Etiological Distinctions Research Articles

Exploring the intestinal ecosystem: from gut microbiota to associations with subtypes of inflammatory bowel disease.

Significant differences have been discovered between subtypes of Crohn's disease (CD) and ulcerative colitis (UC). The role of gut microbiota in promoting the onset of UC and CD is established, but conclusions regarding subtype-specific analyses remain limited. This study aims to explore the influence of gut microbiota on subtypes of UC and CD, offering novel insights into the pathogenesis and treatment of UC and CD.Two-sample Mendelian randomization (MR) analysis was employed to examine the causal relationship between subtypes of UC and CD and gut microbiota composition. Gut microbiota data were sourced from the International Consortium MiBioGen, while UC and CD data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analytical approaches such as inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS were utilized. Sensitivity analyses including MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were conducted for quality control. Subsequently, we employed multivariable IVW, MR-Egger, weighted median, and LASSO regression methods to identify independently significant genera or families and conducted sensitivity analyses. We have determined that Hungatella, Acidaminococcaceae, and 15 other microbial taxa act as protective factors for various CD and UC subtypes, while Terrisporobacter, Anaerostipes, and 23 other microbial taxa are associated with increased risk for different CD and UC subtypes. Furthermore, through multivariable MR analysis, we have identified significant genera or families with independent effects. Our study confirms a causal relationship between dysbiosis of gut microbiota and the occurrence of CD and UC subtypes. Furthermore, it validates etiological distinctions among different subtypes of CD and UC. A novel approach to adjunctive therapy involving distinct UC or CD subtypes may involve the use of probiotics and represents a potential avenue for future treatments.

Clonal Hematopoiesis of Indeterminate Potential (CHIP) Related to the Etiology of Ischemic Stroke

Introduction: Clonal Hematopoiesis of Indeterminate Potential (CHIP) is associated with cardiovascular disease, including acute myocardial infarction and ischemic stroke, due to immune system dysregulation leading to increased atherosclerotic plaque formation and inflammation. Approximately 25-40% of ischemic strokes have an unknown cause even after a comprehensive etiological study and are eventually categorized as cryptogenic strokes. Our hypothesis is that the presence of CHIP could represent a biomarker for atherosclerotic or cardioembolic ischemic stroke and help to clarify the origin of cryptogenic strokes. Therefore, the objective of this study was to analyze the prevalence of CHIP in patients with different subtypes of ischemic stroke and its prognostic impact on cardiovascular risk. Methods: This prospective observational study included consecutive patients over 60 years of age with no prior history of neoplasia or cytotoxic treatment, who experienced embolic ischemic stroke between September 2021 and August 2022. Ischemic strokes were classified into cardioembolic (CE), atherothrombotic (AT) or cryptogenic (CRYP) etiologies after performing a systematic etiological study. During the stroke admission, peripheral blood samples were obtained in order to analyze the 13 genes most frequently associated with CHIP ( DNMT3A, TET2, ASXL1, JAK2, PPM1D, TP53, SF3B1, GNB1, SRSF2, CHEK2, CBL, GNAS, NRAS) through targeted next generation sequencing. Libraries were prepared using the KAPA HyperPlus capture chemistry (Roche) and were sequenced on a MiSeq platform (Illumina) following a 2x150bp paired-end read standard protocol, allowing the detection of variants with a variant allelic frequency (VAF) of ≥1%. The analysis was conducted using an in-house developed pipeline. Patients with one or more mutations in these genes with a VAF ≥2% were considered CHIP carriers. Cardiovascular risk factors including: hypertension, diabetes mellitus, dyslipidemia, smoking and obesity, were also analyzed. Results: Seventy-eight patients with stroke were included (50% female, median age 72 years (range: 59-90). Ischemic strokes were classified etiologically as: 36 CE (46.2%), 34 AT (43.6%) and 8 CRYP (10.3%) (Table 1). CHIP was detected in 21/78 (31.3%) patients, with the following gene mutation frequencies among CHIP carriers: DNMT3A (47.6%), TET2 (28.5%), SRSF2 (14.2%), PPM1D (9.5%), ASXL1 (4.8%), CBL (4.8%), CHEK2 (4.8%) and JAK2 (4.8%). The median VAF detected was 4.85% (range: 2.1%-43.7%), and 23.8% (5/21) of cases presented more than one mutation. The incidence of CHIP varied according to stroke etiology: CE etiology: 38.9% (14/36); AT etiology: 17.6% (6/34) and CRYP etiology: 12.5% (1/8) (p=0.046) (Figure 1). Moreover, only CE strokes showed mutations in TET2 (16.7% (6/36)) compared to AT (0/34) and CRYP (0/8) (p=0.015). No significant differences were observed in the blood counts (Hb, MCV, RDW, neutrophil count, monocytes, platelets or PCR) between stroke patients with CHIP and non-CHIP (Table 1). Finally, in the multivariate analysis, TET2 mutations were associated with CE stroke independently of age, coronary artery disease and classic cardiovascular risk factors (OR 8.1; Cl: 1.35-48.47; p=0.012). Conclusions: Our findings identify that CHIP is common in patients with ischemic strokes, especially in those of cardioembolic etiology, with TET2 being the most frequently mutated gene. The presence of CHIP TET2 could represent a novel cardiovascular risk factor, contributing to a more precise etiological distinction between the different etiologies of ischemic stroke. Funding source: this project is supported by health research fund of Carlos III health institute. FIS PI20/00881

