Search Results (147)

Clinical and animal studies suggest that multiple brain systems are involved in mediating reward-motivated and related emotional behavior including the consumption of commonly used drugs and palatable food, and there is evidence that the repeated ingestion of or exposure to these rewarding substances may in turn stimulate these brain systems to produce an overconsumption of these substances along with co-occurring emotional disturbances. To understand this positive feedback loop, this review focuses on a specific population of hypothalamic peptide neurons expressing melanin-concentrating hormone (MCH), which are positively related to dopamine reward and project to forebrain areas that mediate this behavior. It also examines neurons expressing the peptide hypocretin/orexin (HCRT) that are anatomically and functionally linked to MCH neurons and the molecular systems within these peptide neurons that stimulate their development and ultimately affect behavior. This report first describes evidence in animals that exposure in adults and during adolescence to rewarding substances, such as the drugs alcohol, nicotine and cocaine and palatable fat-rich food, stimulates the expression of MCH as well as HCRT and their intracellular molecular systems. It also increases reward-seeking and emotional behavior, leading to excess consumption and abuse of these substances and neurological conditions, completing this positive feedback loop. Next, this review focuses on the model involving embryonic exposure to these rewarding substances. In addition to revealing a similar positive feedback circuit, this model greatly advances our understanding of the diverse changes that occur in these neuropeptide/molecular systems in the embryo and how they relate, perhaps causally, to the disturbances in behavior early in life that predict a later increased risk of developing substance use disorders. Studies using this model demonstrate in animals that embryonic exposure to these rewarding substances, in addition to stimulating the expression of peptide neurons, increases the intracellular molecular systems in neuroprogenitor cells that promote their development. It also alters the morphology, migration, location and neurochemical profile of the peptide neurons and causes them to develop aberrant neuronal projections to forebrain structures. Moreover, it produces disturbances in behavior at a young age, which are sex-dependent and occur in females more than in males, that can be directly linked to the neuropeptide/molecular changes in the embryo and predict the development of behavioral disorders later in life. These results supporting the close relationship between the brain and behavior are consistent with clinical studies, showing females to be more vulnerable than males to developing substance use disorders with co-occurring emotional conditions and female offspring to respond more adversely than male offspring to prenatal exposure to rewarding substances. It is concluded that the continued consumption of or exposure to rewarding substances at any stage of life can, through such peptide brain systems, significantly increase an individual’s vulnerability to developing neurological disorders such as substance use disorders, anxiety, depression, or cognitive impairments. Full article

