Depression In Offspring Research Articles

The Interaction of Second Trimester Prenatal Maternal Inflammation and Psychosocial Stress on Offspring Depressive Symptoms in Adolescence

BackgroundHigher second trimester (T2) prenatal maternal inflammation (PNMI) and prenatal maternal psychosocial stress have been shown to independently contribute to offspring depression risk. Similarly, interactions between sources of inflammation and maternal daily life stress in T2, previously have been associated with increased offspring adolescent depressive symptoms. We aimed to extend previous findings by examining the potential interaction between exposure to higher T2 PNMI and maternal daily life stress on offspring depressive symptoms in adolescence. Methods614 mother-offspring dyads from the Child Health and Development Studies (CHDS) had data available for T2 maternal serum interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptor-II (sTNF-RII), presence/absence of maternal reported daily life stress coded from interviews primarily conducted in T2, and adolescent offspring (ages 15-18 years) depressive symptoms assessed via self-report. Interactions were evaluated using hierarchical multiple regressions, controlling for maternal education. ResultsMaternal daily life stress interacted with higher serum levels of maternal T2 IL-6 and T2 IL-8 to predict adolescent offspring depressive symptoms. Higher IL-6 and higher IL-8 were only associated with offspring depression in the presence of daily life stress. Maternal T2 IL-1ra and sTNF-RII were not associated with offspring adolescent depressive symptoms. ConclusionThe interaction of the adverse impacts of maternal daily life stress and higher maternal IL-6 and/or IL-8 levels during the second trimester may contribute significantly to exacerbate depression risk in adolescent offspring. These results have potential implications for multiple targets of future early intervention and prevention research.

A guide for planning triangulation studies to investigate complex causal questions in behavioural and psychiatric research.

At the basis of many important research questions is causality - does X causally impact Y? For behavioural and psychiatric traits, answering such questions can be particularly challenging, as they are highly complex and multifactorial. 'Triangulation' refers to prospectively choosing, conducting and integrating several methods to investigate a specific causal question. If different methods, with different sources of bias, all indicate a causal effect, the finding is much less likely to be spurious. While triangulation can be a powerful approach, its interpretation differs across (sub)fields and there are no formal guidelines. Here, we aim to provide clarity and guidance around the process of triangulation for behavioural and psychiatric epidemiology, so that results of existing triangulation studies can be better interpreted, and new triangulation studies better designed. We first introduce the concept of triangulation and how it is applied in epidemiological investigations of behavioural and psychiatric traits. Next, we put forth a systematic step-by-step guide, that can be used to design a triangulation study (accompanied by a worked example). Finally, we provide important general recommendations for future studies. While the literature contains varying interpretations, triangulation generally refers to an investigation that assesses the robustness of a potential causal finding by explicitly combining different approaches. This may include multiple types of statistical methods, the same method applied in multiple samples, or multiple different measurements of the variable(s) of interest. In behavioural and psychiatric epidemiology, triangulation commonly includes prospective cohort studies, natural experiments and/or genetically informative designs (including the increasingly popular method of Mendelian randomization). The guide that we propose aids the planning and interpreting of triangulation by prompting crucial considerations. Broadly, its steps are as follows: determine your causal question, draw a directed acyclic graph, identify available resources and samples, identify suitable methodological approaches, further specify the causal question for each method, explicate the effects of potential biases and, pre-specify expected results. We illustrated the guide's use by considering the question: 'Does maternal tobacco smoking during pregnancy cause offspring depression?'. In the current era of big data, and with increasing (public) availability of large-scale datasets, triangulation will become increasingly relevant in identifying robust risk factors for adverse mental health outcomes. Our hope is that this review and guide will provide clarity and direction, as well as stimulate more researchers to apply triangulation to causal questions around behavioural and psychiatric traits.

