The Interleukin 1 Beta (IL1B) Gene Is Associated with Failure to Achieve Remission and Impaired Emotion Processing in Major Depression

Baune, Bernhard T.; Dannlowski, Udo; Domschke, Katharina; Janssen, Debbie G. A.; Jordan, Margaret A.; Ohrmann, Patricia; Bauer, Jochen; Biroš, Erik; Arolt, Volker; Kugel, Harald; Baxter, Alan G.; Suslow, Thomas

doi:10.1016/j.biopsych.2009.11.004

Cited by 179 publications

(109 citation statements)

References 47 publications

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“…SSRIs) treatment response accounts for genetic factors, progress in uncovering the particular genetic polymorphisms has been slow [112]. As described in Table 1, candidate gene studies have pointed to a number of genes and SNPs that may influence antidepressant treatment outcomes [6, 7, 8-10, 26, 27, 54], including polymorphisms within the COMT [8,30], HTR2A [54,86,121], HTR1A [26], CNR1 [26], SLC6A4 [9], NPY [6], MAOA [27,30], IL1B [7,30], GRIK4 [64], BDNF [30,86], GNB3 [30], FKBP5 [86], CYP2D6 [31,121], CYP2C19 [31,121], and ABCB1 [12,86] genes (Table 1). For example, a negative influence of a higher activity COMT 158 val/val genotype on antidepressant treatment response was shown [].…”

Section: Ssris Treatment For Major Depressive Disordermentioning

confidence: 99%

“…Depression and Sequence of Treatment study The Depression and Sequence of Treatment (DAST) study is a prospective naturalistic treatment study of 746 inpatients diagnosed with a major depressive disorder of adult age (> 18 years of age) collected at the Department of Psychiatry and Psychotherapy at the University of Münster, Germany [7,8,37]. MDD was diagnosed using a structured clinical diagnostic interview (SCID).…”

Section: International Ssri Pharmacogenomics Consortium Studymentioning

confidence: 99%

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Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

2017

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Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry. So far, the progress of uncovering single nucleotide polymorphisms (SNPs) underpinning treatment efficacy in mood disorders (e.g., SNPs associated with selective serotonin re-uptake inhibitors or lithium treatment response in patients with bipolar disorder and major depressive disorder) are encouraging, but not adequate. Genetic studies have pointed to a number of SNPs located at candidate genes that possibly influence response to; (a) antidepressants COMT, HTR2A, HTR1A, CNR1, SLC6A4, NPY, MAOA, IL1B, GRIK4, BDNF, GNB3, FKBP5, CYP2D6, CYP2C19, and ABCB1 and (b) mood stabilizers (lithium) 5-HTT, TPH, DRD1, FYN, INPP1, CREB1, BDNF, GSK3β, ARNTL, TIM, DPB, NR3C1, BCR, XBP1, and CACNG2. We suggest three alternative and complementary strategies to implement knowledge gained from pharmacogenomic studies. The first strategy can be to implement diagnostic, therapeutic, or prognostic genetic testing based on candidate genes or gene products. The second alternative is an integrative analysis (systems genomics approach) to combine omics data obtained from the different pillars of omics investigation, including genomics, epigenomes, proteomics, metabolomics and microbiomes. The main goal of system genomics is an identification and understanding of biological pathways, networks, and modules underlying drug-response. The third strategy aims to the development of multivariable diagnostic or prognostic algorithms (tools) combining individual's genomic information (polygenic score) with other predictors (e.g., omics pillars, neuroimaging, and clinical characteristics) to finally predict therapeutic outcomes. An integration of molecular science with that of traditional clinical practice is the way forward to drug discoveries and novel therapeutic approaches and to characterize psychiatric disorders leading to a better predictive, preventive, and personalized medicine (PPPM) in psychiatry. With future advances in the omics technology and methodological developments for data integration, the goal of PPPM in psychiatry is promising.

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Section: Ssris Treatment For Major Depressive Disordermentioning

confidence: 99%

Section: International Ssri Pharmacogenomics Consortium Studymentioning

confidence: 99%

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

2017

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“…The G allele of the rs16944 polymorphism (located within the promoter of the IL-1b gene) has been associated with SSRI non-response (Yu et al 2003;Tadic et al 2008;Baune et al 2010) and with recurrent major depression (Borkowska et al 2011). In addition, IL-1b promoter polymorphism rs1143627 was also associated with recurrent major depression (Borkowska et al 2011).…”

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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“…Among various factors of inflammation, IL-1β appears to have particularly strong association with depression [17,18,20,42]. Recent studies have reported the association between the polymorphism of IL1-β promoter and major depression [43], and they have even implicated IL-β gene polymorphism (specifically its rs16944 variant, which results in the increased IL1-β levels) in the lack of response to SSRI [44].…”

Section: Il-1ra Monotherapymentioning

confidence: 99%

Interleukin-1beta Causes Fluoxetine Resistance in an Animal Model of Epilepsy-Associated Depression

et al. 2012

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Depression represents a common comorbidity of epilepsy and is frequently resistant to selective serotonin reuptake inhibitors (SSRI). We tested the hypothesis that the SSRI resistance in epilepsy associated depression may be a result of a pathologically enhanced interleukin-1β (IL1-β) signaling, and consequently that the blockade of IL1-β may restore the effectiveness of SSRI. Epilepsy and concurrent depression-like impairments were induced in Wistar rats by pilocarpine status epilepticus (SE). The effects of the 2-week long treatment with fluoxetine, interleukin-1 receptor antagonist (IL-1ra), and their combination were examined using behavioral, biochemical, neuroendocrine, and autoradiographic assays. In post-SE rats, depression-like impairments included behavioral deficits indicative of hopelessness and anhedonia; the hyperactivity of the hypothalamo-pituitaryadrenocortical axis; the diminished serotonin output from raphe nucleus; and the upregulation of presynaptic serotonin 1-A (5-HT1A) receptors. Fluoxetine monotherapy exerted no antidepressant effects, whereas the treatment with IL-1ra led to the complete reversal of anhedonia and to a partial improvement of all other depressive impairments. Combined administration of fluoxetine and IL-1ra completely abolished all hallmarks of epilepsy-associated depressive abnormalities, with the exception of the hyperactivity of the hypothalamopituitary-adrenocortical axis, the latter remaining only partially improved. We propose that in certain forms of depression, including but not limited to depression associated with epilepsy, the resistance to SSRI may be driven by the pathologically enhanced interleukin-1β signaling and by the subsequent upregulation of presynaptic 5-HT1A receptors. In such forms of depression, the use of interleukin-1β blockers in conjunction with SSRI may represent an effective therapeutic approach.

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The Interleukin 1 Beta (IL1B) Gene Is Associated with Failure to Achieve Remission and Impaired Emotion Processing in Major Depression

Cited by 179 publications

References 47 publications

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

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

Interleukin-1beta Causes Fluoxetine Resistance in an Animal Model of Epilepsy-Associated Depression

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