| 1. |
- Konki, Mikko, et al.
(författare)
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Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease.
- 2019
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Ingår i: Clinical Epigenetics. - : BioMed Central. - 1868-7083 .- 1868-7075. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alzheimer's disease results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. Environmental and lifestyle factors largely modulate the disease risk and may influence the pathogenesis through epigenetic mechanisms, such as DNA methylation. As environmental and lifestyle factors may affect multiple tissues of the body, we hypothesized that the disease-associated DNA methylation signatures are detectable in the peripheral blood of discordant twin pairs.RESULTS: Comparison of 23 disease discordant Finnish twin pairs with reduced representation bisulfite sequencing revealed peripheral blood DNA methylation differences in 11 genomic regions with at least 15.0% median methylation difference and FDR adjusted p value ≤ 0.05. Several of the affected genes are primarily associated with neuronal functions and pathologies and do not display disease-associated differences in gene expression in blood. The DNA methylation mark in ADARB2 gene was found to be differentially methylated also in the anterior hippocampus, including entorhinal cortex, of non-twin cases and controls. Targeted bisulfite pyrosequencing of the DNA methylation mark in ADARB2 gene in 62 Finnish and Swedish twin pairs revealed that, in addition to the disease status, DNA methylation of this region is influenced by gender, age, zygosity, APOE genotype, and smoking. Further analysis of 120 Swedish twin pairs indicated that this specific DNA methylation mark is not predictive for Alzheimer's disease and becomes differentially methylated after disease onset.CONCLUSIONS: DNA methylation differences can be detected in the peripheral blood of twin pairs discordant for Alzheimer's disease. These DNA methylation signatures may have value as disease markers and provide insights into the molecular mechanisms of pathogenesis. We found no evidence that the DNA methylation marks would be associated with gene expression in blood. Further studies are needed to elucidate the potential importance of the associated genes in neuronal functions and to validate the prognostic or diagnostic value of the individual marks or marker panels.
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| 2. |
- Einarsdottir, Elisabet, et al.
(författare)
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Identification of NCAN as a candidate gene for developmental dyslexia.
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- A whole-genome linkage analysis in a Finnish pedigree of eight cases with developmental dyslexia (DD) revealed several regions shared by the affected individuals. Analysis of coding variants from two affected individuals identified rs146011974G > A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD in the pedigree. This variant prompted us to consider this gene as a putative candidate for DD. The RNA expression pattern of the NCAN gene in human tissues was highly correlated (R > 0.8) with that of the previously suggested DD susceptibility genes KIAA0319, CTNND2, CNTNAP2 and GRIN2B. We investigated the association of common variation in NCAN to brain structures in two data sets: young adults (Brainchild study, Sweden) and infants (FinnBrain study, Finland). In young adults, we found associations between a common genetic variant in NCAN, rs1064395, and white matter volume in the left and right temporoparietal as well as the left inferior frontal brain regions. In infants, this same variant was found to be associated with cingulate and prefrontal grey matter volumes. Our results suggest NCAN as a new candidate gene for DD and indicate that NCAN variants affect brain structure.
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| 3. |
- Härkönen, Juho, et al.
(författare)
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Education is the strongest socio-economic predictor of smoking in pregnancy
- 2018
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 113:6, s. 1117-1126
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate socio-economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions. Design Cross-sectional analysis with linked survey and register data. Setting South-western Finland. Participants A total of 2667 pregnant women [70% of the original sample (n=3808)] from FinnBrain, a prospective pregnancy cohort study. Measurements The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire-based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio-economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated. Findings Mother's education was the strongest socio-economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI)=1.2-3.9; P=0.011] for tertiary vocational education, 4.4 (95% CI=2.1-9.0; P<0.001) for combined general and vocational secondary education, 2.9 (95% CI=1.4-6.1; P=0.006) for general secondary education, 9.5 (95% CI 5.0-18.2; P<0.001) for vocational secondary education and 14.4 (95% CI=6.3-33.0; P<0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR=1.8; 95% CI=1.1-3.1; P=0.022). Antenatal stress predicted SIP (aOR=2.0; 95% CI=1.4-2.8; P<0.001), but did not attenuate its socio-economic disparities. Conclusions In Finland, socio-economic disparities in smoking in pregnancy are attributable primarily to differences in the mother's educational level (low versus high) and orientation (vocational versus general).
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| 4. |
- Kotimäki, Sanni, et al.
(författare)
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Educational differences in prenatal anxiety and depressive symptoms and the role of childhood circumstances
- 2020
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Ingår i: SSM - Population Health. - : Elsevier BV. - 2352-8273. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Despite interest in unequal maternal and child health, previous research has not focused on educational differences in anxiety and depressive symptoms during pregnancy, although they threaten maternal and child wellbeing. Using the prospective FinnBrain Cohort Study data on 2763 pregnant women over the three pregnancy trimesters and Finnish register data, we estimated multilevel regressions to describe educational differences in prenatal anxiety and depressive symptoms and to analyze whether they can be explained by socioeconomic background, parental mental disorders and adverse experiences during childhood. Prenatal anxiety was measured by the Symptom Checklist (SCL-90-anxiety subscale) and depressive symptoms by the Edinburgh Postnatal Depression Scale (EPDS). The results showed less anxiety and depressive symptoms among more educated pregnant women. In accounting for the educational differences, we found support for both the social selection and the social causation perspectives. Adverse childhood experiences partly explained the educational differences, highlighting the role of an undisturbed childhood environment in prenatal mental health disparities. Results from the regression models as well as sensitivity analyses also suggested that education is likely to buffer against prenatal distress.