Neonatal Maternal Separation Impairs Cognitive Function and Synaptic Plasticity in Adult Male CD-1 Mice

Maternal separation (MS) increases the risk of occurrence of anxiety, depression, and learning and memory impairment in offspring. However, the underlying molecular biological mechanisms remain unclear. In the current study, offspring CD-1 mice were separated from their mothers from postnatal day 4 to postnatal day 21. At 3 months of age, the male offspring were selected for the evaluation of anxiety- and depression-like behaviors and learning and memory function. Western blotting and RT-PCR were used to examine the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin. Long-term potentiation (LTP) and long-term depression (LTD) were recorded at Schaffer collateral/CA1 synapses. Furthermore, basal synaptic transmission was evaluated via the recording of the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). The results showed that adult offspring CD-1 mice displayed anxiety- and depressive-like behaviors as well as impaired spatial learning and memory abilities. Electrophysiological analysis indicated that MS impaired LTP, enhanced LTD, and reduced the frequency of mEPSCs in pyramidal neurons in the CA1 region. Our findings suggested that MS can lead to anxiety, depression, and cognitive deficits, and these effects are associated with alterations in the levels of synaptic plasticity-associated proteins, consequently, also synaptic plasticity.

Negative impact of maternal depressive symptoms on infancy neurodevelopment: a moderated mediation effect of maternal inflammation.

Maternal depression promotes maternal inflammation and the risk of neurodevelopmental disorder in offspring, but the role of inflammation on the association between depression and neurodevelopment in offspring has not been extensively studied in humans. This study aims to examine the mediating role of maternal inflammation on the relationship between maternal depression and neurodevelopment in infants. 146 mother-child pairs were identified from Tianjin Maternal and Child Health Education and Service Cohort (Tianjin MCHESC). Maternal depression was investigated by the Center for Epidemiologic Studies Depression Scale and the Edinburgh Postnatal Depression Scale, and depressive trajectories were identified by latent class growth analysis. Inflammatory biomarkers in the three trimesters were assessed with enzyme-linked immunoassay. The Children Neuropsychological and Behavior Scale-Revision 2016 was used to measure neurodevelopment in infants. Principal component analysis was performed to identify inflammatory condition. Stepwise multiple linear regression analysis and mediation analysis were used to identify association among maternal depression, maternal inflammation and neurodevelopment in infants. Offspring in the low and moderate maternal depression groups exhibited higher adaptive behavior development quotient than those in the high maternal depression group. Higher maternal c-reactive protein level and higher inflammatory level in acute-phase of inflammation in the first trimester, and moderate maternal depression were associated with lower adaptive behavior quotients of infants. Inflammatory level in acute-phase of inflammation in the first trimester significantly mediated the association between maternal depression and adaptive behavior development of infants, with explaining 11.85% of the association. Maternal depression could impair adaptive behavior development in infants by inflammation.

Language use in depressed and non-depressed mothers and their adolescent offspring

BackgroundApproximately 10% of mothers experience depression each year, which increases risk for depression in offspring. Currently no research has analysed the linguistic features of depressed mothers and their adolescent offspring during dyadic interactions. We examined the extent to which linguistic features of mothers' and adolescents' speech during dyadic interactional tasks could discriminate depressed from non-depressed mothers. MethodsComputer-assisted linguistic analysis (Linguistic Inquiry and Word Count; LIWC) was applied to transcripts of low-income mother-adolescent dyads (N = 151) performing a lab-based problem-solving interaction task. One-way multivariate analyses were conducted to determine linguistic features hypothesized to be related to maternal depressive status that significantly differed in frequency between depressed and non-depressed mothers and higher and lower risk offspring. Logistic regression analyses were performed to classify between dyads belonging to the two groups. ResultsThe results showed that linguistic features in mothers' and their adolescent offsprings' speech during problem-solving interactions discriminated between maternal depression status. Many, but not all effects, were consistent with those identified in previous research using primarily written text, highlighting the validity and reliability of language behaviour associated with depressive symptomatology across lab-based and natural environmental contexts. LimitationsOur analyses do not enable to ascertain how mothers' language behaviour may have influenced their offspring's communication patterns. We also cannot say how or whether these findings generalize to other contexts or populations. ConclusionThe findings extend the existing literature on linguistic features of depression by indicating that mothers' depression is associated with linguistic behaviour during mother-adolescent interaction.

