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Background: The classification of mental, behavioural and neurodevelopmental disorders in the World Health Organization's International Classification of Diseases 11th revision (ICD‐11) includes a comprehensive set of behavioural indicators (BIs) within the neurodevelopmental disorders grouping. BIs can be used to assess the severity of disorders of intellectual development in situations in which standardised measures of intellectual functioning and adaptive behaviours are not available or feasible. This international study examines the implementation characteristics of the BIs and compares them to standardised measures for assessing the severity of intellectual impairment and adaptive behaviours in disorders of intellectual development and autism spectrum disorder (ASD). The clinical utility of the ICD‐11 and the fidelity of its application in international clinical settings were also assessed. Methods: A total of 116 children and adolescents (5–18 years old) with a suspected or established diagnosis of disorders of intellectual development were included across four sites [Italy (n = 18), Sri Lanka (n = 19) and two sites in India (n = 79)]. A principal component analysis was conducted to evaluate the application of the ICD‐11 guidance for combining severity levels. Results: Assessment using the BIs showed a higher proportion of individuals classified with mild severity, whereas the standardised measures indicated a higher proportion of severe ratings. Additionally, individuals with co‐occurring ASD tended to have more severe impairments compared with those without ASD, as indicated by both BIs and standardised measures. Overall, the BIs were considered clinically useful, although more time and consideration were required when applying the guidelines for individuals with a co‐occurring disorder of intellectual development and ASD. The principal component analysis revealed one principal component representing overall disorders of intellectual development severity levels. Conclusions: The ICD‐11 BIs can be implemented as intended in international clinical settings for a broad range of presentations of individuals with neurodevelopmental disorders. Use of the BIs results in similar severity diagnoses to those made using standardised measures. The BIs are expected to improve the reliability of severity assessments in settings where appropriate standardised measures for intellectual and adaptive behaviours are not available or feasible. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) has approved the 11th Revision of the International Classification of Diseases (ICD‐11). A version of the ICD‐11 for Mental, Behavioural and Neurodevelopmental Disorders for use in clinical settings, called the Clinical Descriptions and Diagnostic Requirements (CDDR), has also been developed. The CDDR includes behavioural indicators (BIs) for assessing the severity of disorders of intellectual development (DID) as part of the section on neurodevelopmental disorders. Reliable and valid diagnostic assessment measures are needed to improve identification and treatment of individuals with DID. Although appropriately normed, standardised intellectual and adaptive behaviour assessments are considered the optimal assessment approach in this area, they are unavailable in many parts of the world. This field study tested the BIs internationally to assess the inter‐rater reliability, concurrent validity, and clinical utility of the BIs for the assessment of DID. Methods: This international study recruited a total of 206 children and adolescents (5–18 years old) with a suspected or established diagnosis of DID from four sites across three countries [Sri‐Lanka (n = 57), Italy (n = 60) and two sites in India (n = 89)]. Two clinicians assessed each participant using the BIs with one conducting the clinical interview and the other observing. Diagnostic formulations using the BIs and clinical utility ratings were collected and entered independently after each assessment. At a follow‐up appointment, standardised measures (Leiter‐3, Vineland Adaptive Behaviour Scales‐II) were used to assess intellectual and adaptive abilities. Results: The BIs had excellent inter‐rater reliability (intra‐class correlations ranging from 0.91 to 0.97) and good to excellent concurrent validity (intra‐class correlations ranging from 0.66 to 0.82) across sites. Compared to standardised measures, the BIs had more diagnostic overlap between intellectual and adaptive functioning. The BIs were rated as quick and easy to use and applicable across severities; clear and understandable with adequate to too much level of detail and specificity to describe DID; and useful for treatment selection, prognosis assessments, communication with other health care professionals, and education efforts. Conclusion: The inclusion of newly developed BIs within the CDDR for ICD‐11 Neurodevelopmental Disorders must be supported by information on their reliability, validity, and clinical utility prior to their widespread adoption for international use. BIs were found to have excellent inter‐rater reliability, good to excellent concurrent validity, and good clinical utility. This supports use of the BIs within the ICD‐11 CDDR to assist with the accurate identification of individuals with DID, particularly in settings where specialised services are unavailable. [ABSTRACT FROM AUTHOR]

