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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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest No affiliation, financial agreement, or other involvement of the authors with any companies has affected the preparation of this manuscript. All other authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2023 The Authors. Developmental Psychobiology published by Wiley Periodicals LLC.)

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., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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., (© 2023. The Author(s).)

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., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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 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., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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., (© 2022 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

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., (© 2021 The Authors. European Journal of Oral Sciences published by John Wiley & Sons Ltd on behalf of Scandinavian Division of the International Association for Dental Research.)

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.

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.

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., (© 2021. The Author(s).)

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., Competing Interests: Declarations of interest: none., (© 2021 The Authors.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kataja, Rodrigues, Scheinin, Nolvi, Korja, Häikiö, Ekholm, Sousa, Karlsson and Karlsson.)

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, η 2 p = 0.029) and higher DDF ( p = 0.044, η 2 p = 0.026) remained significantly associated with lower Sensitivity and higher EOT remained significantly associated with lower Non-hostility ( p = 0.030, η 2 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ahrnberg, Korja, Scheinin, Nolvi, Kataja, Kajanoja, Hakanen, Karlsson, Karlsson and Karukivi.)

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).

Genetic variants in the oxytocin receptor (OTR) have been linked to distinct social phenotypes, psychiatric disorders and brain volume alterations in adults. However, to date, it is unknown how OTR genotype shapes prenatal brain development and whether it interacts with maternal prenatal environmental risk factors on infant brain volumes. In 105 Finnish mother-infant dyads (44 female, 11-54 days old), the association of offspring OTR genotype rs53576 and its interaction with prenatal maternal anxiety (revised Symptom Checklist 90, gestational weeks 14, 24, 34) on infant bilateral amygdalar, hippocampal and caudate volumes were probed. A sex-specific main effect of rs53576 on infant left hippocampal volumes was observed. In boys compared to girls, left hippocampal volumes were significantly larger in GG-homozygotes compared to A-allele carriers. Furthermore, genotype rs53576 and prenatal maternal anxiety significantly interacted on right hippocampal volumes irrespective of sex. Higher maternal anxiety was associated both with larger hippocampal volumes in A-allele carriers than GG-homozygotes, and, though statistically weak, also with smaller right caudate volumes in GG-homozygotes than A-allele carriers. Our study results suggest that OTR genotype enhances hippocampal neurogenesis in male GG-homozygotes. Further, prenatal maternal anxiety might induce brain alterations that render GG-homozygotes compared to A-allele carriers more vulnerable to depression., (Copyright © 2020. Published by Elsevier B.V.)

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men., (© 2020 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Despite interest in unequal maternal and child health, previous research has not focused on educational differences in anxiety and depressive symptoms during pregnancy, although they threaten maternal and child wellbeing. Using the prospective FinnBrain Cohort Study data on 2763 pregnant women over the three pregnancy trimesters and Finnish register data, we estimated multilevel regressions to describe educational differences in prenatal anxiety and depressive symptoms and to analyze whether they can be explained by socioeconomic background, parental mental disorders and adverse experiences during childhood. Prenatal anxiety was measured by the Symptom Checklist (SCL-90-anxiety subscale) and depressive symptoms by the Edinburgh Postnatal Depression Scale (EPDS). The results showed less anxiety and depressive symptoms among more educated pregnant women. In accounting for the educational differences, we found support for both the social selection and the social causation perspectives. Adverse childhood experiences partly explained the educational differences, highlighting the role of an undisturbed childhood environment in prenatal mental health disparities. Results from the regression models as well as sensitivity analyses also suggested that education is likely to buffer against prenatal distress., Competing Interests: None., (© 2020 The Authors.)

Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother-infant dyads (44 female, 11-54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Importance: Early life stress (ELS) has been shown to affect brain development and health outcomes. Recent animal studies have linked paternal early stress exposures with next-generation outcomes. Epigenetic inheritance through the male germline has been suggested to be one of the mechanisms., Objectives: To test whether paternal ELS, as measured using the Trauma and Distress Scale, is associated with neonate brain development., Design, Setting, and Participants: This cohort study included data from participants from the prospective 2-generation FinnBrain Birth Cohort, which was collected from 2011 to 2015. Pregnant women and the fathers were consecutively recruited at gestational week 12 from maternity clinics in Finland. Magnetic resonance imaging data were analyzed in 2019. Participants in this study were 72 families (infant, father, mother)., Exposure: Paternal exposure to ELS., Main Outcomes and Measures: Fractional anisotropy (FA) values in the major white-matter tracts of the newborn brain., Results: A total of 72 trios (infant, mother, and father) were analyzed. At the time of delivery, the mean (SD) age was 31.0 (4.4) years for fathers and 30.3 (4.5) years for mothers. Forty-one infants (57%) were boys; mean (SD) child age at inclusion was 26.9 (7.2) days from birth and 205 (8) days from estimated conception. Increasing levels of paternal ELS were associated with higher FA values in the newborn brain in the body of the corpus callosum, right superior corona radiata, and retrolenticular parts of the internal capsule. This association persisted after controlling for maternal ELS, maternal socioeconomic status (SES), maternal body mass index, maternal depressive symptoms during pregnancy, child sex, and child age from birth and gestation corrected age when imaged. In additional region-of-interest analyses, the association between FA values and paternal Trauma and Distress Scale sum scores remained statistically significant in the earliest maturing regions of the brain, eg, the genu of the corpus callosum (in the regression models, β = 0.00096; 95% CI, 0.00034-0.00158; P = .003) and the splenium (β = 0.00090; 95% CI, 0.00000-0.00180; P = .049)., Conclusions and Relevance: This cohort study found a statistically significant association between paternal ELS and offspring brain development. This finding may have far-reaching implications in pediatrics, as it suggests the possibility of a novel route of intergenerational inheritance of ELS on next-generation brain development.

After 5 months of age, infants begin to prioritize attention to fearful over other facial expressions. One key proposition is that amygdala and related early-maturing subcortical network, is important for emergence of this attentional bias - however, empirical data to support these assertions are lacking. In this prospective longitudinal study, we measured amygdala volumes from MR images in 65 healthy neonates at 2-5 weeks of gestation corrected age and attention disengagement from fearful vs. non-fearful facial expressions at 8 months with eye tracking. Overall, infants were less likely to disengage from fearful than happy/neutral faces, demonstrating an age-typical bias for fear. Left, but not right, amygdala volume (corrected for intracranial volume) was positively associated with the likelihood of disengaging attention from fearful faces to a salient lateral distractor (r = .302, p = .014). No association was observed with the disengagement from neutral or happy faces in equivalent conditions (r = .166 and .125, p = .186 and .320, respectively). These results are the first to link the amygdala volume with the emerging perceptual vigilance for fearful faces during infancy. They suggest a link from the prenatally defined variability in the amygdala size to early postnatal emotional and social traits., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study sought to investigate if parental divorce in childhood increases the risk for depressive symptoms in pregnancy., Methods: Women were recruited during their ultrasound screening in gestational week (gwk) 12. The final study sample consisted of 2,899 pregnant women. Questionnaires (including the Edinburgh Postnatal Depression Scale) were completed at three measurement points (gwk 14, 24 and 34). Prenatal depressive symptoms were defined as Edinburgh Postnatal Depression Scale score ≥ 13. Parental divorce and other stressful life events in childhood were assessed at gwk 14. Parental divorce was defined as separation of parents who were married or cohabiting. Questionnaire data was supplemented with data from Statistics Finland and the Finnish Medical Birth Register., Results: Parental divorce in childhood increased the risk for depressive symptoms during pregnancy (OR 1.47; 95% CI 1.02-2.13), but the connection was no longer significant after adjusting for socioeconomic status, family conflicts and witnessing domestic violence in the childhood family (OR 0.80; 95% CI 0.54-1.18)., Conclusions: Parental divorce alone does not predict depressive symptoms during pregnancy.

Maternal postpartum depression is a prominent risk factor for aberrant child socioemotional development, but there is little understanding about the neural phenotypes that underlie infant sensitivity to maternal depression. We examined whether newborn white matter fractional anisotropy (FA), a measure of white matter maturity, moderates the association between maternal postpartum depressive symptoms and infant negative reactivity at 6 months. Participants were 80 mother-infant dyads participating in a prospective population-based cohort, and included families whose newborns underwent a magnetic resonance/diffusion tensor imaging scan at 2-5 weeks of age and whose mothers reported their own depressive symptoms at 3 and 6 months postpartum and infant negative emotional reactivity at 6 months. The whole-brain FA moderated the association between maternal depressive symptoms and mother-reported infant negative reactivity at 6 months after adjusting for the covariates. Maternal depressive symptoms were positively related to infant negative reactivity among infants with high or average FA in the whole brain and in corpus callosum and cingulum, but not among those with low FA. The link between maternal depressive symptoms and infant negative reactivity was moderated by newborn FA. The variation in white matter microstructure might play a role in child susceptibility to parental distress., (© The Author(s) 2020. Published by Oxford University Press.)