Background: Antenatal depression and anxiety contribute significantly to maternal morbidity and adverse pregnancy outcomes. However, structured screening and targeted interventions are largely absent from standard prenatal care in many Eastern European countries, including Bulgaria. This study examines the prevalence and psychosocial predictors of antenatal psychosocial risk using the validated Antenatal Risk Questionnaire–Revised (ANRQ-R) in a nationally underrepresented population. Methods: A cross-sectional survey was conducted among 216 third-trimester pregnant women in Bulgaria. Data on sociodemographic characteristics, health behaviours, and reproductive history were collected. Multivariate logistic regression identified predictors of elevated psychosocial risk. Results: A total of 65.7% of participants met the criteria for elevated psychosocial risk. Significant risk factors included passive smoking exposure during pregnancy (OR = 5.03, p < 0.001), physical activity prior to pregnancy (OR = 1.81, p = 0.004), and a family history of hereditary disease (OR = 42.67, p < 0.001). Protective factors were better self-rated current health (OR = 0.37, p = 0.004), the presence of chronic illness (OR = 0.42, p = 0.049), previous childbirth experience (OR = 0.11, p = 0.032), and residence in Northwestern Bulgaria (OR = 0.31, p = 0.028). Despite the high prevalence of psychosocial vulnerability, only 9.5% of affected women sought professional help. Conclusions: While our findings point to important unmet needs in antenatal mental health, further research is required before national screening policies can be implemented. Pilot programs, cultural validation of tools, and system-level readiness assessments should precede broad adoption. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the most abundant ω-3 fatty acids in the membrane phospholipids of the mammalian brain, and dietary DHA plays an important role in brain development and maintenance of brain structure. In this study, we investigated whether peri-natal supplementation of DHA can alleviate autistic-like behaviors in a genetic risk/stress mouse model and how it alters lipid peroxidation activity and GABAergic system gene expression in the forebrain. Pregnant heterozygous serotonin transporter knockout (SERT-KO) and wild-type (WT) dams were placed in either non-stressed control conditions or chronic variable stress (CVS) conditions and fed either a control diet or a DHA-rich (1% by weight) diet. Offspring of each group were assessed for anxiety and autism-associated behavior at post-natal day 60 using an open field test, elevated plus maze test, repetitive behavior, and the 3-chamber social approach test. A liquid chromatography-mass spectrometry (LC-MS)-based method was used to follow changes in levels of lipid peroxidation products in the cerebral cortex. Male offspring of prenatally stressed SERT-het KO dams exhibited decreased social preference behaviors and increased repetitive grooming behaviors compared to WT control offspring. Moreover, DHA supplementation in male SERT-het mice decreased frequency of grooming behaviors albeit showing no associated effects on social behaviors. Regardless of stress conditions, supplementation of DHA to the WT mice did not result in alterations in grooming nor social interaction in the offspring. Furthermore, no apparent changes were observed in the lipid peroxidation products comparing the stressed and non-stressed brains. Gad2 was downregulated in the cortex of female offspring of prenatally stressed SERT-KO dams, and this change appeared to be rescued by DHA supplementation in offspring. Gad2 was upregulated in the striatum of male offspring of prenatally stressed SERT-KO dams, but DHA did not significantly alter the expression compared to the control diet condition. Full article

Background: Tricuspid regurgitation (TR) is increasingly recognized as a detectable finding during routine fetal echocardiography. Although previous studies have explored its potential role as an indirect marker for congenital heart disease (CHD) in the first trimester, the prognostic significance of isolated mild TR in chromosomally normal and low-risk fetuses during the second and third trimesters remains unclear. Clarifying the clinical relevance of this commonly encountered Doppler finding is essential to guide appropriate prenatal management and avoid unnecessary interventions in low-risk pregnancies. Materials and Methods: This retrospective study reviewed fetal echocardiography reports of 1592 pregnant women referred to a pediatric cardiology clinic after the 20th gestational week between 1 January 2024 and 1 January 2025. Following exclusion criteria, 1072 low-risk pregnancies were included. A total of 136 fetuses with TR were identified, and among them, postnatal echocardiographic outcomes of 60 neonates who underwent transthoracic echocardiography within the first 10 days after birth were analyzed. Results: Among the 1072 low-risk pregnancies included in the study, a total of 136 fetuses were diagnosed with TR on fetal echocardiography. The majority of these cases were characterized as mild and isolated, without accompanying structural abnormalities. Postnatal echocardiographic assessments revealed no major congenital cardiac anomalies, reinforcing the interpretation that isolated mild TR in the context of low-risk pregnancies represents a benign and likely transient physiological finding. Conclusion: Isolated mild TR, particularly in low-risk and chromosomally normal pregnancies, appears to be a transient and clinically insignificant finding. These results support the interpretation of fetal TR in the context of overall clinical and structural evaluation, helping to avoid unnecessary interventions and reduce parental anxiety. Full article

