Associations between maternal pre-pregnancy BMI and infant striatal mean diffusivity.

BACKGROUND: It is well-established that parental obesity is a strong risk factor for offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring's brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring's brain during in utero development. METHODS: We used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 [66 males, 50 females], mean gestational weeks at birth [39.88], SD = 1.14; at scan [43.56], SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index (BMI) and infant striatal mean diffusivity. RESULTS: High maternal pre-pregnancy BMI was associated with higher mean MD values in the infant's left caudate nucleus. Results remained unchanged after the adjustment for covariates. CONCLUSIONS: In utero exposure to maternal adiposity might have a growth-impairing impact on the mean diffusivity of the infant's left caudate nucleus. Considering the involvement of the caudate nucleus in regulating eating behavior and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early-life caudate nucleus development and weight trajectories of the offspring.

Negative associations between maternal prenatal hair cortisol and child socioemotional problems.

Maternal prenatal distress can participate in the programming of offspring development, in which exposure to altered maternal long-term cortisol levels as measured by hair cortisol concentrations (HCC) may contribute. Yet, studies investigating whether and how maternal prenatal HCC associates with problems in child socioemotional development are scarce. Furthermore, questions remain regarding the timing and potential sex-specificity of fetal exposure to altered cortisol levels and whether there are interactions with maternal prenatal distress, such as depressive symptoms. The subjects were drawn from those FinnBrain Birth Cohort families that had maternal reports of child socioemotional problems (the Brief Infant-Toddler Social and Emotional Assessment [BITSEA] at 2 years and/or the Strengths and Difficulties Questionnaire [SDQ] at 5 years) as follows: HCC1 population: maternal mid-pregnancy HCC measured at gestational week 24 with 5 cm segments to depict cortisol levels from the previous five months (n = 321); and HCC2 population: end-of-pregnancy HCC measured 1-3 days after childbirth (5 cm segment; n = 121). Stepwise regression models were utilized in the main analyses and a sensitivity analysis was performed to detect potential biases. Negative associations were observed between maternal HCC2 and child BITSEA Total Problems at 2 years but not with SDQ Total difficulties at 5 years, and neither problem score was associated with HCC1. In descriptive analyses, HCC2 was negatively associated with Internalizing problems at 2 years and SDQ Emotional problems at 5 years. A negative association was observed among 5-year-old girls between maternal HCC1 and SDQ Total Difficulties and the subscales of Conduct and Hyperactivity/inattentive problems. When interactions were also considered, inverse associations between HCC2 and BITSEA Internalizing and Dysregulation Problems were observed in subjects with elevated prenatal depressive symptoms. It was somewhat surprising that only negative associations were observed between maternal HCC and child socioemotional problems. However, there are previous observations of elevated end-of-pregnancy cortisol levels associating with better developmental outcomes. The magnitudes of the observed associations were, as expected, mainly modest. Future studies with a focus on the individual changes of maternal cortisol levels throughout pregnancy as well as studies assessing both maternal and child HPA axis functioning together with child socioemotional development are indicated.

Trajectories of maternal depressive and anxiety symptoms and child's socio-emotional outcome during early childhood.

Maternal symptoms of depression and anxiety during pregnancy and early postnatal years are suggested to impose differential negative effects on child's socio-emotional development depending on the characteristics of the symptoms, such as timing, intensity, and persistence. The aim of this study was to identify trajectories of maternal depressive and anxiety symptoms from pregnancy until 2 years postpartum and to examine their relationship with child socio-emotional problems and competence at 2 and 5 years of age. The sample included 1208 mother-infant dyads from FinnBrain Birth Cohort study. Latent growth mixture modelling (LGMM) was utilized to model the trajectories of maternal depressive symptoms, measured using the Edinburgh Postnatal Depression Scale (EPDS), and general anxiety, measured with Symptom Checklist-90 (SCL-90) at 14, 24, and 34 weeks' gestation (gw) and at 3, 6 and 24 months postpartum. Maternal depression was also assessed at 12 months. Child socio-emotional problems and competence were evaluated using the Brief Infant Toddler Social Emotional Assessment (BITSEA) at 2 years and Strengths and Difficulties Questionnaire (SDQ) at 5 years. Relevant background factors and maternal concurrent symptomatology were controlled for. The trajectories of maternal depressive and anxiety symptoms were associated negatively with differential aspects of child long term socio-emotional outcomes from early toddlerhood to preschool years. The trajectories of depressive symptoms and high-level persistent symptoms that continued from pregnancy to two years of child age had the strongest negative association with child outcomes. This highlights the importance of identifying and treating maternal symptomatology, especially that of depression, as early as possible.