Decoding cell-type contributions to the cfRNA transcriptomic landscape of liver cancer

BackgroundLiquid biopsy, particularly cell-free RNA (cfRNA), has emerged as a promising non-invasive diagnostic tool for various diseases, including cancer, due to its accessibility and the wealth of information it provides. A key area of interest is the composition and cellular origin of cfRNA in the blood and the alterations in the cfRNA transcriptomic landscape during carcinogenesis. Investigating these changes can offer insights into the manifestations of tissue alterations in the blood, potentially leading to more effective diagnostic strategies. However, the consistency of these findings across different studies and their clinical utility remains to be fully elucidated, highlighting the need for further research in this area.ResultsIn this study, we analyzed over 350 blood samples from four distinct studies, investigating the cell type contributions to the cfRNA transcriptomic landscape in liver cancer. We found that an increase in hepatocyte proportions in the blood is a consistent feature across most studies and can be effectively utilized for classifying cancer and healthy samples. Moreover, our analysis revealed that in addition to hepatocytes, liver endothelial cell signatures are also prominent in the observed changes. By comparing the classification performance of cellular proportions to established markers, we demonstrated that cellular proportions could distinguish cancer from healthy samples as effectively as existing markers and can even enhance classification when used in combination with these markers.ConclusionsOur comprehensive analysis of liver cell-type composition changes in blood revealed robust effects that help classify cancer from healthy samples. This is especially noteworthy, considering the heterogeneous nature of datasets and the etiological distinctions of samples. Furthermore, the observed differences in results across studies underscore the importance of integrative and comparative approaches in the future research to determine the consistency and robustness of findings. This study contributes to the understanding of cfRNA composition in liver cancer and highlights the potential of cellular deconvolution in liquid biopsy.

P5 DISCOVERY OF A NEW HATTR GENETIC VARIANT: A CASE REPORT OF A PATIENT WITH CARDIAC UPTAKE AT 99–MTC–DIPHOSPHONATES SCINTIGRAPHY AND ABNORMAL MONOCLONAL PROTEINS TESTS

