Familial Transmission Research Articles

Paternal alcohol exposure reduces acquisition of operant alcohol self-administration and affects Bdnf DNA methylation in male and female offspring.

Familial transmission of alcohol use disorder reflects genetic and environmental factors. Paternal alcohol exposure may affect rodent offspring via epigenetic modifications transmitted through the male germ line. While such exposure alters alcohol sensitivity in mouse offspring, no studies examined if it impacts the development of operant alcohol self-administration in rats. We exposed male (sires) Wistar rats to chronic intermittent ethanol in vapour chambers (16 h/day; 5days/week) or to air for 6weeks. Eight weeks later, rats were mated with alcohol-naive females. Adult alcohol- and control-sired F1 offspring were assessed in acquisition of alcohol self-administration in which increasing alcohol concentrations (2.5%, 5% and 10%, v/v) were delivered after one lever press (fixed ratio 1 or FR1). Prior to alcohol sessions, rats were trained to lever press for food delivery under an FR1 schedule of reinforcement. DNA methylation levels of the brain derived neurotrophic factor (Bdnf) gene were measured in sperm, nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) in sires and in offspring. Alcohol-exposed sires had lower Bdnf DNA methylation levels in NAc and greater methylation levels in mPFC. Although this pattern was not recapitulated in offspring, alcohol-sired offspring of both sexes did show aberrant Bdnf DNA methylation patterns compared to control-sired offspring. Alcohol-sired offspring self-administered less alcohol (5% and 10%) with no group differences in food responding. Results indicate that paternal alcohol exposure prior to conception protects against alcohol's initial reinforcing effects but the pattern of dysregulated Bdnf methylation in reward-related circuitry did not mimic changes seen in sires.

Parental Factors Related to Adolescent Girls' Suicide Attempts: A Cross-Sectional Study from 2015 to 2018.

Adolescent suicide is a serious global health concern. Although familial transmission of suicidal behaviors has been identified in previous research, the effects of parental gender remain unknown. This study identified the influence of parental suicidal behaviors on suicide attempts among adolescent girls. We collected data through a cross-sectional, nationwide, population-based survey in South Korea and evaluated data from 890 adolescent girls (aged 12–18 years) who had attempted suicide and their parents. Hierarchical logistic regression was used to analyze the risk factors related to suicide attempts among adolescent girls. The final model indicated that mothers’ suicidal plans and attempts (OR = 6.39, OR = 12.38, respectively) were important risk factors for suicide attempts in adolescent girls. Future studies should identify specific methods for effective prevention and treatment through path analysis of the related factors affecting suicidal behavior of adolescents according to their parents’ gender.

Vital personality scores and healthy aging: Life-course associations and familial transmission

ObjectivesPersonality traits are linked with healthy aging, but it is not clear how these associations come to manifest across the life-course and across generations. To study this question, we tested a series of hypotheses about (a) personality-trait prediction of markers of healthy aging across the life-course, (b) developmental origins, stability and change of links between personality and healthy aging across time, and (c) intergenerational transmission of links between personality and healthy aging. For our analyses we used a measure that aggregates the contributions of Big 5 personality traits to healthy aging: a “vital personality” score. MethodsData came from two population-based longitudinal cohort studies, one based in New Zealand and the other in the UK, comprising over 6000 study members across two generations, and spanning an age range from birth to late life. ResultsOur analyses revealed three main findings: first, individuals with higher vital personality scores engaged in fewer health-risk behaviors, aged slower, and lived longer. Second, individuals’ vital personality scores were preceded by differences in early-life temperament and were relatively stable across adulthood, but also increased from young adulthood to midlife. Third, individuals with higher vital personality scores had children with similarly vital partners, promoted healthier behaviors in their children, and had children who grew up to have more vital personality scores themselves, for genetic and environmental reasons. ConclusionOur study shows how the health benefits associated with personality accrue throughout the life-course and across generations.

Cultural transmission and perception of vessel shapes among Hebron potters

While craft apprenticeship can be understood as socially mediated individual learning, the ensuing prediction of individual and cultural object traits within craft communities has not been investigated. Here we provide an assessment of vessel shape variations occurring through cultural transmission and their visual perception by the craftsmen. To this end, 26 Hebron potters distributed through nine familial transmission units were asked to produce vessels of three different pottery types, then 21 of the participants were invited to visually identify their proper vessels and those of five other potters. We used the Elliptical Fourier method to analyze vessel shape variation among the productions. Our findings demonstrated that the learning process modified the ceramic shape, the cultural morphological traits being combined with new individual traits. Moreover, the individual morphological traits overtook the cultural ones, which is supposed to lead to divergence of vessel shapes within the transmission chain. If certain cultural morphological traits perpetuate through generations, this certainly does not result from fidelity copying occurring through learning but from stabilizing mechanisms such as consumer demand. Our results showed that potters do perceive the subtle same-type vessel shape variations and thereby could select the individual variant they prefer to produce.

