A splice site variant in MADD affects hormone expression in pancreatic ß cells and pituitary gonadotropes.

MAPK activating death domain (MADD) is a multifunctional protein regulating small GTPases RAB3 and RAB27, MAPK signaling, and cell survival. Polymorphisms in the MADD locus are associated with glycemic traits, but patients with biallelic variants in MADD manifest a complex syndrome affecting nervous, endocrine, exocrine, and hematological systems. We identified a homozygous splice site variant in MADD in 2 siblings with developmental delay, diabetes, congenital hypogonadotropic hypogonadism, and growth hormone deficiency. This variant led to skipping of exon 30 and in-frame deletion of 36 amino acids. To elucidate how this mutation causes pleiotropic endocrine phenotypes, we generated relevant cellular models with deletion of MADD exon 30 (dex30). We observed reduced numbers of ß cells, decreased insulin content, and increased proinsulin-to-insulin ratio in dex30 human embryonic stem cell-derived pancreatic islets. Concordantly, dex30 led to decreased insulin expression in human ß cell line EndoC-ßH1. Furthermore, dex30 resulted in decreased luteinizing hormone expression in mouse pituitary gonadotrope cell line LßT2 but did not affect ontogeny of stem cell-derived GnRH neurons. Protein-protein interactions of wild-type and dex30 MADD revealed changes affecting multiple signaling pathways, while the GDP/GTP exchange activity of dex30 MADD remained intact. Our results suggest MADD-specific processes regulate hormone expression in pancreatic ß cells and pituitary gonadotropes.

Saviour siblings in India: A reminder of our existing challenges and biases.

Saviour babies or saviour siblings are conceived specifically to be sources of biological materials - ranging from cord blood, stem cells or even organs - to save another child, usually an older sibling, who is suffering from a disease like thalassemia that can be cured with this biological material. In 2020, the media reported about the birth of India's first saviour baby, in the state of Gujarat [1]. In January 2023, there was a report of the birth of another saviour baby, in the state of Maharashtra [2]. Ethical concerns relating to saviour siblings find a place in the western bioethics discourse. However, it is little discussed in the Indian context.

Sibling adjustment to diabetes and educational needs: A literature review.

ABSTRACT: As cases of type 1 diabetes mellitus (T1DM) increase, so do their impact on sibling relationships. This literature review of four databases from 2010 to 2024 discusses findings from five studies and the themes that emerged: education needs and family functioning. Improvements in family-centered care and education are needed for siblings of children with T1DM.

Frequency of vitamin D deficiency in children with iron deficiency anaemia and factors associated with vitamin D deficiency.

Objective: To evaluate vitamin D deficiency in children with iron-deficiency anaemia, and to identify the risk factors for such deficiency. METHODS: The cross-sectional study was conducted at the Children's Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from October 2021 to March 2022, and comprised children aged 1-5 years who had been diagnosed with iron-deficiency anaemia. Quantitative variables, like age, height, weight, gender, socioeconomic status and sibling status, were controlled by stratification. Data was compared to assess the risk factors of vitamin D deficiency among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 236 children with iron-deficiency anaemia, 159(67.5%) also had vitamin D deficiency; 95(59%) girls and 65(41%) boys. Overall, 104(65.4%) subjects were aged 4-5 years and 55(34.6%) were aged 1-3 years. Vitamin D deficiency had significant association with female gender, older age, height and weight <5th centiles, educated parents, low to middle socioeconomic status, urban residence and higher number of siblings (p<0.05). CONCLUSIONS: The prevalence of vitamin D deficiency among children with iron-deficiency anaemia was found to be high.

The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives.

BACKGROUND: Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance. METHODS: We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals. RESULTS: First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills. LIMITATIONS: We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis. CONCLUSIONS: Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles.

Follow-up report of fundus findings of tuberous sclerosis-associated retinal astrocytoma of two siblings.

