An exploratory study of diet in childhood and young adulthood and adult-onset multiple sclerosis.
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ABSTRACT:
SUBMITTER: Black LJ
PROVIDER: S-EPMC8286980 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBipolar disorder (BD) is a severe mental illness that can have high costs for youths (<18 years old) and adults. Relative to healthy controls (HC), individuals with BD often show impaired attention, working memory, executive function, and cognitive flexibility (the ability to adapt to changing reward/punishment contingencies). In our study of youths and young adults with BD, we investigated 1) how cognitive flexibility varies developmentally in BD, and 2) whether it is independent of other executive function deficits associated with BD.MethodsWe measured errors on a reversal-learning task, as well as spatial working memory and other executive function, among participants with BD (N=75) and HC (N=130), 7-27 years old. Regression analyses focused on the effects of diagnosis on reversal-learning errors, controlling for age, gender, IQ, spatial span, and executive function. Similar analyses examined non-reversal errors to rule out general task impairment.ResultsParticipants with BD, regardless of age, gender, or cognitive ability, showed more errors than HC on the response reversal stages of the cognitive flexibility task. However, participants with BD did not show more errors on non-reversal stages, even when controlling for other variables.LimitationsStudy limitations include the cross-sectional, rather than longitudinal, design; inability to measure non-linear age effects; and inclusion of medicated participants and those with psychiatric comorbidity.ConclusionsIndividuals with BD show a specific impairment in reversing a previously rewarded response, which persists across the transition from childhood to young adulthood. Tailored interventions targeting this deficit may be effective throughout this developmentally turbulent time.
| S-EPMC4975956 | biostudies-literature
Project description:OBJECTIVE: To identify CSF biomarkers for multiple sclerosis (MS) in children with an initial acquired CNS demyelinating syndrome (ADS). METHODS: CSF was collected from a cohort of 39 children with initial ADS, 18 of whom were diagnosed with MS and 21 of whom had a monophasic disease course. Proteomic analysis of trypsinized CSF (20 ?L) was performed by nano-liquid chromatography Orbitrap mass spectrometry. Univariate statistical analysis was used to identify differentially abundant proteins between childhood-onset MS and monophasic ADS. RESULTS: A total of 2,260 peptides corresponding to 318 proteins were identified in the total set of samples. Of these 2,260 peptides, 88 were identified as being most distinctive between MS and ADS. Fifty-three peptides, corresponding to 14 proteins, had higher abundance in children with MS compared to children with monophasic ADS. Twelve of these 14 proteins were linked to neuronal functions and structures, such as synapses, axons, and CNS proteases (e.g., neurofascin, carboxypeptidase E, brevican core protein, and contactin-2). The other 2 were functionally related to immune function. The 35 peptides identified with decreased abundance in children with MS corresponded to 7 proteins. Six of them were linked to innate immune function (e.g., haptoglobin, haptoglobin-related protein, C4b-binding protein alpha chain, and monocyte differentiation antigen CD14) and 1 was linked to cellular adhesion (protein diaphanous homolog 1). CONCLUSION: At first onset of ADS, CSF of children diagnosed with MS showed increased abundance of CNS gray matter-related proteins, whereas CSF of children with a monophasic disease course showed increased abundance of innate immunity-related proteins.
| S-EPMC4582906 | biostudies-other
Project description:ObjectiveTo describe a case of childhood-onset progressive multiple sclerosis with dementia and evidence of extensive cortical demyelination from brain biopsy specimen.DesignCase report.SettingMayo Clinic, Rochester, Minnesota.PatientA 26-year-old man with a history of behavioral changes starting at the age of 13 years followed by progressive dementia.InterventionsNeurological examination, magnetic resonance imaging, cerebrospinal fluid studies, neuropsychological testing, and brain biopsy.ResultsMagnetic resonance imaging scans showed numerous T2-weighted hyperintensities throughout the central nervous system not associated with contrast enhancement. Brain biopsy specimens showed cortical and subcortical demyelination. All 3 types of cortical demyelinating lesions were observed: leukocortical, intracortical, and subpial. Lesions were associated with profound microglial activation. The patient continued to progress despite attempts to treat with multiple sclerosis disease-modifying therapies.ConclusionsMultiple sclerosis should be considered in the diagnosis of progressive dementia in children and young adults. Cortical demyelination may contribute to cognitive decline in patients with dementia due to multiple sclerosis.
| S-EPMC3077570 | biostudies-literature
Project description:ObjectiveTo determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth.MethodsWhole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2-11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects.ResultsSignificant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10(-4)). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups.ConclusionsOur results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS.