Introduction: Alexithymia, a personality construct characterized by difficulties in identifying and expressing emotions, and an externally oriented thinking style, has been associated with a number of stress-related disorders, and physiological markers of stress. We examined the relationships of alexithymia and hair cortisol concentrations (HCC), a measure of long-term cortisol levels, in pregnant women., Methods: Participants were 130 women from the FinnBrain Birth Cohort study. Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). Analysis of covariance and regression analyses were used to assess the associations between alexithymia and HCC. Educational level, current depressive symptoms, and body mass index (BMI) were applied as covariates., Results: In the adjusted analyses, individuals with moderate to high alexithymic traits had significantly higher HCC ( F = 5.11, partial η ² = 0.040 , p = 0.026) compared to non-alexithymics. Regression analyses in the whole sample revealed that, of the individual dimensions of alexithymia, Difficulty Identifying Feelings (DIF) was associated with HCC (β = 0.187, t = 2.064, p = 0.041)., Conclusions: Alexithymia, and especially its dimension DIF, were associated with higher HCC and, therefore, may be linked to increased chronic physiological stress. Implications for pregnancy outcomes and infant development are discussed., (Copyright © 2020 Kajanoja, Karukivi, Mustonen, Scheinin, Kortesluoma, Rodrigues, Karlsson and Karlsson.)

Poor maternal sleep quality during pregnancy may act as a prenatal stress factor for the fetus and associate with neonate neurocognition, for example via fetal programming. The impacts of worsened maternal sleep on neonatal development and, more specifically on neonatal auditory brain responses, have not been studied. A total of 155 mother-neonate dyads drawn from the FinnBrain Birth Cohort Study participated in our study including maternal self-report questionnaires on sleep at gestational week 24 and an event-related potential (ERP) measurement among 1-2-day-old neonates. For sleep quality assessment, the Basic Nordic Sleep Questionnaire (BNSQ) was used and calculated scores for (1) insomnia, (2) subjective sleep loss and (3) sleepiness were formed and applied in the analyses. In the auditory ERP protocol, three emotionally uttered pseudo words (in happy, angry and sad valence) were presented among neutrally uttered pseudo words. To study the relations between prenatal maternal sleep quality and auditory emotion-related ERP responses, mixed-effects regression models were computed for early (100-200 ms) and late (300-500 ms) ERP response time-windows. All of the selected BNSQ scores were associated with neonatal ERP responses for happy and angry emotion stimuli (sleep loss and sleepiness in the early, and insomnia, sleep loss and sleepiness in the late time-window). For sad stimuli, only maternal sleep loss predicted the neonatal ERP response in the late time-window, likely because the overall ERP was weakest in the sad condition. We conclude that maternal sleep quality during pregnancy is associated with changes in neonatal auditory ERP responses.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been successfully used to probe the intrinsic functional organization of the brain and to study brain development. Here, we implemented a combination of individual and group independent component analysis (ICA) of FSL on a 6-min resting-state data set acquired from 21 naturally sleeping term-born (age 26 ± 6.7 d), healthy neonates to investigate the emerging functional resting-state networks (RSNs). In line with the previous literature, we found evidence of sensorimotor, auditory/language, visual, cerebellar, thalmic, parietal, prefrontal, anterior cingulate as well as dorsal and ventral aspects of the default-mode-network. Additionally, we identified RSNs in frontal, parietal, and temporal regions that have not been previously described in this age group and correspond to the canonical RSNs established in adults. Importantly, we found that careful ICA-based denoising of fMRI data increased the number of networks identified with group-ICA, whereas the degree of spatial smoothing did not change the number of identified networks. Our results show that the infant brain has an established set of RSNs soon after birth., (© 2020 The Authors. Developmental Neurobiology published by Wiley Periodicals LLC.)

