effects of genetic variants on treatment outcomes with the aim of providing tailored treatments, thereby maximizing efficacy and tolerability. After two decades of pharmacogenetic research, variants in genes coding for the cytochromes involved in ADs metabolism (CYP2D6 and CYP2C19) are now considered biomarkers with sufficient scientific support for clinical application, despite the lack of conclusive cost/effectiveness evidence. The effect of variants in genes modulating ADs mechanisms of action (pharmacodynamics) is still controversial, because of the much higher complexity of ADs pharmacodynamics compared to ADs metabolism. Considerable progress has been made since the era of candidate gene studies: the genomic revolution has made possible to assess genetic variance on an unprecedented scale, throughout the whole genome, and to analyze the cumulative effect of different variants. The results have revealed key information on the biological mechanisms mediating ADs effect and identified hypothetical new pharmacological targets. They also paved the way for future availability of polygenic pharmacogenetic panels to predict treatment outcome, which are expected to explain much higher variance in ADs response compared to CYP2D6 and CYP2C19 only. As the demand and availability of AD pharmacogenetic testing is projected to increase, it is important for clinicians to keep abreast of this evolving area to facilitate informed discussions with their patients. Psychiatry Investig 2019;16(9):645-653cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/bync/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

show abstract

“…Genes candidates were selected based on previous data implicating an association with the studies SNPs and clinical syndrome of depression [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]; anxiety [42][43][44] or stress [45] diagnosed according to Diagnostic and Statistical Manual of Mental Disorders and/or International Statistical Classification of Diseases. The genotyping analysis of candidate genes polymorphism was analyzed using Agene ® MassARRAY platform.…”

Section: Mass Array Genotypingmentioning

confidence: 99%

“…These genes may be associated with depression or anxiety; however, there are ample studies which have failed to replicate the same results in the candidate gene literature [29][30][31]. One explanation for this lack of success in producing the replicable main effect of these genes is that the certain genetic variants are highly dependent on the gender, population, and disease-related outcomes [32]; even though these studies have recruited patients with major depressive disorder [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]; anxiety disorder [42][43][44]; and post-traumatic stress disorders [45] diagnosed according to Diagnostic and Statistical Manual of Mental Disorders and/or International Statistical Classification of Diseases. This has led to increasing skepticism about the true association or lack thereof between candidate genes and psychological symptoms of depression, anxiety and/or stress.…”

Section: Introductionmentioning

confidence: 99%

Association Analysis of 14 Candidate Gene Polymorphism with Depression and Stress among Gestational Diabetes Mellitus

Lee

Ching

Ramachandran

et al. 2019

Genes

View full text Add to dashboard Cite

The association of candidate genes and psychological symptoms of depression, anxiety, and stress among women with gestational diabetes mellitus (GDM) in Malaysia was determined in this study, followed by the determination of their odds of getting psychological symptoms, adjusted for socio-demographical background, maternal, and clinical characteristics. Single nucleotide polymorphisms (SNPs) recorded a significant association between SNP of EPHX2 (rs17466684) and depression symptoms (AOR = 7.854, 95% CI = 1.330-46.360) and stress symptoms (AOR = 7.664, 95% CI = 1. 579-37.197). Associations were also observed between stress symptoms and SNP of OXTR (rs53576) and (AOR = 2.981, 95% CI = 1.058-8.402) and SNP of NRG1 (rs2919375) (AOR = 9.894, 95% CI = 1.159-84.427). The SNP of EPHX2 (rs17466684) gene polymorphism is associated with depression symptoms among Malaysian women with GDM. SNP of EPHX2 (rs17466684), OXTR (rs53576) and NRG1 (rs2919375) are also associated with stress symptoms.

show abstract

Pleiotropic genes in psychiatry: Calcium channels and the stress-related FKBP5 gene in antidepressant resistance

Cited by 36 publications

References 57 publications

<b><i>FKBP5</i></b> Gene Variants May Modulate Depressive Features in Bipolar Disorder

<b><i>FKBP5</i></b> Gene Variants May Modulate Depressive Features in Bipolar Disorder

Pharmacogenetics and Depression: A Critical Perspective

Association Analysis of 14 Candidate Gene Polymorphism with Depression and Stress among Gestational Diabetes Mellitus

Contact Info

Product

Resources

About