Infants' sex affects neural responses to affective touch in early infancy.

Social touch is closely related to the establishment and maintenance of social bonds in humans, and the sensory brain circuit for gentle brushing is already active soon after birth. Brain development is known to be sexually dimorphic, but the potential effect of sex on brain activation to gentle touch remains unknown. Here, we examined brain activation to gentle skin stroking, a tactile stimulation that resembles affective or social touch, in term-born neonates. Eighteen infants aged 11-36 days, recruited from the FinnBrain Birth Cohort Study, were included in the study. During natural sleep, soft brush strokes were applied to the skin of the right leg during functional magnetic resonance imaging (fMRI) at 3 cm/s velocity. We examined potential differences in brain activation between males (n = 10) and females (n = 8) and found that females had larger blood oxygenation level dependent (BOLD) responses (brushing vs. rest) in bilateral orbitofrontal cortex (OFC), right ventral striatum and bilateral inferior striatum, pons, and cerebellum compared to males. Moreover, the psychophysiological interactions (PPI) analysis, setting the left and right OFC as seed regions, revealed significant differences between males and females. Females exhibited stronger PPI connectivity between the left OFC and posterior cingulate or cuneus. Our work suggests that social touch neural responses are different in male and female neonates, which may have major ramifications for later brain, cognitive, and social development. Finally, many of the sexually dimorphic brain responses were subcortical, not captured by surface-based neuroimaging, indicating that fMRI will be a relevant technique for future studies.

Effect of number of diffusion encoding directions in neonatal diffusion tensor imaging using Tract-Based Spatial Statistical analysis.

Diffusion tensor imaging (DTI) has been used to study the developing brain in early childhood, infants and in utero studies. In infants, number of used diffusion encoding directions has traditionally been smaller in earlier studies down to the minimum of 6 orthogonal directions. Whereas the more recent studies often involve more directions, number of used directions remain an issue when acquisition time is optimized without compromising on data quality and in retrospective studies. Variability in the number of used directions may introduce bias and uncertainties to the DTI scalar estimates that affect cross-sectional and longitudinal study of the brain. We analysed DTI images of 133 neonates, each data having 54 directions after quality control, to evaluate the effect of number of diffusion weighting directions from 6 to 54 with interval of 6 to the DTI scalars with Tract-Based Spatial Statistics (TBSS) analysis. The TBSS analysis was applied to DTI scalar maps, and the mean region of interest (ROI) values were extracted using JHU atlas. We found significant bias in ROI mean values when only 6 directions were used (positive in fractional anisotropy [FA] and negative in fractional anisotropy [MD], axial diffusivity [AD] and fractional anisotropy [RD]), while when using 24 directions and above, the difference to scalar values calculated from 54 direction DTI was negligible. In repeated measures voxel-wise analysis, notable differences to 54 direction DTI were observed with 6, 12 and 18 directions. DTI measurements from data with at least 24 directions may be used in comparisons with DTI measurements from data with higher numbers of directions.

Childhood trauma and fear of childbirth: findings from a birth cohort study.

The aim of this study is to investigate if experiencing childhood trauma (emotional abuse, emotional neglect, physical abuse, physical neglect, or sexual abuse) or a greater total burden of childhood trauma increase the risk of fear of childbirth (FOC). This study included 2556 women living in Southwest Finland. Women were recruited during routine ultrasound visits at gestational week (gwk) 12. Experiencing childhood trauma was assessed in retrospect with the Trauma and Distress Scale (TADS) questionnaire completed at gwk 14. Information on the diagnosis of FOC (ICD-10 diagnosis O99.80) was obtained from the Finnish Medical Birth Register. Associations between childhood trauma (domains and total TADS score) and FOC were analyzed with logistic regression in unadjusted and adjusted models. Emotional abuse (aOR 1.25, 95% CI 1.10-1.42), emotional neglect (aOR 1.26, 95% CI 1.08-1.46), and a greater total burden of trauma (TADS total score) (aOR 1.06, 95% CI 1.02-1.10) increased the risk for FOC. We found no evidence for physical abuse (aOR 1.15, 95% CI 1.00-1.32), physical neglect (aOR 1.06, 95% CI 0.92-1.22), and sexual abuse (aOR 1.24, 95% CI 0.99-1.56) associating with FOC. Childhood emotional abuse, emotional neglect, and a greater total burden of childhood trauma increase the risk for FOC. However, the childhood traumatic events were inquired in retrospect, which could distort the events.

