@article{pmid42320794,

title = {Prenatal metabolic adversity reprograms insulin-responsive transcription in the developing nucleus accumbens},

author = {Bonnie Alberry and Barbara Barth and Aashita Batra and Marcio Bonesso Alves and Patricia Maidana Miguel and Nicholas O'Toole and Sachin Patel and Derek Lupinsky and Tie Yuan Zhang and Xianglan Wen and Danusa Mar Arcego and Daniela Pereira Laureano and Irina Pokhvisneva and Roberta Dalle Molle and Patricia Pelufo Silveira},

doi = {10.1016/j.molmet.2026.102405},

issn = {2212-8778},

year  = {2026},

date = {2026-08-01},

journal = {Mol Metab},

volume = {110},

pages = {102405},

abstract = {Prenatal metabolic adversity, including fetal growth restriction (FR), programs long-term alterations in systemic and neural insulin sensitivity, yet its impact on insulin signaling within reward-circuit plasticity across development remains poorly understood. Using a rodent model of gestational FR, we examined how early metabolic stress alters insulin regulation of mesolimbic reward circuits using in vivo chronoamperometry to measure nucleus accumbens (NAc) dopamine (DA) release during palatable food exposure, with and without peripheral insulin. We assessed longitudinal consumption behavior and conducted transcriptomic profiling (RNA-Seq) at birth (P0), weaning (P21), and adulthood (P90) following saline or insulin administration. FR blunted immediate NAc DA release in response to palatable food, a deficit specifically reversed by peripheral insulin, indicating altered insulin sensitivity of mesolimbic reward circuits. FR animals also display accelerated initial palatable food consumption. Transcriptomic analysis revealed that FR reprograms the NAc's molecular response to insulin. Across development and sex, only 2-9% of insulin-responsive genes overlap between FR and controls. FR generated condition-specific and frequently inverted transcriptional signatures, affecting genes linked to synaptic plasticity (Cplx3, Rab3b) and neurodevelopment (Ccn3). These findings demonstrate that prenatal adversity reconfigures the NAc by altering its molecular and neurochemical responsiveness to insulin. This developmental reprogramming reveals how early metabolic stress reshapes insulin sensitivity within reward circuitry, a mechanism that may contribute to both metabolic and psychiatric disease vulnerability.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42463550,

title = {Birthweight predicts unfavorable adolescent immunometabolic trajectories leading to adult atypical depression in the ALSPAC cohort},

author = {Qizhou Xia and Carine Parent and Guillaume Elgbeili and Irina Pokhvisneva and Patricia Pelufo Silveira},

doi = {10.1038/s43856-026-01788-z},

issn = {2730-664X},

year  = {2026},

date = {2026-07-01},

journal = {Commun Med (Lond)},

abstract = {BACKGROUND: Lower birthweight, a marker of prenatal adversity, is associated with adverse health outcomes, including psychopathology and immune-metabolic alterations. This study tests whether longitudinal trajectories of chronic immune-metabolic alteration across adolescence, a period of rapid physiological changes, are predicted by birthweight and associated with subsequent depression risk, notably the atypical subtype. We aim to clarify pathways linking prenatal adversity to psychopathology.nnMETHODS: We derived a latent immune-metabolic factor at ages 15, 17, and 24 from standardized C-reactive protein and Homeostatic measurement of insulin resistance in participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N = 3000). We used latent class mixed modeling to identify immune-metabolic trajectory classes. Depression at 24 was measured on the International Classification of Diseases-10 criteria; atypical features were operationalized as the presence of neurovegetative symptoms (e.g. hypersomnia, hyperphagia). Inverse-probability weighting was used to mitigate selection bias.nnRESULTS: Here we show that a four-class quadratic model best fits the data. Membership in the late-adolescence-peaking trajectory is associated with higher odds of depression at 24 (Weighted-Beta=0.767, p = 0.047, OR = 2.15, 95%CI:1.20-3.88), and, notably, of depression with atypical symptoms (Weighted-Beta=1.25, p = 0.0035, OR = 3.50, 95%CI:1.50-8.11). Birthweight is inversely associated with odds of experiencing an unfavourable late-peak trajectory group (Weighted-Beta = -1.99, robust p = 0.0313, OR = 0.14, 95%CI:0.02-0.84). Sex demonstrates a marginal moderating effect (p = 0.050), with the association between birthweight and late-peak trajectory membership being more pronounced in females.nnCONCLUSIONS: Findings provide longitudinal evidence that prenatal adversity, indexed by lower birthweight, predicts individuals experiencing unfavourable adolescent immune-metabolic trajectories that are associated with adult depression, particularly with atypical features. Results suggest that developmental immune-metabolic trajectories could eventually inform patient clinical stratification and point to late adolescence as a possible intervention window.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41380478,

