Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder

Étain, Bruno; Dumaine, Anne; Bellivier, Frank; Pagan, Cécile; Francelle, Laetitia; Goubran‐Botros, Hany; Moreno, Sarah; Deshommes, Jasmine; Moustafa, Khaled; Dudal, K. Le; Mathieu, Flavie; Henry, Chantal; Kahn, Jean‐Pierre; Launay, Jean‐Marie; Mühleisen, Thomas W.; Cichon, Sven; Bourgeron, Thomas; Leboyer, Marion; Jamain, Stéphane

doi:10.1093/hmg/dds227

Cited by 96 publications

(74 citation statements)

References 48 publications

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“…The presented results are in agreement with reports by Gałecki et al [35] and Etain et al [36], showing that a single-nucleotide polymorphism (SNP) in ASMT gene expression was associated with depression (a group of 181 patients with rDD and 149 controls). The presence of AA genotype of rs4446909 polymorphism and of GG genotype of rs5989681 polymorphism was associated with lower risk for having rDD (odds ratio=0.1;95% CI=0.03–0.58; p =0.007).…”

Section: Discussionsupporting

confidence: 93%

ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder

et al. 2014

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BackgroundRecurrent depressive disorder is a multifactorial disease; one of the typical features is cognitive impairment. The purpose of this study was analysis of ASMT gene expression both on mRNA and protein levels in patients with recurrent depressive disorder (rDD) and assessment of the relationship between plasma level of ASMT protein, gene expression on mRNA level, and cognitive performance.Material/MethodsThe study included 236 subjects: patients with rDD (n=131) and healthy subjects (n=105, CG). Cognitive function assessment was based on: Trail Making Test, The Stroop Test, Verbal Fluency Test (VFT), and Auditory Verbal Learning Test (AVLT).ResultsBoth mRNA and protein expression levels of ASMT gene were significantly higher in healthy subjects when compared to rDD. The average ASMT mRNA expression level measured for the entire group was M=0.21 (SD=0.09), and the protein level was M=12.84 (SD=3.29). In patients with rDD, statistically significant correlations occurred between both mRNA and protein expression levels and part A of the TMT (negative correlation) and verbal fluency test (positive correlation). In the group CG, there was no statistically significant association between the analyzed variables. In the entire group there was a statistically significant correlation between both ASMT mRNA and protein expression levels and all the neuropsychological tests used in the survey.Conclusions1. Our study confirms previous results showing decreased mRNA and protein expression levels of ASMT gene in depression. 2. Our data suggest a relationship between decreased mRNA and protein expression levels of ASMT gene and cognitive impairment.

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Section: Discussionsupporting

confidence: 93%

ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder

et al. 2014

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“…In contrast, natural product methyltransferases (NPMTs) comprise a diverse group of enzymes that frequently transfer methyl groups to small molecules from SAM as the methyl donor. Many NPMTs, including NNMT, are specifically expressed in nervous system tissues, and defects in function are associated with neurological disorders (summarized in Supplemental Figure 1A) (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). We interrogated the relative expression levels and prognostic significance of 11 NPMTs in the 2 largest GBM datasets, TCGA and REMBRANDT.…”

Section: Gbms Overexpress Nicotinamide (Nam) N-methyltransferase (Nnmt)mentioning

confidence: 99%

Nicotinamide metabolism regulates glioblastoma stem cell maintenance

Jung¹,

Kim²,

Wang³

et al. 2017

JCI Insight

109

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“…Consistent with these considerations, a CLOCK dominant negative mutation in mice, which may produce phase delay or delaying non-24-hour rhythms67 has been claimed to be a possible rodent model for mania 68. The ASMT rs4446909 G allele promotes phase delay possibly by delaying melatonin synthesis, thus promoting depression and bipolar disorder 32,69. An altered circadian relationship of BHLHE40 and PER2 was suggested in assays of depressed brains70 and may interact with CLOCK and CRY1 in bipolar disorder.…”

Section: Discussionmentioning

confidence: 95%

Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles

Kripke

Klimecki

Nievergelt

et al. 2014

Psychiatry Investig

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People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.

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Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder

Cited by 96 publications

References 48 publications

ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder

ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder

Nicotinamide metabolism regulates glioblastoma stem cell maintenance

Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles

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