Association of cumulative prenatal adversity with infant subcortical structure volumes and child problem behavior and its moderation by a coexpression polygenic risk score of the serotonin system.

Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother-infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.

Prenatal maternal depressive symptoms are associated with neonatal left amygdala microstructure in a sex-dependent way.

Exposures to prenatal maternal depressive symptoms (PMDS) may lead to neurodevelopmental changes in the offspring in a sex-dependent way. Although a connection between PMDS and infant brain development has been established by earlier studies, the relationship between PMDS exposures measured at various prenatal stages and microstructural alterations in fundamental subcortical structures such as the amygdala remains unknown. In this study, we investigated the associations between PMDS measured during gestational weeks 14, 24 and 34 and infant amygdala microstructural properties using diffusion tensor imaging. We explored amygdala mean diffusivity (MD) alterations in response to PMDS in infants aged 11 to 54 days from birth. PMDS had no significant main effect on the amygdala MD metrics. However, there was a significant interaction effect for PMDS and infant sex in the left amygdala MD. Compared with girls, boys exposed to greater PMDS during gestational week 14 showed significantly higher left amygdala MD. These results indicate that PMDS are linked to infants' amygdala microstructure in boys. These associations may be relevant to later neuropsychiatric outcomes in the offspring. Further research is required to better understand the mechanisms underlying these associations and to develop effective interventions to counteract any potential adverse consequences.

Maternal psychological distress associates with alterations in resting-state low-frequency fluctuations and distal functional connectivity of the neonate medial prefrontal cortex.

Prenatal stress exposure (PSE) has been observed to exert a programming effect on the developing infant brain, possibly with long-lasting consequences on temperament, cognitive functions and the risk for developing psychiatric disorders. Several prior studies have revealed that PSE associates with alterations in neonate functional connectivity in the prefrontal regions and amygdala. In this study, we explored whether maternal psychological symptoms measured during the 24th gestational week had associations with neonate resting-state network metrics. Twenty-one neonates (nine female) underwent resting-state fMRI scanning (mean gestation-corrected age at scan 26.95 days) to assess fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). The ReHo/fALFF maps were used in multiple regression analysis to investigate whether maternal self-reported anxiety and/or depressive symptoms associate with neonate functional brain features. Maternal psychological distress (composite score of depressive and anxiety symptoms) was positively associated with fALFF in the neonate medial prefrontal cortex (mPFC). Anxiety and depressive symptoms, assessed separately, exhibited similar but weaker associations. Post hoc seed-based connectivity analyses further showed that distal connectivity of mPFC covaried with PSE. No associations were found between neonate ReHo and PSE. These results offer preliminary evidence that PSE may affect functional features of the developing brain during gestation.

Allometry in the corpus callosum in neonates: Sexual dimorphism.

The corpus callosum (CC) is the largest fiber tract in the human brain, allowing interhemispheric communication by connecting homologous areas of the two cerebral hemispheres. In adults, CC size shows a robust allometric relationship with brain size, with larger brains having larger callosa, but smaller brains having larger callosa relative to brain size. Such an allometric relationship has been shown in both males and females, with no significant difference between the sexes. But there is some evidence that there are alterations in these allometric relationships during development. However, it is currently not known whether there is sexual dimorphism in these allometric relationships from birth, or if it only develops later. We study this in neonate data. Our results indicate that there are already sex differences in these allometric relationships in neonates: male neonates show the adult-like allometric relationship between CC size and brain size; however female neonates show a significantly more positive allometry between CC size and brain size than either male neonates or female adults. The underlying cause of this sexual dimorphism is unclear; but the existence of this sexual dimorphism in neonates suggests that sex-differences in lateralization have prenatal origins.

Sex-specific associations between maternal pregnancy-specific anxiety and newborn amygdalar volumes - preliminary findings from the FinnBrain Birth Cohort Study.