A late adolescent with tuberous sclerosis (TS) presented with reduced vision in one eye to our tertiary care university hospital 4 years ago. Fundus examination revealed multiple retinal astrocytic hamartomas (RAHs) in both eyes. His younger sibling, who also had TS, was found to have RAH on retinal screening. The swept-source optical coherence tomography (SS-OCT) findings were typical of RAH. We further noted that some of the RAH lesions showed segmental whitening of the outer walls of the arterioles, which traversed through them. The segmental whitening may suggest the enveloping of normal retinal vessels by the tumour. En-face and B-scan SS-OCT angiography of patients with TS showed vascularity within the tumour. The vessels within the tumour appeared to be in continuity with the retinal vasculature. Both siblings were reviewed annually. At the end of 4 years, there was no change in visual acuity, tumour size, number, vascularity and behaviour.

Analysis of admixed Greenlandic siblings shows that the mean genotypic values for metabolic phenotypes differ between Inuit and Europeans.

BACKGROUND: Disease prevalence and mean phenotype values differ between many populations, including Inuit and Europeans. Whether these differences are partly explained by genetic differences or solely due to differences in environmental exposures is still unknown, because estimates of the genetic contribution to these means, which we will here refer to as mean genotypic values, are easily confounded, and because studies across genetically diverse populations are lacking. METHODS: Leveraging the unique genetic properties of the small, admixed and historically isolated Greenlandic population, we estimated the differences in mean genotypic value between Inuit and European genetic ancestry using an admixed sibling design. Analyses were performed across 26 metabolic phenotypes, in 1474 admixed sibling pairs present in a cohort of 5996 Greenlanders. RESULTS: After FDR correction for multiple testing, we found significantly lower mean genotypic values in Inuit genetic ancestry compared to European genetic ancestry for body weight (effect size per percentage of Inuit genetic ancestry (se), -0.51 (0.16) kg/%), body mass index (-0.20 (0.06) kg/m2/%), fat percentage (-0.38 (0.13) %/%), waist circumference (-0.42 (0.16) cm/%), hip circumference (-0.38 (0.11) cm/%) and fasting serum insulin levels (-1.07 (0.51) pmol/l/%). The direction of the effects was consistent with the observed mean phenotype differences between Inuit and European genetic ancestry. No difference in mean genotypic value was observed for height, markers of glucose homeostasis, or circulating lipid levels. CONCLUSIONS: We show that mean genotypic values for some metabolic phenotypes differ between two human populations using a method not easily confounded by possible differences in environmental exposures. Our study illustrates the importance of performing genetic studies in diverse populations.

Assessing structural models of neighborhood and family sociodemographic characteristics and their relations with externalizing psychopathology.

Externalizing psychopathology has been found to have small to moderate associations with neighborhood and family sociodemographic characteristics. However, prior studies may have used suboptimal operationalizations of neighborhood sociodemographic characteristics and externalizing psychopathology, potentially misestimating relations between these constructs. To address these limitations, in the current study we test different measurement models of these constructs and assess the structural relations between them. Using a population-representative sample of 2,195 twins and siblings from the Georgia Twin Study and data from the National Neighborhood Data Archive and 2000 U.S. Census, we assessed the fit of competing measurement models for family sociodemographic, neighborhood sociodemographic, and neighborhood environment characteristics. In structural models, we regressed a general externalizing dimension on different operationalizations of these variables separately and then simultaneously in a final model. Latent variable operationalizations of family sociodemographic, neighborhood sociodemographic, and neighborhood environment characteristics explained no more variance in broad externalizing psychopathology than other operationalizations. In an omnibus model, family sociodemographic characteristics showed a small association with externalizing psychopathology, while neighborhood sociodemographic and environmental characteristics did not. Family sociodemographic characteristics showed small associations with neighborhood sociodemographic and environmental characteristics, and neighborhood sociodemographic characteristics were moderately associated with neighborhood environment. These findings suggest that family sociodemographic characteristics are more associated with the development of broad externalizing psychopathology in youth than neighborhood sociodemographic characteristics and neighborhood environment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Case of Hallervorden-Spatz Syndrome: A Tale of Twin Sisters.