Abstract Introduction Cardiac amyloidosis is an infiltrative disease that remains an under–diagnosticated cause of heart failure. Diagnostic algorithms focus on identifying the two most frequent forms of the disease, light chains amyloidosis (AL) and transthyretin amyloidosis (ATTR), by the initial use of 99mTc–DPD scintigraphy coupled to assessment of monoclonal proteins. Etiological distinction is and of pivotal importance since the availability of specific disease modifying treatments. Case Description We report the case of a 61–year–old man hospitalized for new onset of heart failure. Past medical history highlights bilateral carpal tunnel syndrome and monoclonal gammopathy of undetermined significance (MGUS). Cardiovascular examination reveals clinical signs of pulmonary and peripheric congestion. ECG shows conduction disturbances and low QRS voltage. Transthoracic echocardiography reveals left ventricular hypertrophy, normal systolic function (LVEF 58%), 3rd degree LV diastolic disfunction and mild pericardial effusion. Laboratory tests shows abnormal levels of TnT and pro–BNP. A diagnosis of cardiac amyloidosis is considered, and further exams are executed: cardiac magnetic resonance, haematological laboratory tests and 99mTc–DPD scintigraphy (tab. 1). Since both bone scintigraphy and monoclonal proteins tests are positive, diagnosis of cardiac amyloidosis cannot be made without non–invasive modalities (fig.1) and the patient is referred to an Amyloidosis Centre. Haematological evaluation and abdominal fat pad biopsy show stability of haematological disease and confirms the deposition of amyloidogenic TTR both in wild–type and mutated Ile88Arg variants. The results of genetic analysis confirms the presence of a heterozygous mutation of TTR gene (p.Ile88Arg – c.263T>G) (fig. 2). This mutation is not reported in database ClinVar nor in gnomAD, but according to the ACMG criteria it can be considered likely pathogenic. Considering the final diagnosis of cardiac hATTR the patient is considered eligible for treatment with Tafamidis. Discussion and Conclusion Despite clinical history with cardiac conduction system abnormalities and bilateral carpal tunnel syndrome, some gene TTR variants can bring false negative results at 99mTc–DPD scintigraphy, so ATTR form should not be excluded basing on non–invasive modalities. Performing a compete diagnostic workup led us to discover a new TTR pathogenic variant and confirm ATTR form without performing endomyocardial biopsy.

High-resolution vessel wall magnetic resonance imaging in intracranial vasculopathies: an experience from eastern India.

To evaluate the role of high-resolution intracranial vessel wall imaging (HR-IVWI) in differentiation of various intracranial vasculopathies in addition to luminal and clinical imaging in the largest cohort of Indian stroke patients. A single-center, cross-sectional study was undertaken recruiting consecutive stroke or TIA patients presenting within a month of onset, with luminal irregularity/narrowing upstream from the stroke territory. The patients were initially classified into TOAST and Chinese ischemic stroke sub-classification (CISS) on the basis of clinical and luminal characteristics and reclassified again following incorporation of HR-IVWI findings. In our cohort of 150 patients, additional use of HR-IVWI led to a 10.7 and 14% change in initial TOAST and CISS classification respectively (p < 0.001). In TOAST classification, 12 "undetermined aetiology" were reclassified into intracranial atherosclerotic disease (ICAD), 1 "undetermined aetiology" into CNS angiitis and 1 "undetermined aetiology" into arterial dissection. Similarly, in CISS 19 "undetermined aetiology" was reclassified into 16 large artery atherosclerosis (LAA) and 3 "other aetiology" consisting of one CNS angiitis, Moyamoya disease (MMD) and arterial dissection each. Two initial classification of MMD by CISS and TOAST were changed into ICAD. The observed change in diagnosis following incorporation of HR-IVWI was proportionately highest in ICAD (LAA) subgroup (TOAST-9.3%, CISS-12%). Adjunctive use of HR-IVWI, to clinical and luminal assessment, can significantly improve diagnostic accuracy during evaluation of intracranial vasculopathies, with its greatest utility in diagnosing in ICAD, CNS angiitis and dissection. HR-IVWI allows clearer etiological distinction of intracranial vasculopathies having therapeutic and prognostic implications.

Identification of Pre-Renal and Intrinsic Acute Kidney Injury by Anamnestic and Biochemical Criteria: Distinct Association with Urinary Injury Biomarkers.

Acute kidney injury (AKI) is a syndrome of sudden renal excretory dysfunction with severe health consequences. AKI etiology influences prognosis, with pre-renal showing a more favorable evolution than intrinsic AKI. Because the international diagnostic criteria (i.e., based on plasma creatinine) provide no etiological distinction, anamnestic and additional biochemical criteria complement AKI diagnosis. Traditional, etiology-defining biochemical parameters, including the fractional excretion of sodium, the urinary-to-plasma creatinine ratio and the renal failure index are individually limited by confounding factors such as diuretics. To minimize distortion, we generated a composite biochemical criterion based on the congruency of at least two of the three biochemical ratios. Patients showing at least two ratios indicative of intrinsic AKI were classified within this category, and those with at least two pre-renal ratios were considered as pre-renal AKI patients. In this study, we demonstrate that the identification of intrinsic AKI by a collection of urinary injury biomarkers reflective of tubular damage, including NGAL and KIM-1, more closely and robustly coincide with the biochemical than with the anamnestic classification. Because there is no gold standard method for the etiological classification of AKI, the mutual reinforcement provided by the biochemical criterion and urinary biomarkers supports an etiological diagnosis based on objective diagnostic parameters.

