| 1. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 2. |
- Hibar, D. P., et al.
(författare)
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Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d='0.293; P=1.71 × 10 '21), left fusiform gyrus (d='0.288; P=8.25 × 10 '21) and left rostral middle frontal cortex (d='0.276; P=2.99 × 10 '19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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| 3. |
- Belov, Vladimir, et al.
(författare)
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Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures
- 2024
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
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| 4. |
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| 5. |
- Nordberg, B, et al.
(författare)
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The effect of weekly interactive text-messaging on early infant HIV testing in Kenya: a randomised controlled trial (WelTel PMTCT)
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 22652-
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Tidskriftsartikel (refereegranskat)abstract
- Mother-to-child transmission of HIV remains a significant concern in Africa despite earlier progress. Early infant diagnosis (EID) of HIV is crucial to reduce mortality among infected infants through early treatment initiation. However, a large proportion of HIV-exposed infants are still not tested in Kenya. Our objective was to investigate whether weekly interactive text-messages improved prevention of mother-to-child transmission (PMTCT) of HIV care outcomes including EID HIV testing. This multicentre, parallel-group, randomised, open-label trial included six antenatal care clinics across western Kenya. Pregnant women living with HIV, aged 18 years or older, with mobile phone access, were randomised in a 1:1 ratio to weekly text messages that continued until 24 months postpartum, asking “How are you?” (“Mambo?”) to which they were asked to respond within 48 h, or a control group. Healthcare workers contacted participants reporting problems and non-responders by phone. Participants in both groups received routine PMTCT care. The prespecified secondary outcome reported in this paper is EID HIV testing by eight weeks of age (blinded outcome assessment). Final 24-months trial results will be published separately. We estimated risk ratios using Poisson regression with robust standard errors. Between June 2015–July 2016, we screened 735 pregnant women, of whom 600 were enrolled: 299 were allocated to the intervention and 301 to the control group. By eight weeks of age, the uptake of EID HIV testing out of recorded live births was 85.5% in the intervention and 84.7% in the control group (71.2% vs. 71.8% of participants randomised, including miscarriages, stillbirths, etc.). The intention-to-treat risk ratio was 0.99; 95% CI: 0.90–1.10; p = 0.89. The proportion of infants diagnosed with HIV was 0.8% in the intervention and 1.2% in the control group. No adverse events were reported. We found no evidence to support that the WelTel intervention improved EID HIV testing. A higher uptake of EID testing than expected in both groups may be a result of lower barriers to EID testing and improved PMTCT care in western Kenya, including the broader standard use of mobile phone communication between healthcare workers and patients. (ISRCTN No. 98818734. Funded by the European-Developing Countries Clinical Trial Partnership and others).
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| 6. |
- Färnert, Anna, et al.
(författare)
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Transmission-dependent tolerance to multiclonal Plasmodium falciparum infection
- 2009
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Ingår i: Journal of Infectious Diseases. - Chicago : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 200:7, s. 1166-1175
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Tidskriftsartikel (refereegranskat)abstract
- Whether the number of concurrent clones in asymptomatic Plasmodium falciparum infections reflects the degree of host protection was investigated in children living in areas with different levels of transmission on the coast of Kenya. The number of concurrent clones was determined on the basis of polymorphism in msp2, which encodes the vaccine candidate antigen merozoite surface protein 2. In a low-transmission area, most children had monoclonal infections, and diversity did not predict a risk of clinical malaria. In an area of moderate transmission, asymptomatic infections with 2 clones were, compared with 1 clone, associated with an increased risk of subsequent malaria. In a comparative assessment in a high-transmission area in Tanzania, multiclonal infections conferred a reduced risk. The different nonlinear associations between the number of clones and malaria morbidity suggest that levels of tolerance to multiclonal infections are transmission dependent as a result of cumulative exposure to antigenically diverse P. falciparum infections.
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| 7. |
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| 8. |
- Landén, Mikael, 1966, et al.
(författare)
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Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5124-5139
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
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| 9. |
- Macfarlane, Tatiana V, et al.
(författare)
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Orofacial pain in young adults and associated childhood and adulthood factors: results of the population study, Wales, United Kingdom.
- 2009
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Ingår i: Community dentistry and oral epidemiology. - : Wiley. - 1600-0528 .- 0301-5661. ; 37:5, s. 438-50
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the study was to investigate the prevalence of orofacial pain (OFP) among young adults (30-31 years old) and to determine the effect of childhood and adulthood risk factors on the occurrence of OFP. METHODS: Prospective cohort study to investigate dental and social effects of malocclusion and effectiveness of orthodontic treatment was conducted in Wales, United Kingdom. At 20-year follow-up 337 subjects aged 30-31 participated (74% from previous follow-up aged 19-20 and 33% from the baseline) and were asked about OFP. RESULTS: The prevalence of OFP was 23% (95% CI: 19%, 28%). Childhood factors, socio-demographic, lifestyle, health behavior factors, history of orthodontic treatment and tooth wear were not associated with OFP. Participants with OFP were more likely to report that their teeth did not fit together properly [odds ratio (OR) = 12.4, 95% CI: 2.7-56.5) and reported previous trauma to the jaws (2.3; 1.3-4.2). Both diurnal and nocturnal teeth clenching and grinding were significantly associated with OFP (3.1; 1.4-7.1). Participants with frequent headaches had increased risk of having OFP (3.7; 1.6-8.4) while having reported 4-10 types of pain in other parts of the body other than the head, was associated with OR = 9.2 (3.7-23.0). An increased tendency to have OFP was seen in those individuals with higher levels of psychological distress (2.3; 1.4-3.9), high score on Life Event Inventory (2.6; 1.3-5.3), depressive symptoms (2.2; 1.2-4.0) and stress (2.2; 1.2-4.0). High self-esteem associated with lower risk of OFP (0.5; 0.3-0.9). CONCLUSIONS: This study shows that OFP is frequently reported by young adults aged 30-31 and supports a multifactorial etiology with factors from many domains, including local mechanical factors, psychological and co-morbidities. However, none of the childhood factors considered in this study were associated with OFP in adulthood.
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