Depression is a widespread mental health condition that affects millions of women globally. In the United States (U.S.), more than half of maternal mental health-related deaths occur during the postpartum period, making it the leading cause of mortality during this time. This urban U.S. single-site quasi-experimental study aimed to evaluate the effectiveness of social support integrated into group prenatal care as an intervention for postpartum depression. The study employed a dual methodological approach, combining prospective participant recruitment with a retrospective analysis of medical records. It compared the Edinburgh Postnatal Depression Scale (EPDS) scores from group prenatal care to those from traditional individualized prenatal care, specifically focusing on Black and Hispanic women. In all, 200 postpartum women participated in the study, comprising (n = 100) group prenatal care and (n = 100) traditional individualized care. Most participants were Black (97%), with an average age of 26.8 years (SD = 5.9). At six weeks postpartum, 97% of the participants underwent depression screening, which indicated a mean EPDS score of 3.79 (SD = 4.7). Among the participants, 25% exhibited mild to moderate postpartum depression, while 3% experienced severe depression. No significant differences were observed between the models of care in terms of total scores (T = 2.0, p = 0.46) or score ranges (χ² = 5.8, p = 0.12). It is noteworthy that no severe cases of depression were identified within the group prenatal care model. Suggesting group prenatal care may still benefit Black and Hispanic women in urban areas with a history of anxiety or depression. Full article

Background: A growing body of literature suggests that there are two variants of callous–unemotional (CU) traits—primary (with low anxiety) and secondary (with high anxiety)—although whether these traits differ in emotional regulation is unknown. The present study aimed to further our understanding of these variants by comparing the two variant groups (high CU/low anxiety and high CU/high anxiety) with two control groups (low CU/low anxiety and low CU/high anxiety) on emotional regulation, along with a variety of psychosocial and externalizing behavioral measures. Methods: A community sample of children aged 8 to 10 years (N = 340) from the northeast United States and their main caregivers participated in this study. Children completed an emotional regulation task while their sympathetic and parasympathetic nervous system activities were recorded. Prenatal and postnatal adversity and externalizing behaviors of the children were assessed using caregiver and child reports. Results: It was found that children with high CU/high anxiety were characterized by elevated parasympathetic activities during the emotional regulation task, along with more adversity and externalizing behaviors. Conclusions: These findings extend our knowledge on CU by highlighting the emotional dysregulation and more severe clinical picture that were associated with more psychosocial adversity in the high CU/high anxiety variants. Full article

The intrauterine environment is increasingly recognised as a critical period for the emergence of mental health vulnerabilities. This review explores how adverse maternal exposures, such as psychological stress, infection, malnutrition, and environmental toxins, can disrupt foetal neurodevelopment via epigenetic mechanisms, contributing to the risk of psychiatric and neurodevelopmental disorders. Focusing primarily on human studies, we synthesise evidence on DNA methylation, histone modifications, and non-coding RNAs as key pathways through which the intrauterine environment influences gene regulation in the developing brain. We examine how timing of exposure, foetal sex, and gene–environment interactions modulate these effects, with particular attention to disorders such as schizophrenia, autism spectrum disorder, depression, and anxiety. The placenta emerges as a central mediator, both reflecting and shaping epigenetic changes in response to maternal signals. We also discuss the reversibility of epigenetic marks and highlight emerging interventions, including nutritional supplementation and maternal mental health support, that may buffer or reverse prenatal epigenetic programming. Methodological challenges are addressed, including tissue specificity and causal inference, and future directions are proposed toward integrating epigenetic biomarkers into early risk assessment and precision mental health and psychiatry. This review emphasises the importance of the prenatal period as a window of vulnerability and opportunity for shaping lifelong mental health. Full article

The increasing incidence of autism spectrum disorder (ASD) increases the urgency of establishing the mechanism of its development for effective prevention and treatment. ASD’s etiology includes genetic predisposition and environmental triggers, both of which can play a role in the changed microbiota. Recent research has proved the impact of maternal microbiota on the neurodevelopment of the child. To investigate the co-play of genetic and microbiota factors in ASD development, we performed fecal microbiota transplantation (FMT) from children with ASD to female Shank3b^+/− mice and studied the autism-like symptoms in the male Shank3b^−/− and wild-type (WT) offspring. WT animals with prenatal exposure to ASD microbiota had delayed neurodevelopment and impaired food intake behavior, but also elevated plasma leptin concentration and body weight. Shank3b^−/− mice after FMT ASD exhibited impaired learning and exacerbated anxiety-like behavior in adulthood. Interestingly, FMT ASD improved learning in adolescent Shank3b^−/− mice. Prenatal exposure to ASD microbiota decreased the activity of hypocretin neurons of the lateral hypothalamic area in both genotypes. The combination of genetic predisposition and FMT ASD led to an increased colon permeability, evaluated by zonula occludens (ZO1, ZO3) and claudin factors. These results suggest the effect of parental FMT exposure on shaping offspring behavior in Shank3b^−/− mice and the potential of microbiota in the modulation of ASD. Full article