Fetal Exposure to Tobacco Metabolites and Depression During Adulthood: Beyond Binary Measures.

Sibling studies of maternal smoking during pregnancy and subsequent risk of depression have produced mixed results. A recent study identified not considering the amount of maternal smoking and age of onset as potentially masking a true association. We examine these issues and also the amount of maternal smoking during pregnancy as a determinant of the severity of depressive symptoms. We analyzed data from the community-based National Longitudinal Survey of Youth (US, 1994-2016). Mothers reported smoking during pregnancy (none, <1 pack/day, ≥1 pack/day). We assessed offspring's lifetime depression (i.e., ≥8 symptoms) and symptom counts with the Centers for Epidemiologic Studies Depression scale. We estimated the risk of these two outcomes in the full sample (n = 7172) and among siblings (n = 6145) using generalized linear mixed-effects models with random intercepts by family and family-averaged means for sibling analyses. Among siblings, we observed dose-dependent elevations for both risk of depression (smoking during pregnancy <1 pack/day adjusted risk ratio [aRR] = 1.18; 95% confidence interval [CI] = 1.07, 1.30; smoking ≥1 aRR = 1.36; 95% CI = 1.19, 1.56) and severity of depressive symptoms (smoking <1 pack/day aRR = 1.12; 95% CI = 1.08, 1.16); smoking ≥1 pack/day aRR = 1.25; 95% CI = 1.18, 1.31). Among both samples, the P for trend was <0.01. In analysis limited to offspring diagnosed before age 18, results for severity were attenuated. This evidence supports the existence of an independent association between maternal smoking during pregnancy and both the risk of depression and the severity of depressive symptoms. The results highlight the utility of considering the amount of smoking, severity of symptoms, and age of onset.

Hippocampal Crhr1 conditional gene knockout ameliorated the depression-like behavior and pathological damage in male offspring mice caused by chronic stress during pregnancy

Numerous studies have demonstrated that chronic stress during pregnancy (CSDP) can induce depression and hippocampal damage in offspring. It has also been observed that high levels of corticotropin-releasing hormone (CRH) can damage hippocampal neurons, and intraperitoneal injection of a corticotropin releasing hormone receptor 1 (CRHR1) antagonist decreases depression-like behavior and hippocampal neuronal damage in a mouse depression model. However, whether CSDP causes hippocampal damage and depression in offspring through the interaction of CRH and hippocampal CRHR1 remains unknown and warrants further investigation. Therefore, hippocampal Crhr1 conditional gene knockout mice and C57/BL6J mice were used to study these questions. Depression-related indexs in male offspring mice were examined using the forced swim test (FST), sucrose preference test (SPT), tail suspension test (TST) and open field test (OFT). Serum CRH levels were measured by enzyme-linked immunosorbent assay (ELISA). Golgi-Cox staining was used to examine the morphological changes of hippocampal neuronal dendrites. Neuronal apoptosis in the hippocampal CA3 regions was detected by terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining. The levels of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR) and protein kinase B (AKT) proteins were measured by Western blot analysis. This study showed that CSDP induces depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring mice. Conditional gene knockout of hippocampal Crhr1 in mice reduced CSDP-induced depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring, and counteracted the CSDP-induced decreased expression of p-Akt and mTOR activity in male offspring hippocampus. These findings demonstrated that CSDP might inhibit the Akt/mTOR pathway by increasing the levels of CRH, leading to increased CRH-mediated activation of hippocampal CRHR1, thereby inducing synaptic impairment and apoptosis in hippocampal neurons, which in turn leads to depression-like behavior in offspring.

High Juvenile Mortality Overwhelms Benefits of Mating Potential for Reproductive Fitness.

