To test the retinal dopaminergic hypothesis, which posits deficient blue color perception in ADHD, resulting from hypofunctioning CNS and retinal dopamine, to which blue cones are exquisitely sensitive. Also, purported sex differences in red color perception were explored.30 young adults diagnosed with ADHD and 30 healthy young adults, matched on age and gender, performed a psychophysical task to measure blue and red color saturation and contrast discrimination ability. Visual function measures, such as the Visual Activities Questionnaire (VAQ) and Farnsworth-Munsell 100 hue test (FMT), were also administered.Females with ADHD were less accurate in discriminating blue and red color saturation relative to controls but did not differ in contrast sensitivity. Female control participants were better at discriminating red saturation than males, but no sex difference was present within the ADHD group.Poorer discrimination of red as well as blue color saturation in the female ADHD group may be partly attributable to a hypo-dopaminergic state in the retina, given that color perception (blue-yellow and red-green) is based on input from S-cones (short wavelength cone system) early in the visual pathway. The origin of female superiority in red perception may be rooted in sex-specific functional specialization in hunter-gather societies. The absence of this sexual dimorphism for red colour perception in ADHD females warrants further investigation.The online version of this article (doi:10.1186/1744-9081-10-38) contains supplementary material, which is available to authorized users. Attention-Deficit Hyperactivity Disorder (ADHD) is the most frequently diagnosed psychiatric disorder in childhood, with worldwide prevalence rates estimated at 5.3% . LongituCurrent theories posit that executive function deficits account for many of the poor outcomes in ADHD, which are supported by evidence of delayed maturation and functional anomalies in the prefrontal-striatal circuitry that underpin executive functioning. However, accumulating evidence attests to anomalies in other cortical circuits in ADHD, including the visual network, suggesting that executive dysfunction may not be the dominant neurobiological characteristic of ADHD e.g., .Behavioural manifestations of visual perceptual problems, particularly color perception problems have been associated with ADHD –8. ColorPrevious studies of color perception in ADHD, including our own , have foFrom an evolutionary perspective, it has been proposed that females who served as the primary gatherers may have developed superior red color perception that would allow them to better distinguish among fruits, foliage and insects –12. MoreTo measure color saturation and contrast sensitivity, we employed a paradigm which measures the ability to discriminate test stimuli that differ in saturation/contrast level , 25. In Specifically, we examined three key variables: accuracy , slope  were recruited through college and university accessibility services across the Greater Toronto Area. Inclusion criteria were: 1) current enrolment in a post-secondary program, 2) a previous diagnosis of ADHD, 3) registration with a respective university or college Student Disability Services, which requires documented evidence of a previously confirmed diagnosis of ADHD, 4) aged 19–35 and 5) right handedness. Exclusion criteria were: 1) uncorrected sensory impairment, 2) major neurological dysfunction and psychosis, 3) current use of sedative or mood altering medication, and 4) any known genetic or current vision problems present in first degree family members. Those who are treated with stimulant medication were required to stop any stimulant medication for at least 48 hours prior to the study. Thirty control participants matched on age and gender were recruited through advertisements posted at the same local university and community. All participants provided informed written consent before starting the study. The study was approved by the Institutional Research Ethics Board.All participants  were asked to complete the following measures to assess psychological/emotional distress, cognitive impairments and activation level that may affect task performance.The ASRS  was admiF  = 1.531, p = .228, ES = .06]. Also, we compared participant scores on the 6-item ASRS Set A that was administered orally as part of the initial telephone intake interview (in which participants were required to provide examples of behaviour for each of the 6 items) with their scores for the first 6 items (Set A) from the standard questionnaire version of the ASRS: two of the participants did not complete Set A. Self-reported scores did not differ as a function of modality of gathering the information . Note that about 30% of the ADHD sample in this study also contributed data to a larger-scale reliability study of the ASRS . In each session, participants completed a total of 10 blocks of trials  for each stimulus condition  yielding a total of 1056 trials . Participants were encouraged to take a short break after finishing each block. Between each 10 blocks of a stimulus type , the clinical descriptive  and vision measures  were administered in random order. The cue conditions  were presented to participants in random order. Each cue condition consisted of a total of 704 trials over both days. Present analysis was conducted based on the 704 trials of the neutral cue condition.Participants were invited for two sessions which were conducted on two different days to avoid fatigue effect. The average interval between the sessions was 6 days, and no significant difference was found between the groups  and the red stimuli , but no difference was found with the contrast stimuli.Data points with echnique . Two datA one-way ANOVA on descriptive measures such as ASRS, K-10, CFQ and AD-ACL between the groups was performed. Vision measures such as VAQ total score and FMT  were also compared through one-way ANOVAs between the groups.Color saturation discrimination task data were analyzed in three steps to test for differences among groups, sexes, and hemispheres :F  = 23.860, p = .000; red: F  = 3.199, p = .048, contrast: F  = 15.209, p = .000], which will be discussed in the Part 2 manuscript in more details. Most of the interactions involving Cue type were not significant; Cue type by session , or Cue type by Group . Importantly, there was no main effect of session , and none of the interactions between session and group were significant . We believe that the reason we did not find a main effect of session in our paradigm is because the paradigm tests basic perceptual processing that require very fast stimuli presentation. Thus, in this paper, as in previous studies using this paradigm , as well as more problems in everyday cognitive functioning as measured using the CFQ  and higher emotional distress on the K10 . The two groups did not differ in levels of alertness or tonic arousal as evaluated with the AD-ACL  = 4.08, p = .048].One-way ANOVAs conducted on the VAQ total score revealed no significant difference between the groups  = 5.61, p = .022, ES = .097] and Stimuli . The main effect of Sex was not significant, but there was a significant Sex × Group interaction . None of the other interactions were significant: Group × Stimuli interaction , Sex × Stimuli interaction , and Group × Sex Stimuli × Stimuli interaction .A 2 × 2 × 3 repeated measures ANOVA in accuracy revealed a significant main effect for Group  and red saturation  than control participants, but no sex differences were present in contrast sensitivity accuracy. Analysis of the slope parameters is consistent with the findings from the analysis of accuracy. Specifically, female control participants showed a steeper