Familial Risk Research Articles

βIV spectrin abundancy, cellular distribution and sensitivity to AKT/GSK3 regulation in schizophrenia.

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV spectrin protein levels were reduced in neurons of the dorsolateral prefrontal cortex in SCZ postmortem samples compared to healthy control (HC) from the Human Brain Collection Core (HBCC). To investigate potential links between βIV spectrin and the AKT/GSK3 pathway, we analyzed the PsychEncode dataset, revealing elevated SPTBN4 and AKT2 mRNA levels with correlated gene transcription in both HCs and individuals with SCZ. Next, computational tools were employed to identify potential AKT and GSK3 phosphorylation sites on βIV spectrin, and two GSK3 sites were validated through in vitro assays. To assess whether βIV spectrin distribution and sensitivity to AKT/GSK3 are altered in SCZ, we used iPSC-derived neurons from two independent cohorts of patients with significantly increased familial genetic risk for the disorder. Alteration in βIV spectrin levels and sensitivity to AKT/GSK3 inhibitors were consistently observed across both cohorts. Importantly, a Random Forest classifier applied to βIV spectrin imaging achieved up to 98% accuracy in classifying cells by diagnosis in postmortem samples, and by diagnosis or diagnosis × perturbation in iPSC samples. These findings reveal altered βIV spectrin levels and AKT/GSK3 sensitivity in SCZ, identifying βIV spectrin image-based endophenotypes as robust, generalizable predictive biomarkers of SCZ, with the potential for scalable clinical applications.

Dynamic respiratory sinus arrhythmia self-regulation and coregulation in response to caregiving challenges in at-risk mother-child and father-child dyads.

We examined how mother-preschooler and father-preschooler dyads differed in dynamic self-regulation and time-lagged coregulation of respiratory sinus arrhythmia (RSA) when having to transition from play into a challenging disciplinary context, and how individual and dyadic regulatory responses to this challenge varied by parenting risk. Participants included 78 mother-preschooler and 51 father-preschooler dyads (53% female, 63.3% non-Hispanic White) oversampled for familial risk. At 2½ years, parents self-reported harsh parenting. At 3 years, parent-child RSA was collected during free play and cleanup tasks. Multilevel models of time-lagged RSA (i.e., parent RSA predicting child RSA in the next time unit and vice versa) were conducted. In response to a task with increased challenge and parenting demands, mothers and children showed expected individual RSA decreases (indicating active regulation), whereas fathers showed increases in RSA (suggesting decreasing arousal or disengagement). Mother-driven negative time-lagged RSA coregulation and father-driven positive time-lagged RSA coregulation were observed during play, but not during cleanup. Harsh parenting was associated with altered RSA responses to challenge: During cleanup, harsher mothers showed no active regulation, suggesting disengagement, harsher fathers showed more stability in RSA self-regulation, and child-driven negative RSA coregulation with harsher fathers was observed. Findings suggest that during preschool, (a) parents are the typical drivers of RSA coregulation, (b) challenging contexts and parenting risk alter dynamic RSA self-regulation and time-lagged RSA coregulation, and (c) typical and atypical RSA self-regulation and time-lagged coregulation patterns differ between mother-child and father-child dyads. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Familial patterns of alopecia areata: A systematic review and meta-analysis.