AbstractAn individual's access to mates (i.e., its "mating potential") can constrain its reproduction but may also influence its fitness through effects on offspring survival. For instance, mate proximity may correspond with relatedness and lead to inbreeding depression in offspring. While offspring production and survival might respond differently to mating potential, previous studies have not considered the simultaneous effects of mating potential on these fitness components. We investigated the relationship of mating potential with both production and survival of offspring in populations of a long-lived herbaceous perennial, Echinacea angustifolia. Across 7 years and 14 sites, we quantified the mating potential of maternal plants in 1,278 mating bouts and followed the offspring from these bouts over 8 years. We used aster models to evaluate the relationship of mating potential with the number of offspring that emerged and that were alive after 8 years. Seedling emergence increased with mating potential. Despite this, the number of offspring surviving after 8 years showed no relationship to mating potential. Our results support the broader conclusion that the effect of mating potential on fitness erodes over time because of demographic stochasticity at the maternal level.

Antidepressant effects of esketamine via the BDNF/AKT/mTOR pathway in mice with postpartum depression and their offspring

Postpartum depression (PPD) is a serious mental health problem that can negatively affect future generations. BDNF/AKT/mTOR signaling in the frontal lobe and hippocampus in mice is associated with depression, but its role in mice with PPD and their offspring is unknown. This study was aimed at investigating the effects of esketamine (ESK), a drug approved for treatment of refractory depression, on the BDNF/AKT/mTOR pathway in mice with PPD and their offspring. A model of chronic unpredictable mild stress with pregnancy was used. ESK was injected into postpartum mice, and behavioral tests were conducted to predict the severity of symptoms at the end of lactation and in the offspring after adulthood. Both mice with PPD and their offspring showed significant anxiety- and depression-like behaviors that were ameliorated with the ESK intervention. ESK enhanced exploratory behavior in unfamiliar environments, increased the preference for sucrose, and ameliorated the impaired BDNF/AKT/mTOR signaling in the frontal and hippocampal regions in mice. Thus, ESK may have great potential in treating PPD and decreasing the incidence of depression in offspring.

Association of Postpartum Depression with Maternal Serum Magnesium Levels, Infant Growth, and Neurodevelopmental Indices.

Postpartum depression (PPD) can exert both short-term and long-term effects on a child's health. Offspring born to mothers who suffer from PPD face an elevated susceptibility to encountering psychological disturbances and developmental delays. Moreover, there has been conjecture surrounding a plausible connection between maternal magnesium (Mg) levels and psychiatric manifestations. This study aims to investigate the relationship between maternal Mg levels and PPD and the correlation between PPD and an infant's growth and neurodevelopment at 6 and 12 months. This longitudinal study is a sub-study derived from the "PERSIAN Birth Cohort Study," encompassing 224 mother-infant pairs randomly enlisted during 2019-2020 in Isfahan. Maternal serum magnesium (Mg) levels were measured at 38 weeks of gestation. PPD was evaluated employing the Edinburgh Postpartum Depression Scale (EPDS) four weeks postpartum. Measurements of birth size were undertaken, adhering to standardized protocols at birth, 6 months, and 12 months. Anthropometric parameters and the Persian version of the validated Ages and Stages Questionnaires (ASQ) were employed to assess infant neurodevelopmental status at 6 and 12 months. Overall, 22.3% of mothers grappled with PPD. The mean (standard deviation) maternal magnesium levels (Mg) were 1.95 ± 0.23 mg/dL. No statistically significant association was detected between maternal serum magnesium (Mg) levels and the incidence of PPD. Correspondingly, no significant association emerged between PPD and indices of growth. However, a noteworthy distinction materialized in the communication scores of offspring born to depressed and non-depressed mothers following adjustments for confounding variables at 12 months (β = 1.81; 95% confidence interval: 0.32-3.30). Furthermore, a substantial regression in communication skills became apparent between 6 and 12 months. This study failed to establish a significant association between maternal serum magnesium (Mg) levels and PPD. Nevertheless, research lends credence to an inverse correlation between maternal depression and subsequent behavioral difficulties in offspring, such as communication skills. Thus, the imperative nature of screening for PPD should be underscored to facilitate its early detection and intervention, thereby enhancing infant well-being.