slope for blue  and red  saturation in comparison to female ADHD participants. This difference was not found for the contrast discrimination task. Within males, no significant difference in discrimination accuracy was found between male participants in the ADHD and control groups across the three stimuli . No significant difference in slope was found among the male participants in the ADHD and control groups across the three stimuli . Results of the POE-PSE analysis revealed no significant sex difference between male and female participants, indicating no sex-related perceptual biases.To explore the significant Sex × Group interaction and also to test our a-priori hypotheses concerning group differences in color perception accuracy within male and female groups , we conducted separate one-way ANOVAs for each stimuli within each sex and also within groups. Within the control group, accuracy data in the neutral cue condition revealed that female participants were significantly more accurate in discriminating higher red saturation than males . No sex differences were found for blue saturation discrimination or for contrast discrimination . Analysis within the ADHD group revealed no significant sex differences in terms of accuracy, slope and POE-PSE for each stimulus  in the neutral cue condition .Next, we tested for the a-priori hypothesis that female controls would show superior red color saturation discrimination compared to males, by conducting one-way ANOVAs on three stimuli separately within the control group and within the ADHD group. F  = 8.22, p = .01, ES = .13] in red (control > ADHD), whereas no main effect of hemisphere or Hemisphere × Group interaction was present. Lastly, there was a significant main effect of hemisphere for contrast discrimination . A post hoc analysis indicated that accuracy was significantly higher when contrast stimuli were presented to the LVF/RH. Neither the main effect of group nor the Group × Hemisphere interaction was significant  only females with ADHD showed impairments in both blue and red color saturation discrimination compared to controls, but they did not differ in contrast sensitivity Table ; and 2) Our findings are only partly consistent with the retinal dopaminergic hypothesis of color vision, which posits that the ADHD group should be less accurate in distinguishing blue saturation compared to controls, but would not differ in either red or contrast discrimination abilities . By contThe seemingly contradictory finding of differences in both red and blue color perception in females with ADHD can be explained by the multistage color vision model , 46, whiOnly female ADHD participants showed significantly poorer accuracy in colour saturation discrimination compared to control female participants; no significant differences were present between male ADHD and control participants. Also, a phenotypic sex difference in discriminating red color saturation was found within control group, which was not present in the ADHD group.A sexual dimorphism in red color perception found in the control group can be explained with an evolutionary perspective which proposes that sex-specific functional behaviour in human hunter-gatherer societies would have allowed females to better distinguish ripe fruit , 49, 50.Notably, females with ADHD did not manifest this advantage in red saturation discrimination and showed poorer discrimination accuracy in both red and blue compared to females in control group. The absence of this sexual dimorphism in ADHD females may be attributable to a higher density and delayed pruning of dopamine receptors in the striatum found in females with ADHD during peri-adolescence . ExtensiAlthough group differences in color saturation discrimination were significant, no reliable differences were found for hue discrimination as measured by the FMT. Our results are inconsistent with findings of previous studies which reported hue discrimination differences for individuals with ADHD, specifically in the ability to discriminate blue-yellow stimuli –8. One pOur study also revealed the both the ADHD and control groups showed subtle, but significantly higher accuracy on contrast discrimination for those stimuli presented to the LVF/RH. Our results on RH superiority in contrast discrimination are in line with findings from several previous studies –64. ReceThe present study has some limitations. First, we did not verify the presence or absence of familial vision problems, nor could we verify the absence of heterozygosity in X-linked cone photopigment expression or its nature (protan vs. deutan) in female participants, which could influence chromatic sensitivity. Second, our findings may not generalize to the larger populations of adults with ADHD. Given that our participants were recruited from post-secondary institutions, they may have greater functioning than those who have not received post-secondary education, and thus, may not share the characteristics of the general population of adults with ADHD. Third, we did not confirm either the ADHD diagnosis, nor did we assess for comorbid disorders , which may themselves be associated with color perception problems e.g., . Lastly,Keeping in mind the aforementioned limitations, the current study provided evidence of decreased perceptual abilities in females with ADHD in terms of discriminating the saturation of pure red and pure blue colors, but no differences in perception of contrast in achromatic stimuli. Our findings suggest that the retinal dopaminergic hypothesis requires modification: namely to account for the fact that human perception of red implicates input from both L and S cone receptors. Also, our finding suggests that the color perception anomalies are restricted to female ADHD. Furthermore, given that attention is known to influence visual perception e.g., , 25, it Glossary.(DOCX 54 KB)Additional file 1:DKL coordinates for blue and red stimuli.(DOCX 17 KB)Additional file 2:


Children from disadvantaged socioeconomic backgrounds are at greater risk of a range of negative outcomes throughout their life course than their peers; however the specific mechanisms by which socioeconomic status relates to different health outcomes in childhood are as yet unclear.The current study investigates the relationship between socioeconomic disadvantage in childhood and attention deficit/hyperactivity disorder (ADHD), and investigates putative mediators of this association in a longitudinal population-based birth cohort in the UK.Data from the Avon Longitudinal Study of Parents and Children was used  to explore the relationship between different measures of socioeconomic status at birth-3 years and their association with a diagnosis of ADHD at age 7. A multiple mediation model was utilised to examine factors occurring between these ages that may mediate the association.Financial difficulties, housing tenure, maternal age at birth of child and marital status were significantly associated with an outcome of ADHD, such that families either living in financial difficulty, living in council housing, with younger or single mothers’ were more likely to have a child with a research diagnosis of ADHD at age 7. Financial difficulties was the strongest predictor of ADHD (OR 2.23 95% CI 1.57-3.16). In the multiple mediation model, involvement in parenting at age 6 and presence of adversity at age 2-4 mediated 27.8% of the association.Socioeconomic disadvantage, conceptualised as reported difficulty in affording basic necessities  has both direct and indirect impacts on a child’s risk of ADHD. Lower levels of parent involvement mediates this association, as does presence of adversity; with children exposed to adversity and those with less involved parents being at an