Parent–offspring variation transmission in full-sib families revealed predominantly paternal inheritance of chloroplast DNA in Pinus massoniana (Pinaceae)

Parent–offspring variation transmission in full-sib families revealed predominantly paternal inheritance of chloroplast DNA in Pinus massoniana (Pinaceae)

The role of CTCF in the organization of the centromeric 11p15 imprinted domain interactome.

DNA methylation, chromatin-binding proteins, and DNA looping are common components regulating genomic imprinting which leads to parent-specific monoallelic gene expression. Loss of methylation (LOM) at the human imprinting center 2 (IC2) on chromosome 11p15 is the most common cause of the imprinting overgrowth disorder Beckwith-Wiedemann Syndrome (BWS). Here, we report a familial transmission of a 7.6 kB deletion that ablates the core promoter of KCNQ1. This structural alteration leads to IC2 LOM and causes recurrent BWS. We find that occupancy of the chromatin organizer CTCF is disrupted proximal to the deletion, which causes chromatin architecture changes both in cis and in trans. We also profile the chromatin architecture of IC2 in patients with sporadic BWS caused by isolated LOM to identify conserved features of IC2 regulatory disruption. A strong interaction between CTCF sites around KCNQ1 and CDKN1C likely drive their expression on the maternal allele, while a weaker interaction involving the imprinting control region element may impede this connection and mediate gene silencing on the paternal allele. We present an imprinting model in which KCNQ1 transcription is necessary for appropriate CTCF binding and a novel chromatin conformation to drive allele-specific gene expression.

SARS-CoV-2 seroprevalence in students and teachers: a longitudinal study from May to October 2020 in German secondary schools

ObjectiveTo quantify the number of SARS-CoV-2 infections in secondary schools after their reopening in May 2020.DesignRepeated SARS-CoV-2 seroprevalence study after the reopening of schools and 4 months later.SettingSecondary school in...

Behavioral and Neural Markers of Reward Processing Deficits in Adolescents at High Familial Risk for Depressive Disorders

A parental history of major depressive disorder (MDD) is a well-established risk factor for adolescent MDD, thus elucidating the mechanisms associated with familial risk transmission is critical. Reward processing abnormalities has emerged as a promising candidate mechanism. The aim of this study was to test behavioral measures of reward responsiveness and underlying frontostriatal resting activity in healthy adolescents with (high-risk) versus without (low-risk) a maternal history of MDD.

Event centrality and secondary traumatization among Holocaust survivors' offspring and grandchildren: A three-generation study

The present study examined the intergenerational transmission of the Holocaust trauma in relation to levels of secondary traumatization and event centrality across three generations in a cross-sectional survey. Participants included 92 Holocaust survivor-offspring-grandchild triads (Holocaust G1-G2-G3) and 67 comparison triads (Comparison G1-G2-G3). Holocaust G1 reported higher levels of post-traumatic stress disorder (PTSD) symptoms relative to Comparison G1. Holocaust G2 and G3 reported significantly higher secondary traumatization relative to Comparison G2 and G3, respectively. Holocaust G3 also reported significantly higher scores in event centrality relative to Comparison G3. In survivor families, the indirect effect of PTSD symptoms in Holocaust G1 predicted Holocaust G2's secondary traumatization, which subsequently predicted Holocaust G3's secondary traumatization. Moreover, PTSD symptoms in Holocaust G1 predicted Holocaust G3's event centrality through secondary traumatization in both Holocaust G2 and G3 and event centrality in Holocaust G2. In the comparison groups, trauma transmission was not observed in three generations. Findings elucidate unique intergenerational transmission of the Holocaust trauma in survivor families, which comprise both personal and societal constituents. Moreover, the findings show that event centrality is a distinctive mechanism in intergenerational transmission in survivor families.