Parental reflective functioning (PRF) refers to a parent's effort to see his/her child as a separate individual person from early on, and to be curious of the child's own thoughts and feelings. Parenting abilities are affected by the parent's emotion regulation and emotional availability. Alexithymia as a personality construct with emotional deficits and poor imagination could potentially affect also PRF, but studies on parental alexithymia are still scarce. The aim of the present study was to examine the association between parental alexithymic traits and PRF, which to date has not been explored. As most of the parenting research concern only mothers, an additional aim was to study also fathers. The 20-item Toronto Alexithymia Scale (TAS-20) and the 14-item Parental Reflective Functioning Questionnaire (PRFQ-Fi) were filled by 1882 mothers and 994 fathers at six months postpartum as part of the FinnBrain Birth Cohort Study. A significant negative association between TAS-20 total score and PRFQ-Fi total score among both genders was found. The main alexithymia dimension responsible for this association was Externally Oriented Thinking. The results suggest that alexithymic traits indeed are related to parental reflective functioning, but more studies are needed to explore the direction of this relation., Competing Interests: Declaration of Competing Interests None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Birth is a traumatic event with molding forces directed to the fetal skull, which may result in intracranial hemorrhages. However, the knowledge on prevalence and risk factors of incidental brain magnetic resonance imaging (MRI) findings in infants is still inconclusive. Methods: The prevalence and nature of incidental MRI findings were assessed in a birth cohort of 175 asymptomatic infants. The role of delivery method as well as other potential risk factors for intracranial hemorrhages were evaluated. The infants underwent 3T MRI at the age of 2-5 weeks, and the neurological status of the infants with an incidental finding was evaluated by a pediatric neurologist. Information on the delivery method, duration of delivery, parity, used anesthesia, oxytocin induction, and Apgar score was gathered to evaluate their association with the prevalence of hemorrhages. Results: Incidental intracranial hemorrhages were detected in 12 infants (6.9%), all following spontaneous or assisted vaginal delivery. Vacuum-assistance was found to be a risk factor for subdural hemorrhages with an odds ratio (OR) of 4.7 (95% CI [1.18; 18.9], p = 0.032). All infants were evaluated to develop normally by their clinical status. Conclusions: Incidental intracranial hemorrhages are relatively common among infants born by vaginal delivery. They are often of little clinical significance within the first years of life and have unlikely consequences for later neurodevelopment either. Despite their benign character, investigators should be prepared to share this information with parents competently as the findings can cause parental anxiety, and especially as the popularity of MRI as a research tool is increasing., (Copyright © 2020 Kumpulainen, Lehtola, Tuulari, Silver, Copeland, Korja, Karlsson, Karlsson, Merisaari, Parkkola, Saunavaara, Lähdesmäki and Scheinin.)