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Self-reported depressive symptoms at adolescent follow-up. A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

Geniposide improves depression-like behavior in prenatal stress male offspring through restoring HPA axis- and glucocorticoid receptor-associated dysfunction

AimsPrenatal stress (PS) has an important impact on the brain development of offspring, which can lead to attention deficits, anxiety and depression in offspring. Geniposide (GE) is a kind of iridoid glycoside extracted from Gardenia jasminoides Ellis. It has various pharmacological effects and has been proved that have antidepressant effects. The aim of this study was to investigate the effect of GE on depression-like behavior in PS-induced male offspring mice and explore the possible molecular mechanisms. MethodsWe used a prenatal restraint stress model, focusing on male PS-induced offspring mice to study the effects of GE. Key findingsThe results showed that GE administration for 4 weeks significantly improved the depression-like behavior in PS offspring mice, which was manifested by markedly increasing the sucrose preference of PS offspring and the activity in the open field test, and reducing the immobility time in the forced swimming test. In addition, GE significantly reduced the levels of hypothalamic-pituitary-adrenal (HPA) axis-related hormones and exceedingly increased the protein expression of MAP2 and GAP43 in PS offspring. Furthermore, GE increased Glucocorticoid receptors (GR) nuclear translocation in the hippocampus of PS offspring, and enhanced the expression of synaptic plasticity-related proteins. ConclusionThe results of this study showed that GE exerts antidepressant effects in male PS offspring mice by regulating the HPA axis, GR function and proteins related to synaptic plasticity.

The Relationship between Maternal Perinatal Depression and Offspring Depression: A Meta-Analysis

Background: Antepartum depression, with an incidence of 20.7%, is a pressing global public health concern due to its detrimental effects on both the physical and mental health of pregnant women, as well as the potential risk it poses for depression in their offspring. Nevertheless, there is a lack of consensus among existing studies regarding this issue. Here, we systematically evaluated the relationship between maternal perinatal depression and offspring depression by meta-analysis. Methods: We conducted a comprehensive search for relevant studies in Pubmed, Embase, The Cochrane Library, CNKI, Wanfang, VIP, and Chinese Biomedical Literature Service System databases. The prospective cohort studies, which were published in English or Chinese, reported the occurrence of maternal prenatal and/or postnatal depression within one year postpartum and assessed the subsequent development of depression in their offspring, were included. Study quality was assessed with the Newcastle-Ottawa Scale. Review Manager 5.4 software was used for meta-analysis. Subgroup analysis was performed. Publication bias was evaluated with a funnel plot. Results: Totally, 12 studies were included. The meta-analysis found that maternal perinatal depression increased the risk of offspring depression by 1.64 (95% confidence interval (95% CI): 1.37, 1.96, p &lt; 0.001). Subgroup analysis showed that the risk of offspring depression was significantly increased in the European population with maternal perinatal depression (odds ratio (OR) = 1.90, 95% CI (1.49, 2.42), p &lt; 0.001), but not in the Australian and the American populations. The combined effect sizes of maternal antepartum and postpartum depression were (OR = 1.70, 95% CI (1.27, 2.27), p &lt; 0.001) and (OR = 1.74, 95% CI (1.31, 2.32), p &lt; 0.001), respectively. The combined effect size of the relationship of maternal perinatal depression with offspring depression in childhood and adulthood was (OR = 1.70, 95% CI (1.28, 2.25), p &lt; 0.001) and (OR = 1.60, 95% CI (1.27, 2.02), p &lt; 0.001), respectively. The adjusted and unadjusted combined effect sizes were (OR = 1.44, 95% CI (1.14, 1.82), p &lt; 0.001) and (OR = 1.97, 95% CI (1.49, 2.60), p &lt; 0.001), respectively. There may be some publication bias in the included studies. Conclusions: Maternal perinatal depression is associated with an increased risk of depression in offspring. Effective prevention and management of depression in perinatal women is necessary to mitigate the risk of depression in offspring.