The General Theory of Crime Revisited: Comparing the Relative Effects of Parental Responsiveness and Parental Behavioral Control on Aggressive and Nonaggressive Antisocial Behavior in Adolescence

ABSTRACT Using data collected from middle schools in China in 2018, we extend the general theory of crime beyond its focus on low self-control as the leading cause of all crimes and compare the relative impact of parental behavioral control and parental responsiveness on adolescent antisocial behavior. We highlight the etiological distinctions between aggressive and nonaggressive antisocial behavior and find that maternal responsiveness reduces adolescents’ aggressive antisocial behavior through fostering students’ self-control and reduces nonaggressive antisocial behavior through boosting students’ self-esteem.

Headache diagnosis in an urgency and emergency unit: Public Health Relevance and its relationship with cost

BackgroundHeadache is a common symptom that affects a significant portion of the general population. It constitutes a challenge for diagnosis in urgency and emergency care services, due to headache’s clinical variability and diverse possible etiologies, besides the limited time and resources of these facilities. Because of this insufficiency and the potential severity associated with the condition, headaches generate considerable expenditures to health systems, related to both diagnostic discrimination and treatment.ObjectiveEvaluating the diagnostic resources used on headache patients care, as well as its Public Health Relevanceand relation to cost in an Emergency and Urgency Care unit.MethodsCross-section study analyzing 450 medical records of patients with headache complaints in the time frame from January 1, 2019, and December 31, 2019. Patients were categorized according to the type of headache (primary and secondary), specialized evaluation, complementary exams used in the diagnosis, hospital observation time, and the final expenditure in each patient’s care.ResultsThe total estimated expenditures related to headache care equaled US$90,855.60 (average US$201.90 per patient). 38.9% of cases corresponded to primary headaches and 31.1% to secondary headaches. 30% of cases could not be classified. The resources utilized for secondary headaches diagnosis differed significantly from those used in primary headache diagnosis. However, the final expenditures were similar to both groups.ConclusionThe socio-economic impact caused by headaches is unquestionable. It is a highly frequent symptom and both its etiological distinction and adequate treatment require solid evaluation. Due to the resources spent in its evaluation and monitoring, headaches can be considered a public health problem. Therefore, this study suggests that resources should be allocated in the health education and professional training for the proper conduction of these patients, so that they may benefit from an optimized treatment of theircondition without overwhelming the health system.

Phenotype variants of invasive breast cancer differ in associations between the primary tumor size and its Ki-67 value.

e12588 Background: Epidemiological studies report that Ki-67 values are higher in larger invasive breast cancers (IBC). This relation was investigated in 1040 consecutive IBC patients with various immunohistological phenotypes (ER+/-; HER2 0, 1+ to 3+), all treated at a single Croatian hospital. Methods: A scatter plot of 1040 Ki-67 values with their cancer diameter (in cms) have produced an LOWESS nonparametric curve that almost overlapped with the logarithmic function of the same data set (Ki-67% = 18.39+20.63*log(D), where D is a tumor diameter in cm). The next step in using this logarithmic function as a model, was to convert D values into log(D) for linear correlations, amenable to tests of significance. Results: Among all 1040 pts, only ER positive phenotype variants Ki-67% correlated with log(D): Among ER positive tumors, the HER2 expression has decreased the correlation significance and the slope of regression lines, suggesting that the HER2 presence increases Ki67% in small tumors, while larger tumors have Ki67% less augmented than among HER2 absent tumors. Thus the highest slope of the line was found among HER2 absent ER+ patients. Conclusions: Since only ER positive tumors have shown correlation of Ki67% with the log of their tumor size, tumor biology (estimated by Ki67%) of the ER negative IBCs seems unrelated with their size. This possibly suggests that the clinical course of ER negative IBC patients is less predictable due to some etiological distinction the ER positive and ER negative breast cancers. [Table: see text]

Urinary TCP1-eta: A Cortical Damage Marker for the Pathophysiological Diagnosis and Prognosis of Acute Kidney Injury.