Hallervorden-Spatz syndrome, now known as pantothenate kinase-associated neurodegeneration (PKAN), is a rare autosomal recessive disorder that is characterized by cerebral iron deposition and leads to progressive extrapyramidal dysfunction and dementia. Most commonly seen in the first two decades of a person's life, it is a differential for patients presenting with atypical progressive extrapyramidal disorder and cognitive impairment. It is characterized by progressive degeneration of the basal ganglia, globus pallidus, and the reticular part of the substantia nigra due to iron accumulation. The characteristic MRI brain pattern of the disease shows the eye-of-the-tiger sign. We report cases of early onset PKAN in two sisters of the same family, in which diagnosis was based on clinical features, lab parameters, and MRI imaging findings. This report aims to differentiate PKAN from other static and progressive neurological illnesses.

Comparable outcomes of allogeneic peripheral blood versus bone marrow hematopoietic stem cell transplantation from a sibling donor for pediatric patients.

Traditionally, bone marrow (BM) has been preferred as a source of stem cells (SCs) in pediatric hematopoietic SC transplantation (HSCT); however, the use of peripheral blood SCs (PBSC) has recently increased. With advancing graft-versus-host disease (GVHD) prophylaxis, whether the BM is still a better SC source than PB in sibling donor HSCT remains controversial. Here, we compared the results of BM transplantation (BMT) and PBSC transplantation (PBSCT) in pediatric patients with malignant or non-malignant diseases receiving sibling HSCT using a total of 7.5 mg/kg of anti-thymocyte globulin (ATG). We retrospectively reviewed children who received HSCT from a sibling donor between 2005 and 2020 at Seoul National University Children's Hospital. Of the 86 patients, 40 underwent BMT, and 46 underwent PBSCT. Fifty- six patients had malignant diseases, whereas thirty patients had non-malignant diseases. All conditioning regimens comprised ATG. Busulfan-based myeloablative conditioning regimens were administered to patients with malignant diseases and approximately half of those with non-malignant diseases. The remaining half of the patients with non-malignant diseases were administered cyclophosphamide-based reduced- intensity conditioning regimens. According to studies conducted at our center, all BM donors received G-CSF before harvest to achieve early engraftment. In all 86 patients (47 males and 39 females), the median age at the time of HSCT was 11.4 (range, 0.7 - 24.6) years. The median follow-up period was 57.9 (range, 0.9-228.6) months, and the corresponding values for those with BM and PBSC were 77 (range, 2.4-228.6) months and 48.7 (range, 0.9-213.2) months, respectively. Engraftment failure occurred in one patient with BM and no patient with PBSC. The cumulative incidence of acute GVHD with grades II-IV was higher in PBSC (BM 2.5%, PBSC 26.1%, p = 0.002), but there was no significant difference in those with grades III-IV acute GVHD (BM 0%, PBSC 6.5%, p = 0.3703) and extensive chronic GVHD (BM 2.5%, PBSC 11.6%, p = 0.1004). There were no significant differences in treatment-related mortality (TRM) (BM 14.2%, PBSC 6.8%, p = 0.453), 5-year event-free survival (EFS) (BM 71.5%, PBSC 76.2%, p = 0.874), and overall survival (OS) rates (BM 80.8%, PBSC 80.3%, p = 0.867) between BM and PBSC in the univariate analysis. In the multivariate analysis, which included all factors with p < 0.50 in the univariate analysis, there was no significant prognostic factor for EFS or OS. There was no significant difference in the relapse incidence between BM and PBSC among patients with malignant diseases (BM 14.2%, PBSC 6.8%, p = 0.453). Additionally, there were no significant differences in the TRM, 5-year EFS, and OS rates between malignant and non-malignant diseases nor between the busulfan-based myeloablative regimen and reduced-intensity chemotherapy using cyclophosphamide. In this study, we showed no significant differences in EFS, OS, TRM, and GVHD, except for acute GVHD grades II-IV, between BMT and PBSCT from sibling donors, using ATG (a total of 7.5 mg/kg). Therefore, PB collection, which is less invasive for donors and less labor-intensive for doctors, could also be considered an acceptable SC source for sibling donor HSCT in children.

Clinical course of two siblings with potassium voltage-gated channel modifier subfamily V member 2 (KCNV2)-associated retinopathy.

BACKGROUND: KCNV2-associated retinopathy causes a phenotype reported as "cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356)," featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR. CASE REPORTS: Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient's decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a "squaring (trough-flattened)" a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient's vision gradually worsened, and faint bilateral bull's eye maculopathy was observed at the age of 27 years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T > C (p.Cys177Arg), in the KCNV2 gene. Patient 2: The second patient was Patient 1's younger sister, who was brought to our hospital at 3 years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients' decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24 years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene. CONCLUSIONS: The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic "squaring" a-waves in patients with CDSRR.