Background: Mental health problems that can appear in women during pregnancy include fear, anxiety, feelings of vulnerability, stress, and depression. Mindfulness (MF) is a specific meditation technique that can help during treatment for prenatal mood disorders, emotional distress, and psychological strains. The aim of this study is to determine the effectiveness of a specific meditation approach in women during pregnancy on these mental health problems. Methods: This systematic review analysed data from PubMed, Scopus, and CINAHL. The search equation used was “mindfulness [title] AND pregnancy [title] AND (trial OR clinical trial OR RCT OR quasi-experimental OR experimental OR randomised clinical trial OR randomised controlled trial OR quasi-experimental study)”. This analyses experimental studies published in the last 10 years that include interventions based on MF, applying cognitive behavioural therapies to reduce stress, depression, and anxiety and in which the participants completed a questionnaire related to these variables. Standardised means effect size meta-analysis was performed with RevMan Web. Results: All the included studies (n = 13) reported that the intervention led to a decrease in negative symptoms related to prenatal pressure, apprehension, and melancholy. The duration of the MF programmes was 6 to 8 weeks. The meta-analysis showed that MF during pregnancy is an effective approach, with a standardised mean difference of −0.73 for anxiety, −0.67 for depression, and −0.74 for stress. Conclusions: Mindfulness programmes during pregnancy are a useful and effective means of reducing maternal stress, anxiety, and depression. Including MF programmes during pregnancy should be considered depending on resources availability. In person vs. online effectiveness should be investigated. Full article

Background: Exposure to early life stress significantly increases the risk of psychopathology later in life. However, the impact of early life stress on the gut microbiome and its potential role in mental health outcomes remains insufficiently understood. This narrative review examines the current knowledge on how early life stress and its associated consequences may affect the gut microbiome, with a particular focus on conditions such as anxiety, depression, and post-traumatic stress disorder. Method: A comprehensive literature search was conducted in the PubMed and Web of Science databases between January and February 2025, covering studies published between 2015 and 2025. Results: Early life stress can profoundly impact cognitive function and neurodevelopment, with maternal early-life nutrition playing a significant role in modulating the effects of prenatal and postnatal stress. Early life stress influences the gut microbiome, disrupting its composition and function by altering the synthesis of microbial metabolites, neurotransmitters, and the activation of key metabolic pathways. However, the precise role of the gut microbiome in modulating stress responses during childhood and adolescence has not yet been fully elucidated. Conclusions: Several studies have demonstrated an association between early life stress and the gut microbiome. However, causality has not yet been established due to the numerous intrinsic and extrinsic factors influencing the microbiome-gut–brain axis. In the coming years, research on key microbial regulators, such as short-chain fatty acids, amino acids, and psychobiotics, may represent a promising approach for addressing central nervous system alterations linked to early life stress. Thus, further studies will be necessary to evaluate their potential as therapeutic agents. Full article