The earliest publications in the field of marriage and family therapy introduced interventions conducted with families experiencing complex health conditions. This strategic review captures an evaluation of efficacy for 87 couple and family interventions published between 2010 and 2019 with a focus on the leading causes of mortality in the United States. These health conditions include chromosomal anomalies and accidents with infants aged 0–4 years; accidents and cancer among children aged 5–14; accidents among adolescents aged 15–24; and heart disease, cancer, accidents, chronic lower respiratory diseases, stroke, Alzheimer's disease, diabetes, influenza/pneumonia, and nephritis/nephrosis among adults 25 and older. Results support the need for greater inclusion of couples and families in assessments and interventions. The greatest chasm in efficacy research was with minoritized couples and families. Implications include ways to initiate couple and family interventions in the context of health conditions with attention given to accessibility, recruitment, retention, and evaluation. [ABSTRACT FROM AUTHOR]

Background: Parents are increasingly pursuing weight loss in medical weight management programs, yet little is known about the presenting behaviors and practices of children who have parents initiating these programs. Objective: To describe congruence in weight control practices, sedentary and screen time behaviors, and family functioning and communication between parents initiating a medical weight management program and their children (ages 7–18). Methods: Twenty‐three dyads were enrolled and had measured height/weight and research packets completed including perceived weight status, weight control practices, sedentary and screen‐time behaviors, and family functioning and communication. Paired t‐tests and intraclass correlations assessed congruence; independent t‐tests determined differences based on child demographics (age, sex, and weight status). Results: Parents underestimated children's use of weight control practices compared to child reports. Children with overweight, males, and older in age had increased weight control practices and sedentary and screen‐time behaviors. Children who perceived themselves to have overweight reported more impaired family communication than children perceived to be a healthy weight. Conclusions: This study highlights the discrepancy between dyads' reports of children's behaviors, and identifies that specific child populations with overweight, older in age, and males are at‐risk of experiencing less healthy behaviors and impaired family communication. Future research should monitor changes over time in parental weight management programs to determine effects based on parental weight loss. [ABSTRACT FROM AUTHOR]

Summary: Objective: Spouses are known to influence the outcomes of an individual's attempt at weight loss, but little is known about the broader influence of, and on, the family. The objectives were to explore: (a) the effects of an adult weight management program on the family and (b) family factors that help or hinder patient weight loss. Methods: A qualitative design was employed to explore triadic family members' experiences of patient participation in a weight management program. Semi‐structured interviews were conducted with patients, partners and children (ages 7‐18). Questions included support for patient participation and weight loss, dietary choices, meal preparation, physical activity routines, the home‐food environment, communication about health and family dynamics. Thematic analysis was used, where codes and categories of codes were then grouped together to create themes and subthemes. Results: Nineteen triadic interviews were conducted (57 total). Seven themes emerged, including four related to Outcomes (objective 1): (a) shift in family dynamics, (b) family behaviour change, (c) child observations of family change, (d) indirect benefit to partner; and three related to Process (objective 2): (e) level of accountability, (f) patient perception of support and (g) support is essential and flexible. Conclusions: Future research and clinical applications from these themes should seek to determine the positive behaviour change that was evident in the families that were interviewed, where the culmination of family interactions, expectations and concurrent partner weight loss indicates the potential longevity of weight management programs beyond patients' own participation. [ABSTRACT FROM AUTHOR]

Discrimination based on an individual's weight has been observed in health care, education, retail, and other public sectors (Puhl & Huer, Obesity, 17, 941, 2007). Such inequity, known as "weight bias," generates negative short-term and long-term consequences for the individuals that experience it (Puhl & Brownell, Weight bias in health care settings, 2007). Past research has shown that healthcare trainees exhibit weight bias (Phelan et al., Obesity, 22, 1201, 2014; Wigton & McGaghie, Journal of General Internal Medicine, 16, 262, 2001), yet little focus is given to weight bias in marriage and family therapy (MFT) education. The purpose of this study was to survey MFT students (N = 162) to explore weight bias and how contextual factors associate with weight bias. Participants in MFT programs reported explicit weight bias, with specific contextual factors associating with more bias. Female participants reported more fear of gaining weight, and individuals who identified as overweight had higher rates of explicit weight bias. Contextual differences and implications for training programs are discussed. [ABSTRACT FROM AUTHOR]