Alopecia Areata (AA) is a T cell-mediated autoimmune disease characterized by sudden hair loss. It is associated with a significant familial predisposition and comorbidities such as thyroid disease, diabetes, atopic dermatitis, and vitiligo. This study aims to systematically review and meta-analyze the prevalence of familial AA and its associated comorbidities to better understand the hereditary nature of the disease. A systematic review and meta-analysis were conducted following the PRISMA guidelines. Relevant studies were identified from databases including EMBASE, Cochrane Library, PubMed, and Web of Science up to October 15, 2023. Studies were included if they reported on AA patients with a confirmed diagnosis and a family history of AA or related comorbidities. Data extraction and quality assessment were performed by two independent reviewers, with discrepancies resolved by a third reviewer. Pooled prevalence estimates were calculated using a random effects model. The meta-analysis included 67 studies, encompassing 24,226 AA patients and their relatives. The prevalence of a family history of alopecia areata (AA) was found to be 17.6%, indicating that 17.6% of individuals with AA have a positive family history of the condition. (CI: 14.9%-20.6%, I2=96%). The prevalence among relatives was 0.90% (CI: 0.55%-1.47%, I2=98%), with the highest prevalence observed in first-degree relatives at 3.22% (CI: 2.31%-4.48%, I2=94%). Comorbid conditions were present in 9.61% (CI: 6.98%-13.1%, I2=95%) of family members across first-, second-, and third-degree relatives of individuals with alopecia areata have comorbid autoimmune or related conditions, including thyroid disease (4.7%), diabetes (10.1%), atopic dermatitis (18.9%), vitiligo (5.5%), and other autoimmune disease (12.1%). This systematic review and meta-analysis highlight the significant familial risk and comorbidities in family members of AA patients. The findings emphasize the need for comprehensive family monitoring, which includes regular health screenings for autoimmune and related conditions among relatives of AA patients, and genetic counseling to educate families on hereditary risks and to guide early intervention and monitoring strategies. It can lead to improved outcomes. In the future, large population-based studies focusing on second and third-degree relatives are needed to further elucidate these associations.

Young Adult Resilience for Recovery From Substance Addiction in Assam, India: Lived Experience Insights From a Photo-Led Interview Study.

Substance addiction can be considered a form of social injustice grounded in interactions between individual, family and community-level risk factors. Although prevention and treatment of substance use disorder is a key target of the United Nations sustainable development goal Good Health and Well-Being, many low-and-middle-income countries lack a culturally validated approach for its management. We contend that a resilience approach may provide a sound basis from which to develop such an approach in non-western, low-resource settings. Hence, the aim of this study is to identify factors supporting resilience for recovery from substance addiction in the lived experience of young adults in Assam, India. We used photo-led interviews to centre the lived experience of young adult addicts-in-recovery (11 men, 5 women; 19-24 years) recruited through two rehabilitation services and their networks. Reflexive thematic analysis of the data produced three clusters of themes: (i) precursors to recovery; (ii) repairing relationships; and, (iii) structuring a life of recovery. Findings are discussed and potential areas for intervention are identified to support a multi-level, culturally informed, community-driven approach to recovery from substance addiction.

Genetic insights into psychotic major depressive disorder: bridging the mood-psychotic disorder spectrum.

Psychotic major depressive disorder (MDD), a subtype of MDD characterised by psychotic symptoms that occur exclusively during mood episode, is clinically significant yet underexplored genetically due to its rarity. This study comprehensively examines the genetic basis of psychotic MDD and elucidates its position within the mood-psychotic spectrum. This population-based cohort study used Swedish and Danish registry data for over 5.1M individuals born between 1958 and 1993/1996. Specialist-diagnosed psychotic MDD was defined using ICD-10 sub-codes of MDD, F32.2/F32.3. We estimated familial aggregation/coaggregation using generalised estimating equations, heritability and genetic correlations using structural equation modelling. We also analysed ∼30,000 genotyped MDD cases from the UK Biobank and a Swedish cohort to explore which polygenic risk score (PRS) may predispose individuals to psychotic MDD. With over 10,000 psychotic MDD identified from the two nationwide patient registers, this study highlights the familial aggregation of psychotic MDD, co-aggregation with mood and psychotic disorders, and its stronger genetic correlation with schizophrenia compared to non-psychotic MDD. The familial risks increased with closer biological relatedness, suggesting genetic influence. Pedigree-heritability of psychotic MDD was 30.17% (95% CI 23.53-36.80%). While the genetic correlation between psychotic and non-psychotic MDD was high (0.82, 95% CI 0.73-0.92), the psychotic subgroup showed a higher genetic correlation with schizophrenia than non-psychotic MDD (0.67 vs 0.46, p-value 7.55∗10-4). Within 30,000 genotyped MDD cases, individuals with psychotic MDD had higher mean PRS for schizophrenia and BD but a lower MDD PRS than non-psychotic MDD. PRS for BD type-I was associated with increased odds of psychotic MDD, while BD type-II PRS showed no significant association with psychotic MDD. This study provides evidence for the genetic basis of psychotic MDD, underscoring its unique position bridging the spectrum of mood and psychotic disorders. These findings advance our understanding of the aetiology of psychotic MDD and contribute to the limited body of evidence on this phenotype by utilising large-scale population-based data. European Research Council; US National Institutes of Mental Health; European Union Horizon 2020 Program; Swedish Research Council; Research Council of Norway; Swedish Foundation for Strategic Research; Hjärnfonden.

