Selective serotonin reuptake inhibitors (SSRIs) are considered safe and are frequently used during pregnancy. However, two case-control studies suggested an association between prenatal SSRI exposure ...with childhood autism.
To prospectively determine whether intra-uterine SSSRI exposure is associated with childhood autistic symptoms in a population-based study.
A total of 376 children prenatally exposed to maternal depressive symptoms (no SSRI exposure), 69 children prenatally exposed to SSRIs and 5531 unexposed children were included. Child pervasive developmental and affective problems were assessed by parental report with the Child Behavior Checklist at ages 1.5, 3 and 6. At age 6, we assessed autistic traits using the Social Responsiveness Scale (n = 4264).
Prenatal exposure to maternal depressive symptoms without SSRIs was related to both pervasive developmental (odds ratio (OR) = 1.44, 95% CI 1.07-1.93) and affective problems (OR = 1.44, 95% CI 1.15-1.81). Compared with unexposed children, those prenatally exposed to SSRIs also were at higher risk for developing pervasive developmental problems (OR = 1.91, 95% CI 1.13-3.47), but not for affective problems. Children prenatally exposed to SSRIs also had more autistic traits (B = 0.15, 95% CI 0.08-0.22) compared with those exposed to depressive symptoms only.
Our results suggest an association between prenatal SSRI exposure and autistic traits in children. Prenatal depressive symptoms without SSRI use were also associated with autistic traits, albeit this was weaker and less specific. Long-term drug safety trials are needed before evidence-based recommendations are possible.
Background
Prenatal depressive symptoms have been associated with multiple adverse outcomes. Previously, we demonstrated that prenatal depressive symptoms were associated with impaired growth of the ...fetus and increased behavioral problems in children aged between 1.5 and 6 years. In this prospective study, we aimed to assess whether prenatal maternal depressive symptoms at 3 years have long‐term consequences on brain development in a cohort of children aged 6–10 years. As a contrast, the association of paternal depressive symptoms during pregnancy and brain morphology was assessed to serve as a marker of background confounding due to shared genetic and environmental family factors.
Methods
We assessed parental depressive symptoms during pregnancy with the Brief Symptom Inventory. At approximately 8 years of age, we collected structural neuroimaging data, using cortical thickness, surface area, and gyrification as outcomes (n = 654).
Results
We found that exposure to prenatal maternal depressive symptoms during pregnancy was associated with a thinner superior frontal cortex in the left hemisphere. Additionally, prenatal maternal depressive symptoms were related to larger caudal middle frontal area in the left hemisphere. Maternal depressive symptoms at 3 years were not associated with cortical thickness, surface area, or gyrification in the left and right hemispheres. No effects of paternal depressive symptoms on brain morphology were observed.
Conclusions
Prenatal maternal depressive symptoms were associated with differences in brain morphology in children. It is important to prevent, identify, and treat depressive symptoms during pregnancy as it may have long‐term consequences on child brain development.
Depression during pregnancy is highly prevalent and has a multitude of potential risks of the offspring. Among confirmed consequences is a higher risk of psychopathology. However, it is unknown how ...maternal depression may impact the child’s brain to mediate this vulnerability. Here we studied amygdala functioning, using task-based functional MRI, in children aged 6–9 years as a function of prenatal maternal depressive symptoms selected from a prospective population-based sample (The Generation R Study). We show that children exposed to clinically relevant maternal depressive symptoms during pregnancy (
N
= 19) have increased amygdala responses to negative emotional faces compared to control children (
N
= 20)
F
(1,36) 7.02,
p
= 0.022. Strikingly, postnatal maternal depressive symptoms, obtained at 3 years after birth, did not explain this relation. Our findings are in line with a model in which prenatal depressive symptoms of the mother are associated with amygdala hyperresponsivity in her offspring, which may represent a risk factor for later-life psychopathology.
Maternal care is an important environmental factor for rats early in life. Adult offspring from dams exhibiting extremely high versus low maternal care differ remarkably in dendritic complexity and ...long‐term synaptic potentiation in the CA1 area. However, > 70% of the pups do not belong to these extreme categories of maternal care, questioning the general relevance of these observations. Therefore, the present study investigated whether the influence of maternal care is discernable over its entire range and can serve as an index predicting later CA1 structure and function. The amount of licking and grooming (%LG) received was determined for each pup during the first postnatal week. In males, both total apical branch length and dendritic complexity correlated significantly and positively with %LG. In females, we observed a nonsignificant negative correlation, also when controlled for variations in oestradiol and progesterone levels. The correlation in females was significantly different from that in males. No significant correlation was observed between the %LG and the amount of synaptic potentiation, either in male or in female offspring, regardless of whether slices had been treated with corticosterone or vehicle. However, in male rats, the degree of potentiation seen after corticosterone compared to vehicle treatment was almost significantly related to the %LG received early in life; this differed significantly from that observed in females. The data from the present study suggest that %LG received early in life results in mild, yet sex‐dependent effects on adult CA1 structure and function.