increased risk of having ADHD. This study highlights the importance of home and environmental factors as small but important contributors toward the aetiology of ADHD. Groups and individuals differ in societal position by the amount and type of resources held, be these economic, social or political . IndividLow SES has been linked to poor health in childhood, specifically (but not limited to) an increased risk of dental caries , behavioThe current study focusses on associations between socioeconomic disadvantage and ADHD. ADHD is a psychiatric disorder with onset in childhood, which can persist throughout the life course . ADHD isThe association between socioeconomic disadvantage and ADHD appears to be complex and potentially mediated by other factors that may co-occur with low SES . This maAn alternate explanation for the association between SES and ADHD is passive gene-environment correlation, whereby the environment and the genes provided to children by their parents may themselves be correlated . For exaExisting literature suggests a strong association between ADHD and SES, and possible mediators in the family and home environment as these have been highlighted as potential mechanisms to explain the association , 26. PutParental depression is known to negatively affect child outcomes , and parUsing a large, population—based birth cohort from the UK, our objectives for the current study were to:-Assess if there are there individual-level associations between parental income, occupation, education and single-parent status and ADHD in the childEstablish which of these socioeconomic associations with ADHD is strongestExamine proximal home and family factors such as parent mental health, parenting involvement and psychosocial adversity as potential mediators of this effectWe hypothesised that indicators of SES would be independently negatively associated with an outcome of ADHD, and that parental education would be the strongest predictor of this association due to genetic confounding . We also hypothesised that the association between ADHD and SES would be mediated in part by family and home environmental factors such as parental psychopathology, family adversity  and parenting involvement.st April 1991 and 31st December 1992 were initially invited to enrol in the study, with supplementary recruitment taking place in two further phases. Of the 15,458 foetuses, 14,775 were live births and 14,701 were alive at one year of age.This study utilises longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Full details of the methodology and profiles of the cohort are published elsewhere –41. In bMothers, their partners [the term ‘partner’ will be used henceforth to encompass both fathers’ and partners’ of the mother who are not the study child’s biological parent] and the study child have been followed up by a combination of questionnaires, clinic visits and assessments . Sample SES was measured in eight ways in order to test the relative predictive abilities of different indicators. The exact wording of the questions that parents responded to can be seen in Parental income: Self-reported family income (mother report) was measured when the study child was 33 months old. This was reported in five increments of £100, from less than £100 per week, to £400 and over. A binary measure ‘financial difficulties’ was also included, when the parent reported difficulty in affording heating, clothing, rent/ mortgage, food and/or things for the study child .Parent Education: Mother and partner education levels were classified as less than GCSE, GCSE , and higher than GCSE. GCSE’s are the UKs standard exams at age 16, and mark the end of mandatory schooling. The educational attainment of mothers was recorded at 32 weeks gestation; however data on partners’ education level was not available until the child was aged eight. It is unlikely however, that many partners’ education substantially changed during that time, as most of the study sample will have completed their education prior to having children.Parent Employment: Employment of mothers and partners (as reported by mothers) was recorded 32 weeks into the pregnancy and was classified into four categories; unemployed; housewife/husband or retired; in education/training and employed.Marital Status/Family structure: Mothers provided information at 8–12 weeks gestation about their family structure which was classified into single/ cohabiting /married.Maternal age at birth of study child: Mothers’ age in years at the birth of the study child was recorded.Housing Tenure: Mothers reported on their housing status at 8–12 weeks gestation. This was divided into renting through the council/housing association ; private renting and home owner.Large family size: Mothers who had reported living with more than three biological children or more than two other children during the period where the study child was aged 0–2 was classed as large family size. Having a large family is known to put pressure on a household’s economic resources  and so wThe DAWBA was used to evaluate psychological disorders in the study children at 7 years 7 months old. It is a validated instrument combining structured and semi-structured questions related to DSM and ICD diagnostic criteria . There aWhen exploring aetiological theories or mediational models, the use of longitudinal as opposed to cross-sectional data are important, as researchers can ensure that the exposure is measured before the mediator and the mediator is measured prior to the outcome . Due to Parental psychopathology: Mother and partners were classed as being depressed if they had a score of 13 or more on the Edinburgh Postnatal Depression Scale, a scale validated for use both during and outside of pregnancy . Data waParenting activities age 6: Mothers were asked in detail when the child was aged 6 years 9 months about activities herself and her partner engaged in with the child. This gave a total score out of 75 for each parent, with higher scores indicating more involvement in activities with the child.Fizzy drinks/caffeine consumption at 3 years old: Parents were asked to report on how often their child drank cola and fizzy drinks, which was aggregated to form a variable for each time point of “never” “less than once a week” and “more than once a week”, based on reports of the frequency the child was drinking fizzy drinks or cola.Family adversity age 2–4: The family adversity index (FAI)  is an inContinuous variables were checked to ensure that they were normally distributed. For ease of interpretation, scores were reversed so for all the mediators an increase in score represented a more negative impact . Descriptive statistics detailed differences in means/frequencies between those with an outcome of ADHD and those without for the predictors and mediators. Unadjusted logistic regression was carried out between each SES predictor and ADHD outcome. Multivariable regression was then used with those significant predictors to derive an SES model that explained the largest possible variance in the outcome.binary_mediation “and “bootstrap” in Stata 13 [The predictor with the strongest relationship to the outcome was then used in a mediation model. Multiple mediation analysis was carried out as recommended by Preacher and Hayes  using thStata 13 .mi impute command in Stata 13.To assess the effect of missing data, descriptive statistics were reported to examine differences in the predictors between the entire ALSPAC cohort and the study sample (a subsample who completed the DAWBA assessment at age 7). These are shown in Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. The University of Exeter Medical School Research and Ethics Committee also provided approval for the current