Disparities and barriers in germline testing among patients with early-onset gastrointestinal cancers.

35 Background: Early-onset gastrointestinal cancers (EOGIC) are strongly associated with hereditary predisposition, making germline testing essential for treatment and familial risk management. Disparities in germline testing persist. This study investigates disparities and barriers to germline testing in EOGIC. Methods: This IRB-approved retrospective analysis included 864 patients aged 18-49 with GI cancers at the University of Chicago (2018-2023). Data collected included race, gender, age, insurance, family cancer history, and subtype. Outcomes were physician referrals for germline testing and completion. Chi-square tests and logistic regression models assessed predictors of recommendations and completion. Results: Of 864 patients, 473 (54.7%) received germline testing recommendations, and 323 (37.4%) completed testing. Completion rates: 30.2% for no insurance, 29.1% for Medicare/Medicaid, and 40.3% for private insurance (p=0.032). Patients with family history of cancer were more likely to be recommended for testing (62.9% vs. 39.5%, p<0.001) and complete it (44.0% vs. 23.7%, p<0.001). In our cohort, no significant racial disparities were observed (p=0.712 and p=0.358). Females were more likely to receive recommendations (59.1%) and complete testing (41.2%) than males (50.9% referral, 34.0% completion, p=0.016 and p=0.029). Patients under 30 had the highest rates of testing recommendation (66.1%) and completion (46.4%), followed by 30-39 (61.7%, 44.4%) and 40-49 (51.2%, 34.0%), p=0.006 and p=0.009. By cancer subtype, colorectal cancer (CRC) patients had the highest referral (66.1%) and completion (45.9%) rates, while anal cancer had the lowest (13.2% referral, 5.3% completion, OR 0.08, p<0.0001). Gastric cancer (52.3% referral, 29.2% completion, OR 0.49, p=0.005) and esophageal cancer (36.9% referral, 20.0% completion, OR 0.31, p<0.0001) also had lower testing rates. Liver cancer (35.4% referral, 27.1% completion, OR 0.38, p<0.0001) and cholangiocarcinoma (45.5% referral, 22.7% completion, OR 0.28, p=0.016) showed similarly low rates. Conclusions: Disparities in germline testing were seen among uninsured patients, males, and those with public insurance. CRC had the highest testing rates, while anal, esophageal, liver, and cholangiocarcinoma had lower rates, likely due to lower suspicion of hereditary predisposition. Targeted interventions are needed to improve testing uptake and completion, especially among uninsured and underrepresented populations.

Young Healthy Individuals With a First-Degree Relative With Type 1 Diabetes Displayed Adverse Lipid Changes.

Timeline of atherosclerosis in children with type 1 diabetes is unknown. We aimed to investigate if familial risk of type 1 diabetes is associated with pro-atherosclerotic changes. Young first-degree relatives to patients with paediatric type 1 diabetes and sex and age matching controls were enrolled at Skåne University Hospital, Sweden between 2006 and 2015. Conventional lipids, human leukocyte antigen DQ2/8, inflammatory biomarkers, and history of respiratory infections were determined. A total of 117 first-degree relatives and 43 controls were recruited (50% boys) at median of 13.4 years of age (IQR 8.0). Relatives had lower BMI Z-score (p = 0.03) and frequency of respiratory infections (p = 0.03) compared to controls, but higher low-density lipoprotein (LDL, p = 0.04) and total cholesterol (p = 0.01). In multivariable regression models adjusted for confounders LDL was 0.35 mmol/L higher (95% CI 0.10-0.61) and total cholesterol was 0.46 mmol/L higher (95% CI 0.15-0.77) in relatives. Relatives with ≥ 4 respiratory infections/year had higher LDL than controls with < 4 infections/year (p = 0.035). Human leukocyte antigen DQ2/8 frequency and inflammatory biomarkers did not differ between groups. Healthy young relatives to patients with type 1 diabetes display adverse lipid changes, probably related to their genetic susceptibility to this disease and recent respiratory infections.