Acute kidney injury (AKI) is a serious syndrome with increasing incidence and health consequences, and high mortality rate among critically ill patients. Acute kidney injury lacks a unified definition, has ambiguous semantic boundaries, and relies on defective diagnosis. This, in part, is due to the absence of biomarkers substratifying AKI patients into pathophysiological categories based on which prognosis can be assigned and clinical treatment differentiated. For instance, AKI involving acute tubular necrosis (ATN) is expected to have a worse prognosis than prerenal, purely hemodynamic AKI. However, no biomarker has been unambiguously associated with tubular cell death or is able to provide etiological distinction. We used a cell-based system to identify TCP1-eta in the culture medium as a noninvasive marker of damaged renal tubular cells. In rat models of AKI, TCP1-eta was increased in the urine co-relating with renal cortical tubule damage. When kidneys from ATN rats were perfused in situ with Krebs-dextran solution, a portion of the urinary TCP1-eta protein content excreted into urine disappeared, and another portion remained within the urine. These results indicated that TCP1-eta was secreted by tubule cells and was not fully reabsorbed by the damaged tubules, both effects contributing to the increased urinary excretion. Urinary TCP1-eta is found in many etiologically heterogeneous AKI patients, and is statistically higher in patients partially recovered from severe AKI. In conclusion, urinary TCP1-eta poses a potential, substratifying biomarker of renal cortical damage associated with bad prognosis.

The genetic and environmental structure of fear and anxiety in juvenile twins.

Fear and anxiety are conceptualized as responses to acute or potential threat, respectively. Adult twin studies found substantial interplay between genetic and environmental factors influencing fear disorders (phobias) and anxiety disorders. Research in children, however, has largely examined these factors independently. Thus, there exists a substantial knowledge gap regarding the underlying etiologic structure of these closely-related constructs during development. Symptom counts for five fear (criticism, the unknown, death, animal, medical) and four anxiety (generalized, panic, separation, social) dimensions were obtained for 373 twin pairs ages 9-14. Multivariate twin modeling was performed to elucidate the genetic and environmental influences distributed amongst these dimensions. The best fitting model contained one genetic, two familial environmental, and two unique environmental factors shared between fear and anxiety symptoms plus dimension-specific genetic and unique environmental factors. Although several environmental factors were shared between fear and anxiety dimensions, one latent factor accounted for genetic influences across both domains. While adult studies find somewhat distinct etiological differences between anxiety and phobic disorders, the current results suggest that their relative genetic and environmental influences are not as clearly demarcated in children. These etiological distinctions are more nuanced, likely contributing to the highly diffuse symptom patterns seen during development.

Etiological Distinction Across Dimensions of Math Anxiety.

Analyses have suggested math anxiety is a multidimensional construct. However, previous behavioral genetic work examining math anxiety was unidimensional. Thus, the purpose of the present study was to examine different approaches for specifying behavioral genetic models of math anxiety as a multidimensional construct. Three models were compared: a unidimensional model, a three dimension multidimensional model, and a bi-factor model, which partitioned variance into one common factor shared across three dimensions of math anxiety and examined residual variance in each dimension. The best fitting model was a bi-factor AE model, which suggested moderate heritability of general math anxiety and that each dimension of math anxiety had unique etiological influences not accounted for by shared variance with the general math anxiety factor. Thus, while there was evidence of shared etiology, there was also evidence of some etiological distinction across dimensions of math anxiety. The results demonstrate the importance of taking into account the dimensionality of the scale when interpreting similarity across twins.

A longitudinal twin study of the association between childhood autistic traits and psychotic experiences in adolescence.