study.Mothers of children with ADHD had slightly lower levels of education, and proportionately more of the ADHD group had incomes within the lowest two bands see . The ADHAs shown in A multivariable regression model see  using siParent report of financial difficulties was regressed on ADHD with adjustment for gender.Four mediators were then tested in one model with financial difficulties at age 0–2 as the predictor and ADHD diagnosis at age 7 as the outcome. These were mother and partner involvement with the study child, maternal depression and presence of family adversity. In the multiple mediation model, bias corrected confidence intervals excluded zero  for the direct effect see , the totOur findings confirmed there were associations between some indicators of socio-economic disadvantage, namely financial difficulties, social housing tenure, younger maternal age, single-parent status and ADHD in the child. Although ADHD was more prevalent in families whose parents had lower occupational status, and lower educational levels, these indicators did not show significant association with ADHD in children in the current sample. Financial difficulty, conceptualised as reported difficulty in affording heating, clothing, rent/ mortgage, food and/or things for the study child, was the socioeconomic indicator which was associated with the greatest increased odds for ADHD. Those whose mothers were classed as in financial difficulty when the child was aged 0–2 were 2.23 times more likely to have a research diagnosis of ADHD at age 7 than their peers. This association was mediated by how involved both parents were with their child and by the presence of family adversity, such that children with less involved parents and with at least one type of family adversity were more likely to receive a diagnosis of ADHD.Although we hypothesised that parental education would be the strongest predictor of ADHD, this was not the case. The reasoning behind this hypothesis was that gene-environment correlation was likely to be high for ADHD and educational attainment, therefore those who did not attain highly in education would be more likely to have ADHD-like traits and pass these genes on to their children. Instead, financial difficulties emerged as the strongest predictor. Financial difficulties may be an indicator of very severe deprivation, which may be alter the aetiology of ADHD whereas more common, albeit disadvantageous, family circumstances did not emerge as a strong risk factor.A substantial proportion of the relationship between financial difficulties and ADHD was mediated by adverse family factors and adversity risk (28% of the relationship was mediated by the factors tested). This lends weight to theory that parent involvement mediates the relationship between SES and ADHD. Severe financial difficulties may co-exist with extremely under-resourced parenting, in some cases leading to lack of parent involvement. There are numerous studies that show ADHD is more common in extremely challenging home environments: for example among children who are looked after, neglected or who have been abused , 55. TheWebb  suggestsSES has been defined as “a broad concept that refers to the placement of persons, families, with respect to the capacity to create or consume goods that are valued in our society” . The breOur findings concur with recent research that found that home learning environment, which included aspects such as reading to children (overlapping with current study measure of parent involvement), mediated the relationship between SES and ADHD . With reBeing a single parent has been associated with an increased risk of ADHD for the child both in the current study and previously , 27, 61.It is of interest that having married parents decreases the risk of ADHD more so than does having cohabiting parents. In the Millennium Cohort Study, single parent families have substantially lower household incomes than cohabiting parents, and married parents have a higher income than cohabiting parents, reflecting an interaction between marital status and other aspects of SES . There iIn the current sample, ADHD is more prevalent among the children of younger mothers, although this association is small. Mothers’ age again ties in with socioeconomic status; as wealth and resources accumulate over time, younger mothers are often financially worse off than their older counterparts, and their education may have been interrupted by their pregnancy. Being a younger mother may also represent an increased likelihood of the study child being the first-born and unplanned, and this could manifest in differences in parenting experience and management of disruptive behaviour between younger and older mothers with single or multiple children. If the child was unplanned this may also reflect on the mother’s own ADHD-like tendencies; poor planning and risk taking behaviour, known facets of ADHD, may result in unplanned pregnancy.We found that 27.8% of the direct effect of financial difficulty was mediated. This implies that there is a direct consequence of a family suffering financial difficulty on aspects of parenting and the family/home environment that exacerbate expression of a child’s ADHD symptoms. Such family stressors could compound hyperactive behaviour. It may also be that other aspects of the home environment which lie on this pathway that were not investigated in the current study further mediate the SES-ADHD association, for example through disorganised attachment patterns .The current study has many strengths; a large, representative longitudinal birth cohort allowed for modelling of causal processes that may occur throughout childhood. ADHD was measured in the whole population, as opposed to the selection biases inherent in a clinically referred sample, giving a much clearer picture of underlying risk. Multiple imputation was used to address the limitation of missing data in the first parts of the analysis, however the binary mediation with bootstrapping and multiple imputation commands were mutually incompatible, therefore the mediation analysis was carried out with the original data. Logistic regression using the original (missing cases omitted) data are shown in As discussed by Wolke,  due to tFuture studies using a sample exposed to a wider variety of adversities (such as the E-Risk study ) may be Our results raise the question of whether, and to what extent the development of ADHD is influenced by the social, and specifically home and family context. Although relative effects of socioeconomic, home and family factors are likely to be small, they are important because unlike genetic predisposition or genetic risk, they can be current targets for intervention. The results also underline that the notion of ADHD as an entirely fixed underlying biological entity requires qualification, as noted elsewhere .Clinicians should be aware that children and young people presenting with symptoms of ADHD are likely to have complex and often difficult family circumstances. Taking a holistic approach to treatment and referral on to other services that may support the families’ to cope with their socioeconomic situation are important aspects of care for these children. On a societal level the results of this study question whether the current benefits system in the UK provides sufficient support for families with children to afford basic necessities such as food, heating and clothing, which are necessary in order to promote health and wellbeing. Cross-cultural research exploring the prevalence of ADHD in societies with differing social support systems may further elicit the impact that inadequate living conditions has on rates of ADHD.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.