A qualitative study of physician perceptions and experiences of caring for critically ill patients in the context of resource strain during the first wave of the COVID-19 pandemic

BackgroundThe COVID-19 pandemic has led to global shortages in the resources required to care for critically ill patients and to protect frontline healthcare providers. This study investigated physicians’ perceptions and experiences of caring for critically ill patients in the context of actual or anticipated resource strain during the COVID-19 pandemic, and explored implications for the healthcare workforce and the delivery of patient care.MethodsWe recruited a diverse sample of critical care physicians from 13 Canadian Universities with adult critical care training programs. We conducted semi-structured telephone interviews between March 25–June 25, 2020 and used qualitative thematic analysis to derive primary themes and subthemes.ResultsFifteen participants (eight female, seven male; median age = 40) from 14 different intensive care units described three overarching themes related to physicians’ perceptions and experiences of caring for critically ill patients during the pandemic: 1) Conditions contributing to resource strain (e.g., continuously evolving pandemic conditions); 2) Implications of resource strain on critical care physicians personally (e.g., safety concerns) and professionally (e.g. practice change); and 3) Enablers of resource sufficiency (e.g., adequate human resources).ConclusionsThe COVID-19 pandemic has required health systems and healthcare providers to continuously adapt to rapidly evolving circumstances. Participants’ uncertainty about whether their unit’s planning and resources would be sufficient to ensure the delivery of high quality patient care throughout the pandemic, coupled with fear and anxiety over personal and familial transmission, indicate the need for a unified systemic pandemic response plan for future infectious disease outbreaks.

A Nationwide Cohort Study of Nonrandom Mating in Schizophrenia and Bipolar Disorder.

Nonrandom mating in parents with schizophrenia or bipolar disorder increases the population-level genetic variance among the offspring generation and creates familial (risk) environments likely to be shaped by specific conditions. The objective of this study was to investigate the occurrence of mental disorder and levels of cognitive and social functioning in individuals who have children by partners with schizophrenia or bipolar disorder compared to controls. The Danish High Risk and Resilience Study VIA 7 is a population-based cohort study conducted in Denmark between 2013 and 2016. This study focus on parents diagnosed with schizophrenia (n = 150) or bipolar disorder (n = 100) and control parents (n = 182), as well as their partners without schizophrenia or bipolar disorder (n = 440). We used linear mixed-effect models, and main outcomes were mental disorders, intelligence, processing speed, verbal working memory, and social functioning. We found that parents having children by a partner with schizophrenia or bipolar disorder more often fulfilled the criteria for a mental disorder and had poorer social functioning compared to parents having children by a partner without schizophrenia or bipolar disorder. Furthermore, parents having children by a partner with schizophrenia performed poorer on processing speed compared to parents in the control group. The presence of nonrandom mating found in this study has implications for our understanding of familial transmission of these disorders and our findings should be considered in future investigations of potential risk factors for children with a parent with schizophrenia or bipolar disorder.

Painful papules on the dorsum of the tongue

A 10-year-old boy presented with a 5-day history of a painful eruption of the tongue, accompanied by difficulty in feeding, excessive salivation and intermittent fever. Physical examination revealed multiple pink papules on the anterior part of the dorsum of the tongue (Fig. 1). There were no other mucosal, labial or skin lesions. He had submental and submandibular lymphadenopathy. What is the most likely diagnosis? (Answer on page ••) The topography of the lesions corresponded to the location of fungiform papillae. A clinical diagnosis of eruptive familial lingual papillitis (EFLP) was made. The eruption resolved spontaneously within 5 days. EFLP is an acute inflammatory condition involving the fungiform papillae of the tongue that affects especially children, with a median age of 3.5 years.1 Although the exact aetiology is unknown, viral infections have been suggested as a trigger factor.2 Clinically, EFLP is characterised by an acute onset of multiple erythematous, whitish to yellow or pink papules that correspond to enlarged fungiform papillae. The eruption involves typically on the tip, the lateral borders and/or the dorsum of the tongue.3 Pain, burning or itch, difficulty in feeding and excessive salivation are usually associated. Fever and cervical lymphadenopathy may also be noted. Familial transmission is possible.2 In our case, no other family members had experienced a lingual eruption. Spontaneous resolution is seen in 1 day to 3 weeks. However, recurrence is possible.1

Philipp Jolly and his 1913 "the heredity of psychosis": Homogeneity versus heterogeneity of familial transmission and an early look at Mendelian models for manic-depressive illness and dementia praecox.

