| 1. |
- Backlund, Lena, et al.
(författare)
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Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder.
- 2011
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 13:5-6, s. 500-8
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene.
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| 2. |
- Hukic, Dzana Sudic, et al.
(författare)
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Cognitive Manic Symptoms in Bipolar Disorder Associated with Polymorphisms in the DAOA and COMT Genes
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.Methodology:Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. Results: The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. Conclusion:Identifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population. © 2013 Hukic et al.
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| 3. |
- Hukic, Dzana Sudic
(författare)
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Genetic association studies of symptoms, comorbidity and outcome in bipolar disorder and schizophrenia
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Schizophrenia and bipolar disorder are complex brain disorders. Research has focused on applying brain research to understand the etiology, as well as clinical research to improve treatment, prognosis and progression. Schizophrenia and bipolar disorder are not lethal in and of themselves, but suicide and the presence of associated physical illnesses are of great concern, since these are the major causes of shortened life in afflicted individuals. In particular, the prevalence of type 2 diabetes and cardiovascular disease are twice as great in schizophrenia and bipolar disorder. By shifting the focus to underlying, sometimes comorbid causes, it is possible to increase knowledge of morbidity and mortality in cardiovascular disease, and thus improve the prognosis and progression for individuals with schizophrenia and bipolar disorder. Another interesting strategy for better understanding such complex disorders is to limit examination to symptoms in order to distinguish the genetics of the symptoms from the disorder itself. Genetic association studies are often used to investigate complex disease. The aim of this thesis was to investigate genetic associations between gene variants and metabolic risk factors in schizophrenia and bipolar disorder patients. An additional aim was to investigate known psychiatric risk genes in the dopamine system and their association to cognitive function. In Study I, D-amino acid oxidase activator gene (DAOA) and catechol-O-methyltransferase gene (COMT) were analyzed for allelic association to cognitive dysfunction in bipolar disorder patients. In Studies II-V, common metabolic risk gene variants were analyzed for allelic association to metabolic risk factors in schizophrenia and bipolar disorder patients, and to disorders per se. In Study VI, metabolic risk variants were analyzed for possible association to high-sensitive troponin T levels, which is a sensitive biomarker of cardiovascular damage in patients with acute coronary syndrome. In study I, single nucleotide polymorphisms in D-amino acid oxidase activator gene (DAOA) and catechol-O-methyltransferase gene (COMT) were associated to cognitive dysfunction in bipolar disorder patients. Data also suggest interaction between these genes. In studies II-V, single nucleotide polymorphisms in common metabolic risk genes: insulin-like growth factor II mRNA binding protein 2 (IGF2BP2), neurogenic locus notch homolog 2 (NOTCH2), thyroid adenoma associated (THADA), wolfram syndrome 1 (WFS1), purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7), and melatonin receptor 1B (MTNR1B) were associated with increased fasting plasma glucose in schizophrenia. Peroxisome proliferatoractivated receptor delta gene (PPARD) was associated with schizophrenia independent of glucose levels. Single nucleotide polymorphisms in common metabolic risk genes: calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), melanoma inhibitory activity family, member 3 (MIA3), purinergic receptor P2X, ligand-gated ion channel, 7 gene (P2RX7), muscle RAS oncogene homolog gene (MRAS), SMAD family member 3 gene (SMAD3), peroxisome proliferator-activated receptor delta gene (PPARD), melatonin receptor 1B gene (MTNR1B), neurogenic locus notch homolog 2 gene (NOTCH2), HNF1 homeobox B gene (HNF1B) were associated with increased waist circumference in schizophrenia patients. Peroxisome proliferator-activated receptor delta gene (PPARD), melatonin receptor 1B gene (MTNR1B), neurogenic locus notch homolog 2 gene (NOTCH2), and homeobox B gene (HNF1B) were associated with schizophrenia irrespective of waist circumference. A genetic overlap between schizophrenia and bipolar disorder was identified through an association between melatonin receptor 1B gene (MTNR1B) and increased fasting plasma glucose also in bipolar disorder patients. Neurogenic locus notch homolog 2 gene (NOTCH2) was associated to bipolar disorder per se. In study VI, melatonin receptor 1B gene (MTNR1B) and neurogenic locus notch homolog 2 gene (NOTCH2) were associated with high-sensitive troponin T levels in schizophrenia women. Our genetic findings regarding D-amino acid oxidase activator gene (DAOA) and catecholO-methyltransferase gene (COMT) are in line with the dopamine hypothesis of cognitive function. Single nucleotide polymorphisms that increase metabolic risk in the general population are associated with elevated plasma glucose and increased waist circumference among schizophrenia and bipolar disorder patients, as well as with schizophrenia and bipolar disorder per se. The melatonin receptor 1B gene (MTNR1B) –dependent vulnerability for elevated fasting plasma glucose levels is evident in both schizophrenia and bipolar disorder. Neurogenic locus notch homolog 2 gene (NOTCH2) is associated to both to schizophrenia and bipolar disorder type 1 per se. These findings may reflect increased metabolic genetic vulnerability in schizophrenia and bipolar disorder patients, as well as common genetics between type 2 diabetes mellitus and these psychiatric disorders. In addition, in women with schizophrenia, there is a possible metabolic genetic component affecting high-sensitive troponin T levels, a biomarker for cardiovascular damage in individuals with acute coronary syndrome (chest pain).
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| 4. |
- Hukic, Dzana Sudic, et al.
(författare)
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Troponin T levels associated with genetic variants in NOTCH2 and MTNR1B in women with psychosis
- 2017
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 250, s. 217-220
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Tidskriftsartikel (refereegranskat)abstract
- Psychosis patients have increased prevalence of metabolic disorders, which increase the risk for cardiovascular disease. Elevated troponin T level is an early biomarker of cardiovascular damage. We tested for association between troponin T levels and genetic risk variants of elevated blood glucose level in psychosis. Glucose and troponin T levels correlated positively. MTNR1B rs10830963 and NOTCH2 rs10923931 associated with troponin T levels in women, adjusted for glucose levels. These findings may indicate metabolic genetic influences on troponin T levels among women with psychosis.
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| 5. |
- Olsson, Eric, et al.
(författare)
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Diabetes and glucose disturbances in patients with psychosis in Sweden
- 2015
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Ingår i: BMJ Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication.METHOD:We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ(2) test, and factors associated with antidiabetic treatment were evaluated with logistic regression.RESULTS:Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1-6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness.CONCLUSIONS:The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.
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