A Systematic Review of the Literature on Risk Factors for Intimate Partner Violence From 2012 to 2023

The increasing body of studies on intimate partner violence (IPV) and its’ high prevalence worldwide signify heightened scholarly and societal interest. This is especially pertinent as IPV has recently penetrated broader contexts, including the digital world, and manifested in more diverse and complex forms. Building on Capaldi et al. (2012), this review aimed to provide a comprehensive understanding of emerging IPV risk factors by reviewing studies published from 2012 to 2023. We systematically reviewed 156 peer-reviewed articles published in English-speaking Western countries, utilizing a dynamic developmental systems perspective. The risk factors of IPV were organized into three domains: (a) contextual and demographic factors, such as age, gender, SES, and community contexts; (b) developmental characteristics, including family risk factors, history of IPV, peer-related factors, school- and work-related factors, psychological and behavioral factors, and cognition; and (c) relational characteristics, including relationship discord, conflict, and interactional patterns. This review expands on Capaldi et al.’s (2012) previous work by adopting more inclusive approaches, examining both perpetration and victimization, including sexual minority participants, incorporating technological forms of IPV, and utilizing comprehensive measures to provide a more thorough understanding of IPV. Furthermore, this review provides recommendations and future directions for practitioners, policymakers, and researchers working to address IPV.

Integrating BRCA testing into routine prostate cancer care: a multidisciplinary approach by SIUrO and other Italian Scientific Societies

Prostate cancer (PCa) ranks among the most prevalent malignancies in men, with notable associations to Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Lynch Syndrome, both linked to germline likely pathogenetic variant/pathogenetic variant (LPV/PV) in genes involved in DNA repair. Among these genes, BRCA2 in PCa patients is the most frequently altered. Despite progresses, challenges in BRCA carriers detection persist, with a quarter of PCa cases lacking family history.To address these challenges, a multidisciplinary expert panel from six Italian Scientific Societies, formulated a care pathway to integrate BRCA testing into routine clinical practice in different Italian geographical areas.The development process, promoted by the Italian Society of Uro-Oncology (SIUrO), involved three key stages. A preliminary meeting convened teams from different Italian regions to establish minimal requirements for a mini-counseling program (defined as a pre-test consultation carried out by clinicians responsible of patients’ management) and propose care pathway models. At the same time, a comprehensive survey was launched to highlight regional variations in BRCA testing and identify eventual obstacles to testing activities. A subsequent meeting synthesized care pathway proposals and formulated a unified framework, acknowledging regional legislative variations as enriching factors. Lastly, implementation of the unified framework was promoted by the project faculty and identified regional team leaders.Survey results revealed significant regional disparities in BRCA testing, reimbursement policies, and access to genetic counseling. The proposed mini-counseling program outlined essential steps for patient identification, information provision, and multidisciplinary review, aiming to streamline BRCA testing processes.Expert recommendations emphasized offering tumor genetic testing to metastatic PCa patients eligible for PARP-i treatment and outlined criteria for genetic counseling and germline testing. Key considerations included family history and tumor characteristics.In conclusion, the proposed care pathway represents a critical step towards integrating BRCA testing into routine PCa care, aiming to optimize patient management and familial risk assessment within the constraints of the Italian healthcare system.

P1297 Family History of Inflammatory Bowel Disease: Prevalence and Its Relationship with Clinical and Genetics Factors in Patients with Ulcerative Colitis and Crohn’s Disease in a SouthAmerican Cohort