Philipp Jolly's 1913 extensive monograph "The Heredity of Psychoses" provides, in both his detailed literature review and new pedigree study, an extensive assessment of a key issue in the psychiatric genetics of his day: the degree to which the familial transmission of psychiatric disorders was specific (or homogeneous) versus nonspecific (or heterogeneous). Contrary to a number of earlier observations, Jolly concludes that heterogeneous transmission is rare. Multiple psychiatric disorders can occur in one family because members of a family may have elevated predispositions to more than one disorder rather than one predisposition which increases risk for a wide range of conditions. A notable exception to this, he notes, is within manic-depressive illness (MDI), where different forms of illness run together within families. Jolly is also among the earliest investigators to evaluate simple Mendelian models for MDI and dementia praecox (DP). While his methods were primitive and contained only "eye-ball" examinations rather than statistical modeling, Jolly demonstrated considerable conceptual sophistication in the early application of such models. He concludes that DP is likely a recessive disorder. MDI, he states, is either a recessive condition or demonstrates "gender-based dominant heredity" where heterozygote females are affected, and heterozygote males are not.

Effectiveness of family-focused home visiting for maternal mental illness: A systematic review and meta-analysis.

WHAT IS KNOWN ON THE SUBJECT?: Maternal mental illness reduces a mothers' ability to bond with their infant and may adversely affect other family members. Family-focused practice is an approach which has the potential to support mothers with mental illnesses and reduce the risk of familial transmission of mental illness to children. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Findings suggest that current interventions are not effective in reducing depression or stress among mothers. The majority of interventions included in this review employed relatively low levels of family-focused practice. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: While there is a growing integration of family-focused practice into home visiting guidelines, this may be based on poor evidence. There is a need for the development of rigorously tested interventions which seek to include the whole family. ABSTRACT: Introduction The evidence on effectiveness of family-focused home visiting for maternal mental illness has yet to be comprehensively synthesized. Aim The aim of this study was to assess current home visiting treatments and interventions for mothers with mental illness and their families. Method The primary and secondary outcomes of interest were depression and maternal stress, respectively, both were included in meta-analyses. We identified 13 (n=5,540 participants) studies which met inclusion criteria. Eight studies were included in meta-analyses; five studies were reported narratively. Results Findings from the meta-analysis suggest that home visiting interventions are not effective in reducing depression (SMD -0.13, 95% CI -0.33 to 0.07, p=.21) and maternal stress (MD 0.59, 95% CI -5.19 to 6.38, p=.84). Discussion and Implications for practice Findings suggest that current interventions are not effective in reducing depression or stress among mothers. While there is a growing integration of family-focused practice into home visiting guidelines, this may be based on poor evidence.

MITF p.Arg217Thr Variant Identified in a Han Chinese Family with Tietz/Waardenburg Syndrome

Waardenburg syndrome (WS) is a group of rare genetic disorders characterized by hearing loss, changes in coloring of hair, skin, and eyes, and alterations in the shape of the face. Tietz syndrome is another rare disorder which presented similar phenotypes to WS. Patients with Tietz/Waardenburg syndrome often present with pale blue eyes, albino skin, and distinctive hair coloring, such as a patch of white hair or hair that prematurely turns gray. At present, more than six candidate genes are responsible for four types of Waardenburg syndrome and Tietz syndrome. This study is aimed at identifying the pathogenic gene variants in a three-generation Han Chinese family with hearing loss, blue-gray iris, albino skin, and white hair. In order to discover the molecular genetic lesion underlying the disease phenotype, whole exome sequencing in the proband, with Tietz/Waardenburg syndrome phenotypes, of a Han Chinese family from HeBei, China, was conducted. A novel heterozygous c.650G>C/p.Arg217Thr variant in melanocyte inducing transcription factor (MITF) was identified. Sanger sequencing further validated that this mutation existed in three affected individuals and absent in healthy family members. Bioinformatics analysis predicted that this mutation was deleterious. Our study further identified the genetic lesion of the family. Simultaneously, our study may also contribute to genetic counseling, embryonic screening of in vitro fertilized embryos, and prenatal genetic diagnosis of patients with Tietz/Waardenburg syndrome, especially for the proband, unmarried and unpregnant women, to reduce familial transmission in this Han Chinese family.

Sars-Cov-2 Transmission in Family: Study of 18 Families and 51 People without Asymptomatic Secondary Cases in a General Medicine Clinic of Toledo (Spain). Social Factors Lose Importance in Families without Asymptomatic Cases

Sars-Cov-2 Transmission in Family: Study of 18 Families and 51 People without Asymptomatic Secondary Cases in a General Medicine Clinic of Toledo (Spain). Social Factors Lose Importance in Families without Asymptomatic Cases

'I Think it Highly Necessary to Have it Done Before They Go Out into the World': Inoculation, Responsibility and Patterns of Familial Transmission of Smallpox

This paper examines two research streams. First, it will discuss some contemporary familial perspectives on smallpox inoculation in the eighteenth century. This is followed by a look at the level of provision of the practice in Oxfordshire and some of its contiguous counties. Second, the paper will present some findings on the nature of the transmission of smallpox during local early eighteenth century epidemics in Banbury, Oxfordshire and Aynho, Northamptonshire. Finally, the paper will put forward some conclusions which encompass these two streams.