We aimed to determine whether early parenting is associated with externalizing and internalizing symptoms in children with attention-deficit hyperactivity disorder (ADHD) and whether such an association is affected by the brain-derived neurotrophic factor (BDNF) val66met polymorphism.The participants included 92 patients with ADHD aged 6–15 years. Measures of parenting in early life and externalizing and internalizing symptoms and the genotype of the BDNF Val66Met polymorphism were obtained.p = 0.011).The degree to which the baby’s autonomy was allowed was significantly and negatively correlated with the CDI scores in ADHD children . After adjusting for the child’s gender, the child’s age, the family’s gross annual income, and the maternal education level, there was a significant interaction for the BDNF genotype and mother’s positive feelings about caring in relation to the development of childhood anxiety/depression in ADHD children (F = 2.51, Our results provide evidence of an interaction between the BDNF met allele and early parenting on the development of depression/anxiety symptoms. Attention-deficit hyperactivity disorder (ADHD) affects 8% to 12% of school-aged children . From thGiven the wide heterogeneity and complex manifestations of the disorder, recent theoretical work has suggested the importance of a developmental perspective that views ADHD as a multi-factorial disorder with multiple, causal processes and pathways through development , 6. GiveIndeed, much of the research literature has focused on the association between family factors and ADHD symptomatology –9, ratheA recent review focused on family characteristics associated with ADHD  providedAlthough there is a paucity of studies that examined family factors contributing to the development of comorbid symptoms of ADHD , many studies conducted in general population found that dysfunctional parenting was shown to their offspring’s externalizing and internalizing problems. For example, high level of behavioral control by parent is related to low levels of externalizing problems , 12 and Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily, which includes growth factors that promote cell survival, differentiation and death. BDNF has key effects on the serotonergic , glutamaThe BDNF gene, located on human chromosome 11p13, has a guanine-to-adenine single-nucleotide polymorphism (SNP) at nucleotide 196 (rs6265) that results in an amino acid substitution of methionine (Met) for valine  at codon 66. This substitution changes the 5-prime proregion of the human BDNF protein and appears to lower depolarization-induced secretion of BDNF in the brain, leading to a decrease in available BDNF and a possible impairment of the central nervous system , 28. TheIn this study, we investigated the effect of early parenting on the development of ADHD and the relationship between parenting in early life and externalizing  or internalizing  symptoms during childhood among children with ADHD. Based on previous studies in general population , 18, 19,et al. [Children and adolescents with ADHD were recruited from the Department of Psychiatry at the Seoul National University Hospital in Korea. The recruited children were between 6 and 15 years old and had been diagnosed with ADHD according to the DSM-IV criteria as ascertained by a child psychiatrist and a semi-structured interview. To diagnose ADHD and comorbid disorders, we used the Korean Kiddie-Schedule for Affective Disorders and Schizophrenia—Present and Lifetime Version (K-SADS-PL). The Korean version of K-SADS-PL was standardized by Kim et al. . The KorWe evaluated mother-child interactions and maternal parenting style during infancy or toddlerhood using the self-report questionnaires developed by the Mater University Study of Pregnancy and its Outcomes (MUSP) group . The MUSMothers were asked a series of 6 items about their feelings toward caring for their babies during the first year after birth . These items were assessed using a 5-point Likert-type scale (1 = strongly disagree to 5 = strongly agree). Scores of some items were reversed, and high scores represented positive feelings about caring for the baby. The scale produced a good reliability coefficient (Cronbach α =0.75) .Mothers were asked a series of 4 items about the time spent teaching their babies during the first year after birth . These items were assessed using a 5-point Likert-type scale (1 = strongly disagree to 5 = strongly agree). The scores for all of the items were reversed, and high scores represented high involvement in teaching the baby. The scale showed acceptable reliability (Cronbach α =0.65) .Mothers were asked a series of 3 items about their parenting styles with regard to their babies’ dominance during the first year after birth . Items were assessed using a 5-point Likert-type scale (1 = strongly disagree to 5 = strongly agree). Some items were reversed, and high scores represented a highly dominant baby.Mothers were asked a series of 3 items about their parenting styles with regard to their babies’ autonomy during toddlerhood . Items were assessed using a 5-point Likert-type scale (1 = strongly disagree to 5 = strongly agree). All of the items were reversed, and high scores represented high autonomy/low control. The scale showed a Cronbach’s α value of 0.48 .Children with ADHD completed the Korean version of the Children’s Depression Inventory . The motGenomic DNA was extracted from the blood (stored frozen) using a G-DEX II Genomic DNA Extraction Kit . The detection of a single nucleotide polymorphism was based on the analysis of primer extension products generated from the genomic DNA that was previously amplified using a chip-based MALDITOF mass spectrometry platform . All primers in the PCR and homogenous mass extension reactions were designed using Assay Designer 3.1   .p-value less than 0.013 (=0.05/4 parenting variables) was considered to be significant. We also noted any finding with a p-value less than 0.05.Pearson correlation analyses were conducted to elucidate the relationships between parenting variables in toddlerhood and the ADHD and comorbid symptom manifestation in children with ADHD. We then performed linear regression analyses in which all parenting variables were concurrently entered along with the child’s gender, age, the family’s gross annual income, and the maternal education level. Next, we conducted multivariate modeling to examine the relationships among the parenting variables, the BDNF Val66Met genotypes, and the ADHD and comorbid symptoms; the child’s gender, the child’s age, the family’s gross annual income, and the maternal education level were included as covariates. A genotype-by-parenting variables interaction term was also included in the model. In these models, the genotype variable dichotomized subjects into two groups - children with the BDNF Val/Val genotype and children with another genotype, because several previous studies found that there were some differences in availability of BDNF protein  and clinA total of 92 children with ADHD  and 41 healthy controls  participated in the study. Table Table p >0.05). There were no significant differences in comorbid symptom severity between ADHD children with the BDNF Val/Val genotype and those with the Val/Met or Met/Met genotypes (p >0.05).Among the children with ADHD, the Val/Met genotype (50.6%) showed the highest frequency among the BDNF Val66Met polymorphism. The Val/Val genotype (27.1%) showed the next highest frequency and the remaining 22.3% of children had the Met/Met genotype. The genetic distributions of the Val66Met polymorphism of BDNF coincided with the expected values of the Hardy-Weinberg Equilibrium (p = 0.011)  Table . The intB = −0.59, 95% CI = −1.15 to −0.04, p = 0.035), although this association was not significant when adjusted with Bonferroni correction. However, for the subjects with the BDNF Val/Val genotype, no associations were found   or maternal psychopathology  could not be examined. Fourth, there was no control group. To determine whether the influence of the BDNF genotype-parenting variable interaction on the child’s comorbid symptoms is specific to ADHD patients, we should have obtained parenting, symptomatic, and genetic data from healthy controls. Finally, the sample size of the present study was very small for genotypic analysis; thus, the results should be carefully interpreted and further work is needed to confirm the findings of this study.Despite these limitations, our results provide evidence of an interaction between the BDNF met allele and early parenting on the development of depression/anxiety symptoms. However, owing to our small sample size, these results should be considered preliminary in nature and require careful interpretation. Additional prospective, controlled studies in a larger sample are warranted to evaluate the association between parenting in early life and the development of comorbid symptoms in ADHD as well as the effects of a G X E interaction.