Previous literature links maternal pregnancy-specific anxiety (PSA) with later difficulties in child emotional and social cognition as well as memory, functions closely related to the amygdala and the hippocampus. Some evidence also suggests that PSA affects child amygdalar volumes in a sex-dependent way. However, no studies investigating the associations between PSA and newborn amygdalar and hippocampal volumes have been reported. We investigated the associations between PSA and newborn amygdalar and hippocampal volumes and whether associations are sex-specific in 122 healthy newborns (68 males/54 females) scanned at 2-5 weeks postpartum. PSA was measured at gestational week 24 with the Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2). The associations were analyzed with linear regression controlling for confounding variables. PSA was associated positively with left amygdalar volume in girls, but no significant main effect was found in the whole group or in boys. No significant main or sex-specific effect was found for hippocampal volumes. Although this was an exploratory study, the findings suggest a sexually dimorphic association of mid-pregnancy PSA with newborn amygdalar volumes.

Alexithymic traits and parental postpartum bonding: Findings from the FinnBrain Birth Cohort Study.

In the postpartum period, some parents experience problems in bonding with the infant, which can lead to difficulties in adjusting to the parental caregiving role. Alexithymia, through deficits in emotional processing, could potentially be associated with problems in parental postpartum bonding. In the current study, this association has been explored in a large population-based sample of mothers and fathers, and to our knowledge, this is the first study to investigate this association. The study population (n = 2,671) was part of the FinnBrain Birth Cohort study and included 1,766 mothers and 905 fathers who returned The Postpartum Bonding Questionnaire (PBQ) at three months postpartum and the 20-item Toronto Alexithymia Scale (TAS-20) at six months postpartum. Correlation analyses and hierarchical regression modeling, adjusted for selected background factors, were performed separately for mothers and fathers. The alexithymia dimension "Difficulty Identifying Feelings" (DIF) in mothers and fathers, and additionally dimensions of "Difficulty Describing Feelings" (DDF) and "Externally Oriented Thinking" (EOT) in fathers were associated with weaker postpartum bonding, when related background factors were controlled for. To our knowledge this was the first study to investigate the relationship between parents' alexithymic traits and postpartum bonding within a large birth cohort study population. The main finding was that especially higher levels of maternal DIF and paternal EOT were associated with weaker postpartum bonding. Longitudinal studies are needed to establish the potential causality of this relationship.

Gender-specific associations between the dimensions of alexithymia personality trait and dental anxiety in parents of the FinnBrain Birth Cohort Study.

We evaluated gender-specific associations of two dimensions of dental anxiety (anticipatory and treatment-related dental anxiety) with three dimensions of alexithymia: difficulty in identifying feelings, difficulty in describing feelings, and externally oriented thinking. The sample comprised 2558 parents from the general population participating in the FinnBrain Birth Cohort Study. Dental anxiety was measured with the Modified Dental Anxiety Scale and alexithymia with the 20-item Toronto Alexithymia Scale. Associations between dental anxiety and alexithymia dimensions were modelled using linear regression analysis adjusting for general anxiety and depressive symptoms, age, and education. Structural equation modeling assessed their interrelationships. In women, anticipatory dental anxiety was associated only with difficulty in identifying feelings, but treatment-related dental anxiety was associated with difficulty in identifying feelings, difficulty in describing feelings, and externally oriented thinking. In men, anticipatory dental anxiety was associated with only externally oriented thinking, whereas treatment-related dental anxiety was associated with difficulty in describing feelings, and with externally oriented thinking. Structural equation modelling showed that difficulty in identifying feelings was associated with anticipatory and treatment-related dental anxiety in women, whereas in men, only difficulty in describing feelings was associated with both types of dental anxiety. Anticipatory and treatment-related dental anxiety have different associations with alexithymia dimensions.

Successful suppression of musical hallucinations with low-frequency rTMS of the left temporo-parietal junction: A case report.

BACKGROUND: Inhibitory low frequency repetitive transcranial magnetic stimulation (rTMS) of the temporo-parietal area has been applied to treat both auditory verbal hallucinations as well as tinnitus. OBJECTIVE: We hypothesized that 1 Hz rTMS to the left temporoparietal junction (TPJ) may be beneficial in alleviating musical hallucinations (MH), another condition with auditory experiences in the absence of an external source. METHODS: Here we describe a patient with almost insufferable life-long MH with comorbid depression, who received inhibitory rTMS to the left TPJ as well as the right dorsolateral prefrontal cortex (DLPFC). RESULTS: The intrusiveness and frequency of her MH as well as her depressive symptoms alleviated quickly and substantially, and once-a-week maintenance therapy with rTMS seemed to preserve this amelioration. Future studies will hopefully reveal whether this is a viable treatment approach for other patients suffering from MH with or without comorbid depression.