title = {Sex-specific interaction effects of Syntaxin 1A coexpression network and childhood trauma on adult depressive symptoms},

author = {Danusa Mar Arcego and Carla Dalmaz and Irina Pokhvisneva and Zihan Wang and Barbara Barth and Sachin Patel and Qizhou Xia and Randriely Merscher Sobreira de Lima and Euclides J de Mendonça Filho and Michael S Kobor and Kieran O'Donnell and Michael J Meaney and Patrícia P Silveira},

doi = {10.1016/j.ebiom.2025.106062},

issn = {2352-3964},

year  = {2026},

date = {2026-01-01},

journal = {EBioMedicine},

volume = {123},

pages = {106062},

abstract = {BACKGROUND: Disruptions in synaptic function and exposure to early life trauma are both implicated in the development of depression, though the underlying mechanisms remain poorly understood.nnMETHODS: To investigate this relationship, we developed an expression-based polygenic score (ePRS) that captures individual variations in the expression of genes co-expressed with the synaptic protein Syntaxin 1A (STX1A) in the prefrontal cortex (PFC). This polygenic score allows us to explore the impact of variations on synaptic function and childhood trauma on the susceptibility to depressive symptoms in adulthood.nnFINDINGS: Our findings indicate that the PFC-ePRS-STX1A score moderates the effects of childhood trauma on the diagnosis of depression in adult females from the UK Biobank (Logistic regression, β = -0.150, p = 0.001, N = 72,812). A similar result was found in an independent cohort (ALSPAC), where PFC-ePRS-STX1A moderated the effects of childhood trauma on depressive symptoms in younger adult females, confirming the sex-specific moderation effect (GEE analysis, ages 22-23, β = -1.063, p = 0.0046, N = 1846). Functional enrichment analysis of the STX1A-coexpressed network revealed key biological processes related to protein synthesis, with 25.8% associated gene products localised to synaptic components at both pre and postsynaptic sites.nnINTERPRETATION: This highlights the critical role of synaptic plasticity function in the PFC in shaping the long-term effects of early trauma on depression. Our methodology and results offer valuable insights into individual vulnerability to depression following early trauma and highlight synaptic function as a potential target for interventions aimed at mitigating depression risk.nnFUNDING: JPB Foundation; Hope for Depression Research Foundation; CAPES; Fonds de recherche du Québec, and CIHR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41510815,

title = {Genome-wide methylation patterns associated with chronic stress},

author = {Nicholas O'Toole and Tie-Yuan Zhang and Eamon Fitzgerald and Xianglan Wen and Josie Diorio and Patricia P Silveira and Benoit Labonté and Eric J Nestler and Michael J Meaney},

doi = {10.1080/17501911.2026.2613012},

issn = {1750-192X},

year  = {2026},

date = {2026-01-01},

journal = {Epigenomics},

volume = {18},

number = {1},

pages = {73--88},

abstract = {BACKGROUND: Chronic social defeat stress (CSDS) is a validated animal model for depression that produces sustained behavioral and transcriptional changes in the brain, notably the nucleus accumbens (nAcc).nnRESEARCH DESIGN AND METHODS: We used genome-wide analysis of cytosine methylation patterns in mouse nAcc following CSDS to identify candidate epigenetic mechanisms.nnRESULTS: CSDS produced extensive differential methylation, increasing CG hypermethylation compared to control conditions; non-CG methylation showed the opposite trend. Highly differentially methylated (DM) regions included several genes implicated in behavioral effects of CSDS, including estrogen receptor alpha (Esr1).nnCONCLUSIONS: Analysis of DM sites within gene bodies revealed ß-catenin as a hub gene of a network including the ß-catenin-related WNT/frizzled signaling pathway. Analysis of DM sites upstream of transcription start sites revealed a gene network with the Tcf4 transcription factor as a hub. Genes DM within the gene body were enriched for synaptic function and primarily expressed in D1+ and D2+ medium spiny neurons, which, like the WNT/ß-catenin pathway, are estrogen sensitive and implicated in the behavioral effects of CSDS. We found significant overlap between DM genes associated with CSDS and those associated with major depressive disorder in genome-wide association studies, suggesting that effects on DNA methylation are implicated in the molecular pathways that link chronic stress to depression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41034507,