To scale up evidence-based treatment of conduct problems, parent management training, Oregon model (PMTO) has been disseminated throughout Norway. This study examined whether Attention Deficit Hyperactivity Disorder (ADHD) predicted the outcomes of PMTO. Of 253 children and families, 97 were reported to have an ADHD diagnosis. Although different at intake, the groups with and without ADHD had close to an equal change in behavioral status following treatment. Maternal depression and family income predicted the combined group's behavior following PMTO. The study indicates that reductions in conduct problems following PMTO are of the same magnitude in children with or without ADHD. However, some characteristics may differentially predict outcomes for children with combined problems. Children with conduct problems (CP) and co-occurring Attention Deficit Hyperactivity Disorder (ADHD) problems have been identified as being at high risk of lifelong trajectories of antisocial and delinquent behavior  is an effective treatment for children with conduct problems  and lower on social skills and academic competence at intake, we wanted to examine whether this was the case in the present study. We also examined whether individual differences in behavioral change in the combined CP and ADHD group would be predicted by variables previously demonstrated to moderate outcomes in the treatment of children with CP or ADHD . Specifically, the research questions were:During the recruitment period between January 2001 and April 2005, 331 children with conduct problems and their families received PMTO via Child and Adolescent Mental Health agencies and Child Welfare Services , and of these 236 (73.1%) were boys. The average gross annual family income was NOK 416.558 (SD = 222.069), approximately US$68,625 (SD = $36.58), which in Norway represents a lower to middle income level. The average age of the reporting parent was 37.67 years (SD = 6.3). Thirty-five percent were single parents, 30% had a college or higher university degree, 52% had finished high school, and 18% had completed junior high or elementary school. Most of the parents (94% of n = 266) were of Norwegian ethnic background. Children could be referred irrespective of being medicated or not, but on condition that no changes could occur during treatment. Children who were on medication at intake were asked to continue this during treatment, and children who were not on medication were asked not to start during the trial.Children under the age of 12 and their parents (or guardians) could be referred for treatment (Two-hour assessments were conducted before (pre) and after (post) PMTO treatment. Eligible families were informed about the study and signed written consent forms. The parent who reported to have spent the most time with the child rated the child's behavior. If parents agreed, then children's teachers were asked to fill out questionnaires about the child's behavior. Parents received NOK 300 (about US$50) and teachers received NOK 100 (about US$17) as compensation for their participation.The Child Behavior Checklist (CBCL) and Teacher Report Form , in which higher scores represent greater symptomatology. Alpha coefficients at preassessment and postassessment were found to be within an acceptable range (from .73 to .96). Of the 253 included at preassessment, 19% of CBCL and 22% of the TRF assessments were missing at postassessment.The Social Skills Rating System . At postassessment, scores were missing for 10% of the 202 school-aged children in the study.The Parent Daily Report (PDR) has shown to be a reliable and valid measure of conduct problems  were measured by the Symptom Checklist-5 (SCL-5) which is a five-item scale based on SCL-25 has been proven valid and reliable in earlier Norwegian studies  = 0.24, p = .65). All families who started PMTO-treatment were asked to participate in the data assessments, regardless of how many sessions of treatment they received.The treatment is principle-based and conducted according the PMTO manual or handbook . Problem solving helps family members negotiate disagreements, establish house rules, and specify consequences for following or violating rules  procedure . Imputation was performed on missing items only, thereby leaving out cases in which entire scales were missing. A missing completely at random (MCAR) test was carried out for each EM, and if this test failed, then regression analysis was used to impute missing values. Outliers were identified and inspected both at preassessment and postassessment, and the 5% trimmed mean was compared with the original mean. The outliers had little impact on the original mean and were therefore not modified. All scales were found to be within an acceptable range of skewness and kurtosis (+/−2), and consequently, no transformations of variables were conducted.T-scores, based on gender-specific standardizations of the measures in Norwegian samples  and representative high and low scores  for the continuous variables. To verify the statistical significance of the interactions, simple slope tests were conducted  = 20.15, p < .001; externalizing problems, F = 7.42, p < .001; and social problems, F = 11.35, p < .001, than those without. The teacher reports (TRF) showed that children with ADHD scored significantly higher on attention problems, F = 15.61, p < .001; externalizing problems, F = 5.36, p < .05; and social problems, F = 7.11, p < .01; but also lower on social skills, F = 9.36, p < .01; and academic competence, F = 5.51, p < .05. This indicates that the group reported to have the ADHD diagnosis scored significantly higher on both parent and teacher ratings of attention problems, indicating the validity of the parent and/or therapist reports of ADHD. Furthermore, based on normative scores adjusted for age and gender, the mean T-score was 84.36 for the group with ADHD diagnosis on the Child Behavior Checklist (CBCL) attention problem scale. Thus, the average child in the group reported to have an ADHD diagnosis scored about 3.5 standard deviations above the normative mean for Norwegian children.At intake, the parent reports demonstrated that children with an ADHD diagnosis scored significantly higher on attention problems, t = −2.52, p < .01. Furthermore, children in the included group scored higher on CBCL attention problems, t = 2.41, p < .02; and TRF attention problems, t = 2.85, p < .005. In order to probe this finding, we ran an ANOVA to test for differences between the excluded group, the ADHD group, and the group without ADHD. The ANOVAs (using Bonferroni post hoc test criteria) revealed a significant difference between the ADHD group and the excluded group on both measures, while differences were nonsignificant between the excluded group and the group without ADHD. This indicates that most of the excluded cases did not qualify for a diagnosis of ADHD.The children reported to have a diagnosis of ADHD were compared with those who were excluded from analyses because of missing information about ADHD. At pretreatment, parent age was significantly lower in the included group , Of all the families, 232 (92%) completed one or more of the instruments at postassessment. At pretreatment, there were no significant differences between the attrition group and the completers on background and child behavior variables.children with and without diagnosed ADHD were compared on demographic characteristics, there were no significant baseline differences between the two groups on child age, family income, parent