Abstract Background Relatives of inflammatory bowel disease (IBD) patients have a higher risk of developing the condition than the general population. Approximately 12% of IBD cases are familial. We aim to evaluate the prevalence of family history of IBD (FH-IBD) in Crohn’s disease (CD) and ulcerative colitis (UC) patients, identify clinical characteristics linked to a higher FH-IBD risk, and develop a polygenic risk score (PRS) for FH-IBD. Methods Patients were recruited from a Chilean IBD referral center between 2019 and 2024, yielding clinical data from 412 individuals. The FH-IBD prevalence was based on affected first-degree relatives. Clinical characteristics were compared between groups with and without FH-IBD using chi-square and Mann-Whitney U tests. Significant variables were analyzed with univariate and multivariate methods, adjusted for age, sex, diagnosis age, and smoking. A subset of 232 IBD patients was genotyped with the Illumina Infinium array, and we constructed a FH-IBD polygenic risk score from IBD risk variants in European and Asian populations. Results A total of 16% (67/412) had FH-IBD: 15% (15/100) in the Crohn’s disease (CD) group and 16% (52/314) in the ulcerative colitis (UC) group. In the CD group, active smoking significantly increased the risk of FH-IBD, with 18% of patients without FH-IBD reporting a history of smoking compared to 47% with FH-IBD (p = 0.03). Diagnosis age differences per the Montreal classification showed that among those without FH-IBD, 4 (5%) were A1, 50 (60%) A2, and 30 (35%) A3; while in the FH-IBD group, 4 (26.5%) were A1, 4 (26.5%) A2, and 7 (47%) A3 (p = 0.01). In the UC group, 60 of 260 patients (23%) without FH-IBD had extraintestinal manifestations, compared to 23 of 52 (44%) with FH-IBD (p = 0.004). Hospitalization history was also more common in the FH-IBD group, at 56% (29/52) versus 38% (98/260) without FH-IBD (p = 0.01). Table 1 summarizes significant risk associations between clinical variables and FH-IBD for each disease, and Figure 1 presents the PRS for FH-IBD. Conclusion FH-IBD prevalence was 16%, aligning with existing literature. Active smoking in CD was significantly linked to FH-IBD, unlike in UC. A CD onset age of 17 to 40 years was associated with a lower FH-IBD risk. In UC, those with FH-IBD had higher rates of extraintestinal manifestations and hospitalization. A lower median PRS was observed in the FH-IBD group, but no significant differences emerged. Recognizing these risk factors emphasizes the need for a family approach in IBD assessment, which could enhance prevention and treatment strategies. Further studies are required to validate these findings. References Moller FT, Andersen V, Wohlfahrt J, Jess T. Familial risk of inflammatory bowel disease: a population-based cohort study 1977-2011. Am J Gastroenterol. 2015;110(4):564-571. doi:10.1038/ajg.2015.50 Liu Z, Liu R, Gao H, et al. Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries. Nat Genet. 2023;55(5):796-806. doi:10.1038/s41588-023-01384-0

Mental Health Issues Associated With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

The goal of this review is to move beyond summarizing what is known about psychosexual development in females with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency-commonly studied as a natural experiment to understand prenatal androgen effects in 46,XX individuals. Instead, it will explore the various aspects of the condition that significantly impact the daily lives of both male and female patients and their families, with a particular focus on the implications for psychosocial, educational, and vocational adaptation. This work represents a selective, yet balanced review of papers highlighting potential threats to positive psychological adaptation in both male and female individuals with CAH. This review outlines the effects of both cross-cutting risks (such as challenges related to parenting and healthcare management) and CAH-specific risks (including growth and appearance changes, psychiatric and neurocognitive issues, reduced reproductive function and interest in parenting, and masculinization in girls and women) on psychosocial adaptation. Opportunities for optimizing psychological outcomes of those with CAH are presented. Routine psychosocial screening of patient and family risk and resilience factors is recommended to identify areas of concern applicable to individual patients and families. Such screening should include assessment of both cross-cutting and condition-specific factors. This, in turn, provides a pathway forward for providing quality team-based patient-centered care.

Familial risk and phenotypic variation of sarcoidosis in the Icelandic population