Maternal pre-pregnancy BMI associates with neonate local and distal functional connectivity of the left superior frontal gyrus.

Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony and distal connectivity in the neonate brain. 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 ± 6.28 days, 12 male). The neonates were scanned with a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Seed-based connectivity analysis with multiple regression was subsequently performed with seed-ROI derived from ReHo analysis. Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (SFG) (FWE-corrected p < 0.005). Additionally, we found both positive and negative associations (p < 0.05, FWE-corrected) for maternal pre-pregnancy BMI and seed-based connectivity between left SFG and prefrontal, amygdalae, basal ganglia and insular regions. Our results imply that maternal pre-pregnancy BMI associates with local and distal functional connectivity within the neonate left superior frontal gyrus. These findings add to the evidence that increased maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks.

Prenatal Glucocorticoid-Exposed Infants Do Not Show an Age-Typical Fear Bias at 8 Months of Age - Preliminary Findings From the FinnBrain Birth Cohort Study.

Synthetic glucocorticoids (sGC) are frequently administered to pregnant women at risk for preterm delivery to promote fetal lung maturation. Despite their undeniable beneficial effects in lung maturation, the impact of these hormones on developing brain is less clear. Recent human studies suggest that emotional and behavioral disorders are more common among sGC-exposed vs. non-exposed children, but the literature is sparse and controversial. We investigated if prenatal sGC exposure altered fear bias, a well-established infant attention phenotype, at 8-months. We used eye tracking and an overlap paradigm with control, neutral, happy, and fearful faces, and salient distractors, to evaluate infants' attention disengagement from faces, and specifically from fearful vs. neutral and happy faces (i.e., a fear bias) in a sample (N = 363) of general population from the FinnBrain Birth Cohort Study. sGC exposed infants (N = 12) did not differ from non-exposed infants (N = 351) in their overall probability of disengagement in any single stimulus condition. However, in comparison with non-exposed infants, they did not show the age-typical fear bias and this association remained after controlling for confounding factors such as prematurity, gestational age at birth, birth weight, sex, and maternal postnatal depressive symptoms. Prenatal sGC exposure may alter emotional processing in infants. The atypical emotion processing in turn may be a predictor of emotional problems later in development. Future longitudinal studies are needed in order to evaluate the long-term consequences of sGC exposure for the developing brain.

Maternal Alexithymic Traits Are Related to Lower Maternal Sensitivity and Higher Hostility in Maternal Caregiving Behavior-The FinnBrain Birth Cohort Study.

Background: The quality of parental caregiving behavior with their child plays a key role in optimal mother-infant interaction and in supporting child adaptive development. Sensitive caregiving behavior, in turn, requires the ability to identify and understand emotions. Maternal alexithymia, with difficulties in identifying and describing feelings or emotions, as well as a concrete way of thinking, could potentially complicate the quality of caregiving. In this study, we aim to explore the possible association between maternal alexithymic traits and the quality of maternal caregiving behavior. Methods: The study sample consisted of 158 mother-infant dyads within the FinnBrain Birth Cohort Study population with an available report of maternal alexithymic traits at 6 months postpartum and observational data on maternal caregiving behavior at 8 months postpartum. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) including three alexithymia dimensions-Difficulty Identifying Feelings, Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Maternal caregiving behavior was assessed using the Emotional Availability Scale and in this study, all four parent dimensions (Sensitivity, Structuring, Non-intrusiveness and Non-hostility) were included. Maternal depressive and anxiety symptoms at 6 months postpartum were controlled for as potential confounders. In addition, background factors of mother's age and gestational weeks at the time of child birth, maternal educational level, monthly income and parity, as well as relationship status and the gender of the baby were assessed. Results: Maternal TAS-20 total score correlated negatively with Sensitivity (r = -0.169, p = 0.034) and with non-intrusiveness (r = -0.182, p = 0.022). In addition, maternal DDF correlated negatively with Sensitivity (r = -0.168, p = 0.035) and EOT with Non-hostility (r = -0.159, p = 0.047). Furthermore, in regression analyses with controlling for the associated background factors, maternal total score of alexithymic traits (p = 0.034, η2 p = 0.029) and higher DDF (p = 0.044, η2 p = 0.026) remained significantly associated with lower Sensitivity and higher EOT remained significantly associated with lower Non-hostility (p = 0.030, η2 p = 0.030). Conclusions: In this explorative study we found preliminary evidence for the hypothesis that higher maternal alexithymic traits associate with lower maternal sensitivity and more hostile maternal caregiving behavior. Further studies are needed to explore these hypotheses and to investigate their possible implications for child development.