age and education, and number of siblings. In addition, single-parent status, child's ethnicity, and receiving welfare did not differentiate the two groups. Significantly more children diagnosed with ADHD were recruited from Child and Adolescent Mental Health services (N = 61) than from Child Welfare Services  and the majority were boys. Gender and type of organization were therefore included as covariates in the main analyses.When ADHD or not predicted only 1of 14 outcomes in this study ; children with an ADHD diagnosis were rated by their parents to score lower on social skills, F = 2.69, p < .10, after PMTO treatment  = 3.89, p < .05, and parent reported, F = 9.33, p < .004, attention problems; and on teacher, F = 5.02, p < .04, and parent reported, F = 4.17, p < .05, social competence. However, on parent- and teacher-reported externalizing and social problems, and on academic competence, the groups did not differ significantly.In all models, prescores for the outcome, the type of treatment organization, and child gender were controlled. Overall, the variable N = 26 of 97) moved from the clinical to the nonclinical range on parent-reported externalizing problems compared with 30% of children with CP only. Furthermore, among the children with or without co-occurring ADHD, an equal proportion of 16% moved from the clinical range to the nonclinical in teacher ratings of externalizing problems. The percentage remaining in the clinical range on externalizing behavior problems across treatment was the same in both groups (47% in parent ratings), while on teacher ratings, more children remained above the 90th percentile in the combined CP and ADHD group (57%) than in the CP group (45%). The difference was, however, not significant, χ2 (1) = .57, p = .51.Among the children with CP and ADHD, 36% , CBCL externalizing behavior , TRF externalizing behavior , and academic competence . When examining the simple slopes for these interaction effects, ADHD combined with high scores on SCL-5 consistently showed poorer outcomes on PDR , parent-reported externalizing behavior , academic competence , and teacher-reported externalizing behavior . By contrast, for children without ADHD, high scores on maternal depression/anxiety were associated with lower scores on teacher-reported externalizing behavior problems . For children without ADHD, all other slopes were nonsignificant  moderated the effects of ADHD on the following outcomes: the PDR , TRF externalizing behavior , and TRF attention problems . The simple slope analyses consistently showed that ADHD combined with low family income predicted poorer outcomes on parent-reported social skills , TRF externalizing behavior , and TRF attention problems . By contrast, for children without reports of an ADHD diagnosis, the simple slope analysis indicated that high family income was associated with poorer outcome on teacher-rated attention problems . All other slopes were nonsignificant. Thus, the results indicated that the combination of ADHD and low family income predicted less benefit from PMTO treatment in 3 of 14 analyses.As illustrated in Figure F = 4.63, p < .03, M = 87.62, SD = 8.68) than children without reports of ADHD, M = 98.21, SD = 12.27, F = 13.70, p < .01, F = 3.42, p < .10, ADHD combined with single-parent status predicted poorer outcome on parent-reported social skills, n = 51). In the ANCOVAs, significant predictions of medication appeared for only 1 out of 14 analyses: Children who were medicated had poorer outcomes on teacher-reported attention problems, F = 5.44, p < .05, F = 3.69, p < .06, Additional analyses were carried out to examine whether the outcomes among children with ADHD were influenced by whether they were reported to be medicated or not  refer children to these services when they recognize or suspects ADHD. Except for a lower change in parent-rated social skills for children with ADHD, there were no main effects of ADHD on child behavioral outcomes at termination of treatment. Although different at intake, their change in behavioral status did not differ significantly from pretreatment to posttreatment and the two groups did not differ at the end of treatment in terms of their externalized problem behavior and social problems, neither at home nor at school. However, despite a similar magnitude of change, the group with both ADHD and CP still showed higher scores of both teacher- and parent-reported attention problems and social competence at the end for treatment compared to the CP-only group. So, on the one hand, findings indicate that PMTO has produces beneficial change regardless of ADHD. On the other hand, and paradoxically, the higher scores on attention problems and social competence in the group with both ADHD and CP may suggest otherwise.Examination of interaction effects indicated some interesting findings. First, mothers of children with ADHD who experienced a high degree of depression/anxiety reported significantly poorer outcomes following PMTO on scores on both teacher- and parent-reported externalizing problem behavior. Second, the combination of ADHD and low family income predicted less positive outcomes on parent and teacher ratings of child problem behavior . Single-parent status did not predict outcomes, except for lower scores on parent-rated social skills. The findings also indicated that medication had a negligible effect on children with ADHD's behavioral status following PMTO, predicting differences in only 1 of 14 outcome variables.Considering the clinical significance of the outcomes, one third of the children moved from the clinical to the nonclinical range of the externalizing problem behavior according to parent ratings, but only half as many did so according to the teachers. Analyzing movement between the clinical and nonclinical range of externalizing behavior, the children with combined CP and ADHD improved less following PMTO according to teachers than according to parents. However, it should also be mentioned that very few children in the entire group of participants moved from the nonclinical to the clinical range of externalizing problems during treatment; 2% according to parents and 9% according to teachers.DSM-IV manual , this study was unable to demonstrate that the changes were attributable to the intervention given the lack of a comparison group. Furthermore, attrition cannot be dismissed as a potential influence on the findings of the present study, although no significant differences emerged between the attrition group and the completers when compared on background and child behavior/adjustment variables. Behavioral changes following PMTO were analyzed in a pre-post design, and future studies should include follow-up assessments in order to investigate long-term outcomes of PMTO for children with a co-occurring ADHD condition. The current study, carried out in regular services, substantiates the view that co-occuring ADHD did not predict behavioral change in children over and above conduct problems  predicted less beneficial child outcomes. Maybe families struggling with multiple problems will respond better if PMTO incorporates a multisystemic and flexible approach when needed. For instance, enhancements can be made to address the particular needs of mentally distressed mothers who receive parent training (Kjøbli et al.,