BackgroundThe familial risk of sarcoidosis is heterogeneous, previous studies demonstrate conflicting results. The present study maps the pattern of familial distribution of all known, biopsy-verified sarcoidosis in the Icelandic population (1981–2021).MethodsAll cases were re-confirmed and categorized into one of the five phenotypic groups described by Schuppet al., and in different groups based on disease severity. Distant relationships were accurately traced for relatives of sarcoidosis patients and their mates using the nationwide Icelandic Genealogy Database. This allows creation of matched control groups for the calculation of Relative Risk (RR) and Kinship Coefficient (KC).Results462 patients with biopsy-proven diagnoses of sarcoidosis were included. We identified 282 extended families and seven sibling pairs with sarcoidosis. Twenty families had five or more affected individuals. RR was 3.7 (95%CI: 1.54–8.55) in 1st-degree relatives (p=0.003), 1.65 (1.05–1.92) in 4th-degree relatives, (p=0.014) and 1.57 (1.08–1.70) in 5th-degree relatives (p=0.003). RRs among 1st-5th degree relatives of the patients’ mates were not significant. KC for sarcoidosis was only significant for the first two meiosis (KC=1.06, p&lt;0.008 and KC=1.01, p=0.011, respectively). The most common sarcoidosis phenotypes were pulmonary-lymphonodal (47.6%), ocular-cardiac-cutaneous and central nervous system (OCCC) (21.6%), and musculoskeletal cutaneous (MSC) (20.9%). There seems to be no clustering of a single phenotype or resistant sarcoidosis in the extended sarcoidosis families.ConclusionOur study does not consider heritability a strong risk factor for sarcoidosis. The risk is highest for first-degree relatives of patients with sarcoidosis. Single phenotypes and resistant sarcoidosis do not cluster in distinct families.

Exploring family profiles in explaining heterogeneity in parenting program engagement and effectiveness.

Parenting programs have proven effective in reducing disruptive child behavior. However, not all families benefit equally, and, to date, we have little insight into who benefits more or less and why. One possible solution is to explore how different potential moderators cluster together in individual families and whether such family profiles predict who benefits more or less from these programs. This study explores (a) how family, child, and parenting risk factors for disruptive behavior cluster together in families enrolled in the popular and evidence-based Incredible Years Parenting Program using latent profile analyses; (b) how family profiles relate to covariate family characteristics; and (c) whether profiles predict program engagement (i.e., number of sessions attended by caregivers) and effectiveness of (i.e., pre-post changes in disruptive behavior). Individual participant data from six studies across four countries (Norway, the Netherlands, England, Portugal) were used, including a total sample of 772 families with children aged 2.5-9 years (M = 5.14; SD = 1.10; 58.0% boys). Families could be profiled into a low- and high-risk profile, which differed on most child and family (but not parenting) risk factors as well as on covariate family characteristics, such as severity of disruptive behavior. Profile membership predicted engagement in, but not effectiveness of, the program. These findings provide useful insights into the heterogeneity in families participating in parenting programs, although there is a need for further research on how such differences may relate to differences in program effectiveness. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

The prevalence and risk factors among people with diabetes mellitus in a selected rural community of kerala

The recent statistics of India in 2023 suggest a prevalence of 10.1 crores of diabetes in the community, with three in four adults with diabetes living in low- and middle-income countries, and half of them are unaware of their condition. This study aims to assess the prevalence of diabetes mellitus among people in a selected rural community and to identify the risk factors among people with diabetes mellitus.A quantitative research approach with a descriptive, cross-sectional study design was adopted. The participants were 824 adults, males, and females, aged above 21 years, and selected using a convenience sampling method. Data was collected from two selected wards of Athirampuzha panchayat, Kottayam, Kerala. Data were collected from a larger survey conducted in this area. The tool used was a structured questionnaire with three parts: a socio-demographic tool, lifestyle-related factors, and a specific part for collecting diabetes-related information. The results indicated that nearly 15.90% of the population had diabetes mellitus (n=131), and majority were above above 50 years. A majority of the diabetes-affected people were females (n 69, 52.67%), married (n= 104, 79.39%), unemployed (n =76, 58.02%), homemakers (n=72, 54.96%), and belonged to nuclear families (n=81, 61.83%). Most of them have been diagnosed with diabetes mellitus for the past 5-10 years and are on treatment with oral hypoglycemic agents (n=107, 81.68%). About 32% of them had familial risk factors (n=42). Among the comorbid conditions, 41.98% (n= 55) had hypertension. A majority of the participants were having a BMI above normal (51.15%, n-= 67, BMI=25.0 -29.9) and were following sedentary lifestyle habits (n=113, 86.26%). : The study highlight the importance of targeting the lifestyle risk factors for preventing diabetes mellitus in the community at an early stage.