Germline MYOF1::WNK4 and VPS25::MYOF1 Chimeras Generated by the Constitutional Translocation t(17;19)(q21;p13) in Two Siblings With Myelodysplastic Syndrome.

BACKGROUND/AIM: Constitutional chromosomal aberrations are rare in hematologic malignancies and their pathogenetic role is mostly poorly understood. We present a comprehensive molecular characterization of a novel constitutional chromosomal translocation found in two siblings - sisters - diagnosed with myelodysplastic syndrome (MDS). MATERIALS AND METHODS: Bone marrow and blood cells from the two patients were examined using G-banding, RNA sequencing, PCR, and Sanger sequencing. RESULTS: We identified a balanced t(17;19)(q21;p13) translocation in both siblings' bone marrow, blood cells, and phytohemagglutinin-stimulated lymphocytes. The translocation generated a MYO1F::WNK4 chimera on the der(19)t(17;19), encoding a chimeric serine/threonine kinase, and a VPS25::MYO1F on the der(17), potentially resulting in an aberrant VPS25 protein. CONCLUSION: The t(17;19)(q21;p13) translocation found in the two sisters probably predisposed them to myelodysplasia. How the MYO1F::WNK4 and/or VPS25::MYO1F chimeras, perhaps especially MYO1F::WNK4 that encodes a chimeric serine/threonine kinase, played a role in MDS pathogenesis, remains incompletely understood.

Risk of congenital anomalies in children who have a sibling with cancer: A matched cohort study.

PURPOSE: We assessed the risk of congenital anomalies in children who have a sibling with cancer. METHODS: We performed a matched cohort study of children born between 2006 and 2022 in Quebec. The exposure was having a sibling with cancer. Exposed children were matched to unexposed children based on sex, number of siblings, birth order, and year. The outcome included heart defects, orofacial clefts, and other anomalies. Using conditional logistic regression, we estimated odds ratios (OR) and 95 % confidence intervals (CI) for the association between having a sibling with cancer and the likelihood of having a congenital anomaly. RESULTS: A total of 2403 children who had a sibling with cancer were matched to 240,257 unexposed children. Congenital anomalies were more frequent in children who had a sibling with cancer compared with unexposed children (10.3 % vs 8.9 %). Overall, having a sibling with cancer was only weakly associated with congenital anomalies (OR 1.18, 95 % CI 1.04-1.35). Exposed children tended to have greater odds of polydactyly/syndactyly (OR 1.89, 95 % CI 1.11-3.21) and urinary defects (OR 1.50, 95 % CI 1.09-2.08) compared with unexposed children. CONCLUSIONS: Children who have a sibling with cancer have an only weakly elevated risk of congenital anomalies.

Development of a blueprint for sibling psychosocial services: A nationwide study.

BACKGROUND: Siblings of youth with cancer have heightened risk for poor long-term psychosocial outcomes. Although sibling psychosocial care is a standard in pediatric oncology, this standard is among those least likely to be met. To address barriers to providing sibling services, a blueprint for systematic psychosocial screening and support of siblings was developed based on feedback from a national sample of psychosocial providers. PROCEDURE: Semi-structured interviews were conducted with a purposive sample of psychosocial care providers (N = 27) of various disciplines working in US pediatric cancer centers, varied in size, type, and extent of sibling support. Interviews queried providers' suggestions for the future of sibling psychosocial care and impressions of a blueprint for sibling service delivery, which was iteratively refined based on respondents' feedback. Interviews were analyzed using applied thematic analysis. RESULTS: Based on existing literature and refined according to providers' recommendations, the Sibling Services Blueprint was developed to provide a comprehensive guide for systematizing sibling psychosocial care. The blueprint content includes: (i) a timeline for repeated sibling screening and assessment; (ii) a stepped model of psychosocial support; (iii) strategies for circumventing barriers to sibling care; and (iv) recommendations for how centers with varying resources might accomplish sibling-focused care. The blueprint is available online, allowing providers to easily access and individualize the content. Providers indicated enthusiasm and high potential utility and usability of the blueprint. CONCLUSIONS: The Sibling Services Blueprint may be a useful tool for systematizing sibling psychosocial care, promoting wider availability of sibling-focused services, and addressing siblings' unmet needs.