Maternal psychological distress during pregnancy (PPD) 1 has been associated with changes in offspring amygdalar and hippocampal volumes. Studies on child amygdalae suggest that sex moderates the vulnerability of fetal brains to prenatal stress. However, this has not yet been observed in these structures in newborns. Newborn studies are crucial, as they minimize the confounding influence of postnatal life. We investigated the effects of maternal prenatal psychological symptoms on newborn amygdalar and hippocampal volumes and their interactions with newborn sex in 123 newborns aged 2-5 weeks (69 males, 54 females). Based on earlier studies, we anticipated small, but statistically significant effects of PPD on the volumes of these structures. Maternal psychological distress was measured at gestational weeks (GW) 2 14, 24 and 34 using Symptom Checklist-90 (SCL-90, anxiety scale) 3 and Edinburgh Postnatal Depression Scale (EPDS) 4 questionnaires. Newborn sex was found to moderate the relationship between maternal distress symptoms at GW 24 and the volumes of left and right amygdala. This relationship was negative and significant only in males. No significant main effect or sex-based moderation was found for hippocampal volumes. This newborn study provides evidence for a sex-dependent influence of maternal psychiatric symptoms on amygdalar structural development. This association may be relevant to later psychopathology., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Sleep disturbances relate to altered levels of inflammatory mediators in general population, but not much is known about the associations between sleep disturbances and inflammatory mediators during pregnancy. The present exploratory study investigated whether insomnia, tiredness, general sleep quality, and insufficient sleep duration during pregnancy relate to the concentrations of maternal peripheral circulating cytokines. As sleep disturbances are frequently observed in mood disorders, the results were controlled for symptoms of depression and anxiety., Methods: 137 participants were randomly drawn from a representative FinnBrain Birth Cohort. Serum concentrations of selected cytokines were analyzed using Multiplex bead arrays from blood samples drawn at the gestational week 24. The sleep disturbances were evaluated using the Basic Nordic Sleep Questionnaire. Depressive and anxiety symptoms were measured with the Edinburgh Postnatal Depression Scale and the anxiety subscale of the self-rated Symptom Checklist 90, respectively., Results: Enhanced tiredness was associated with cytokine concentrations of IL-2, IL-10, IL-12, IL-13, and TNF-α. The observed associations resembled a reversed U-shaped curve rather than being linear. Having a good general sleep quality was associated with higher logarithmic cytokine concentrations of IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, and IFN-γ. There was no evidence for associations between insomnia or sleep loss and cytokines., Conclusions: Maternal subjective tiredness and good general sleep quality were associated with altered levels of immunological markers during pregnancy. The association was independent from symptoms of depression and anxiety., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Maternal prenatal cortisol levels have been inconsistently associated with self-reports of prenatal psychological distress (PD). Previous research has linked hair cortisol concentration (HCC) evaluating cumulatively the previous months with cross-sectional PD measures that usually cover the past week(s), which may lead to misleading conclusions on their relations. We aimed to investigate how maternal HCC relates to cumulative PD measures across pregnancy., Methods: Subjects (N = 595) were drawn from the FinnBrain Birth Cohort Study. Maternal HCC was measured from hair samples collected at gestational week (gwk) 24 (HCC1, n = 467) and at delivery (HCC2, n = 222). As HCC1 and HCC2 comprised mostly of different subjects, they were considered as independent populations. Maternal PD assessments at gwks 14, 24, and 34 were the Edinburgh Postnatal Depression Scale (EPDS), the anxiety subscale of the Symptom Checklist (SCL-90), the Pregnancy-Related Anxiety Questionnaire -Revised2 (PRAQ-R2), and a daily hassles scale. Cumulative PD comprised of the mean scores of two consecutive assessments (mean1 = gwks 14 and 24; mean2 = gwks 24 and 34). In addition, EPDS and SCL scores were modelled by using growth mixture modelling to identify symptom trajectory categories. Regression models were adjusted for age, body mass index, education and use of selective serotonin/serotonin-norepinephrine reuptake inhibitor medication., Results: In the adjusted regression model, higher HCC2 was related to the "consistently elevated" prenatal depressive symptoms trajectory in comparison to "consistently low" (β =.71, p =.021) and "low and increasing" (β =.82, p = .011) symptom trajectories. Additionally, the cumulative mean (mean 1) of daily hassles in relationships was associated with HCC1 (β = 0.25, p = .004). General or pregnancy-related anxiety symptoms were unrelated to HCC after adjustment for the covariates., Conclusions: The assessment of cumulative or trajectory measures of PD can reveal important associations with maternal prenatal HCC, even though the associations are generally weak. Of the different dimensions of PD, prenatal trajectories of depressive symptoms were most consistently linked with end-pregnancy HCC levels., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The gross anatomy of the infant brain at term is fairly similar to that of the adult brain, but structures are immature, and the brain undergoes rapid growth during the first 2 years of life. Neonate magnetic resonance (MR) images have different contrasts compared to adult images, and automated segmentation of brain magnetic resonance imaging (MRI) can thus be considered challenging as less software options are available. Despite this, most anatomical regions are identifiable and thus amenable to manual segmentation. In the current study, we developed a protocol for segmenting the amygdala and hippocampus in T2-weighted neonatal MR images. The participants were 31 healthy infants between 2 and 5 weeks of age. Intra-rater reliability was measured in 12 randomly selected MR images, where 6 MR images were segmented at 1-month intervals between the delineations, and another 6 MR images at 6-month intervals. The protocol was also tested by two independent raters in 20 randomly selected T2-weighted images, and finally with T1 images. Intraclass correlation coefficient (ICC) and Dice similarity coefficient (DSC) for intra-rater, inter-rater, and T1 vs. T2 comparisons were computed. Moreover, manual segmentations were compared to automated segmentations performed by iBEAT toolbox in 10 T2-weighted MR images. The intra-rater reliability was high ICC ≥ 0.91, DSC ≥ 0.89, the inter-rater reliabilities were satisfactory ICC ≥ 0.90, DSC ≥ 0.75 for hippocampus and DSC ≥ 0.52 for amygdalae. Segmentations for T1 vs. T2-weighted images showed high consistency ICC ≥ 0.90, DSC ≥ 0.74. The manual and iBEAT segmentations showed no agreement, DSC ≥ 0.39. In conclusion, there is a clear need to improve and develop the procedures for automated segmentation of infant brain MR images., (Copyright © 2019 Hashempour, Tuulari, Merisaari, Lidauer, Luukkonen, Saunavaara, Parkkola, Lähdesmäki, Lehtola, Keskinen, Lewis, Scheinin, Karlsson and Karlsson.)