Placental DNA methylation marks are associated with maternal depressive symptoms during early pregnancy.

Maternal depressive symptoms during pregnancy are a significant risk factor for adverse developmental and health outcomes of the offspring. The molecular mechanisms mediating the long-term effects of this exposure are not well understood. Previous studies have found association between prenatal exposure to maternal psychological distress and placental DNA methylation of candidate genes, which can influence placental barrier function and development of the fetus. Our objective in this study was to determine epigenome wide association of maternal depressive symptoms in early pregnancy with the placental DNA methylation. For this purpose we examined DNA methylomes of 92 placental samples by using reduced representation bisulfite sequencing. The placental samples were collected after deliveries of 39 girls and 59 boys, whose mothers had Edinburgh Postnatal Depression Score ranging from 0 to 19 at gestational week 14. According to our results maternal depressive symptoms are associated with DNA methylation of 2833 CpG sites, which are particularly over-represented in genic enhancers. The genes overlapping or nearest to these sites are functionally enriched for development of neurons and show expression enrichment in several regions of developing brain. The genomic regions harboring the DNA methylation marks are enriched for single nucleotide polymorphisms associated with mental disease trait class. Potential cellular signaling cascades mediating the effects include inflammatory and hormonal pathways. As a conclusion our results suggest that maternal depressive symptoms during early pregnancy are associated with DNA methylation marks in placenta in genes, which are important for the development and long-term health of the brain. Whether similar marks can be detected in exposed children remains to be elucidated in further studies.

Neonatal amygdala volumes and the development of self-regulation from early infancy to toddlerhood.

Objective: At the broadest level, self-regulation (SR) refers to a range of separate, but interrelated, processes (e.g., working memory, inhibition, and emotion regulation) central for the regulation of cognition, emotion, and behavior that contribute to a plethora of health and mental health outcomes. SR skills develop rapidly in early childhood, but their neurobiological underpinnings are not yet well understood. The amygdala is one key structure in negative emotion generation that may disrupt SR. In the current study, we investigated the associations between neonatal amygdala volumes and mother-reported and observed child SR during the first 3 years of life. We expected that larger neonatal amygdala volumes would be related to poorer SR in children. Method: We measured amygdala volumes from magnetic resonance imaging (MRI) performed at age M = 3.7 ± 1.0. We examined the associations between the amygdala volumes corrected for intracranial volume (ICV) and (a) parent-reported indicators of SR at 6, 12, and 24 months (N = 102) and (b) observed task-based indicators of SR (working memory and inhibitory control) at 30 months of age in a smaller subset of participants (N = 80). Results: Bilateral neonatal amygdala volumes predicted poorer working memory at 30 months in girls, whereas no association was detected between amygdalae and inhibitory control or parent-reported SR. The left amygdala by sex interaction survived correction for multiple comparisons. Conclusions: Neonatal amygdala volume is associated with working memory, particularly among girls, and the association is observed earlier than in prior studies. Moreover, our findings suggest that the neural correlates for parent-reported, compared to observed early life SR, may differ. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Early-life adversities and adult attachment in depression and alexithymia.

Alexithymia is a personality construct characterized by difficulties in identifying and verbalizing feelings, a restricted imagination, and an externally oriented thinking style. As alexithymia shows marked overlap with depression, its independent nature as a personality construct is still being debated. The etiology of alexithymia is unknown, although childhood emotional neglect and attachment formation are thought to play important roles. In the FinnBrain Birth Cohort Study, experiences of early-life adversities (EA) and childhood maltreatment (CM) were studied in a sample of 2,604 men and women. The overlap and differences between depression and alexithymia were investigated by comparing their associations with EA types and adult attachment style. Alexithymia was specifically associated with childhood emotional neglect (odds ratio (OR) 3.8, p < .001), whereas depression was related to several types of EA. In depression co-occurring with alexithymia, there was a higher prevalence of emotional neglect (81.3% vs. 54.4%, p < .001), attachment anxiety (t = 2.38, p = .018), and attachment avoidance (t = 4.03, p < .001). Early-life adversities were markedly different in the alexithymia group compared to those suffering from depression, or healthy controls. Depression with concurrent alexithymia may represent a distinct subtype, specifically associated with childhood experiences of emotional neglect, and increased attachment insecurity compared to non-alexithymic depression.