| S-EPMC4276405 | biostudies-literature
Project description:BackgroundPaediatric-onset multiple sclerosis (POMS) therapeutic approach derives from of adult-onset multiple sclerosis (AOMS) tailored algorithms.ObjectivesTo evaluate in a common clinical scenario the efficacy and safety of alemtuzumab (ALZ) in POMS and AOMS.MethodsAll patients switching from natalizumab (NTZ) to ALZ for safety concerns (high anti-John Cunningham Virus Antibody Index value, anti-JCV Index) were enrolled in this single-centre, retrospective, case-control open-label study.ResultsTen POMS and 27 AOMS were followed up for 51.3 months. After month 12, we found a lower risk of clinical or radiological relapses among AOMS patients and among patients with older age at ALZ (both p < 0.05). Survival analysis revealed an increased risk of relapse in POMS compared with AOMS (logrank p = 0.00498) and patients starting ALZ before age 22.75 years than the elder ones (logrank p = 0.0018). Survival analysis did not disclose any difference between AOMS and POMS (logrank p = 0.27) in terms of progression independent of any relapse activity (PIRA). In addition, no evidence of relapse-associated worsening was observed. Autoimmune events were reported by 5 AOMS and no POMS (29.4% versus 0.0%, p = 0.057), and survival analysis was not significant (logrank p = 0.0786).ConclusionALZ seems more effective in AOMS than in POMS following NTZ. These findings underrate ALZ effectiveness when shifting from NTZ in POMS.
| S-EPMC10559704 | biostudies-literature
Project description:ImportanceCognitive impairment in multiple sclerosis (MS) can lead to reduced quality of life, social functioning, and employment. Few studies have investigated cognitive outcomes among patients with pediatric-onset MS (POMS) over the long term.ObjectiveTo compare long-term information-processing efficiency between patients with POMS and adult-onset MS (AOMS).Design, setting, and participantsThis population-based longitudinal cohort study accessed the Swedish MS Registry (SMSreg), which collates information from all 64 neurology clinics in Sweden. Registered cases with definite MS in the SMSreg with an onset before April 15, 2018, and at least 2 Symbol Digit Modalities Test (SDMT) scores recorded were included. Only persons aged 18 to 55 years and with duration of disease of less than 30 years at the time of SDMT administration were included, to ensure comparable ranges between patients with POMS and AOMS. Of 8247 persons with an SDMT recorded in the SMSreg, 5704 met inclusion criteria, 300 (5.3%) of whom had POMS. Data were collected from April 1, 2006, through April 15, 2018 and analyzed from April through August 2018.ExposuresPediatric-onset MS (onset <18 years of age) vs AOMS (onset ≥18 years of age).Main outcomes and measuresInformation-processing efficiency measured every 6 or 12 months by the SDMT. Linear mixed-effects models were used to compare all available SDMT scores between patients with POMS and those with AOMS. Persons with cognitive impairment (ever vs never) were identified using regression-based norms and compared between POMS and AOMS groups using logistic regression.ResultsOf the 5704 participants, 4015 were female (70.4%), and 5569 had a relapsing-onset disease course (97.6%). Most participants were exposed to a disease-modifying therapy (DMT) during follow-up (98.8%). Median age at baseline for the POMS group was 25.6 years (interquartile range, 21.0-31.7 years) and for the AOMS group, 38.3 years (interquartile range, 31.4-45.2 years). A total of 46 429 unique SDMT scores were analyzed. After adjustment for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and DMT exposure, the SDMT score for patients with POMS was significantly lower than that of patients with AOMS (β coefficient, -3.59 [95% CI, -5.56 to -1.54]). The SDMT score for patients with POMS declined faster than that of patients with AOMS (β coefficient, -0.30 [95% CI, -0.42 tp -0.17]). The odds of cognitive impairment were also significantly elevated in the POMS group (odds ratio, 1.44; 95% CI, 1.06-1.98).Conclusions and relevanceIn adulthood, patients with POMS demonstrated a more rapid reduction in information-processing efficiency over time and were more likely to experience cognitive impairment than patients with AOMS, independent of age or disease duration. Further investigation is required to understand the mechanisms by which early MS onset influences cognitive outcomes.
| S-EPMC6580443 | biostudies-literature
Project description:ObjectiveTo comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS).MethodsIn this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8-18 years) and 40 patients with adMS (23-65 years) and blood specimens from 66 controls (1-55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA.ResultsFrequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M.ConclusionsWe demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS.