Background: Prenatal anxiety is a common problem affecting a large number of women. The presence of anxiety during pregnancy is associated with adverse consequences for both the mother and the baby. The main objective of this review was to determine the risk factors associated with anxiety during pregnancy in European women. Specifically, we wanted to know if these factors are the same as those found in other continents and if they are similar to those associated with depression during this stage. Methods: A literature review was carried out on studies that were published in the last 10 years in the PsycInfo, Medline, and SCOPUS databases. Thirteen studies were selected for the purposes of this review. Results: Sociodemographic risk factors associated with a higher level of anxiety during pregnancy included having a lower educational level and socioeconomic status. Obstetric and pregnancy-related risk factors included having had complications during pregnancy. Having a history of mental health problems, low social support, high levels of stress, and being exposed to adverse life events were the most relevant psychological factors for presenting prenatal anxiety. Furthermore, these factors are largely common to those associated with prenatal anxiety in other continents of the world and to those associated with prenatal depression. Conclusions: This review shows that there are multiple factors that contribute to women experiencing prenatal anxiety. Most can be identified at the beginning of pregnancy, and some factors, such as psychological ones, are potentially modifiable. This underlines the importance of carrying out a proper screening for anxiety during pregnancy in order to prevent its onset or treat it appropriately. Furthermore, the fact that risk factors are common for both prenatal anxiety and depression implies that the same intervention could reduce the probability of the onset of both pathologies and the possible consequences associated with them. Full article

Background/Objectives: Prenatal hypoxia (PH) is a leading cause of nervous system disorders in early childhood and subsequently leads to a decline in the cognitive and mnemonic functions of the central nervous system (such as memory impairment, reduced learning ability, and information processing). It also increases anxiety and the risk of brain disorders in adulthood. Compensatory–adaptive mechanisms of the mother–placenta–fetus system, which enhance the fetus’s CNS resilience, are known, including the activation of endogenous neuroprotection in response to hypoxic brain injury through the pharmacological modulation of HSP₇₀. Methods: To evaluate the effect of HSP₇₀ modulators—Cerebrocurin, Angiolin, Tamoxifen, Glutaredoxin, Thiotriazoline, and HSF-1 (heat shock factor 1 protein), as well as Mildronate and Mexidol—on the motor skills, exploratory behaviors, psycho-emotional activities, learning, and memories of offspring after PH. Experimental PH was induced by daily intraperitoneal injections of sodium nitrite solution into pregnant female rats from the 16th to the 21st day of pregnancy at a dose of 50 mg/kg. The newborns received intraperitoneal injections of Angiolin (50 mg/kg), Thiotriazoline (50 mg/kg), Mexidol (100 mg/kg), Cerebrocurin (150 µL/kg), L-arginine (200 mg/kg), Glutaredoxin (200 µg/kg), HSF-1 (50 mg/kg), or Mildronate (50 mg/kg) for 30 days. At 1 month, the rats were tested in the open field test, and at 2 months, they were trained and tested for working and spatial memory in the radial maze. Results: Modeling PH led to persistent impairments in exploratory activity, psycho-emotional behavior, and a decrease in the cognitive–mnestic functions of the CNS. It was found that Angiolin and Cerebrocurin had the most pronounced effects on the indicators of exploratory activity and psycho-emotional status in 1-month-old animals after PH. They also exhibited the most significant cognitive-enhancing and memory-supporting effects during the training and evaluation of skill retention in the maze in 2-month-old offspring after PH. Conclusions: for the first time, we obtained experimental data on the effects of HSP₇₀ modulators on exploratory activity, psycho-emotional behavior, and cognitive–mnestic functions of the central nervous system in offspring following intrauterine hypoxia. Based on the results of this study, we identified the pharmacological agents Angiolin and Cerebrocurin as promising neuroprotective agents after perinatal hypoxia. Full article

