Biological factors in late life depression: A population-based approach

__Abstract__ Community epidemiological surveys that examined the prevalence of psychiatric disorders have been conducted since the end of World War II. We now know that up to half the general population meet criteria for one or more lifetime DSM disorder. Depressive disorders are the most frequent psychiatric problem with a life- time incidence of around 25%. Although the published reports of high prevalence estimates initially were met with a good deal of scepticism, clinical reappraisal showed that they were accurate. Public health experts now acknowledge that depression is one of the most important causes of disability world wide. Some expect it to become the number one cause of disability and premature death by 2020

Longitudinal Associations Between White Matter Microstructure and Psychiatric Symptoms in Youth

Objective: Associations between psychiatric problems and white matter (WM) microstructure have been reported in youth. Yet, a deeper understanding of this relation has been hampered by a dearth of well-powered longitudinal studies and a lack of explicit examination of the bidirectional associations between brain and behavior. We investigated the temporal directionality of WM microstructure and psychiatric symptom associations in youth. Method: In this observational study, we leveraged the world's largest single- and multi-site cohorts of neurodevelopment: the Generation R (GenR) and Adolescent Brain Cognitive Development Studies (ABCD) (total n scans = 11,400; total N = 5,700). We assessed psychiatric symptoms with the Child Behavioral Checklist as broad-band internalizing and externalizing scales, and as syndrome scales (eg, Anxious/Depressed). We quantified WM with diffusion tensor imaging (DTI), globally and at a tract level. We used cross-lagged panel models to test bidirectional associations of global and specific measures of psychopathology and WM microstructure, meta-analyzed results across cohorts, and used linear mixed-effects models for validation. Results: We did not identify any longitudinal associations of global WM microstructure with internalizing or externalizing problems across cohorts (confirmatory analyses) before, and after multiple testing corrections. We observed similar findings for longitudinal associations between tract-based microstructure with internalizing and externalizing symptoms, and for global WM microstructure with specific syndromes (exploratory analyses). Some cross-sectional associations surpassed multiple testing corrections in ABCD, but not in GenR. Conclusion: Uni- or bi-directionality of longitudinal associations between WM and psychiatric symptoms were not robustly identified. We have proposed several explanations for these findings, including interindividual differences, the use of longitudinal approaches, and smaller effects than expected. Study registration information: Bidirectionality Brain Function and Psychiatric Symptoms; https://doi.org/10.17605/OSF.IO/PNY92</p

Intrauterine Exposure to Antidepressants or Maternal Depressive Symptoms and Offspring Brain White Matter Trajectories From Late Childhood to Adolescence

Background: During pregnancy, both selective serotonin reuptake inhibitor (SSRI) exposure and maternal depression have been associated with poor offspring neurodevelopmental outcomes. In a population-based cohort, we investigated the association between intrauterine exposure to SSRIs and depressive symptoms and offspring white matter development from childhood to adolescence. Methods: Self-reported SSRI use was verified by pharmacy records. In midpregnancy, women reported on depressive symptoms using the Brief Symptom Inventory. Using diffusion tensor imaging, offspring white matter microstructure, including whole-brain and tract-specific fractional anisotropy (FA) and mean diffusivity, was measured at 3 assessments between ages 7 to 15 years. The participants were divided into 4 groups: prenatal SSRI exposure (n = 37 with 60 scans), prenatal depression exposure (n = 229 with 367 scans), SSRI use before pregnancy (n = 72 with 95 scans), and reference (n = 2640 with 4030 scans). Results: Intrauterine exposure to SSRIs and depressive symptoms were associated with lower FA in the whole-brain and the forceps minor at 7 years. Exposure to higher prenatal depressive symptom scores was associated with lower FA in the uncinate fasciculus, cingulum bundle, superior and inferior longitudinal fasciculi, and corticospinal tracts. From ages 7 to 15 years, children exposed to prenatal depressive symptoms showed a faster increase in FA in these white matter tracts. Prenatal SSRI exposure was not related to white matter microstructure growth over and above exposure to depressive symptoms.Conclusions: These results suggest that prenatal exposure to maternal depressive symptoms was negatively associated with white matter microstructure in childhood, but these differences attenuated during development, suggesting catch-up growth.</p

The Associations of Maternal and Neonatal Vitamin D with Dental Development in Childhood

Background: Vitamin D influences the formation and mineralization of teeth. Objective: To investigate the association of maternal and neonatal vitamin D concentrations with the dental development of 10-y-old children, in a population-based prospective cohort study among 3,770 mothers and children in the Netherlands. Methods: Maternal venous blood samples were collected in the second trimester (median 20.4 weeks of gestation; range: 18.5-23.2 wk) whereas umbilical cord blood samples were collected immediately after delivery (median 40.1 weeks of gestation; range 35.9-42.3 wk). Dental development was defined using the Demirjian method. Multivariate regression models were built to analyze the studied associations. Results: High concentrations of 25-hydroxyvitamin D [25(OH)D] during midpregnancy (beta: -0.04; 95% CI: -0.08, -0.01) and at birth (beta: -0.06; 95% CI: -0.10, -0.02) were associated with a lower dental age in children. The children of mothers with severe vitamin D deficiency [25(OH)D /=75.0 nmol/L). Children with vitamin D deficiency [25(OH)D 25.0-49.9 nmol/L] at birth exhibited a higher dental age (beta: 0.11; 95% CI: 0.01, 0.20), higher developmental stages of the mandibular second premolar (beta: 0.27; 95% CI: 0.02, 0.51), and higher developmental stages of the mandibular second molar (beta: 0.24; 95% CI: 0.00, 0.48) compared with children with sufficient-to-optimal values of 25(OH)D (>/=50.0 nmol/L) at birth. Conclusion: Higher maternal and neonatal 25(OH)D concentrations are associated with decelerated dental development in childhood. The lower the vitamin D level during midpregnancy or at birth, the higher the dental age of children, and the higher the developmental stages of the mandibular teeth

Determinants and Predictors of Grief Severity and Persistence: The Rotterdam Study

Objective: We aimed to explore correlates and predictors of bereavement severity and persistence (triggered by “loss of a loved one”; referent group partner loss) in the Rotterdam cohort. Method: We used linear regression to examine factors associated with grief severity using a cross-sectional analysis and logistic regression to determine prospective associations. Results: Cross-sectionaly, females, child-lost, higher depressive symptoms, lower education, and difficulties in daily activities were independently associated with a higher bereavement severity. Prospectively (6 years; response rate 71%), the baseline value of the grief severity was the single predictor significantly associated with grief persistence. Discussion: Our results suggest that only grief severity is independently associated with grief persistence. Further studies are needed to confirm ou

Application of the Instrumental Inequalities to a Mendelian Randomization Study With Multiple Proposed Instruments

BACKGROUND: Investigators often support the validity of Mendelian randomization (MR) studies, an instrumental variable approach proposing genetic variants as instruments, via. subject matter knowledge. However, the instrumental variable model implies certain inequalities, offering an empirical method of falsifying (but not verifying) the underlying assumptions. Although these inequalities are said to detect only extreme assumptio