| S-EPMC5182056 | biostudies-literature
Project description:This study investigates the association between exposure to prospectively-substantiated childhood maltreatment between 0 and 14 years of age and lifetime cannabis use, abuse and dependence reported at 21 years. Data were taken from 2526 (51.6% female) participants in the Mater Hospital-University of Queensland Study of Pregnancy, a pre-birth, prospective, cohort study. Prospectively-substantiated cases of childhood maltreatment, reported to the government child protection agencies between 0 and 14 years of age, were linked to CIDI DSM-IV self-report data from the 21-year follow-up. Exposure to any childhood maltreatment, and childhood neglect in particular, predicted subsequent cannabis abuse with adjusted odds ratios (AORs) of 1.79 and 2.62, respectively. Any childhood maltreatment, physical abuse, emotional abuse and neglect predicted cannabis dependence with AORs of 2.47, 2.81, 2.44 and 2.68, respectively. The associations for an early age of onset of cannabis abuse and dependence were significant and consistent for maltreated children. In addition, frequency of maltreatment substantiations predicted cannabis abuse, dependence and an early age of onset of these disorders. The AORs for cannabis ever use without any DSM-IV cannabis disorder were 1.78 for any maltreatment and 2.15 for emotional abuse. Any childhood maltreatment and neglect predicted lifetime ever cannabis use, as well as cannabis use disorder. There was little evidence for any interaction between gender and different forms of childhood maltreatment and its association with cannabis use disorders. Physical abuse, emotional abuse and neglect, as well as multiple episodes of maltreatment independently predicted cannabis use disorders.
| S-EPMC5603409 | biostudies-other
Project description:ObjectivesChildhood adversities may be important determinants of later illnesses and poor health behaviour. However, large-scale prospective studies on the associations between childhood adversities and the onset of asthma in adulthood are lacking.DesignProspective cohort study with 7-year follow-up.SettingNationally representative study. Data were collected from the Health and Social Support (HeSSup) survey and national registers.ParticipantsThe participants represent the Finnish population from the following age groups: 20-24, 30-34, 40-44, and 50-54 years at baseline in 1998 (24 057 survey participants formed the final cohort of this study). The occurrence of childhood adversities was assessed at baseline with a six-item survey scale. The analyses were adjusted for sociodemographic characteristics, behavioural health risks and common mental disorders.Primary and secondary outcomesThe survey data were linked to data from national health registers on incident asthma during a 7-year follow-up to define new-onset asthma cases with verified diagnoses.ResultsA total of 12 126 (59%) participants reported that they encountered a childhood adversity. Of them 3677 (18% of all) endured three to six adversities. During a follow-up of 7 years, 593 (2.9%) participants were diagnosed with incident asthma. Those who reported three or more childhood adversities had a 1.6-fold (95% CI 1.31 to 2.01) greater risk of asthma compared to those without childhood adversities. This hazard attenuated but remained statistically significant after adjustment for conventional risk factors (HR 1.33; 95% CI 1.06 to 1.67).ConclusionsAdults who report having encountered adversities in childhood may have an increased risk of developing asthma.
| S-EPMC3488721 | biostudies-literature
Project description:OBJECTIVE:Childhood victimization is an important risk factor for later immune-related disorders. Previous evidence has demonstrated that childhood victimization is associated with elevated levels of inflammation biomarkers measured decades after exposure. However, it is unclear whether this association is (1) already detectable in young people, (2) different in males and females, and (3) confounded by genetic liability to inflammation. Here we sought to address these questions. METHOD:Participants were 2232 children followed from birth to age 18years as part of the Environmental Risk (E-Risk) Longitudinal Twin Study. Childhood victimization was measured prospectively from birth to age 12years. Inflammation was measured through C-reactive protein (CRP) levels in dried blood spots at age 18years. Latent genetic liability for high inflammation levels was assessed through a twin-based method. RESULTS:Greater exposure to childhood victimization was associated with higher CRP levels at age 18 (serum-equivalent means were 0.65 in non-victimized Study members, 0.74 in those exposed to one victimization type, and 0.81 in those exposed to poly-victimization; p=0.018). However, this association was driven by a significant association in females (serum-equivalent means were 0.75 in non-victimized females, 0.87 in those exposed to one type of victimization, and 1.19 in those exposed to poly-victimization; p=0.010), while no significant association was observed in males (p=0.19). Victimized females showed elevated CRP levels independent of latent genetic influence, as well as childhood socioeconomic status, and waist-hip ratio and body temperature at the time of CRP assessment. CONCLUSION:Childhood victimization is associated with elevated CRP levels in young women, independent of latent genetic influences and other key risk factors. These results strengthen causal inference about the effects of childhood victimization on inflammation levels in females by accounting for potential genetic confounding.
| S-EPMC5710993 | biostudies-literature