The extent to which the apparent increase in wildfire incidence and burn area in California from 1990 to 2006 is affected by population and temperature increases is examined. Using generalized linear models with random effects, we focus on the estimated impacts of increases in mean daily temperatures and populations in different counties on wildfire in those counties, after essentially controlling for the overall differences between counties in their overall mean temperatures and populations. We find that temperature increase appears to have a significant positive impact on both total burn area and number of observed wildfires. Population growth appears to have a much less pronounced impact on total burn area than do annual temperature increases, and population growth appears to be negatively correlated with the total number of observed wildfires. These effects are especially pronounced in the winter season and in Southern California counties. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: In addition to the APOE locus, there has been considerable success in identifying genetic variants associated with an increased risk of developing Alzheimer's disease (AD). However, there remains considerable uncertainty about the causal genes involved in AD neuropathology and the way in which these loci are functionally regulated by AD risk variants. As the majority of genetic variants are hypothesised to act via disruptions to gene regulation, there is increasing interest in the role of the epigenome, which encompasses a diverse number of chemical modifications to DNA and nucleosomal histone proteins that directly influence gene expression. Methods: We have profiled DNA methylation in 1,284 brain samples from up to two regions (prefrontal cortex and occipital cortex) from 656 individuals in the Brains for Dementia Research (BDR) cohort. After stringent quality control, we performed epigenome‐wide association studies of four quantitative measures of neuropathology, Braak stage, Thal amyloid stage, Lewy Body stage and Cerad stage. Using matched genetic data available for these samples, performed a genome‐wide association study of methylomic variation to identify DNAm quantitative trait loci (mQTLs). These mQTL were then were integrated with results from AD GWAS, using summary data‐based Mendelian randomisation, to identify loci where DNA methylation is associated with AD. Finally, we generated polygenic risk scores for these samples and performed an epigenome‐wide study of genetic risk for AD. Results: We identified multiple differentially methylated positions (DMPs) associated with neuropathology and AD polygenic risk score, replicating previous findings at known loci and implicating genes linked to known neuropathological pathways. Integrating our database of mQTLs with summary data from a recent AD GWAS, we report pleiotropic associations between AD and DNA methylation at several sites in the genome, including associations annotated to genes implicated in AD (e.g. SLC39A13, SPI1, MS4A6A, and BCL3). Conclusions: We identified epigenetic differences associated with detailed measures of neuropathology providing insights on the molecular processes that underlie the disease progression. Furthermore, we characterised the complex relationship between genetic and epigenetic variation, identifying molecular consequences of high genetic risk for AD and prioritising candidate genes for functional follow up. [ABSTRACT FROM AUTHOR]

1 Resprouting capacity (R) and propagule-persistence (P) are traits that are often considered to have evolved where there are predictable crown fires. Because several indicators suggest a stronger selective pressure for such traits in California than in the Mediterranean Basin, we hypothesize that plant species should have evolved to become R+ and P+ more frequently in California than in the Mediterranean Basin. 2 To test this hypothesis we studied the phylogenetic association between R and P states in both California and the Mediterranean Basin using published molecular phylogenies. 3 The results suggest that R and P evolved differently in the two regions. The occurrence of the states differs significantly between regions for trait P, but not for trait R. The different patterns (towards R+ and P+ in California and towards R+ and P– in the Mediterranean Basin) are reflected in the higher abundance and the wider taxonomic distribution of species with both persistence traits (R+P+ species) in California. 4 The differential acquisition of fire persistence mechanisms at the propagule level (P+) supports the idea that fire selective pressures has been higher in California than in the Mediterranean Basin. 5 Our comparative phylogenetic-informed analysis contributes to an understanding of the differential role of the Quaternary climate in determining fire persistence traits in different Mediterranean-type ecosystems and, thus, to the debate on the evolutionary convergence of traits. [ABSTRACT FROM AUTHOR]

Provides information on a study which evaluated the role of fire in altering vegetation structure in three plant communities in inland peninsular Florida. Methods; Results and discussion.