Two siblings with Fanconi anemia (FANCQ, ERCC4/XPF) presenting with tumor-mimicking lesions in the brain and acute neurological deterioration.

The complementation Q group (FANCQ) subtype of Fanconi anemia (FA) caused by the ERCC4/XPF mutation is very rare. Two siblings, aged 13 and 10 with Fanconi phenotypic features, presented with right hemiparesis and focal-onset seizures. In both cases, cranial magnetic resonance imaging (MRI) showed mass-like lesions accompanied by peripheral edema and calcification. In one case, oral steroid treatment and surgical excision were performed, while in the other case, the cranial lesion regressed just with steroid treatment and without surgery. Both siblings remained wheelchair-bound due to neurological dysfunction. One case died due to hepatocellular carcinoma. ERCC4/XPF gene mutation was detected in both siblings.

From classroom to life: Gender differences in the persistent effect of learning disabilities on adult depressive symptoms.

Despite the well-established link between adolescent learning disabilities (LD) and mental health, little is known about its long-term consequences. This study examines the relationship between adolescent LD and adult depressive symptoms, with a focus on gender differences and underlying mechanisms. Using a sibling sample from the National Longitudinal Study of Adolescent to Adult Health (N = 3,414), this study estimated sibling fixed effects models to account for unobserved family-level characteristics such as genes and early childhood family and social context. Sobel mediation analyses were conducted to examine social-psychological mechanisms, including the student-teacher relationship, the student-student relationship, and a sense of school belonging. LD in adolescence was positively associated with depressive symptoms in adulthood (b = 0.823, p < 0.05). This association remained robust when controlling for unobserved family-level confounders as well as educational attainment in adulthood. Gender-stratified models showed that only the association for women is statistically significant (b = 1.935, p < 0.05), and its magnitude is nearly three times that of the association for men. Sobel mediation tests indicate that a decline in a sense of school belonging mediates approximately 17% of the association between adolescent LD and adult depressive symptoms. This study's findings suggest that LD in adolescence is associated with an increase in depressive symptoms in adulthood, particularly in women, and a low sense of school belonging may be a potential mediator. Implementing interventions to improve the school integration of girls with LD could be an effective means of improving their long-term mental health.

Two case reports of a novel missense mutation in the PNPLA6 gene in two siblings with chorioretinal dystrophy, hypogonadotropic hypogonadism, and cerebellar ataxia.

BACKGROUND: Boucher Neuhäuser Syndrome (BNS) is a rare disease with autosomal recessive inheritance defined by the classical triad; early-onset ataxia, hypogonadism and chorioretinal dystrophy. CASE PRESENTATION: We present two siblings diagnosed with BNS at midlife, identified with homozygous state of a novel PNPLA6 missense mutation. One healthy sibling and the mother were heterozygous carriers of the mutation. The proband presented with the classical triad and the other sibling presented with visual problems at first. The proband was referred to our department by a private Neurologist, in early adulthood, because of hypogonadism, cerebellar ataxia, axonal neuropathy, and chorioretinal dystrophy for further evaluation. The sibling was referred to our department for evaluation, at childhood, due to visual problems. Later, the patient displayed the triad of ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. The unusual medical history of the two siblings led to further examinations and eventually the diagnosis of the first BNS cases in Cyprus. WES-based ataxia in silico gene panel analysis revealed 15 genetic variants and further filtering analysis revealed the PNPLA6 c.3323G > A variant. Segregation analysis in the family with Sanger sequencing confirmed the PNPLA6 homozygous variant c.3323G > A, p.Arg1108Gln in exon 29. CONCLUSIONS: This highlights the importance of considering rare inherited causes of visual loss, spinocerebellar ataxia, or/and HH in a neurology clinic and the significant role of genetic sequencing in the diagnostic process.

Association of Very Low Birth Weight Infants With Parental and Sibling Mental Health Care Usage.