BackgroundThis twin study investigated whether autistic traits during childhood were associated with adolescent psychotic experiences.MethodsData were collected from a community sample of approximately 5000 twin pairs, which included 32 individuals with diagnosed autism spectrum conditions (ASC). Parents rated autistic traits in the twins at four points between ages 8–16 years. Positive, negative, and cognitive psychotic experiences were assessed at age 16 years using self- and parent-report scales. Longitudinal twin analyses tested the associations between these measures.ResultsAutistic traits correlated weakly or nonsignificantly with positive psychotic experiences (paranoia, hallucinations, and grandiosity), and modestly with cognitive psychotic experiences (cognitive disorganisation). Higher correlations were observed for parent-rated negative symptoms and self-reported anhedonia, although the proportion of variance in both accounted for by autistic traits was low (10 and 31 %, respectively). The majority of the genetic influences on negative symptoms and anhedonia were independent of autistic traits. Additionally, individuals with ASC displayed significantly more negative symptoms, anhedonia, and cognitive disorganisation than controls.ConclusionsAutistic traits do not appear to be strongly associated with psychotic experiences in adolescence; associations were also largely restricted to negative symptoms. Of note, the degree to which the genetic and environmental causes of autistic traits influenced psychotic experiences was limited. These findings thus support a phenotypic and etiological distinction between autistic traits and psychotic experiences.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0037-9) contains supplementary material, which is available to authorized users.

Neighborhood as a predictor of non-aggressive, but not aggressive, antisocial behaviors in adulthood.

Prior meta-analytic work has highlighted important etiological distinctions between aggressive (AGG) and non-aggressive rule-breaking (RB) dimensions of antisocial behavior. Among these is the finding that RB is influenced by the environment more than is AGG. Relatively little research, however, has sought to identify the specific environmental experiences that contribute to this effect. The current study sought to do just this. We examined whether unrelated adults residing in the same neighborhood (n = 1915 participants in 501 neighborhoods) were more similar in their AGG and RB than would be expected by chance. Analyses focused on simple multi-level models, with the participant as the lower-level unit and the neighborhood as the upper-level unit. Results revealed little to no evidence of neighborhood-level variance in AGG. By contrast, 11+% of the variance in RB could be predicted from participant neighborhood, results that persisted even when considering the possibility of genetic relatedness across participants and neighborhood selection effects. Moreover, 17% of this neighborhood-level variance in RB was accounted for by neighborhood structural characteristics and social processes. Findings bolster prior suggestions that broader contextual experiences, like the structural and social characteristics of one's neighborhood, contribute in a meaningful way to RB in particular. Our results also tentatively imply that this association may be environmental in origin. Future work should seek to develop additional, stronger designs capable of more clearly leveraging genetic un-relatedness to improve causal inferences regarding the environment.

Parameters of Right Ventricle as etiological distinction between ischemic and non-ischemic dilated cardiomyopathy

Background Dilated left ventricular volumes (VE) is one of the main factors of poor cardiovascular prognosis with systolic dysfunction. Myocardial fibrosis detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been recognized in recent years as an independent prognostic factor in dilated cardiomyopathy, in addition to guiding the etiological diagnosis, and most often the only noninvasive way to differentiate ischemic and nonischemic. The aim of our study was to determine the prevalence of myocardial fibrosis in patients with dilated LV and the morphological and functional differences between ischemic and non-ischemic patterns.

Etiological distinction of working memory components in relation to mathematics

Working memory has been consistently associated with mathematics achievement, although the etiology of these relations remains poorly understood. The present study examined the genetic and environmental underpinnings of math story problem solving, timed calculation, and untimed calculation alongside working memory components in 12-year-old monozygotic (n=105) and same-sex dizygotic (n=143) twin pairs. Results indicated significant phenotypic correlation between each working memory component and all mathematics outcomes (r=0.18–0.33). Additive genetic influences shared between the visuo-spatial sketchpad and mathematics achievement were significant, accounting for roughly 89% of the observed correlation. In addition, genetic covariance was found between the phonological loop and math story problem solving. In contrast, despite there being a significant observed relationship between phonological loop and timed and untimed calculations, there was no significant genetic or environmental covariance between the phonological loop and timed or untimed calculation skills. Further analyses indicated that genetic overlap between the visuo-spatial sketchpad and math story problem solving and math fluency was distinct from general genetic factors, whereas g, phonological loop, and mathematics shared generalist genes. Thus, although each working memory component was related to mathematics, the etiology of their relationships may be distinct.