1. Photosynthetic pathway diversity was evaluated for the dominant species in a seasonally aquatic community in the south-western USA using 14C pulse-chase techniques. 2. Under submerged conditions, only about half of the species were clearly C3, three of the 15 dominants were CAM, one species was C4 and three were potentially assimilating carbon with both C3 and C4 fixation. 3. During the brief terrestrial stage in the life history of these amphibious plants, both the CAM and the C3 + C4 species switched to C3, whereas the C4 species did not switch. 4. Numerous variations were apparent; for example, the C4 species, while exhibiting a biochemical pathway indistinguishable from terrestrial C4 plants, lacked Kranz anatomy in the aquatic foliage. Also, despite well-developed CAM in several species, others exhibited low-level diel changes in acidity, apparently not indicative of CAM. 5. Species with C4 or CAM CO2 concentrating mechanisms lacked the capacity for bicarbonate uptake, an alternative CO2 concentrating mechanism found in certain C3 species in this community. 6. Rubisco/PEPC in aquatic foliage was higher in C3 species than in C4, CAM or putative C3 + C4 species. In the terrestrial phase, as expected, the switch from CAM or C3 + C4 to strictly C3 assimilation was associated with a substantial increase in Rubisco/PEPC. Quite unexpected, however, was the substantial increase in this ratio in terrestrial C3 foliage. It is hypothesized that submerged C3 plants utilize PEPC for recycling of respiratory CO2 and/or C4 phototrophism under field conditions of limited CO2 and O2 saturation, and this is lost in the terrestrial foliage. [ABSTRACT FROM AUTHOR]

δ13C values for freshwater aquatic plant matter varies from -11 to -50‰ and is not a clear indicator of photosynthetic pathway as in terrestrial plants. Several factors affect δ13C of aquatic plant matter. These include: (1) The δ13C signature of the source carbon has been observed to range from +1 ‰ for HCO3- derived from limestone to -30‰ for CO2 derived from respiration. (2) Some plants assimilate HCO3-, which is -7 to -11‰ less negative than CO2. (3) C3, C4, and CAM photosynthetic pathways are present in aquatic plants. (4) Diffusion resistances are orders of magnitude greater in the aquatic environment than in the aerial environment. The greater viscosity of water acts to reduce mixing of the carbon pool in the boundary layer with that of the bulk solution. In effect, many aquatic plants draw from a finite carbon pool, and as in terrestrial plants growing in a closed system, biochemical discrimination is reduced. In standing water, this factor results in most aquatic plants having a δ13C value similar to the source carbon. Using Farquhar's equation and other physiological data, it is possible to use δ13C values to evaluate various parameters affecting photosynthesis, such as limitations imposed by CO2 diffusion and carbon source. [ABSTRACT FROM AUTHOR]

Several taxa of cacti are distributed in high elevation tropical alpine habitats between 40004700 m in central Peru. This region has a marked dry season with soil water potentials as low as - 25 MPa. The barrel type cactus Oroya peruviana and the low ceaspitose Tephrocactus floccosus (both the typical hairy form and a hairless form) all exhibited diurnal fluctuations of malic acid (10-100 μmol/g FW), indicative of CAM photosynthesis. δ13C carbon isotope ratios were - 13 to - 14 suggesting that for these CAM plants the bulk of the net carbon gain is through night-time carbon uptake. This occurs in spite of overnight temperatures below 0° C. CAM activity was observed on nights when air temperature dropped to -8 °C and subepidermal temperatures reached as low as -3 °C. In central Peru, the typical form of T. floccosus has a dense covering of long silvery white hairs. Comparisons with an adjacent 'hairless' form showed that the hairy morph maintained a subepidermal temperature several degrees higher during the night. At a site where the 'hairless' morph was rare, the hairy T. floccosus had substantially higher overnight acid accumulation. At another site where the 'hairless' morph was abundant, the hairy T. floccosus had substantially lower acid accumulation relative to the 'hairless' form. [ABSTRACT FROM AUTHOR]