BACKGROUND AND OBJECTIVES: Parents and siblings of very low birth weight, premature infants are at risk for poor mental health outcomes with increased mental health care usage. Knowledge regarding mental health care use patterns could guide interventions. METHODS: This retrospective cohort study included US families with commercial insurance coverage from a single carrier. Neonates born at ≤30 weeks' gestational age or with a birth weight <1500 g were identified by insurance claim data between July 1, 2015, and June 30, 2016. Each case neonate family was matched with up to 4 control families. RESULTS: The study included 1209 case and 1884 control neonates (with 134 deaths among only the case neonates [11.1% of cases]); 2003 case and 3336 control parents (mean [SD] age, 34.6 [5.4] years; 2858 [53.5%] female); and 884 case and 1878 control siblings (mean [SD] age, 6.8 [5.5] years; 1375 [49.8%] female). Compared with controls, more case parents used mental health care over the first year after birth hospitalization discharge. Higher usage was observed for bereaved case parents soon after their child's death. A smaller proportion of bereaved case siblings received mental health care compared with controls. Although nonbereaved case parents returned toward the proportion of use observed in controls, nonbereaved case female siblings, bereaved case female and male siblings, and bereaved male parents experienced continued differences. CONCLUSIONS: Understanding and meeting the mental health care needs of parents and siblings of very low birth weight premature neonates can be guided by these findings, including elevated and prolonged needs of bereaved parents and siblings.

Response to psychotic experiences: Impact of personality traits on perceived levels of distress.

BACKGROUND: This study examined the influence of personality traits on (subclinical) positive symptom distress in patients with a psychotic disorder, their unaffected siblings and healthy controls. METHODS: Data were obtained from the Genetic Risk and Outcome of Psychosis study (GROUP), a Dutch longitudinal multicenter cohort study. Data from 140 patients, 216 unaffected siblings and 102 healthy controls was available for baseline levels of Five Factor Model personality traits and frequency and distress due to psychotic experiences three years later, assessed with the Community Assessment of Psychic Experience questionnaire. Main effects of all five personality traits on symptom distress were investigated as well as moderating effects of Neuroticism, Extraversion and Openness on positive symptom frequency and positive symptom distress. Age, gender, symptom frequency and IQ were controlled for. RESULTS: In both patients and siblings, the observed main effects of Neuroticism and Openness on (subclinical) positive symptom distress three years later either lost significance or had a very small effect size when controlling for covariates, mainly due to the correction for the effect of positive symptoms on personality traits at baseline. In both groups, levels of Openness at baseline moderated the association between positive symptom frequency and positive symptom distress three years later, in the direction that higher levels of Openness were associated with weaker associations between positive symptom frequency and - distress, even when covariates were controlled for. DISCUSSION: The level of Openness to Experiences influences the perceived distress from (subclinical) positive symptoms in both patients and siblings.

The Detection of Environmental Influences on Academic Achievement Appears to Depend on the Analytic Approach.

One long-standing analytic approach in adoption studies is to examine correlations between features of adoptive homes and outcomes of adopted children (hereafter termed 'measured environment correlations') to illuminate environmental influences on those associations. Although results from such studies have almost uniformly suggested modest environmental influences on adopted children's academic achievement, other work has indicated that adopted children's achievement is routinely higher than that of their reared-apart family members, often substantially so. We sought to understand this discrepancy. We examined academic achievement and literacy-promotive features of the home in 424 yoked adoptive/biological families participating in the Early Growth and Development Study (EGDS; i.e., adopted children, adoptive mothers, birth mothers, and biological siblings of the adopted children remaining in the birth homes) using an exhaustive modeling approach. Results indicated that, as anticipated, adopted children scored up to a full standard deviation higher on standardized achievement tests relative to their birth mothers and reared-apart biological siblings. Moreover, these achievement differences were associated with differences in the literacy-promotive features of the adoptive and birth family homes, despite minimal measured environment correlations within adoptive families. A subsequent simulation study highlighted noise in measured environmental variables as an explanation for the decreased utility of measured environment correlations. We conclude that the field's heavy focus on measured environment correlations within adoptive families may have obscured detection of specific environmental effects on youth outcomes, and that future adoption studies should supplement their measured environment analyses with mean differences between reared-apart relatives.