Background/Objectives: Autism is a complex neurodevelopmental disorder characterized by restricted behaviors and impaired social and communication skills. The exact cause of autism remains unknown. One promising animal model for studying autism is the valproic acid rat model. Due to a 1 to 4 bias for males in autism occurrence, most animal model studies investigate only males and neglect females. However, female autism often appears different from that observed in males. Females are said to be less regularly diagnosed because they can “mask” their symptoms. Female autism is as necessary to investigate as male autism. Methods: Fertile adult female Sprague-Dawley rats were impregnated and injected with valproic acid on gestational day 13. Male and female offspring were subjected to behavioral tests to investigate autistic symptoms. Tests included novel object recognition, balance-beam, Y-maze, hole-board, three-chamber, marble burying, olfactory, light/dark and hot plate tests. Results: The tests revealed that VPA-exposed rats had increased anxiety-like behaviors, hyperactivity, and impaired non-verbal communication. However, they did not display repetitive behaviors or cognitive impairments. Notably, male and female rats showed different autism-like traits, with both showing hyperactivity, and males (but not females) additionally showing impaired sociability and increased anxiety. Conclusions: The findings suggest that prenatal exposure to VPA induces autism-like behaviors in both male and female Sprague-Dawley rat offspring. However, males appear more impacted by VPA exposure as evinced by their display of more autism-like symptoms relative to females. This study provides support for including both sexes in all studies modelling autism, as outcomes are seemingly impacted by the sex being observed. Full article

Depressive disorder during pregnancy is a common condition, affecting approximately 10–15% of pregnant women, and is associated with adverse pregnancy outcomes such as inadequate prenatal care, substance abuse, and fetal growth restriction. Beyond neurotransmitter disturbances, increasing evidence suggests that infectious agents may play a role in the pathophysiology of depression through immune system modulation. Toxoplasma gondii infection has been linked to various mental disorders in the general population, including depression and anxiety. This study aimed to investigate whether depressive disorder during pregnancy is associated with chronic T. gondii infection by analyzing cytokine levels involved in inflammatory response modulation. Serum levels of TNF, IFN-γ, TGF-β1, IL-6, IL-8, IL-10, and MIF were measured in 79 pregnant women (18–40 years old) during the third trimester of an uncomplicated pregnancy. Participants were divided into four groups: Group I—depressive disorder and T. gondii seropositive (n = 19); Group II—no depressive disorder and T. gondii seropositive (n = 20); Group III—depressive disorder and T. gondii seronegative (n = 20); and Group IV—no depressive disorder and T. gondii seronegative (n = 20). Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) during routine prenatal visits, and blood samples were collected during standard prenatal examinations. Significant differences in cytokine levels were observed among the study groups. Notably, the group with both depressive disorder and chronic T. gondii infection exhibited a distinct cytokine profile characterized by significantly elevated TNF, IL-6, and IL-10 levels and significantly reduced IL-8 and MIF levels compared to the other groups. These findings suggest that pregnant women with depressive disorder and chronic T. gondii infection exhibit an altered balance of pro- and anti-inflammatory cytokines. This is the first study to investigate the association between serum cytokine levels, depressive disorder, and chronic T. gondii infection in pregnant women. Further research is needed to evaluate the potential of these immunobiomarkers as diagnostic tools or for monitoring therapeutic and prognostic strategies in this context. Full article

We investigated the molecular and clinical profile of five boys carrying the fragile X messenger ribonucleoprotein 1 (FMR1) mutation and who suffered from the effects of prenatal alcohol exposure. Fragile X syndrome (FXS) testing was performed using PCR and Southern Blot analysis, and fragile X messenger ribonucleoprotein protein (FMRP) expression levels were measured by Western blot analysis. Clinical evaluation included cognitive functions, adaptive skills, autism phenotype, and severity of behavior measures. Fetal Alcohol Spectrum Disorder (FASD) was also assessed. Five adopted male siblings were investigated, four of which (cases 1, 2, 3, and 4) were diagnosed with FXS, FASD, and ASD, and one, the fraternal triplet (case 5), was diagnosed with FASD and ASD and no FXS. The molecular profile of case 1 and 2 showed the presence of a hypermethylated full mutation (FM) and the resulting absence of FMRP. Cases 3 and 4 (identical twins) were FM-size mosaics (for the presence of an FM and a deleted allele), resulting in 16% and 50% FMRP expression levels, respectively. FMRP expression level was normal in case 5 (fraternal twin). Severe behavioral problems were observed in all cases, including aggression, tantrum, self-harming, anxiety, and defiant behavior, due to different mutations of the FMR1 gene, in addition to biological exposure, home environmental factors, and potentially to additional background gene effects. Full article