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

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

Higher Education Is Associated with a Lower Risk of Dementia after a Stroke or TIA. The Rotterdam Study

Background: Higher education is associated with a lower risk of dementia, possibly because of a higher tolerance to subclinical neurodegenerative pathology. Whether higher education also protects against dementia after clinical stroke or transient ischemic attack (TIA) remains unknown. Methods: Within the population-based Rotterdam Study, 12,561 participants free of stroke, TIA and dementia were followed for occurrence of stroke, TIA and dementia. Across the levels of education, associations of incident stroke or TIA with subsequent development of dementia and differences in cognitive decline following stroke or TIA were investigated. Results: During 124,862 person-years, 1,463 persons suffered a stroke or TIA, 1,158 persons developed dementia, of whom 186 developed dementia after stroke or TIA. Risk of dementia after a stroke or TIA, compared to no stroke or TIA, was highest in the low education category (hazards ratio [HR] 1.46, 95% CI 1.18-1.81) followed by intermediate education category (HR 1.36, 95% CI 1.03-1.81). No significant association was observed in the high education category (HR 0.62, 95% CI 0.25-1.54). In gender stratified analyses, decrease in risk of dementia with increasing education was significant only in men. Conclusion: Higher education is associated with a lower risk of dementia after stroke or TIA, particularly in men, which might be explained by a higher cognitive reserve. (C) 2016 S. Karger AG, Base

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