Prenatal maternal stress in rats alters the epigenetic and transcriptomic landscape of the maternal-fetal interface across four generations

Prenatal maternal stress (PNMS) determines lifetime mental and physical health. Here, we show in rats that PNMS has consequences for placental function and fetal brain development across four generations (F0-F3). Using a systems biology approach, comprehensive DNA methylation (DNAm), miRNA, and mRNA profiling revealed a moderate impact of PNMS in the F1 generation, but drastic changes in F2 and F3 generations, suggesting compounding effects of PNMS with each successive generation. Both maternal and placental miRNA gene targets included de novo DNA methyltransferases, indicating robust PNMS-induced disruption in the complex epigenetic regulatory network between miRNAs and DNAm. Transgenerational programming mainly involved genes and biological pathways associated with neurological and psychiatric diseases which were linked to maternal-fetal crosstalk facilitated by the placenta. The highly correlated placenta-brain profiles support the use of placenta as a noninvasive biomarker resource to predict pathological changes in the neonatal brain. The transgenerational persistence of critical DNAm, miRNA and mRNA signatures may explain familial non-genetic disease risks.

Cross-species analysis of genetic architecture and polygenic risk scores for non-contact ACL rupture in dogs and humans

Non-contact anterior cruciate ligament (ACL) rupture is a common serious orthopaedic disease in humans and dogs. Familial risk has been recognized in both species but interactions between genetic effects and environmental risk are not understood. We investigated ACL rupture heritability, genetic architecture, selection pressure, sharing of risk genes and biological pathways, and polygenic risk score (PRS) prediction of disease risk. In both species, ACL rupture has moderate heritability, is likely under negative selection, and has a highly polygenic architecture where thousands of variant effects act together to influence disease risk. In dogs, we found hotspots of regional heritability. We also confirmed sharing of multiple risk genes. Our findings challenge the dogma that non-contact ACL rupture is predominantly due to a single overload injury event. Our results also suggest that accurate PRS prediction of ACL rupture risk is an achievable goal in both species, enabling identification of individuals for personalized medical care.

Menopausal hormone therapy is associated with worse levels of Alzheimer's disease biomarkers in APOE ε4-carrying women: An observational study.

Menopausal hormone therapy (MHT), along with the apolipoprotein E (APOE) ε4 allele, has been suggested as a possible risk factor for Alzheimer's disease (AD). However, the relationship between MHT and cerebrospinal fluid (CSF) biomarkers is unknown: we investigated this association, and whether APOE ε4 carrier status moderates it. In an observational study of 136 cognitively unimpaired female participants (Mage=66.0; standard deviation=6.3), we examined whether MHT use alone or in interaction with APOE ε4 carrier status was associated with CSF levels of phosphorylated tau (p-tau), amyloid beta (Aβ)40, Aβ42, p-tau/Aβ42, and Aβ42/40 ratios. Significant interactions were found between APOE ε4 and MHT use for CSF biomarkers. APOE ε4 carriers who were MHT users showed worse levels of CSF p-tau/Aβ42 and Aβ42/40 ratios than all other users and non-users. The presence of both APOE ε4 and MHT may be associated with elevated amyloid deposition and AD pathology in this sample of participants who demonstrated high familial AD risk. Significant interactions were found between apolipoprotein E (APOE) ε4 and menopausal hormone therapy (MHT) use for cerebrospinal fluid (CSF) phosphorylated tau (p-tau)/amyloid beta (Aβ)42 and Aβ42/40 ratios. APOE ε4 carriers who were MHT users showed worse levels of CSF biomarkers than non-users and non-carriers, both users and non-users. Younger age at MHT initiation was associated with worse levels of the p-tau/Aβ42 and Aβ42/40 ratios in carriers only. The presence of both APOE ε4 carriage and MHT use may be associated with elevated amyloid deposition and AD pathology. Further studies with larger sample sizes are necessary to confirm the differences observed in the current study.

Optimizing Engagement: Factors Influencing Family Participation in a Positive Parenting Program among Vulnerable Households with Young Children.