Background: Alzheimer's disease results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. Environmental and lifestyle factors largely modulate the disease risk and may influence the pathogenesis through epigenetic mechanisms, such as DNA methylation. As environmental and lifestyle factors may affect multiple tissues of the body, we hypothesized that the disease-associated DNA methylation signatures are detectable in the peripheral blood of discordant twin pairs., Results: Comparison of 23 disease discordant Finnish twin pairs with reduced representation bisulfite sequencing revealed peripheral blood DNA methylation differences in 11 genomic regions with at least 15.0% median methylation difference and FDR adjusted p value ≤ 0.05. Several of the affected genes are primarily associated with neuronal functions and pathologies and do not display disease-associated differences in gene expression in blood. The DNA methylation mark in ADARB2 gene was found to be differentially methylated also in the anterior hippocampus, including entorhinal cortex, of non-twin cases and controls. Targeted bisulfite pyrosequencing of the DNA methylation mark in ADARB2 gene in 62 Finnish and Swedish twin pairs revealed that, in addition to the disease status, DNA methylation of this region is influenced by gender, age, zygosity, APOE genotype, and smoking. Further analysis of 120 Swedish twin pairs indicated that this specific DNA methylation mark is not predictive for Alzheimer's disease and becomes differentially methylated after disease onset., Conclusions: DNA methylation differences can be detected in the peripheral blood of twin pairs discordant for Alzheimer's disease. These DNA methylation signatures may have value as disease markers and provide insights into the molecular mechanisms of pathogenesis. We found no evidence that the DNA methylation marks would be associated with gene expression in blood. Further studies are needed to elucidate the potential importance of the associated genes in neuronal functions and to validate the prognostic or diagnostic value of the individual marks or marker panels.

Objective: Overweight, obesity, and associated problems in metabolic health are an increasing public health concern. Personality traits and emotional processing styles may play a role in the regulation of food intake and reward. Alexithymia is a personality construct involving difficulties in identifying and expressing emotions and has been previously associated with eating disorders and metabolic problems. We examined associations between alexithymia dimensions, Body Mass Index (BMI) and gestational diabetes in pregnant women., Methods: The participants were 1660 pregnant women living in Finland from the FinnBrain Birth Cohort Study. We investigated the associations between alexithymia and its dimensions as measured by the Toronto Alexithymia Scale (TAS-20), overweight, and gestational diabetes. The effects of age, education, and depressive symptoms were controlled for using hierarchical regression analysis., Results: Alexithymic individuals had a higher prevalence of overweight compared to those with low or moderate levels of alexithymia (66.0% vs. 34.8%, OR 3.6, adjusted OR 3.6, CI95% 1.9-6.8, p < .001). The dimension of Externally Oriented Thinking (EOT) accounted for this association. Compared to the lowest quartile, women in the highest EOT quartile had a higher BMI (24.3 vs. 25.6, p < .001), and a higher prevalence of overweight [adjusted OR 1.94, CI95% 1.43-2.62, p < .001] and gestational diabetes [OR 1.75, CI95% 1.19-2.55, p = .005]., Conclusions: Alexithymia, and especially its dimension of EOT is associated with overweight and gestational diabetes in pregnant women. Future studies should clarify causality and examine potential mechanisms and associations with pregnancy outcomes and fetal health., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diffusion tensor imaging (DTI) has been widely used in children and adults to study the microstructural features of the brain. Its use in neonate brains has been limited. Neonate brains are almost completely unmyelinated, and this together with the tendency for babies to move during a scanning session may affect the reliability of the measurements. Here we divided a 96 direction acquisition into three segments, and analysed the intra scan test-retest reliability for pairs of segments. Each segment was subjected to a rigorous quality control, and from the surviving data we chose 25 diffusion encoding directions from each segment, and assessed the pairwise reliability of the most common DTI metrics. This pairwise reliability was assessed for data from 86 infants. We used tract-based spatial statistics (TBSS), voxelwise and ROI analysis schemes, to see potential differential effects of analysis strategy and post processing on the obtained DTI metrics. We found that intra class correlation coefficient (ICC) values were generally high (ICC > 0.80). Residual motion in the data, after quality control, was not found to associate with the diffusion metrics. The results indicate that DTI metrics from neonate data can be reliable, even at relatively low angular resolution that are common for neonate scans. The results lend confidence to the use of neonate DTI data in cross sectional and longitudinal analyses in brain white matter skeleton. Future studies should assess the reliability of fiber tracking techniques in neonate data., (Copyright © 2019. Published by Elsevier Inc.)

