47 research outputs found
The rare complication of vascular malformations of the limb after sclerotherapy: a report of 3 cases and brief literature review
No full textAbstract Background Vascular malformations are common but complicated types of disease in infants, with unclear causes and lack of effective prevention. The symptoms usually do not disappear and tend to progress without medical intervention. It is extremely necessary to choose correct treatment options for different types of vascular malformations. A large number of studies have confirmed that sclerotherapy has a tendency to become the first-line treatment in near future, but it is also associated with mild or severe complications. Furthermore, to our knowledge, the serious adverse event of progressive limb necrosis has not been systematically analyzed and reported in the literature. Case presentation Three cases (two females and one male) were presented who were all diagnosed as vascular malformations and were treated by several sessions of interventional sclerotherapy. Their previous medical records showed the use of several sclerosants in different sessions including Polidocanol and Bleomycin. The sign of limb necrosis did not occur during the first sclerotherapy, but after the second and third sessions. Furthermore, the short-term symptomatic treatment could improve the necrosis syndrome, but could not change the outcome of amputation. Conclusion Sclerotherapy undoubtedly tends to be the first-line treatment in near future, but the adverse reactions still remain major challenges. Awareness of progressive limb necrosis after sclerotherapy and timely management by experts in centers of experience of this complication can avoid amputation
Developing brain asymmetry shapes cognitive and psychiatric outcomes in adolescence
No full textAbstract Cerebral asymmetry, fundamental to various cognitive functions, is often disrupted in neuropsychiatric disorders. While brain growth has been extensively studied, the maturation of brain asymmetry in children and the factors influencing it in adolescence remain poorly understood. We analyze longitudinal data from 11,270 children aged 10–14 years in the Adolescent Brain Cognitive Development (ABCD) study. Our analysis maps the developmental trajectory of structural brain asymmetry. We identify significant age-related, modality-specific development patterns. These patterns link to crystallized intelligence and mental health problems, but with weak correlations. Genetically, structural asymmetry relates to synaptic processes and neuron projections, likely through asymmetric synaptic pruning. At the microstructural level, corpus callosum integrity emerged as a key factor modulating the developing asymmetry. Environmentally, favorable perinatal conditions were associated with prolonged corpus callosum development, which affected future asymmetry patterns and cognitive outcomes. These findings underscore the dynamic yet predictable interactions between brain asymmetry, its structural determinants, and cognitive and psychiatric outcomes during a pivotal developmental stage. Our results provide empirical support for the adaptive plasticity theory in cerebral asymmetry and offer insights into both cognitive maturation and potential risk for early-onset mental health problems
Genetic influence and neural pathways underlying the dose-response relationships between wearable-measured physical activity and mental health in adolescence
No full textAdolescence is a critical period marked by significant physical and neurocognitive development as well as increased vulnerability to mental health issues. While the benefits of physical activity (PA) on adult mental health (MH) are well-established, the dose-response relationships and underlying neurobiological mechanisms in adolescents remain elusive. This study investigated the dose-response relationships between wearable-measured PA and MH outcomes in over 7000 adolescents (11–12 years) from the ABCD study through linear and nonlinear modeling. We further examined the genetic influence and mediation effects of brain structure and function underlying the relationships. We found that all intensity levels of PA were associated with reduced internalizing and thought problems but not with externalizing problems. Durations of moderate activity around 90 min and vigorous activity around 120 min each day and frequency of physical exercise four days each week were associated with lowest MH burden. Polygenic risk scores (PRSs) for neuropsychiatric disorders were associated with reduced step count and light activity, while PRS for walking was associated with reduced thought problems. Reduced functional connectivity between cingulo-parietal and auditory networks, and between cingulo-opercular network and left putamen is the common neural pathways mediating the associations between different PA measurements and better mental health. These findings suggest that excessive moderate and vigorous activity may not be always better for adolescent mental health. Brain functional integration and segregation centered on cognitive control as well as genetic interplay may be the potential neurobiological factors underlying the link between PA and MH
Decoding anxiety-impulsivity subtypes in preadolescent internalising disorders: findings from the Adolescent Brain Cognitive Development study