title = {Hippocampal SGK1 promotes vulnerability to depression: the role of early life adversity, stress, and genetic risk},

author = {Amira Millette and Milenna T van Dijk and Irina Pokhvisneva and Yifei Li and Rory Thompson and Sachin Patel and Rosemary C Bagot and Aniko Naray-Fejes-Toth and Geza Fejes-Toth and Patricia Pelufo Silveira and Gustavo Turecki and Juan Pablo Lopez and Christoph Anacker},

doi = {10.1038/s41380-025-03269-6},

issn = {1476-5578},

year  = {2025},

date = {2025-12-01},

journal = {Mol Psychiatry},

volume = {30},

number = {12},

pages = {6079--6089},

abstract = {Serum and Glucocorticoid-regulated Kinase 1 (SGK1) is elevated in hippocampal neurons following glucocorticoid exposure and in peripheral blood of depressed patients. However, its mechanistic role in psychopathology and its relevance to the human brain are unknown. To address this gap, we investigated human postmortem brain tissue and found higher SGK1 expression in the hippocampus of depressed suicide decedents compared to healthy subjects who died of natural causes. We observed the highest levels of SGK1 in subjects with reported early life adversity (ELA) - a major risk factor for psychiatric disorders. To determine potential genetic factors underlying increased SGK1 in the hippocampus, we computed expression-based polygenic risk scores (ePRS) for a large population sample from the ABCD study and found that a collection of genetic variants associated with high hippocampal SGK1 expression predicts depression severity and moderates associations between ELA, depressive symptoms, and suicide attempts. Similar to the human brain, hippocampal SGK1 expression was increased in mouse models of ELA, adult chronic stress, and chronic corticosterone exposure, and hippocampal-specific knockdown of SGK1 conferred resilience to stress-induced behavior abnormalities. To test SGK1 as a potential therapeutic target, we injected mice with the small molecule inhibitor, GSK650394, and found that pharmacological inhibition conferred stress resilience, increased adult hippocampal neurogenesis, and rescued stress-induced dentate gyrus hyperactivity. Our cross-species findings reveal a novel role for hippocampal SGK1 in stress resilience, highlight an interaction between ELA and SGK1 on depression and suicide risk, and establish for the first time a functional role for SGK1 in stress-induced psychopathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41006755,

title = {Brain insulin receptor gene network shapes risk for metabolic disease after early-life stress in women},

author = {Angela Marcela Jaramillo-Ospina and Guillaume Elgbeili and Sachin Patel and Irina Pokhvisneva and Patricia Pelufo Silveira},

doi = {10.1038/s42003-025-08750-0},

issn = {2399-3642},

year  = {2025},

date = {2025-09-01},

journal = {Commun Biol},

volume = {8},

number = {1},

pages = {1372},

abstract = {Stress happening during critical periods of development shapes individual physiology and increases the risk for obesity, inflammatory, and metabolic disturbances throughout life. However, there are individual differences and not everyone exposed to stress or adversity early during development develops chronic adult disease. Insulin regulates peripheral glucose metabolism, acts as a neuromodulator in the brain, and is possibly implicated in individual differences in response to early adversity. Expression-based polygenic scores (ePRS) reflect variations in the expression of a tissue-specific gene co-expression network. We have previously shown that brain-based insulin receptor ePRS (ePRS-IR) can identify risk for metabolic and frailty outcomes in older adults. Here, we show that the mesocorticolimbic ePRS-IR moderates the association between early adversity and increased visceral adipose tissue as well as metabolic syndrome in a large sample of adult women (UK Biobank). These findings suggest that variations in the function of the brain insulin receptor network influence the susceptibility to the long-term effects of adversity, highlighting a target system for prevention and novel treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40118225,

title = {Large-scale effects of prenatal inflammation and early life circadian disruption in mice: Implications for neurodevelopmental disorders},