Prenatal stress is associated with child behavioral outcomes increasing susceptibility for psychiatric disorders in later life. Altered fetal brain development might partly mediate this association, as some studies suggest. With this study, we investigated the relation between prenatal stress, child's brain structure and behavioral problems. The association between self-reported maternal pregnancy-related anxiety (PRAQ-R2 questionnaire, second and third trimester) and brain gray matter volume was probed in 27 4-year-old children (13 female). Voxel based morphometry was applied with an age-matched template in SPM for the whole-brain analyses, and amygdala volume was assessed with manual segmentation. Possible pre- and postnatal confounders, such as maternal depression and anxiety among others, were controlled for. Child behavioral problems were assessed with the Strength and Difficulties Questionnaire by maternal report. We found a significant interaction effect of pregnancy-related anxiety and child's sex on child's amygdala volume, i.e., higher pregnancy-related anxiety in the second trimester was related to significantly greater left relative amygdala volume in girls compared to boys. Further exploratory analyses yielded that both maternal pregnancy-related anxiety and child's amygdala volume are related to child emotional and behavioral difficulties: While higher pregnancy-related anxiety was associated with more emotional symptoms, peer relationship problems and overall child difficulties, greater left amygdala volume was related to less of these child difficulties and might partly mediate sex-specific associations between pregnancy-related anxiety and child behavioral difficulties. Our data suggest that maternal prenatal distress leads to sexually dimorphic structural changes in the offspring's limbic system and that these changes are also linked to behavioral difficulties. Our results provide further support for the notion that prenatal stress impacts child development.

Objective: To assess the relation between maternal prenatal psychological distress, comprising depression and anxiety symptoms and relationship quality, and the risk of recurrent respiratory infections (RRIs) in children up to 2 years of age. Children with RRIs frequently use health care services and antibiotics. Prenatal maternal psychological distress can be one, previously unidentified risk factor for RRIs., Study Design: The study population was drawn from a population-based pregnancy cohort in Finland (www.finnbrain.fi). Children with RRIs (n = 204) and a comparison group (n = 1014) were identified by maternal reports at the child age of 12 or 24 months. The Edinburgh Postnatal Depression Scale, Symptom Checklist-90 anxiety subscale, the Pregnancy-Related Anxiety Questionnaire-Revised 2, and the Revised Dyadic Adjustment Scale were used to assess maternal symptoms and parental relationship quality at 34 weeks of gestation. Adjustment for maternal postnatal depressive and anxiety symptoms was performed., Results: Maternal prenatal Edinburgh Postnatal Depression Scale (OR, 1.24; 95% CI, 1.08-1.44), Symptom Checklist-90/Anxiety (OR, 1.40; 95% CI, 1.01-1.76), Pregnancy-Related Anxiety Questionnaire-Revised 2 (OR, 1.28; 95% CI, 1.11-1.47), and Revised Dyadic Adjustment Scale (OR, 1.32; 95% CI, 1.01-1.58) total sum scores were associated with child RRIs by the age of 24 months. Greater number of siblings, shorter duration of breastfeeding, and the level of maternal education were also identified as risk factors for child RRIs., Conclusions: Maternal prenatal psychological distress is linked with a higher risk for child RRIs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Brain development is most rapid during the fetal period and the first years of life. This process can be affected by many in utero factors, such as chemical exposures and maternal health characteristics. The goal of this review is twofold: to review the most recent findings on the effects of these prenatal factors on the developing brain and to qualitatively assess how those factors were generally reported in studies on infants up to 2 years of age. To capture the latest findings in the field, we searched articles from PubMed 2012 onward with search terms referring to magnetic resonance imaging (MRI), brain development, and infancy. We identified 19 MRI studies focusing on the effects of prenatal environment and summarized them to highlight the recent advances in the field. We assessed population descriptions in a representative sample of 67 studies and conclude that prenatal factors that have been shown to affect brain metrics are not generally reported comprehensively. Based on our findings, we propose some improvements for population descriptions to account for plausible confounders and in time enable reliable meta-analyses to be performed. This could help the pediatric neuroimaging field move toward more reliable identification of biomarkers for developmental outcomes and to better decipher the nuances of normal and abnormal brain development., (© 2018 Wiley Periodicals, Inc.)