Background: In addition to the well‐established risk associated with the APOE locus, there has been considerable success in identifying additional genetic variants associated with Alzheimer's disease (AD). Individually these variants confer only a small increase on an individual's overall risk; however, combined into a polygenic risk score (PRS), they represent a powerful tool in genetic epidemiology for the investigation of correlates of high genetic risk. We investigated the clinical and neuropathological outcomes associated with high PRS for AD in the Brains for Dementia Research (BDR) cohort. Method: 693 individuals in the BDR cohort with high quality genetic data and neuropathology measurements, including staging assessments (Braak and Thal) and established diagnostic criteria were included in this study. PRS were calculated for each individual as the number of genetic risk alleles, weighted by the log odds ratio, using the results of the largest available GWAS of AD. Statistical analysis was performed using regression models whilst controlling for age at death, sex and brain bank. Result: We report statistically significant associations between APOE genotype and Braak neurofibrillary tangle stage, a measure of tauopathy, and Thal stage, a measure of Aβ plaque propagation. We also found significant associations between AD PRS and multiple measures of neuropathology (Braak stage, Thal stage, Lewy body stage, and severe cerebral amyloid angiopathy). In order to determine if APOE and AD PRS represent independent predictors of tauopathy (Braak stage) and b‐amyloidosis (Thal stage), we performed a joint analysis finding that APOE and PRS combine in an additive manner to influence both measures of neuropathology. Conclusion: The results from this study characterise how genetic risk for AD influence both the clinical and pathological features of dementia and increases our understanding of the interaction between APOE status and other genetic risk factors. [ABSTRACT FROM AUTHOR]

Summary: Our overall objective was to describe the parent‐child, romantic, and family dynamics of adult weight management program (WMP) patients, and associations with children's and partners' weight status. First, we determined if family functioning mediated the effect between parent‐child feeding practices and perceived child weight status, and romantic relationship anxiety and avoidance and perceived partner weight status. Second, we assessed if perceived child and partner weight status moderated the associations between family functioning and parent‐child feeding practices and romantic relationship anxiety and avoidance, respectively. Patients (N=203) who resided with a child and partner from two WMPs completed assessments of parent‐child feeding practices (Child Feeding Questionnaire), romantic relationship anxiety and avoidance (Relationship Structures Questionnaire), family functioning (Family Assessment Device General Functioning Scale), and perceived child and partner weight status. Bivariate analyses determined differences in weight status and relationship dynamics and family functioning, and mediation and moderation analyses were conducted to answer the two research questions. Family functioning was not a mediator between romantic relationship dynamics and partner weight status or parent‐child dynamics and child weight status. Lower family functioning was associated with higher parent‐child restrictive feeding practices, only among children with overweight/obesity. Similarly, lower family functioning was associated with higher anxiety and avoidance in romantic relationships, only for partners with overweight/obesity. Patients with children and/or partners with overweight/obesity reported more impaired family dynamics and functioning, compared to patients with children and/or partners with a healthy weight status. [ABSTRACT FROM AUTHOR]

Summary: The purpose of this study is to examine the associations between family functioning and youth overweight and obesity in a sample of primary care paediatric patients. Specially, we hypothesize that caregivers of youth with an overweight/obese weight status will report more impaired family functioning. A cross‐sectional descriptive study was conducted with 329 caregivers of youth ages 2 to 18 seen in paediatric primary care. Caregivers completed the Family Assessment Device General Functioning Scale and clinical demographics, including parent‐reported youth height and weight to calculate body mass index (BMI). Family functioning was used as a continuous total variable, and as a dichotomous variable based on clinically impaired or healthy family functioning. Analyses included descriptive statistics, Pearson's correlations, and independent t tests. Caregivers who reported impaired family functioning based on the clinical cutoff score were more likely to report that their youth had a higher BMI and BMI z‐score. Caregivers with impaired family functioning and who identified as being in two‐parent families, with at least a Bachelor's degree, and a moderate to high family income were more likely to report their youth was a higher weight status. Further screening and assessment of family functioning in combination with youth weight status among a larger diverse sample of primary care paediatric patients over time will provide insight into what aspects of family functioning may contribute to maintaining a healthy lifestyle or adopting new health behaviours to prevent and/or treat obesity in youth. [ABSTRACT FROM AUTHOR]