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| 5. |
- Nordberg, Agneta, et al.
(författare)
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A European multicentre PET study of fibrillar amyloid in Alzheimer's disease
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:1, s. 104-114
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. In this study 238 [C-11]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [C-11]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 +/- 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 +/- 8 years) and 51 healthy controls (mean age 67.4 +/- 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 +/- 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. [C-11]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [C-11]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [C-11]PIB retention was observed in MCI ApoE epsilon 4 carriers compared to non-ApoE epsilon 4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. This study demonstrated the robustness of [C-11]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.
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| 6. |
- Porthan, Elviira, et al.
(författare)
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Childhood trauma and fear of childbirth : findings from a birth cohort study
- 2023
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Ingår i: Archives of Women's Mental Health. - 1434-1816 .- 1435-1102. ; 26:4, s. 523-529
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to investigate if experiencing childhood trauma (emotional abuse, emotional neglect, physical abuse, physical neglect, or sexual abuse) or a greater total burden of childhood trauma increase the risk of fear of childbirth (FOC). This study included 2556 women living in Southwest Finland. Women were recruited during routine ultrasound visits at gestational week (gwk) 12. Experiencing childhood trauma was assessed in retrospect with the Trauma and Distress Scale (TADS) questionnaire completed at gwk 14. Information on the diagnosis of FOC (ICD-10 diagnosis O99.80) was obtained from the Finnish Medical Birth Register. Associations between childhood trauma (domains and total TADS score) and FOC were analyzed with logistic regression in unadjusted and adjusted models. Emotional abuse (aOR 1.25, 95% CI 1.10–1.42), emotional neglect (aOR 1.26, 95% CI 1.08–1.46), and a greater total burden of trauma (TADS total score) (aOR 1.06, 95% CI 1.02–1.10) increased the risk for FOC. We found no evidence for physical abuse (aOR 1.15, 95% CI 1.00–1.32), physical neglect (aOR 1.06, 95% CI 0.92–1.22), and sexual abuse (aOR 1.24, 95% CI 0.99–1.56) associating with FOC. Childhood emotional abuse, emotional neglect, and a greater total burden of childhood trauma increase the risk for FOC. However, the childhood traumatic events were inquired in retrospect, which could distort the events.
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| 7. |
- Pulli, E. P., et al.
(författare)
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Prenatal exposures and infant brain: Review of magnetic resonance imaging studies and a population description analysis
- 2019
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 40:6, s. 1987-2000
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Tidskriftsartikel (refereegranskat)abstract
- Brain development is most rapid during the fetal period and the first years of life. This process can be affected by many in utero factors, such as chemical exposures and maternal health characteristics. The goal of this review is twofold: to review the most recent findings on the effects of these prenatal factors on the developing brain and to qualitatively assess how those factors were generally reported in studies on infants up to 2 years of age. To capture the latest findings in the field, we searched articles from PubMed 2012 onward with search terms referring to magnetic resonance imaging (MRI), brain development, and infancy. We identified 19 MRI studies focusing on the effects of prenatal environment and summarized them to highlight the recent advances in the field. We assessed population descriptions in a representative sample of 67 studies and conclude that prenatal factors that have been shown to affect brain metrics are not generally reported comprehensively. Based on our findings, we propose some improvements for population descriptions to account for plausible confounders and in time enable reliable meta-analyses to be performed. This could help the pediatric neuroimaging field move toward more reliable identification of biomarkers for developmental outcomes and to better decipher the nuances of normal and abnormal brain development.
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| 8. |
- Tuulari, Jetro J., et al.
(författare)
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Neural correlates of gentle skin stroking in early infancy
- 2019
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Ingår i: Developmental Cognitive Neuroscience. - : Elsevier BV. - 1878-9293 .- 1878-9307. ; 35, s. 36-41
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Tidskriftsartikel (refereegranskat)abstract
- Physical expressions of affection play a foundational role in early brain development, but the neural correlates of affective touch processing in infancy remain unclear. We examined brain responses to gentle skin stroking, a type of tactile stimulus associated with affectionate touch, in young infants. Thirteen term-born infants aged 11-36. days, recruited through the FinnBrain Birth Cohort Study, were included in the study. Soft brush strokes, which activate brain regions linked to somatosensory as well as socio-affective processing in children and adults, were applied to the skin of the right leg during functional magnetic resonance imaging. We examined infant brain responses in two regions-of-interest (ROIs) known to process gentle skin stroking - the postcentral gyrus and posterior insular cortex - and found significant responses in both ROIs. These results suggest that the neonate brain is responsive to gentle skin stroking within the first weeks of age, and that regions linked to primary somatosensory as well as socio-affective processing are activated. Our findings support the notion that social touch may play an important role in early life sensory processing. Future research will elucidate the significance of these findings for human brain development.
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