The Etiology of the Association Between Child Antisocial Behavior and Maternal Negativity Varies Across Aggressive and Non-Aggressive Rule-Breaking Forms of Antisocial Behavior

There is a robust association between negative parenting and child antisocial behavior problems. However, the etiology of this association remains unclear. Extant literature has reported strikingly different conclusions across studies, with some highlighting genetic mediation and others highlighting environmental mediation. One possible reason for these discrepancies across studies may be the failure to differentiate between aggressive and non-aggressive (rule-breaking) dimensions of childhood antisocial behavior, given their notably different etiologies and developmental trajectories (Burt 2012). The current study sought to examine the phenotypic and etiologic associations of maternal negativity with aggressive and rule-breaking antisocial behavior, respectively. Participants included 824 mothers and their twin children between the ages of 6 and 10. Our results highlighted clear etiologic distinctions in the associations of aggression and rule-breaking with maternal negativity. Aggression was associated with maternal negativity via both genetic and environmental factors, whereas the association between non-aggressive rule-breaking and maternal negativity was entirely environmental in origin. These findings provide additional support for the presence of meaningful distinctions between aggressive and non-aggressive forms of antisocial behavior, and highlight the complex relationship between parenting and child outcome.

The Clinical Syndrome of Paroxysmal Exercise-Induced Dystonia: Diagnostic Outcomes and an Algorithm.

Paroxysmal exercise-induced dyskinesia (PED) is characterized by recurrent episodes of involuntary movement disorders usually precipitated by sustained walking or running. Recently, mutations in the gene encoding for glucose transporter type 1 (GLUT-1) were described in a number of families with autosomal dominant PED. However, the underlying etiology of PED is quite heterogeneous. We describe a large series of patients presenting with PED. Of 16 patients, we reached a conclusive diagnosis for 11 (4 patients with GLUT-1 mutations, 4 patients with early Parkinson's disease, 2 with dopa-responsive dystonia, and one with a psychogenic/functional movement disorder). For the remaining 5 patients, the final diagnosis remained descriptive. Although certain clinical features might allow etiological distinction between cases, clinical examination alone is not always conclusive. Based on our series, we propose a diagnostic algorithm to aid the differential diagnosis of PED.

Genetics of parenting: The power of the dark side.

Reviews of behavioral genetic studies note that “control” aspects of parenting yield low estimates of heritability, while “affective” aspects (parental feelings) yield moderate estimates. Research to date has not specifically considered whether positive and negative aspects of parenting—for both feelings and control—may explain these etiological distinctions. We addressed this issue using parent reports of parenting in a large twin sample in the United Kingdom, at ages 9 (N = 2,260 twin pairs), 12 (N = 3,850 twin pairs) and 14 (N = 2,293 twin pairs) years. Our findings supported previous work indicating that parental feelings show greater heritability (h2) than control (across all ages, mean h2 feelings = .42, control = .13). Of specific interest is our novel finding that for control as well as for feelings, the heritability for negative aspects of parenting was greater than for positive aspects (e.g., across all ages, mean h2 total negativity = .44; total positivity = .12). Results across the 3 ages using common pathway models for all scales further endorsed our hypotheses. Previous research has shown that children’s genetically driven characteristics elicit parenting; our pattern of our results suggests that what is critical is the “dark” side of these characteristics for eliciting negativity from parents, whether feelings toward the child or control strategies are considered. Improving understanding of how the environment is shaped by the dark side is important theoretically and, ultimately, for targeting intervention.

Null Association Between Histology of First and Second Primary Malignancies in Men With Bilateral Testicular Germ Cell Tumors

Testicular germ cell tumors (TGCTs), the most common neoplasms of young men, are categorized histologically as either seminomas or nonseminomas/mixed germ cell tumors. These subtypes differ by age at diagnosis and clinical course, but little is known about etiological distinctions. To test the hypothesis that histological subtypes have distinct sets of unrecognized etiological factors, we used a recently described approach, estimating the association between histological types of first and second tumors of men with 2 primary TGCTs. The study population of 488 men each with 2 primary TGCTs was ascertained through population-based cancer registries in the United States between 1972 and 2006. Univariate logistic regression analysis revealed that the histology of second primary TGCTs was associated with the histology of first TGCTs (odds ratio = 1.70, 95% confidence interval: 1.14, 2.52); however, the association did not persist in analyses adjusted for age at diagnosis of first TGCT (odds ratio = 1.09, 95% confidence interval: 0.71, 1.70). These results would be expected if the subtypes share etiology but experience different rates of progression to diagnosis or if the histological fate of TGCTs is influenced by age-related processes. Men with 2 primary TGCTs provide novel opportunities to learn whether histological subtypes are likely to share etiology, so results may inform research designed to identify causes.