The contribution of resprouts and seedling recruitment to post-fire regeneration of the South African fynbos conifer Widdringtonia nodiflora was compared eight months after wildfires in 1990. Stems on all trees were killed by fire but resprouting success was > 90 % at all but one site. A demographic study of burned skeletons revealed that prior to these fires, nearly all plants were multi-stemmed (4-9 stems/plant) and multi-aged, indicating continuous sprout production between fires. All stems were killed by the 1990 fires and at most sites > 90% of the stems were burned to ground level. All diameter stems were susceptible to such incineration as, at most sites, there was no difference in average diameter of stems burned to ground level and those left standing. Individual genets usually had all ramets incinerated toground level or all ramets charred, but intact, suggesting certain micro-sites burned hotter, whereas other sites were somewhat protected. Although not true of the 1990 fires, there was evidence that occasionally Widdringtonia stems may survive fire. At one site, four of the16 plants sampled had a burned stem twice as old as the oldest burned stem on the other 12 plants at the site, suggesting some stems had survived the previous fire (ca. 1970) and this conclusion was supported by fire-scars on these four stems that dated to ca. 1970. Based onthe highly significant correlation between stem diameter and cone density left standing after the 1990 fires, we calculated that for mostsites > 80% of the initial cone crop was incinerated by fire. This is important because we observed a strong relationship between size ofthe canopy cone crop surviving fire and post-fire seedling recruitment. Under these conditions we hypothesize that sprouting confers a selective advantage to genets when fires cause heavy losses of seed. The infrequent occurrence of sprouting in the Cupressaceae suggests thehypothesis that resprouting is an apomorphic or derived trait in Widdringt [ABSTRACT FROM AUTHOR]

CDKL5 deficiency disorder (CDD) is a genetically caused developmental epileptic encephalopathy that causes severe communication impairments. Communication of individuals with CDD is not well understood in the literature and currently available measures are not well validated in this population. Accurate and sensitive measurement of the communication of individuals with CDD is important for understanding this condition, clinical practice, and upcoming interventional trials. The aim of this descriptive qualitative study was to understand how individuals with CDD communicate, as observed by caregivers. Participants were identified through the International CDKL5 Disorder Database and invited to take part if their child had a pathogenic variant of the CDKL5 gene and they had previously completed the Communication and Symbolic Behavior Checklist (CSBS-DP ITC). The sample comprised caregivers of 23 individuals with CDD, whose ages ranged from 2 to 30 years (median 13 years), 15 were female, and most did not use words. Semistructured interviews were conducted via videoconference and analyzed using a conventional content analysis. Three overarching categories were identified: mode, purpose and meaning, and reciprocal exchanges. These categories described the purposes and mechanism of how some individuals with CDD communicate, including underpinning influential factors. Novel categories included expressing a range of emotions, and reciprocal exchanges (two-way interactions that varied in complexity). Caregivers observed many communication modes for multiple purposes. Understanding how individuals with CDD communicate improves understanding of the condition and will guide research to develop accurate measurement for clinical practice and upcoming medication trials., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Genetic variation within the dopamine D4 receptor (DRD4) gene has been implicated in many neuropsychiatric disorders and behavioral traits. This variation includes the extensively studied exon 3 variably numbered tandem repeat (VNTR), and several 5' polymorphisms including a120-bp duplication and two single-nucleotide polymorphisms at -521 C/T (rs1800955) and -616 C/G (rs747302). Several reports have provided evidence for a functional role for some of these variants using in vitro techniques. This study investigated the functionality of these polymorphisms in 28 human post-mortem brain tissue samples by quantifying DRD4 mRNA expression in relation to genotype. No statistically significant relationship between genotype and mRNA expression levels was found for these four polymorphisms although a weak trend toward the 7-repeat of the exon 3 VNTR reducing DRD4 mRNA expression was found. Employing post-mortem brain tissue, rather than using in vitro techniques may provide a more relevant paradigm to study functional effects of reported risk alleles., ((c) 2010 Wiley-Liss, Inc.)