author = {Tara C Delorme and Danusa M Arcego and Danae Penichet and Nicholas O'Toole and Nikki Huebener and Patrícia P Silveira and Lalit K Srivastava and Nicolas Cermakian},

doi = {10.1016/j.bbi.2025.03.023},

issn = {1090-2139},

year  = {2025},

date = {2025-07-01},

journal = {Brain Behav Immun},

volume = {127},

pages = {409--422},

abstract = {Around 80 % of individuals with neurodevelopmental disorders such as schizophrenia and autism spectrum disorders experience disruptions in sleep/circadian rhythms. We explored whether environmental circadian disruption interacts with prenatal infection, a risk factor for neurodevelopmental disorders, to induce sex-specific deficits in mice. A maternal immune activation (MIA) protocol was used by injecting pregnant mice with viral mimic poly IC or saline at E9.5. Juvenile/adolescent male and female offspring (3-7 weeks old) were then subjected to a standard light:dark cycle (12:12LD) or to constant light (LL). Significant interactions between treatment (MIA, control) and lighting (12:12LD, LL) were evident in behaviors related to cognition, anxiety, and sociability. This pattern persisted in our RNA sequencing analysis of the dorsal hippocampus, where poly IC exposure resulted in numerous differentially expressed genes (DEGs) in males, while exposure to both poly IC and LL led to a marked reduction in DEGs. Through WGCNA analysis, many significant gene modules were found to be positively associated with poly IC (vs. saline) and LL (vs. LD) in males (fewer in females). Many of the identified hub-bottleneck genes were homologous to human genes associated with sleep/circadian rhythms and neurodevelopmental disorders as revealed by GWA studies. The MIA- and LL-associated modules were enriched in microglia gene signatures, which was paralleled by trends of effects of each of the factors on microglia morphology. In conclusion, in a mouse model of prenatal infection, circadian disruption induced by LL during adolescence acts as a modulator of the effects of MIA at behavioral, cellular, and molecular levels.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40581111,

title = {Peripheral leptin receptor gene network modulates the impact of childhood adversity on mental health disorders},

author = {Randriely Merscher Sobreira de Lima and Barbara Barth and Danusa Mar Arcego and Euclides José de Mendonça Filho and Sachin Patel and Zihan Wang and Guillaume Elgbeili and Irina Pokhvisneva and Carine Parent and Robert D Levitan and Michael S Kobor and Carla Dalmaz and Patrícia Pelufo Silveira},

doi = {10.1016/j.bbi.2025.06.035},

issn = {1090-2139},

year  = {2025},

date = {2025-06-01},

journal = {Brain Behav Immun},

volume = {129},

pages = {585--594},

abstract = {Psychiatric disorders are highly prevalent and often co-morbid with metabolic syndrome. Exposure to adversity in early life is a risk factor for both metabolic and behavioral problems, modifying leptin metabolism and signaling. Leptin is not only an energy-balance regulator, being also associated with the development of affective disorders. Our objective was to investigate if individual variations in peripheral leptin receptor (LepR) gene network function moderate the effect of childhood adversity on psychopathology. We created expression-based polygenic scores (ePRS) reflecting genetic variations that affect expression of the liver LepR gene network. We investigated the interaction between the LepR-ePRS and early adversity on mental health outcomes, namely anxiety and depression, in childhood (MAVAN) and adolescence (ALSPAC). In both cohorts, there were interaction effects between early adversity exposure and the liver-based LepR-ePRS, in which adversity was associated with depression only in individuals from the high ePRS group. Our findings suggest that exposure to early adversity is associated with mental health problems in children and adolescents. The liver leptin receptor gene network is an important moderator of these effects, and this may be due to individual differences within metabolic and inflammatory pathways represented by this gene network.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40349327,

title = {Early adversity and the comorbidity between metabolic disease and psychopathology},

author = {Ameyalli Gómez-Ilescas and Patricia Pelufo Silveira},

doi = {10.1113/JP285927},

issn = {1469-7793},

year  = {2025},

date = {2025-05-01},

journal = {J Physiol},

abstract = {Although the co-existence of metabolic and psychiatric disorders in the same individual (comorbidity) is very prevalent, the mechanisms by which these disorders co-occur are poorly understood, but a history of early-life adversity is a common developmental risk factor. Exposure to adverse environments during critical periods of development (e.g. fetal life and infancy) modifies the metabolism and the function of the brain persistently, influencing behaviours that contribute to both metabolic and mental health disarrangements over the life course. We will review molecular and clinical evidence supporting the notion that early adversity is an important risk factor for the comorbidity between metabolic and psychiatric conditions. We will also discuss the possible mechanisms involved: neurometabolic programming, epigenetic alterations and the cumulative effects of altered inflammatory and oxidative pathways linked to early adversity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39938231,