Shapes of Subcortical Structures in Adolescents With and Without Familial History of Substance Use Disorder

Background: To explore if intergenerational transmission of risk for substance use disorder (SUD) manifests in brain anatomy of substance naive adolescents. Differences in anatomical shapes of subcortical structures (SSS) have been detected in neuroimaging studies, even in the absence of volume differences and SSS have been shown to be heritable. Therefore, we examined if the SSS of adolescents with a family history (FH+) of SUD differed from the SSS of adolescents without a family history of SUD (FH-). Because risk for SUD is associated with anxiety and impulsivity, we also examined correlations between these psychological characteristics and SSS. Methods: Using structural MRI, we obtained indices of SSS from 64 FH+ and 58 FH- adolescents and examined group differences and correlations between shape indices, trait anxiety and impulsivity. Findings: FH+ adolescents had a significant inward deformation in the shape of the right anterior hippocampus compared to FH- adolescents, while the volume of the right anterior hippocampus did not differ. Compared to FH- adolescents, the shape deformation of the brainstem, amygdala, hippocampus, putamen, pallidum and nucleus accumbens of FH+ adolescents exhibited an inverted correlational pattern with trait anxiety and impulsivity. Interpretation: SSS appears to capture anatomical features that traditional volumetric analysis does not. The inward shape deformation in the right anterior hippocampus in the FH+ adolescents may be related to the known increased risk for behavioral dysregulation leading to SUD in FH+ offspring. This novel approach may reveal neural correlates of familial transmission of increased vulnerability to problematic substance use. Funding Statement: This study was supported in part by NIDA (5R01 DA038154, PI: Christina W. Hoven) Declaration of Interests: No authors report any financial relationships with commercial interests. Ethics Approval Statement: The New York State Psychiatric Institute’s Institutional Review Board approved this study, and informed consent/assent was obtained from every participant.

Introduction to the special section on the intergenerational transmission of risk for substance use.

Six original research papers were submitted to this Special Section to address questions regarding the intergenerational transmission of risk for cannabis and other substance use. Study teams recruited youth in Iowa, Washington, Oregon, New York, and Arizona in the 1980s-1990s, assessed them into adulthood, and recruited their partners and offspring for another study. All of the studies assessed substance use in 2 or more generations. Other strengths in this section include the strong representation of fathers, the demographic diversity of the samples as a whole, and the demonstrations of varied statistical and replication approaches. The findings highlight features of parental histories of cannabis use during adolescence that are associated with their children's risk for cannabis use and factors that explain or weaken intergenerational similarities. Two groups of prevention scholars also offered commentaries on the implications of these studies for prevention and training, and collaboration. It is hoped that the Special Section will stimulate new hypotheses, replications, and communication among etiological and prevention researchers. Furthermore, the papers highlight that the familial transmission of substance use risk should be taken into account more fully in the design of prevention programs to maximize impacts for youth as well as their future offspring. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Prehistory of Psychiatric Genetics: 1780–1910

While psychiatric genetics has emerged as one of our most dynamic research fields, the historical context in which we view these developments is limited. To provide such a perspective, the author reviews 48 representative texts, published from 1780 to 1910, examining the inheritance of insanity. Six main conclusions emerge. First, most authors viewed heredity as among the strongest risk factors for insanity. Second, most writers concluded that a predisposition to illness rather than the illness itself was transmitted in families. Third, the probabilistic nature of the transmission was noted, as insanity often skipped generations or affected only a few of many siblings. Fourth, authors discussed the homogeneity versus heterogeneity of familial transmission of the various forms of insanities. Heterogeneous transmission was usually seen as the rule-with relatives of insane patients affected with a wide variety of psychiatric, and sometimes neurological, illnesses. Homogeneous transmission ("like begets like") was the exception. Fifth, writers noted that odd and eccentric personality features were common in the relatives of their insane patients. Finally, inheritance was commonly understood to include prior environmental parental experiences, and some authors noted that parent-offspring transmission of insanity could arise from psychological or intrauterine effects. Many of these conclusions, arising solely from clinical experience and without an understanding of biological mechanisms, statistical analyses, or necessary controls, are supported by later, more rigorous methods. Rather than entirely rejecting its value, we might view this literature as a complementary resource, likely more biased, but suffused with the extensive clinical knowledge of our forebears.