Impaired Caregiving, Trauma Exposure, and Psychosocial Functioning in a National Sample of Children and Adolescents.

Impairments in Caregiving (ICG) secondary to mental illness and substance use have been linked to adverse outcomes in children. Little is known, however, about whether outcomes vary by type of ICG, exposure to co-occurring traumas, or mechanisms of maladaptive outcomes. Clinic-referred youth age 7-18 years (n = 3988) were compared on ICG history, demographics, trauma history, and mental health symptoms. Child trauma exposure was tested as a mediator of ICG and child symptoms. Youth with ICG were at heightened risk for trauma exposure, PTSD, internalizing symptoms, total behavioral problems, and attachment problems, particularly youth with multiple types of ICG. Effect sizes were moderate to large for PTSD, internalizing symptoms, and total behavioral problems. Number of trauma types mediated the relationship between ICG and child symptoms. ICG was related to trauma exposure within and outside the family context. Understanding these links has important implications for interrupting intergenerational trauma and psychopathology

Impaired Caregiving, Trauma Exposure, and Psychosocial Functioning in a National Sample of Children and Adolescents

Impairments in Caregiving (ICG) secondary to mental illness and substance use have been linked to adverse outcomes in children. Little is known, however, about whether outcomes vary by type of ICG, exposure to co-occurring traumas, or mechanisms of maladaptive outcomes. Clinic-referred youth age 7-18 years (n = 3988) were compared on ICG history, demographics, trauma history, and mental health symptoms. Child trauma exposure was tested as a mediator of ICG and child symptoms. Youth with ICG were at heightened risk for trauma exposure, PTSD, internalizing symptoms, total behavioral problems, and attachment problems, particularly youth with multiple types of ICG. Effect sizes were moderate to large for PTSD, internalizing symptoms, and total behavioral problems. Number of trauma types mediated the relationship between ICG and child symptoms. ICG was related to trauma exposure within and outside the family context. Understanding these links has important implications for interrupting intergenerational trauma and psychopathology

Low 25-Hydroxyvitamin D Concentrations and Risk of Incident Cognitive Impairment in Black and White Older Adults: The Health ABC Study

Using data from the Health, Aging, and Body Composition study, we examined whether low 25-hydroxyvitamin D (25[OH]D) concentrations were associated with prevalent or incident cognitive impairment. Serum 25(OH)D concentrations were measured in 2,786 older adults and categorized as \u3c20 ng/mL, 20 to \u3c30 ng/mL, or ≥30 ng/mL. Cognitive impairment was defined as a score \u3e1.5 standard deviations below race and education specific means on either digit symbol substitution test or modified mini-mental state test. Logistic regression determined the odds of cognitive impairment at baseline and year 5 by 25(OH)D category. 25(OH)D concentrations were \u3c30 ng/mL in 57.3% of whites and 84.6% of blacks. After excluding participants with baseline cognitive impairment (n = 340), 13% of whites and 13% of blacks developed cognitive impairment by year 5. In whites, 25(OH)D concentrations \u3c30 ng/mL were not associated with prevalent or incident cognitive impairment. Black participants with 25(OH)D concentrations \u3c20 ng/mL had a higher odds of prevalent, but not incident cognitive impairment (OR (95% CI): 2.05 (1.08–3.91), p = 0.03) compared to participants with 25(OH)D concentrations ≥30 ng/mL. Low 25(OH)D concentrations were associated with twofold higher odds of prevalent cognitive impairment in blacks

Low 25-Hydroxyvitamin D Concentrations and Risk of Incident Cognitive Impairment in Black and White Older Adults: The Health ABC Study

Using data from the Health, Aging, and Body Composition study, we examined whether low 25-hydroxyvitamin D (25[OH]D) concentrations were associated with prevalent or incident cognitive impairment. Serum 25(OH)D concentrations were measured in 2,786 older adults and categorized as <20 ng/mL, 20 to <30 ng/mL, or ≥30 ng/mL. Cognitive impairment was defined as a score >1.5 standard deviations below race and education specific means on either digit symbol substitution test or modified mini-mental state test. Logistic regression determined the odds of cognitive impairment at baseline and year 5 by 25(OH)D category. 25(OH)D concentrations were <30 ng/mL in 57.3% of whites and 84.6% of blacks. After excluding participants with baseline cognitive impairment (n = 340), 13% of whites and 13% of blacks developed cognitive impairment by year 5. In whites, 25(OH)D concentrations <30 ng/mL were not associated with prevalent or incident cognitive impairment. Black participants with 25(OH)D concentrations <20 ng/mL had a higher odds of prevalent, but not incident cognitive impairment (OR (95% CI): 2.05 (1.08-3.91), p = 0.03) compared to participants with 25(OH)D concentrations ≥30 ng/mL. Low 25(OH)D concentrations were associated with twofold higher odds of prevalent cognitive impairment in blacks

Low 25-Hydroxyvitamin D Concentrations and Risk of Incident Cognitive Impairment in Black and White Older Adults: The Health ABC Study

Using data from the Health, Aging, and Body Composition study, we examined whether low 25-hydroxyvitamin D (25[OH]D) concentrations were associated with prevalent or incident cognitive impairment. Serum 25(OH)D concentrations were measured in 2,786 older adults and categorized as \u3c20 ng/mL, 20 to \u3c30 ng/mL, or ≥30 ng/mL. Cognitive impairment was defined as a score \u3e1.5 standard deviations below race and education specific means on either digit symbol substitution test or modified mini-mental state test. Logistic regression determined the odds of cognitive impairment at baseline and year 5 by 25(OH)D category. 25(OH)D concentrations were \u3c30 ng/mL in 57.3% of whites and 84.6% of blacks. After excluding participants with baseline cognitive impairment (n = 340), 13% of whites and 13% of blacks developed cognitive impairment by year 5. In whites, 25(OH)D concentrations \u3c30 ng/mL were not associated with prevalent or incident cognitive impairment. Black participants with 25(OH)D concentrations \u3c20 ng/mL had a higher odds of prevalent, but not incident cognitive impairment (OR (95% CI): 2.05 (1.08–3.91), p = 0.03) compared to participants with 25(OH)D concentrations ≥30 ng/mL. Low 25(OH)D concentrations were associated with twofold higher odds of prevalent cognitive impairment in blacks

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway