| 181. |
- Larsson, F., et al.
(författare)
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Bipolar disorder type 1 was the most stable bipolar subdiagnosis
- 2021
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Ingår i: Lakartidningen. - 1652-7518. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- DSM-IV subcategorises bipolar disorders into type 1, type 2, and a third not otherwise specified (NOS) category. Although previous works suggest that these subtypes remain reasonably stable over time, it is unclear if subdiagnoses endure over time or if patients are commonly recategorized within the spectrum in a real-world clinical setting. We assessed subdiagnostic stability in 6,374 individuals with bipolar disorder using data from the Swedish national quality assurance register for bipolar disorders (BipoläR). Diagnoses at baseline registration - that could occur at any time point during the course of illness - were compared with diagnoses at follow-up registration 3 years later. Changes in subdiagnoses were analysed in relation to clinical setting, diagnostic procedure, and patient features. We found that 74 %, 67 %, and 47 % of patients diagnosed with bipolar disorder type 1, type 2, and NOS, respectively, retained the same subdiagnosis at the 3-year follow-up. The following factors were associated with higher rate of subdiagnostic transitions: previous suicide attempts, unemployment or low psychosocial function, treatment with antidepressants, and comorbid anxiety, neuropsychiatric, or personality disorder. Conversely, use and duration of mood stabilizer treatment, the use of structured diagnostic instruments, and treatment at an outpatient unit specialized in managing affective disorders were associated with lower likelihood of subdiagnostic transitions. Our findings confirm that bipolar disorder type 1 is the most stable subdiagnostic group, but findings also indicate a significant degree of subdiagnostic instability, particularly in the NOS group.
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| 182. |
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| 183. |
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| 184. |
- Lautner, Ronald, et al.
(författare)
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Apolipoprotein e genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease.
- 2014
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 71:10, s. 1183-91
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Tidskriftsartikel (refereegranskat)abstract
- Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown.
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| 185. |
- Lautner, Ronald, et al.
(författare)
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Preclinical effects of APOE epsilon 4 on cerebrospinal fluid A beta 42 concentrations
- 2017
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: From earlier studies it is known that the APOE epsilon 2/epsilon 3/epsilon 4 polymorphism modulates the concentrations of cerebrospinal fluid (CSF) beta-amyloid(1-42) (A beta 42) in patients with cognitive decline due to Alzheimer's disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the effect of APOE on CSF A beta 42 varies by age, to understand the association between APOE and the onset of preclinical AD. Methods: APOE genotype and CSF A beta 42 concentration were determined in a cohort comprising 716 cognitively healthy individuals aged 17-99 from nine different clinical research centers. Results: CSF concentrations of A beta 42 were lower in APOE epsilon 4 carriers than in noncarriers in a gene dose-dependent manner. The effect of APOE epsilon 4 on CSF A beta 42 was age dependent. The age at which CSF A beta 42 concentrations started to decrease was estimated at 50 years in APOE epsilon 4-negative individuals and 43 years in heterozygous APOE epsilon 4 carriers. Homozygous APOE epsilon 4 carriers showed a steady decline in CSF A beta 42 concentrations with increasing age throughout the examined age span. Conclusions: People possessing the APOE epsilon 4 allele start to show a decrease in CSF A beta 42 concentration almost a decade before APOE epsilon 4 noncarriers already in early middle age. Homozygous APOE epsilon 4 carriers might deposit A beta 42 throughout the examined age span. These results suggest that there is an APOE epsilon 4-dependent period of early alterations in amyloid homeostasis, when amyloid slowly accumulates, that several years later, together with other downstream pathological events such as tau pathology, translates into cognitive decline.
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| 186. |
- Lavebratt, C., et al.
(författare)
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The KMO allele encoding Arg(452) is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression
- 2014
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 19:3, s. 334-341
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Tidskriftsartikel (refereegranskat)abstract
- The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P = 0.005, n = 19) or schizophrenia (P = 0.02, n = 36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P = 0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P = 0.03) and reduced lymphoblastoid and hippocampal KMO expression (P <= 0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes.
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| 187. |
- Le Clerc, S., et al.
(författare)
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HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 x 10(-3); FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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| 188. |
- Lewis, Katie J S, et al.
(författare)
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Comparison of Genetic Liability for Sleep Traits Among Individuals With Bipolar Disorder I or II and Control Participants.
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:3, s. 303-310
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Tidskriftsartikel (refereegranskat)abstract
- Insomnia, hypersomnia, and an evening chronotype are common in individuals with bipolar disorder (BD), but whether this reflects shared genetic liability is unclear. Stratifying by BD subtypes could elucidate this association and inform sleep and BD research.To assess whether polygenic risk scores (PRSs) for sleep traits are associated with BD subtypes I and II.This case-control study was conducted in the United Kingdom and Sweden with participants with BD and control participants. Multinomial regression was used to assess whether PRSs for insomnia, daytime sleepiness, sleep duration, and chronotype are associated with BD subtypes compared with control participants. Affected individuals were recruited from the Bipolar Disorder Research Network. Control participants were recruited from the 1958 British Birth Cohort and the UK Blood Service. Analyses were repeated in an independent Swedish sample from August 2018 to July 2019. All participants were of European ancestry.Standardized PRSs derived using alleles from genome-wide association studies of insomnia, sleep duration, daytime sleepiness, and chronotype. These were adjusted for the first 10 population principal components, genotyping platforms, and sex.Association of PRSs with BD subtypes, determined by semistructured psychiatric interview and case notes.The main analysis included 4672 participants with BD (3132 female participants [67.0%]; 3404 with BD-I [72.9%]) and 5714 control participants (2812 female participants [49.2%]). Insomnia PRS was associated with increased risk of BD-II (relative risk [RR], 1.14 [95% CI, 1.07-1.21]; P = 8.26 × 10-5) but not BD-I (RR, 0.98 [95% CI, 0.94-1.03]; P = .409) relative to control participants. Sleep-duration PRS was associated with BD-I (RR, 1.10 [95% CI, 1.06-1.15]; P = 1.13 × 10-5) but not BD-II (RR, 0.99 [95% CI, 0.93-1.06]; P = .818). Associations between (1) insomnia PRS and BD-II and (2) sleep-duration PRS and BD-I were replicated in the Swedish sample of 4366 individuals with BD (2697 female participants [61.8%]; 2627 with BD-I [60.2%]) and 6091 control participants (3767 female participants [61.8%]). Chronotype and daytime-sleepiness PRS were not associated with BD subtypes.Per this analysis, BD subtypes differ in genetic liability to insomnia and hypersomnia, providing further evidence that the distinction between BD-I and BD-II has genetic validity. This distinction will be crucial in selecting participants for future research on the role of sleep disturbance in BD.
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| 189. |
- Li, M, et al.
(författare)
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Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.
- 2014
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 19:4
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64 888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10−5, odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10−6). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.
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| 190. |
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