title = {Linking obesity-associated genotype to child language development: the role of early-life neurology-related proteomics and brain myelination},

author = {Jian Huang and Jinyi Che and Michelle Z L Kee and Ai Peng Tan and Evelyn C Law and Patricia Pelufo Silveira and Irina Pokhvisneva and Sachin Patel and Keith M Godfrey and Lourdes Mary Daniel and Kok Hian Tan and Yap Seng Chong and Shiao-Yng Chan and Johan G Eriksson and Dennis Wang and Jonathan Yinhao Huang},

doi = {10.1016/j.ebiom.2025.105579},

issn = {2352-3964},

year  = {2025},

date = {2025-03-01},

journal = {EBioMedicine},

volume = {113},

pages = {105579},

abstract = {BACKGROUND: The association between childhood obesity and language development may be confounded by socio-environmental factors and attributed to comorbid pathways.nnMETHODS: In a longitudinal Singaporean mother-offspring cohort, we leveraged trans-ancestry polygenic predictions of body mass index (BMI) to interrogate the causal effects of early-life BMI on child language development and its effects on molecular and neuroimaging measures. Leveraging large genome-wide association studies, we examined whether the link between obesity and language development is causal or due to a shared genetic basis.nnFINDINGS: We found an inverse association between polygenic risk for obesity, which is less susceptible to confounding, and language ability assessed at age 9. Our findings suggested a shared genetic basis between obesity and language development rather than a causal effect of obesity on language development. Interrogating early-life mechanisms including neurology-related proteomics and language-related white matter microstructure, we found that EFNA4 and VWC2 expressions were associated with language ability as well as fractional anisotropy of language-related white matter tracts, suggesting a role in brain myelination. Additionally, the expression of the EPH-Ephrin signalling pathway in the hippocampus might contribute to language development. Polygenic risk for obesity was nominally associated with EFNA4 and VWC2 expression. However, we did not find support for mediating mechanisms via these proteins.nnINTERPRETATION: This study demonstrates the potential of examining early-life proteomics in conjunction with deep genotyping and phenotyping and provides biological insights into the shared genomic links between obesity and language development.nnFUNDING: Singapore National Research Foundation and Agency for Science, Technology and Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40013320,

title = {The association between temperament and polygenic score for psychopathology from infancy to middle childhood},

author = {Eloise Freitag and Caroline Kelsey and Euclides José de Mendonça Filho and Irina Pokhvisneva and Sachin Patel and Patricia Pelufo Silveira and Michelle Bosquet Enlow and Charles A Nelson},

doi = {10.1111/jcpp.14140},

issn = {1469-7610},

year  = {2025},

date = {2025-02-01},

journal = {J Child Psychol Psychiatry},

abstract = {BACKGROUND: Certain temperament characteristics, such as low effortful control and high negative affectivity, are linked to an elevated likelihood for later psychopathology. Although genetic vulnerability has been associated with a number of psychiatric conditions, little work has examined the genetic architecture underlying temperament or the genetic overlap between early temperament profiles and later mental health outcomes. The present study examined associations of polygenic scores for anxiety (PGS-Anxiety) and ADHD (PGS-ADHD) with temperament characteristics in a longitudinal sample of children assessed from infancy through age 7 years.nnMETHODS: Analyses were conducted in a sample of children (European Ancestry n = 476; Full Sample [European and other ancestries] N = 606).nnRESULTS: We observed an age-by-PGS interaction on effortful control. As children aged, there appeared to be stronger negative associations between PGS-ADHD and effortful control. No associations were observed between PGS-Anxiety and negative affectivity.nnCONCLUSIONS: Overall, the findings suggest some support for associations between genetic underpinnings for externalizing psychopathology and temperament that increase over time.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39814119,

title = {Early environmental influences on the orbito-frontal cortex function and its effects on behavior},

author = {Olivia Ruge and João Paulo Maires Hoppe and Roberta Dalle Molle and Patricia Pelufo Silveira},