Genetic variance has been associated with variations in brain morphology, cognition, behavior, and disease risk. One well studied example of how common genetic variance is associated with brain ...morphology is the serotonin transporter gene polymorphism within the promoter region (5-HTTLPR). Because serotonin is a key neurotrophic factor during brain development, genetically determined variations in serotonin activity during maturation, in particular during early prenatal development, may underlie the observed association. However, the intrauterine microenvironment is not only determined by the child's, but also the mother's genotype. Therefore, we hypothesized that maternal 5-HTTLPR genotype influences the child's brain development beyond direct inheritance. To test this hypothesis, we investigated 76 children who were all heterozygous for the 5-HTTLPR (sl) and who had mothers who were either homozygous for the long (ll) or the short allele (ss). Using MRI, we assessed brain morphology as a function of maternal genotype. Gray matter density of the somatosensory cortex was found to be greater in children of ss mothers compared with children of ll mothers. Behavioral assessment showed that fine motor task performance was altered in children of ll mothers and the degree of this behavioral effect correlated with somatosensory cortex density across individuals. Our findings provide initial evidence that maternal genotype can affect the child's phenotype beyond effects of classical inheritance. Our observation appears to be explained by intrauterine environmental differences or by differences in maternal behavior.
Climate warming is expected to cause a poleward spread of species, resulting in increased richness at mid to high latitudes and weakening the latitudinal diversity gradient. We used pollen data to ...test if such a change in the latitudinal diversity gradient occurred during the last major poleward shift of plant species in Europe following the end of the last glacial period. In contrast to expectations, the slope of the gradient strengthened during the Holocene. The increase in temperatures around 10 ka ago reduced diversity at mid to high latitude sites due to the gradual closure of forests. Deforestation and the introduction of agriculture during the last 5 ky had a greater impact on richness in central Europe than the earlier climate warming. These results do not support the current view that global warming alone will lead to a loss in biodiversity, and demonstrate that non-climatic human impacts on the latitudinal diversity gradient is of a greater magnitude than climate change.
Excessive levels of trait anxiety are a risk factor for psychiatric conditions, including anxiety disorders and substance abuse. High trait anxiety has been associated with altered cognitive ...functioning, in particular with an attentional bias towards aversive stimuli. Decision-making is a crucial aspect of cognitive functioning that relies on the correct processing and control of emotional stimuli. Interestingly, anxiety and decision-making share underlying neural substrates, involving cortico-limbic pathways, including the amygdala, striatum and medial and dorsolateral prefrontal cortices. In the present study, we investigated the relationship between trait anxiety, measured by the State-Trait Anxiety Inventory, and complex decision-making, measured by the Iowa Gambling Task, in healthy male and female volunteers. The main focus of this study was the inclusion of gender as a discriminative factor. Indeed, we found distinct gender-specific effects of trait anxiety: in men, both low and high anxiety groups showed impaired decision-making compared to medium anxiety individuals, whereas in women only high anxiety individuals performed poorly. Furthermore, anxiety affected decision-making in men early in the task, i.e. the exploration phase, as opposed to an effect on performance in women during the second part of the test, i.e. the exploitation phase. These findings were related to different profiles of trait anxiety in men and women, and were independent of performance in the Wisconsin Card Sorting Test and cortisol levels. Our data show gender-specific effects of trait anxiety on emotional decision-making. We suggest gender-specific endophenotypes of anxiety to exist, that differentially affect cognitive functioning.
Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a ...continuous dose-response relationship that would allow predicting the LDL-C-lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to describe the dose-response curve. The overall pooled absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were also assessed with a random effects model. The pooled LDL-C reduction was 0.34 mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose of 2.15 g phytosterols. The impacts of subject baseline characteristics, food formats, type of phytosterols, and study quality on the continuous dose-response curve were determined by regression or subgroup analyses. Higher baseline LDL-C concentrations resulted in greater absolute LDL-C reductions. No significant differences were found between dose-response curves established for plant sterols vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy foods. A larger effect was observed with solid foods than with liquid foods only at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054) towards a slightly lower efficacy of single vs. multiple daily intakes of phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of phytosterols incorporated in various food formats was confirmed and equations of the continuous relationship were established to predict the effect of a given phytosterol dose. Further investigations are warranted to investigate the impact of solid vs. liquid food formats and frequency of intake on phytosterol efficacy.
PDF