No full textBackground Internalising disorders are highly prevalent emotional dysregulations during preadolescence but clinical decision-making is hampered by high heterogeneity. During this period impulsivity represents a major risk factor for psychopathological trajectories and may act on this heterogeneity given the controversial anxiety-impulsivity relationships. However, how impulsivity contributes to the heterogeneous symptomatology, neurobiology, neurocognition and clinical trajectories in preadolescent internalising disorders remains unclear. Aims The aim was to determine impulsivity-dependent subtypes in preadolescent internalising disorders that demonstrate distinct anxiety-impulsivity relationships, neurobiological, genetic, cognitive and clinical trajectory signatures. Method We applied a data-driven strategy to determine impulsivity-related subtypes in 2430 preadolescents with internalising disorders from the Adolescent Brain Cognitive Development study. Cross-sectional and longitudinal analyses were employed to examine subtype-specific signatures of the anxiety-impulsivity relationship, brain morphology, cognition and clinical trajectory from age 10 to 12 years. Results We identified two distinct subtypes of patients who internalise with comparably high anxiety yet distinguishable levels of impulsivity, i.e. enhanced (subtype 1) or decreased (subtype 2) compared with control participants. The two subtypes exhibited opposing anxiety-impulsivity relationships: higher anxiety at baseline was associated with higher lack of perseverance in subtype 1 but lower sensation seeking in subtype 2 at baseline/follow-up. Subtype 1 demonstrated thicker prefrontal and temporal cortices, and genes enriched in immune-related diseases and glutamatergic and GABAergic neurons. Subtype 1 exhibited cognitive deficits and a detrimental trajectory characterised by increasing emotional/behavioural dysregulations and suicide risks during follow-up. Conclusions Our results indicate impulsivity-dependent subtypes in preadolescent internalising disorders and unify past controversies about the anxiety-impulsivity interaction. Clinically, individuals with a high-impulsivity subtype exhibit a detrimental trajectory, thus early interventions are warranted
Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: genomics and cell-specific expression enriched morphometric study
No full textAbstract Background Comorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical differences represent a simple aggregate of the effects on each disorder and if these comorbidity-associated cortical surface differences relate to a distinct genetic underpinning. Methods We studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9–10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (dysthymia, major depressive disorder, disruptive mood dysregulation disorder, agoraphobia, panic disorder, specific phobia, separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder), externalizing (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder) diagnostic groups, a group with comorbidity of the two and a healthy control group. Genome-wide association analysis (GWAS) and cell type specificity analysis were performed on 4468 unrelated European participants from this cohort. Results Smaller cortical surface area but higher thickness was noted across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT differences, while those patient groups without comorbidity had significantly higher thickness compare to healthy controls. Distinct biological pathways were implicated in regional SA and CT differences. Specifically, CT differences were associated with immune-related processes implicating astrocytes and oligodendrocytes, while SA-related differences related mainly to inhibitory neurons. Conclusion The emergence of comorbidity across distinct clusters of psychopathology is unlikely to be due to a simple additive neurobiological effect alone. Distinct developmental risk moderated by immune-related adaptation processes, with unique genetic and cell-specific factors, may contribute to underlying SA and CT differences. Children with the highest risk but lowest resilience, both captured in their developmental morphometry, may develop a comorbid illness pattern
Common and disorder-specific cortical thickness alterations in internalizing, externalizing and thought disorders during early adolescence: an Adolescent Brain and Cognitive Development study
No full textBackground: A growing body of neuroimaging studies has reported common neural abnormalities among mental disorders in adults. However, it is unclear whether the distinct disorder-specific mechanisms operate during adolescence despite the overlap among disorders. Methods: We studied a large cohort of more than 11 000 preadolescent (age 9–10 yr) children from the Adolescent Brain and Cognitive Development cohort. We adopted a regrouping approach to compare cortical thickness (CT) alterations and longitudinal changes between healthy controls (n = 4041) and externalizing (n = 1182), internalizing (n = 1959) and thought disorder (n = 347) groups. Genome-wide association study (GWAS) was performed on regional CT across 4468 unrelated European youth. Results: Youth with externalizing or internalizing disorders exhibited increased regional CT compared with controls. Externalizing (p = 8 × 10−4, Cohen d = 0.10) and internalizing disorders (p = 2 × 10−3, Cohen d = 0.08) shared thicker CT in the left pars opercularis. The somatosensory and the primary auditory cortex were uniquely affected in externalizing disorders, whereas the primary motor cortex and higher-order visual association areas were uniquely affected in internalizing disorders. Only youth with externalizing disorders showed decelerated cortical thinning from age 10–12 years. The GWAS found 59 genome-wide significant associated genetic variants across these regions. Cortical thickness in common regions was associated with glutamatergic neurons, while internalizing-specific regional CT was associated with astrocytes, oligodendrocyte progenitor cells and GABAergic neurons. Limitations: The sample size of the GWAS was relatively small. Conclusion: Our study provides strong evidence for the presence of specificity in CT, developmental trajectories and underlying genetic underpinnings among externalizing and internalizing disorders during early adolescence. Our results support the neurobiological validity of the regrouping approach that could supplement the use of a dimensional approach in future clinical practice.</p