doi = {10.1016/j.neubiorev.2025.106013},

issn = {1873-7528},

year  = {2025},

date = {2025-02-01},

journal = {Neurosci Biobehav Rev},

volume = {169},

pages = {106013},

abstract = {Early-life adversity during pre- and early post-natal phases can impact brain development and lead to maladaptive changes in executive function related behaviors. This increases the risk for a range of psychopathologies and physical diseases. Importantly, exposure to adversities during these periods is also linked to alterations in the orbito-frontal cortex (OFC) which is a key player in these executive functions. The OFC thus appears to be a central node in this association between early life stress and disease risk. Gaining a clear, and detailed understanding of the association between early life stress, OFC function, and executive function, as well as the underlying mechanisms mediating this association is relevant to inform potential therapeutic interventions. In this paper, we begin by reviewing evidence linking early life adversities to 1) alterations in behaviors regulated by the OFC and 2) changes in OFC anatomy and function. We then present insights into the underlying mechanisms for these changes, stemming from early life adversity models, and highlight important future directions for this line of research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41431608,

title = {Early life adversity and the comorbidity of psychopathology and cardiometabolic disorders: insights from the UK Biobank},

author = {Patrícia P Silveira and Andre K Portella and Zihan Wang and João Paulo M Hoppe and Irina Pokhvisneva and Michael J Meaney},

doi = {10.1136/bmjph-2025-003051},

issn = {2753-4294},

year  = {2025},

date = {2025-01-01},

journal = {BMJ Public Health},

volume = {3},

number = {2},

pages = {e003051},

abstract = {INTRODUCTION: Early life adversity is associated with both psychopathology and cardiometabolic diseases, suggesting shared developmental risk factors and biological mechanisms. We aimed to investigate the associations between early life adversity and psychopathology, cardiometabolic diseases and their comorbidity.nnMETHODS: Cross-sectional study with participants from the UK Biobank cohort, composed of 502 543 individuals ranging from 37 to 73 years of age. Samples were collected between 2006 and 2010. Participants were excluded if fitting any of the exclusion criteria-dropouts, inconsistencies in reported versus genotyped sex, inconsistencies in assigned family structure, missing covariates data. We employed generalised estimated equations to evaluate the associations between self-reported adversity and outcomes. Adversity was measured through three scores: prenatal (n=234 817), postnatal (n=151 297) and cumulative (n=82 758). Outcomes were psychopathologies (mental/behaviour disorder due to substance use, mood disorders, schizophrenia, neurotic/stress-related) and cardiometabolic diseases (type 2 diabetes, ischaemic heart disease, atherosclerosis, cerebral infarction, cerebral atherosclerosis).nnRESULTS: The cumulative combined adversity score predicted comorbidity (OR = 1.38, 95% CI 1.31 to 1.45, p<0.01), as well as all outcomes except cerebral infarction. Similar results were observed analysing prenatal (OR=1.27, 95% CI 1.23 to 1.31, p<0.01) and postnatal (OR=1.43, 95% CI 1.36 to 1.50, p<0.01) adversity scores.nnCONCLUSION: Early life adversity may be associated with a common cascade of events linked to both psychopathologic and cardiometabolic diseases, which has profound implications for early prevention, diagnosis and treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39521350,

title = {A mesocorticolimbic insulin receptor gene co-expression network moderates the association between early life adversity and food approach eating behaviour style in childhood},

author = {Angela Marcela Jaramillo-Ospina and Roberta Dalle Molle and Sachin Patel and Shona Kelly and Irina Pokhvisneva and Carolina de Weerth and Patrícia Pelufo Silveira},

