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  • 1
    In: Complex Psychiatry, S. Karger AG, Vol. 4, No. 1 ( 2018), p. 1-6
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder ( 〈 i 〉 N 〈 /i 〉 = 219). We analyzed these variants for a possible association with the suicide severity score (ranging from suicidal ideation/plan to serious suicide attempt) from the Schedule for Clinical Assessment in Neuropsychiatry. We conducted tests of individual variants and gene-based tests. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We found a number of DNA variants in the transforming growth factor beta receptor 1 gene ( 〈 i 〉 TGFBR1 〈 /i 〉 ) to be suggestively associated with suicide severity scores ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.005). The gene-based tests also pointed to 〈 i 〉 TGFBR1 〈 /i 〉 to be associated with suicide severity ( 〈 i 〉 p 〈 /i 〉 = 0.0001). However, these findings were not replicated in an independent bipolar disorder sample. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 We report no significant association between DNA sequences of drug target genes and suicidal behavior. Additional larger sequencing studies could further interrogate associations between variants in drug target genes and suicidal behavior.
    Type of Medium: Online Resource
    ISSN: 2673-3005 , 2673-298X
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 3021167-0
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  • 2
    In: Neuropsychobiology, S. Karger AG, Vol. 69, No. 3 ( 2014), p. 154-158
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Schizophrenia is a severe neuropsychiatric disorder where the role of & #947;-aminobutyric acid (GABA), an inhibitory neurotransmitter, has been implicated in its aetiopathophysiology. Several genes coding for GABA 〈 sub 〉 A 〈 /sub 〉 subunits, including the 〈 i 〉 GABRG2 〈 /i 〉 gene that encodes the & #947; 〈 sub 〉 2 〈 /sub 〉 subunit, are clustered at 5q31-q35, a chromosomal region that is associated with schizophrenia in genome scan studies. We recently reported 〈 i 〉 GABRG2 〈 /i 〉 to be associated with schizophrenia in our case-control and family samples. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We tested eight single-nucleotide polymorphisms spanning the 〈 i 〉 GABRG2 〈 /i 〉 gene for an association with suicidal behaviour in our schizophrenia sample of European ancestry (n = 197), taking into account history of alcohol abuse or dependence. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We found the haplotypes of the rs183294 and rs209356 markers to be significantly associated with history of suicide attempt (p 〈 0.01) as well as suicide specifier scores (p 〈 0.05). The association appeared to be originating in patients with a history of alcohol dependence or abuse. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Taken together, the results of the present study suggest that 〈 i 〉 GABRG2 〈 /i 〉 may be involved in suicidal behaviour in schizophrenia patients with alcohol dependence or abuse, but replications are required. These results may help in the discovery of novel treatments for alcoholism and/or prevention of suicide.
    Type of Medium: Online Resource
    ISSN: 0302-282X , 1423-0224
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
    detail.hit.zdb_id: 1483094-2
    SSG: 5,2
    SSG: 15,3
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  • 3
    In: Neuropsychobiology, S. Karger AG, Vol. 69, No. 1 ( 2014), p. 59-63
    Abstract: 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 Genetic variation in the fat mass- and obesity-associated gene (FTO) has been associated with obesity in the general population. In this study we have investigated these variants for association with antipsychotic-induced weight gain (AIWG). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 218 patients with chronic schizophrenia or schizoaffective disorder treated mostly with clozapine or olanzapine for up to 14 weeks were included in the study. We analyzed 4 polymorphisms in intron 1 of the FTO gene (rs1421085, rs8050136, rs9939609, rs9930506) for association with AIWG using ANCOVA. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 No statistically significant associations were observed between the single nucleotide polymorphisms and AIWG. However, patients homozygous for the A-allele of rs9939609 gained numerically higher weight than the other genotypic groups (AA: 5.26 ± 6.7%; TA: 4.66 ± 5.6%; TT: 4.21 ± 5.3%). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our current observations suggest that the FTO gene variants investigated may not play a major role in AIWG.
    Type of Medium: Online Resource
    ISSN: 0302-282X , 1423-0224
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
    detail.hit.zdb_id: 1483094-2
    SSG: 5,2
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 4
    In: Neuropsychobiology, S. Karger AG, Vol. 74, No. 3 ( 2016), p. 169-175
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Schizophrenia (SCZ) is a chronic severe neuropsychiatric disorder, where pharmacological treatment has been hindered by adverse effects, including antipsychotic-induced weight gain (AIWG) and related complications. Genetic studies have been exploring the appetite regulation and energy homeostasis pathways in AIWG with some promising leads. The serotonin system has been shown to participate in these pathways. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 In the current study, we examined single nucleotide polymorphisms across the serotonin receptor genes 〈 i 〉 HTR3A 〈 /i 〉 and 〈 i 〉 HTR3B 〈 /i 〉 . Prospective weight change was assessed for a total of 149 SCZ patients of European ancestry. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We did not find the tested 〈 i 〉 HTR3A 〈 /i 〉 or 〈 i 〉 HTR3B 〈 /i 〉 gene markers to be associated with AIWG in our sample. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our preliminary findings suggest that these receptors may not play a major role in predicting AIWG.
    Type of Medium: Online Resource
    ISSN: 0302-282X , 1423-0224
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
    detail.hit.zdb_id: 1483094-2
    SSG: 5,2
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 5
    In: Complex Psychiatry, S. Karger AG, Vol. 5, No. Suppl. 1 ( 2019), p. 34-43
    Abstract: Sleep disturbance affects about 75% of depressed individuals and is associated with poorer patient outcomes. The genetics in this field is an emerging area of research. Thus far, only core circadian genes have been examined in this context. We expanded on this by performing a genome-wide association study (GWAS) followed by a preplanned hypothesis-driven analysis with 27 genes associated with the biology of sleep. All participants were diagnosed by their referring physician, completed the Beck Depression Inventory (BDI), and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale at baseline. Our phenotype consisted of replies to 3 questions from these questionnaires. From standard GWAS chip data, imputations were performed. Baseline total BDI scores (n = 364) differed significantly between those with and those without sleep problems. We were unable to find any significant GWAS hits although our top hit was for changes in sleep and an intergenic marker near SNX18 (p = 1.06 × 10–6). None of the markers in our hypothesis-driven analysis remained significant after applying Bonferroni corrections. Our top finding among these genes was for rs13019460 of Neuronal PAS Domain Protein 2 with changes in sleep (p = 0.0009). Overall, both analyses were unable to detect any significant associations in our modest sample though we did find some interesting preliminary associations worth further exploration.
    Type of Medium: Online Resource
    ISSN: 2673-3005 , 2673-298X
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
    detail.hit.zdb_id: 3021167-0
    Location Call Number Limitation Availability
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