Author Correction: Genotype-stratified treatment for monogenic insulin resistance: a systematic review
No full textAdditional file 2 of Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: genomics and cell-specific expression enriched morphometric study
No full textAdditional file 2: Table S1. Demographics of the three transdiagnostic categories and healthy control. Table S2. Frequency of each single mental disorders within each group. Table S3. FUMA summary for main significant loci for cortical thickness. Table S4. FUMA summary for main significant loci for cortical surface area. Table S5. Genes associated with cortical thickness in single internalizing-specific and externalizing-specific regions. Table S6. Genes associated with cortical surface area in comorbid-specific regions. Table S7. Single-cell RNA sequencingdatasets. Table S8. Results of case control for SA between three diagnostic families and healthy controls. Table S9.Results of ANOVA and Turkey Test for SA. Table S10. Results of case control for CT between three diagnostic families and healthy controls. Table S11. Results of ANOVA and Turkey Test for CT. Table S12. Results considering thought disorders. Table S13. FUMA summary for main 76 significant loci for cortical thickness. Table S14. FUMA summary for main 139 significant loci for cortical surface area. Table S15. Genes associated with cortical surface area in comorbid-specific regions. Table S16. Genes associated with cortical thickness in single internalizing-specific and externalizing-specific regions. Table S17. Significantly enriched terms/phenotypes on genes associated with cortical surface area in comorbid-specific regions. Table S18. Significantly enriched terms/phenotypes on genes associated with cortical thickness in single internalizing-specific and externalizing-specific regions. Table S19. Different brain regions share genes involved in biological processes. Table S20. Genes associated with cortical surface area in comorbid-specific regions. Table S21. Genes associated with cortical thickness in single internalizing-specific and externalizing-specific regions. Table S22. Significantly enriched terms/phenotypes on genes associated with cortical surface area in comorbid-specific regions. Table S23. Significantly enriched terms/phenotypes on genes associated with cortical thickness in single internalizing-specific and externalizing-specific regions. Table S24. Cell type specificity analysis for cortical surface area. Table S25. Cell type specificity analysis for cortical thickness. Table S26. The conversion rate between single diagnostic families and comorbidity group. Table S27. Results of case control for stress score between three diagnostic families and healthy controls. Table S28. Results considering ADHD and MDD
Additional file 1 of Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: genomics and cell-specific expression enriched morphometric study
No full textAdditional file 1. Supplementary information
Maternal and fetal genetic predispositions to insulin deficiency and resistance affect fetal growth through distinct pathways.
No full textAIMS/HYPOTHESIS: We aimed to investigate whether maternal and fetal genetic predispositions to insulin deficiency and resistance affect offspring fetal growth through distinct pathways in multi-ethnic populations. METHODS: In 5065 multi-ethnic mother-infant pairs, we examined the conditional associations of maternal and fetal partitioned polygenic risk scores (pPRSs) for type 2 diabetes-related pathways with fetal growth outcomes, including birthweight, sum of skinfold thicknesses (SSF), large-for-gestational-age (LGA) births and small-for-gestational-age (SGA) births. Two-sample Mendelian randomisation (2SMR) in Europeans was performed for triangulation. Exposures were eight type 2 diabetes-related pathways (n=1,812,017), eight beta cell function indices (n=26,356) and two insulin sensitivity indices (n=53,657). Outcomes were maternal and fetal genetically determined birthweight (n=406,063). Mediation analysis was used to assess the mediation effects of maternal glucose levels and BMI on maternal genetic effects and of cord blood C-peptide on fetal genetic effects. Co-localisation analyses were performed to test for shared causal variants. RESULTS: Fetal type 2 diabetes polygenic risk score (PRS) and pPRSs for lipodystrophy-related insulin resistance and impaired fasting glucose (IFG)-related insulin deficiency were associated with lower birthweight and SSF, while maternal type 2 diabetes PRS and pPRSs for IFG-related insulin deficiency and obesity-related insulin resistance were associated with higher offspring birthweight, SSF and LGA. These associations were consistent across five ethnic groups. Maternal post-load hyperglycaemia mediated 44.2% and 34.2% of the effects of type 2 diabetes PRS and IFG pPRS, respectively, while maternal BMI mediated 43.4% of the effect of Obesity pPRS. 2SMR found consistent results in Europeans and further revealed that fetal insulin sensitivity index and corrected insulin response were associated with higher birthweight. Some loci with shared causal variants acted through multiple pathways, including CDKAL1, TCF7L2, ADCY5 and MACF1. CONCLUSIONS/INTERPRETATION: Reduced fetal growth may be driven by lipodystrophy-related insulin resistance and IFG-related insulin deficiency pathways. Targeting pregnant women with high type 2 diabetes PRS/pPRS and prescribing interventions to reduce their post-load hyperglycaemia and BMI may help reduce offspring risk of LGA.</p