doi = {10.1016/j.appet.2024.107762},

issn = {1095-8304},

year  = {2025},

date = {2025-01-01},

journal = {Appetite},

volume = {204},

pages = {107762},

abstract = {Insulin receptors, located in brain regions associated with reward sensitivity and decision-making, facilitate insulin action in the brain, modulating intracellular signaling cascades, gene expression, and neural activity. Here, we tested if variations in the expression of the insulin receptor gene network in the prefrontal cortex (PFC) and striatum (STR) moderate the association between early life adversity and eating behaviour in childhood and if this moderation is sex-specific. Participants from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and Basal Influences on the Baby's Development (BIBO) were included as two independent cohorts. A biologically-informed polygenic score reflecting functional variation of the mesocorticolimbic insulin receptor gene network was created by using insulin receptor co-expression data from the PFC and STR in mice, and validated in humans through filtering by homologous expression in PFC using well-known databases. Early life adversity exposure was measured as a composite score. Eating behaviour was characterized using the Child Eating Behaviour Questionnaire administered to mothers of children aged 4 and 6 years in MAVAN, and 6 years in BIBO. We found that only in those with high expression of the mesocorticolimbic insulin receptor gene network a higher early adversity score associated with a higher desire to drink in 4-year boys and 6-year girls, as well as a higher food approach score and food approach/food avoidance ratio in 4-year girls. Also, a higher early life adversity was associated with higher food responsiveness, food approach score and food approach/food avoidance ratio at 6 years in the MAVAN full sample. The moderation observed on desire to drink was partially replicated in BIBO children aged 6 years. Identifying individual differences in response to early adversity may help to prioritize individuals at high risk for long-term disease and design suitable interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39947656,

title = {Associations of fetal and postnatal growth trajectories with child cognition: the GUSTO cohort study},

author = {Yi Ying Ong and Nicholas Beng Hui Ng and Navin Michael and Shirong Cai and Mya Thway Tint and Delicia Shu Qin Ooi and Ai Peng Tan and Kok Hian Tan and Lynette Shek and Fabian Yap and Yap Seng Chong and Johan Gunnar Eriksson and Shiao-Yng Chan and Birit F P Broekman and Keith M Godfrey and Patricia Pelufo Silveira and Henning Tiemeier and Evelyn C Law and Izzuddin M Aris and Yung Seng Lee},

doi = {10.1093/ije/dyaf012},

issn = {1464-3685},

year  = {2024},

date = {2024-12-01},

journal = {Int J Epidemiol},

volume = {54},

number = {1},

abstract = {BACKGROUND: Using longitudinal ultrasounds as an improved fetal growth marker, we aimed to investigate if increased postnatal growth following fetal abdominal circumference (AC) growth deceleration is associated with improved child cognition.nnMETHODS: Among 797 term-born singletons in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, we derived 2nd-3rd trimester fetal AC growth z-score, fetal AC growth deceleration, standardized height, weight, and body mass index (BMI) growth at early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (3-7 years), and investigated their associations with intelligence quotient (IQ) at ages 4.5 years (verbal, non-verbal) and 7 years (non-verbal-block design, matrix reasoning), adjusting for socio-demographic and biological confounders.nnRESULTS: Among term-born newborns, 23.3% experienced fetal AC growth deceleration, which was associated with lower non-verbal IQ (4.5 years) [β (95% CI), -4.00 (-7.49, -0.51)]. Higher 0-7 years z-BMI gain was associated with lower non-verbal IQ (block design) (7 years) [-1.33 (-2.51, -0.14)]. Higher late infancy z-BMI gain was associated with higher verbal IQ (4.5 years) [3.36 (0.82,5.90)] but lower non-verbal IQ (matrix reasoning) (7 years) [-2.32 (-4.48, -0.17)]. Among those with fetal AC growth deceleration, higher 0-7 years z-weight gain was associated with lower non-verbal IQ (block design) (7 years) (P-interaction = .049); at z-weight gain of +2 standard deviation score (SDS), those with fetal AC growth deceleration had lower IQ [margins (95% CI), -2.6 (-7.1,1.9)]. On average, children with fetal AC growth deceleration caught up in z-height, z-weight, and z-BMI by 7 years.nnCONCLUSION: Fetal AC growth deceleration was associated with lower cognition scores at preschool age. Increased weight or BMI growth from 0-7 years following fetal AC growth deceleration might not be favorable to cognition among generally well-nourished term-born children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39426730,

title = {Early Influences on Development of Sensory Perception and Eating Habits},

author = {Kelly Guedes de Oliveira Scudine and Paula Midori Castelo and João Paulo Maires Hoppe and André Krumel Portella and Patricia Pelufo Silveira},