Early institutional deprivation is a risk factor for Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. However not all individuals are affected. We tested the hypothesis that this heterogeneity is influenced by gene x environment (GxE) interaction and that genetic polymorphisms involved in dopamine neurotransmission moderate the effects of severe early institutional deprivation on symptoms of ADHD (sADHD). Using a prospective-longitudinal design sADHD were measured at ages 6, 11, and 15 years in a sample of individuals who experienced severe institutional deprivation (up to 42 months of age) in Romanian orphanages and a non-institutionalized comparison group. Individuals were genotyped for polymorphisms in the dopamine D4 receptor (DRD4 48-bp VNTR in exon 3) and dopamine transporter gene (DAT1 haplotypes combining a 40-bp VNTR in 3'UTR and a 30-bp VNTR in intron 8). The risk for sADHD associated with early institutional deprivation was moderated by the DAT1 but not the DRD4 genotypes; an effect that was first apparent in early-, and persisted to mid-adolescence. The results (i) provide evidence for developmental continuities in G x E interaction, (ii) explain some of the heterogeneity in ADHD outcomes following institutional deprivation and, (iii) add to our understanding of environmental determinants of sADHD., ((c) 2009 Wiley-Liss, Inc.)

There are conflicting reports suggesting that the parental origin of transmitted risk alleles may play a role in the etiology of attention deficit/hyperactivity disorder (ADHD). A recent report by Hawi and colleagues observed a generalized paternal over-transmission of alleles associated with ADHD. This was not replicated in more recent studies. Using data from a large multicenter study we examined the overall and gene-specific parent of origin effect in 554 independent SNPs across 47 genes. Transmission disequilibrium and explicit parent of origin test were performed using PLINK. Overall parent of origin effect was tested by Chi-square. There was no overall parent of origin effect in the IMAGE sample (chi(1)(2) = 1.82, P = 0.117). Five markers in three genes, DDC, TPH2, and SLC6A2 showed nominal association (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only. Following the initial report by Hawi and co-workers three studies, including this one, found no evidence to support an overall parent of origin effect for markers associated with ADHD. We cannot however, exclude gene-specific parent of origin effect in the etiology ADHD., (Copyright 2007 Wiley-Liss, Inc.)

Previous studies have found heterogeneous association between DAT1-3'-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD., (Copyright 2007 Wiley-Liss, Inc.)

Attention deficit hyperactivity disorder (ADHD) is currently one of the most prevalent childhood behavioral disorders. The disorder is found to be highly heritable, suggesting a large genetic component. Association studies have repeatedly implicated the dopamine transporter (DAT1) gene, and in particular the 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism located in the 3'UTR of the gene. Inconclusive data has been generated from several earlier studies on the functional effects of this polymorphism. Therefore, there is call for further investigation and thus the focus on data described here from TaqMan RT-PCR assays. The expression levels of the DAT1 gene from post-mortem midbrain tissue was measured in relation to the polymorphism present at the 3'UTR VNTR, together with a further VNTR marker located within intron 8 of the gene (Int8 VNTR). The findings suggest that the presence of the 10-repeat allele of the 3'UTR VNTR, the 3-repeat of the intron 8 VNTR and both VNTR markers are correlated with increased levels of the DAT1 transcript in midbrain post-mortem tissue. Further work using linear regression (LR) shows agreement with the correlation analysis, and either nominal significance or a trend in that direction. Given the small sample size, bootstrapping-derived confidence intervals were calculated for the LR. These empirical analyses suggest that the 3'UTR VNTR to show a significant main effect on relative DAT1 expression. Furthermore, a significant effect was found for the combined model (3'UTR and Int8 VNTR markers) on expression. These data provide further evidence on the plausible molecular mechanism underlying the aetiology of the disorder., (2007 Wiley-Liss, Inc.)