Objective: This paper addresses a critical gap in family research by examining the risk of families with young children receiving the Minimum Living Income (MLI) in rejecting targeted social interventions, also known as non-take-up (NTU). Method: We analyze recruting process data from the first invitation to participate in a social benefit including the "Growing Happily in the Family-2" program developed in Madrid, Spain, to their written consent prior to its implementation. Measurements of subjective factors reported as reasons for NTU and objective factors of sociodemographic characteristics and detailed household patterns of prior engagement with social services to study NTU response were based on official records and project data. Results: Descriptive findings reveal that jobless parents with high economic hardship, poorer physical and mental health, heavy demanding childbearing, and poor family-job conciliation aggravated by adverse life events profile the NTU response. Linear probability models predicting the rejection/acceptance decision showed that lack of previous contact with the social services, younger parental age, male, and nonimmigrant status significantly elevate NTU risk. Notably, although a longer stay in social services increases the probability of NTU, this does not occur among the most vulnerable families that have received more intensive support, challenging the idea of intervention fatigue. Conclusions: These findings have implications for the design of policies and practices to support children and family as subjects of rights, underlining the need for preventive and capacity-building strategies that address specific barriers to program uptake. Overall, the study highlights innovation areas that lie in the interception of social and employment benefits to improve the reach of the intended population and the positive impact of parenting interventions aimed at supporting vulnerable families.

Poverty exposure and poverty persistence for large families in Western Europe. A dynamic perspective

AbstractThis paper investigates income poverty in 14 Western European countries from 2004 to 2019, utilizing European statistics on income, social inclusion and living conditions longitudinal data. The study employs descriptive tables and panel regression models to examine poverty exposure and accumulation of poverty events over time for families with dependent children with a focus on large families with three and four or more children. The findings reveal that in all countries the reiteration of poverty spells, net of persistence dynamics, primarily results from higher risks for large families of falling back into poverty. The analysis shows large families experience carousels of poverty reoccurrence, especially among single‐earner households. All in all, analyses suggest the necessity for integrated social policies for large families, combining timely social transfers to mitigate current spells of poverty, with mid‐term follow‐up programs in the form of preventive measures tailored to families with recent poverty experiences.

The Evaluation of Change in Psychosocial Risk With Caregivers of Children With Chronic Kidney Disease: A Short-term Longitudinal Mixed-Methods Study.

The COVID-19 pandemic and its accompanying safeguards intensified many of the ongoing daily challenges faced by caregivers of young people with chronic kidney disease (CKD) both pre-transplant and post-transplant, and also created a variety of new and pressing concerns. Little is known about how these families managed this unexpected adversity in their lives. To evaluate change in psychosocial risk for families of young people with CKD during the COVID-19 pandemic health emergency from the perspective of caregivers. A short-term longitudinal mixed-methods study with a convergent parallel design. Manitoba, Canada. Thirty-six caregivers of young people with CKD participated in a quantitative assessment prior to the pandemic; approximately half were transplant recipients. Thirteen were re-assessed during the pandemic (62% were caregivers of transplant recipients) using both qualitative and quantitative assessments. First, caregivers completed the Psychosocial Assessment Tool (PAT) prior to the pandemic. Second, caregivers were re-assessed using the PAT during the pandemic. They were also interviewed about their experiences. Changes in PAT scores over time were evaluated, including an investigation of whether psychosocial risk was related to transplant status. Interviews were coded using thematic analysis. In the interpretation stage, the qualitative findings were combined with the quantitative results to help explain the latter and reach a more fulsome understanding of caregivers' experience. Quantitatively, overall family psychosocial risk scores increased significantly during the pandemic health emergency, as did the domain of Caregiver Problems. Families of transplant recipients were found to be at significantly lower psychosocial risk pre-pandemic than families of transplant candidates. Coding identified Negative Pandemic Experiences, Positive Pandemic Experiences, and Coping Mechanisms. Mixed-methods analyses revealed several areas of convergence and divergence between the quantitative and qualitative findings. Limitations included a small sample size that limited generalizability, single site data collection, and single caregiver report. Although overall family psychosocial risk increased during the pandemic, caregivers described several resilience processes and characteristics. A mixed-method approach provided a unique perspective that highlighted the value of integrating quantitative and qualitative findings. Results were discussed within the pediatric psychosocial preventive health model framework.