doi = {10.1016/j.advnut.2024.100325},

issn = {2156-5376},

year  = {2024},

date = {2024-12-01},

journal = {Adv Nutr},

volume = {15},

number = {12},

pages = {100325},

abstract = {Infancy and early childhood are important periods for the development of food choices and eating preferences that are tracked into adult life, influencing weight gain, body composition, and metabolism and ultimately affecting the balance between health and disease. In this narrative review, we discuss studies focused on the effects of fetal programming and early food experiences, highlighting recent advances in the discovery of factors that contribute to the development of food preferences and eating behavior. Food preference can be influenced by early direct contact with flavors, textures, and aromas, as well as by environmental adversities during early development. Evidence suggests that exposure to intrauterine growth restriction is associated with increased preferences for highly palatable foods, such as those rich in carbohydrates and fats, over the life course. Early flavor experiences, whether from amniotic fluid or human milk, may also shape the development of food preferences. Finally, children are more likely to accept textures that they are able to manipulate, and early exposure to a range of textures facilitates the acceptance of foods of various textures later on. Improving dietary habits during gestation (fetal) and postnatal periods is of critical importance for the establishment of positive eating habits and healthy growth in infants and should be an important focus of primary prevention efforts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39521843,

title = {Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity},

author = {Barbara Barth and Danusa Mar Arcego and Euclides José de Mendonça Filho and Randriely Merscher Sobreira de Lima and Carine Parent and Carla Dalmaz and André Krumel Portella and Irina Pokhvisneva and Michael J Meaney and Patricia Pelufo Silveira},

doi = {10.1038/s41598-024-78465-5},

issn = {2045-2322},

year  = {2024},

date = {2024-11-01},

journal = {Sci Rep},

volume = {14},

number = {1},

pages = {27349},

abstract = {Cardiometabolic and psychiatric disorders often co-exist and share common early life risk factors, such as low birth weight. However, the biological pathways linking early adversity to adult cardiometabolic/psychiatric comorbidity remain unknown. Dopamine (DA) neurotransmission in the striatum is sensitive to early adversity and influences the development of both cardiometabolic and psychiatric diseases. Here we show that a co-expression based polygenic score (ePGS) reflecting individual variations in the expression of the striatal dopamine transporter gene (SLC6A3) network significantly interacts with birth weight to predict psychiatric and cardiometabolic comorbidities in both adults (UK Biobank, N = 225,972) and adolescents (ALSPAC, N = 1188). Decreased birth weight is associated with an increased risk for psychiatric and cardiometabolic comorbidities, but the effect is dependent on a striatal SLC6A3 ePGS, that reflects individual variation in gene expression of genes coexpressed with the SLC6A3 gene in the striatum. Neuroanatomical analyses revealed that SNPs from the striatum SLC6A3 ePGS were significantly associated with prefrontal cortex gray matter density, suggesting a neuroanatomical basis for the link between early adversity and psychiatric and cardiometabolic comorbidity. Our study reveals that psychiatric and cardiometabolic diseases share common developmental pathways and underlying neurobiological mechanisms that includes dopamine signaling in the striatum.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38991360,

title = {Relationship between maternal biological features, environmental factors, and newborn neuromotor development associated with visual fixation abilities},

author = {Fernanda Rombaldi Bernardi and Marta Knijnik Lucion and Roberta Dalle Mole and Tania Diniz Machado and Bibiana Bolten Lucion Loreto and Bruna Luciano Farias and Tatiane Madeira Reis and Roberta Sena Reis and Solange Mara Bigonha and Maria do Carmo Gouveia Peluzio and Danusa Mar Arcego and Carla Dalmaz and Patrícia Pelufo Silveira},

doi = {10.1016/j.bandc.2024.106202},

issn = {1090-2147},

year  = {2024},

date = {2024-10-01},

journal = {Brain Cogn},

volume = {180},

pages = {106202},

abstract = {Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38677627,

title = {Examining the associations between microglia genetic capacity, early life exposures and white matter development at the level of the individual},

author = {Shi Yu Chan and Eamon Fitzgerald and Zhen Ming Ngoh and Janice Lee and Jasmine Chuah and Joanne S M Chia and Marielle V Fortier and Elizabeth H Tham and Juan H Zhou and Patricia P Silveira and Michael J Meaney and Ai Peng Tan},

doi = {10.1016/j.bbi.2024.04.038},

issn = {1090-2139},

year  = {2024},

date = {2024-07-01},

journal = {Brain Behav Immun},

volume = {119},

pages = {781--791},

abstract = {There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score(ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes.A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors.Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females.We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems.In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA.Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposuresthrough influences on neurodevelopment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}