GluN2A Mediates PS-Induced Depressive-Like Behavior by Activating CaMKII and Inhibiting Myelinization.

Prenatal stress (PS) can induce depression in offspring, but the underlying mechanisms are still unknown. The aim of this work was to investigate the mechanism that underlies PS-induced depressive-like behavior in offspring. A prenatal restraint stress procedure was developed in which pregnant rats at GD14 to GD20 were placed head-first into a well-ventilated bottle three times each day and for 45 min each time. Depressive-like behavior in the male offspring was examined using the sucrose preference test (SPT) and the forced swim test (FST). The level of glutamate and the expression levels of GluN2A, p-CaMKII and myelin basic protein (MBP) in the hippocampus of PS-susceptible (PS-S) offspring were also evaluated. To clarify the mechanism by which PS leads to depression in offspring, the effects of excessive corticosterone were also investigated using an in vitro "injured neuronal" model. The glutamate level in the hippocampus of PS-S male offspring was significantly elevated compared to controls. The expression levels of GluN2A and p-CaMKII were also altered. In addition, the optical density of MBP staining and the expression levels of MBP mRNA and MBP protein were decreased, demonstrating impaired myelinization in the hippocampus. Treatment of PS-S offspring with the GluN2A receptor antagonist NVP-AAM077 resulted in antidepressant-like effects in the FST, as well as rescue of the MBP and p-CaMKII abnormalities. These findings indicate that GluN2A is a promising target in the development of pharmacotherapies for PS-induced depression.

Fathers matter: Supporting new dads during the transition to parenthood

Fathers matter: Supporting new dads during the transition to parenthood Deborah Da Costa, PhD, Associate Professor at the Department of Medicine, McGill University, Scientist at McGill University Health Centre, details promoting and supporting new dads during the transition to parenthood. Approximately one in ten fathers experience mental health difficulties during their partner’s pregnancy and/or the postpartum period. (1-3) Fathers’ mental health difficulties adversely impact parenting, maternal mental health, and couple functioning. A recent systematic review and meta- analysis of 16 observational studies showed that paternal depression was associated with an increased risk of depression in offspring, underscoring the intergenerational transmission of mental health problems. (4) Fathers’ mental health during this life stage is an important public health issue, but it continues to be under-researched, under-recognized, and under-treated.

Types of diabetes during pregnancy and risk of depression and anxiety in offspring from childhood to young adulthood.

To assess maternal pre-existing type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM) during pregnancy and risk of depression and anxiety from childhood to young adulthood in offspring. This birth cohort included singletons born during 1995-2015, followed using electronic medical records through 2020. Cox regression was used to estimate hazard ratio (HR) of depression or anxiety diagnosis during follow-up associated with in-utero exposure to maternal diabetes. Among 439 590 offspring, 29 891 (6.8%) had depression and 51 918 (11.8%) had anxiety. T1D, followed by T2D and GDM requiring antidiabetes medication were associated with risk of depression and anxiety in offspring. Compared with no diabetes during pregnancy, the adjusted HRs (95% confidence interval) of depression in offspring associated with T1D, T2D or GDM requiring medications were 1.44 (1.09-1.91), 1.30 (1.15-1.47) and 1.18 (1.11-1.26) respectively; conversely, HRs were 0.97 (0.82-1.15) for T2D and 0.99 (0.94-1.04) for GDM without medications. The associations with anxiety followed similar patterns. The significant associations were observed for offspring ages 5-12 and >12-18 years and attenuated for 18-25 years. These data suggest that the severity of diabetes (T1D vs. T2D requiring medications vs. GDM requiring medications) during pregnancy may increase the vulnerability of offspring for depression or anxiety.