Physical expressions of affection play a foundational role in early brain development, but the neural correlates of affective touch processing in infancy remain unclear. We examined brain responses to gentle skin stroking, a type of tactile stimulus associated with affectionate touch, in young infants. Thirteen term-born infants aged 11-36days, recruited through the FinnBrain Birth Cohort Study, were included in the study. Soft brush strokes, which activate brain regions linked to somatosensory as well as socio-affective processing in children and adults, were applied to the skin of the right leg during functional magnetic resonance imaging. We examined infant brain responses in two regions-of-interest (ROIs) known to process gentle skin stroking - the postcentral gyrus and posterior insular cortex - and found significant responses in both ROIs. These results suggest that the neonate brain is responsive to gentle skin stroking within the first weeks of age, and that regions linked to primary somatosensory as well as socio-affective processing are activated. Our findings support the notion that social touch may play an important role in early life sensory processing. Future research will elucidate the significance of these findings for human brain development., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A high prevalence of alexithymia has been consistently reported in alcohol- and drug-dependent populations. However, less is known about the role of alexithymia, and its individual dimensions on substance use in healthier populations., Objectives: To examine how different alexithymia dimensions associate with substance use, while controlling for confounding factors., Methods: In the FinnBrain Birth Cohort Study, we analyzed a sample of 994 men. We assessed alexithymia levels (difficulty identifying feelings, difficulty describing feelings and externally oriented thinking (EOT) style), self-reported quantity and frequency of alcohol use in two different time points during and after their partners' pregnancy, as well as cigarette smoking status. Age, education level, and anxiety scores were used as control variables., Results: Men scoring high on EOT style drank more alcohol per occasion, compared to low scorers (Cohen's d = 0.43, p < 0.001 during pregnancy, and Cohen's d = 0.3, p = 0.012 after pregnancy). Individuals in the high EOT quartile were also more likely to be daily smokers (8.7% vs. 17.3%, p = 0.023), and engage in binge drinking (23.7% vs. 43.6%, p = 0.001)., Conclusions: The association of alexithymia and substance use may be specifically explained by EOT, a trait characterized by low levels of introspection and pragmatic thinking. It is important for future studies to distinguish between individual alexithymia dimensions and their specific roles in shaping mental health.

Information on normal brain structure and development facilitates the recognition of abnormal developmental trajectories and thus needs to be studied in more detail. We imaged 68 healthy infants aged 2-5 weeks with high-resolution structural MRI (magnetic resonance imaging) and investigated hemispheric asymmetry as well as the associations of various total and lobar brain volumes with infant age and sex. We found similar hemispheric asymmetry in both sexes, seen as larger volumes of the right temporal lobe, and of the left parietal and occipital lobes. The degree of asymmetry did not vary with age. Regardless of controlling for gestational age, gray and white matter had different age-related growth patterns. This is a reflection of gray matter growth being greater in the first years, while white matter growth extends into early adulthood. Sex-dependent differences were seen in gray matter as larger regional absolute volumes in males and as larger regional relative volumes in females. Our results are in line with previous studies and expand our understanding of infant brain development.

Aims: To investigate socio-economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions., Design: Cross-sectional analysis with linked survey and register data., Setting: South-western Finland., Participants: A total of 2667 pregnant women [70% of the original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study., Measurements: The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire-based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio-economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated., Findings: Mother's education was the strongest socio-economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI) = 1.2-3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1-9.0; P < 0.001) for combined general and vocational secondary education, 2.9 (95% CI = 1.4-6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0-18.2; P < 0.001) for vocational secondary education and 14.4 (95% CI = 6.3-33.0; P < 0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR = 1.8; 95% CI = 1.1-3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95% CI = 1.4-2.8; P < 0.001), but did not attenuate its socio-economic disparities., Conclusions: In Finland, socio-economic disparities in smoking in pregnancy are attributable primarily to differences in the mother's educational level (low versus high) and orientation (vocational versus general)., (© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)