Adolescents at risk for depression show increased white matter microstructure with age across diffuse areas of the brain

Maternal history of depression is a strong predictor of depression in offspring and linked to structural and functional alterations in the developing brain. However, very little work has examined differences in white matter in adolescents at familial risk for depression. In a sample aged 9–14 (n = 117), we used tract-based spatial statistics (TBSS) to examine differences in white matter microstructure between adolescents with (n = 42) and without (n = 75) maternal history of depression. Microstructure was indexed using fractional anisotropy (FA). Threshold-free cluster enhancement was applied and cluster maps were thresholded at whole-brain family-wise error < .05. There was no significant main effect of risk status on FA. However, there was a significant interaction between risk status and age, such that large and diffuse portions of the white matter skeleton showed relatively increased FA with age for youth with a maternal history of depression compared to those without. Most tracts identified by the interaction were robust to controlling for sex, youth internalizing, in-scanner motion, neighborhood SES, and intra-cranial volume, evidence that maternal depression is a unique predictor of white matter alterations in youth. Widespread increases in FA with age may correspond to a global pattern of accelerated brain maturation in youth at risk for depression.

Maternal childhood maltreatment: associations to offspring brain volume and white matter connectivity.

The deleterious effects of adversity are likely intergenerational, such that one generation's adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children's behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.

Intergenerational transmission of trauma and its association with attitudes toward reconciliation.

We aimed to investigate the link between mothers' posttraumatic stress disorder (PTSD) symptoms and their adult offspring's attitudes toward reconciliation and psychopathology among survivors of the 1994 genocide perpetrated against the Tutsi in Rwanda. We also sought to examine whether parenting styles mediate the relationship between mothers' PTSD symptoms and their adult offspring's psychopathology, if any. Mother-child dyads (N = 181) were recruited in Rwanda and completed measures of trauma exposure, PTSD, depression, attitudes toward reconciliation, and parenting styles. Adult offspring of mothers who suffered from more severe PTSD symptoms had less favorable attitudes toward reconciliation, even after controlling for their own PTSD symptoms. Mothers' PTSD symptoms were not associated with their adult offspring's PTSD or depression symptoms. In addition, mothers' PTSD symptoms did not predict their parenting styles. These results suggest that the mental health of survivors of mass violence has repercussions on the intergroup attitudes of the following generation. This study has practical implications for sustainable peacebuilding in postconflict societies. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Paternal Depression and Risk of Depression Among Offspring

Existing epidemiological evidence is equivocal as to whether paternal depression poses a consequent risk of depression in offspring; meta-analysis of findings can help inform preventative intervention efforts. To conduct a systematic review and meta-analysis of observational studies examining the association between paternal and offspring depression. Embase, PubMed, PsycINFO, Scopus, and Web of Science databases were searched between inception and December 2022. The review included all observational studies that investigated the association between paternal and offspring depression and 10 606 studies were initially identified. This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The review protocol was prospectively registered in PROSPERO. Summary odds ratios (ORs) and 95% CIs were pooled using inverse variance weighted random effect meta-analysis. Subgroup and sensitivity analyses were performed. The main outcome of interest was offspring depression measured using recognized depression assessment tools. Sixteen observational studies published between 2002 and 2021 were included, with a combined sample of 7 153 723 father-child dyads. A meta-analysis of these studies showed that paternal depression was associated with an increased risk of depression in offspring (OR, 1.42; 95% CI, 1.17-1.71). The risk was higher among offspring exposed to paternal depressive disorders (OR, 1.65; 95% CI, 1.28-2.12) than those exposed to depression as defined by a nonclinical symptom scale (OR, 1.12; 95% CI, 1.06-1.19). Sensitivity analysis revealed consistent pooled estimates ranging from 1.35 (95% CI, 1.12-1.62) to 1.45 (95% CI, 1.18-1.78). Paternal depression was associated with subsequent offspring depression. This finding shows the intergenerational transmission of mental health problems and suggests that mental health interventions benefit not only the patient but also the family as a whole, including both parents.