Hymenoptera was that of Hymenoptera and, of course, the discovery of many additional species. In producing this checklist we (the authors of the various chapters) have tried to provide a useful entry to the literature dealing with the identification and classification of the species involved, particularly for the less familiar parasitoid groups. The checklist also begins the process of summarising data on species' distribution on a country-level basis. I hope that this will serve to stimulate increased interest in this relatively neglected part of the British and Irish fauna.The last complete checklist of the British and Irish Hymenoptera fauna, and, hopefully, provides a backbone to recording efforts and the underlying taxonomy. Having an endpoint to this project has stimulated much research in to our fauna, including the critical examination of museum collections, and thus pushed some checklist sections to a state they might not otherwise have reached. Of course, a checklist is never finished. The next incarnation will be digital, and the checklist is already in the process of migrating to a Scratchpad (Hymenoptera of the British Isles), where updates will be maintained as and when changes occur.This volume serves as a standard reference point for the British and Irish Additions to the British and Irish list since Hymenoptera is extremely rudimentary. Where practicable, country-level occurrences are listed. The recording units are England, Ireland, Isle of Man, Scotland and Wales. Data on the Channel Islands are not included as they are faunistically  much closer to France. Thus, species known only from the Channel Islands within the UK, and covered by handbooks such as Ichneumonoidea and Chalcidoidea, much of the distribution data have been obtained from systematically checking through the collections of the Natural History Museum, London (NHM), and (for Ichneumonoidea) National Museums of Scotland, Edinburgh (NMS). The collections of the NMS have been invaluable in updating this checklist as Mark Shaw has very actively encouraged taxonomists to use the collections, which contain a large amount of recently collected, often reared, material. Additional valuable distributional and biological data will be contained within the collections of other museums and for other taxa but time and available expertise are constrained. The aculeate superfamilies are much better recorded with distribution data being gathered by the Bees, Wasps and Ants Recording Society and published in a series of atlases (www.bwars.com). Another large group of Hymenoptera, the sawflies, is also covered by an active group of recorders (the Sawfly Study Group) and there is a Nocturnal Ichneumonoidea Recording Scheme (http://www.nhm.ac.uk/research-curation/about-science/staff-directory/life-sciences/g-broad/index.html). Hopefully, recording efforts for parasitoids will gather pace and distribution data will begin to bear more of a resemblance to the real distribution of a species but, for the moment, the majority of British parasitoid Hymenoptera are known from small numbers of specimens in collections.Our knowledge of the distribution of most  atlases . These dHymenoptera as a whole. Where there is an extensive British literature, which is mainly true of the sawflies and the aculeates, synonyms have mostly been restricted to those names that have appeared in the British literature. For most other groups there is little in the way of a body of British literature. In these cases, all  synonyms are listed. Recent catalogues have been used and cited, where such works exist. Deviations from these works, usually from more recent publications, are cited. We have not always followed the most recent taxonomic changes when we have considered these to be incorrect or poorly justified.This is not a catalogue but, nevertheless, we have generally included extensive synonymy and notes on the sources of taxonomic changes, which seemed essential given the shortage of readily accessible resources on the name  [when the combination has since changed]'. Due to the nature of the listing of names in a checklist, some synonymous names appear here in combinations (and hence sometimes specific name endings) that may not have appeared in the literature before. It was felt that this was a better solution than listing all names in their original combinations, which in many cases will hardly ever have been used in the recent literature. Hopefully all specific endings are correct but some errors may well have slipped through the net. A checklist is full of compromises but our guiding intention has been to present all the relevant information in a manner that it as compact and informative as possible.Species names are listed in their current combinations followed by the original combination; synonyms follow the format, 'Hymenoptera, as in many insect groups, are inconsistently applied and, where they are applied, it is generally with very little justification. Where subspecific names have been treated recently as synonymous they are simply listed in the synonymy. Where subspecies have been used as valid taxonomic ranks in recent publications an explanatory footnote has been added.Subspecific names are not listed in the main body of the checklist. Subspecific names in article 45.6 of the ICZN, or when they were described on the basis of British specimens. Sometimes it is unclear whether a varietal name is valid or not and we have included these.In a few cases, names have been included in the format 'sp.W', in anticipation of a forthcoming description of a new species. Varietal names have generally been excluded, except where they have been made available as species-group names under Hymenoptera is now comfortably the largest insect order in the British Isles. That will come as no surprise to those of us who work on them but the disparity between the size of the Hymenoptera fauna and that of the Coleoptera or Lepidoptera may surprise some entomologists. That some sections of this checklist now differ substantially from their 1978 versions is a sign of the progress that has been made; that the checklists of some fairly large families remain very little changed since 1978 is an indication that there is still much work to be done in assessing the true scale of the British fauna. It needs to be emphasised that our knowledge of some families is still rudimentary. For example, the checklist of British and Irish Eurytomidae is still based on a few papers by Claridge and co-workers and on Walker's original descriptions. Similarly, the amount of 'added value' that could be brought to sections of the checklist was highly variable as there was no taxonomic expertise available for several groups; this is particularly true of the family Ceraphronidae. Whilst much unpublished information was added to the Ichneumonoidea checklist, for example, and the literature rather thoroughly surveyed, the same could not be achieved for the Ceraphronidae section, because that knowledge base is simply not there.At 7,761 species, the Vespidae, the relative change reflects the level of actual change in the fauna, with colonisation of Britain by several species. Generally though, the recorded level of change is indicative of the amount of work on that group.In deriving the total species numbers in Table Fig. 1Hymenoptera has been divided into three sub-orders, the 'Symphyta' for the sawflies, 'Parasitica' for the non-aculeate parasitoid wasps and the 'Aculeata' for the aculeates, i.e., the group of ants, bees and wasps that has lost the ability to use the sting as an ovipositor. Although the 'Parasitica' and 'Aculeata' together form a clade, the Apocrita, and the aculeates form a monophyletic group within the Apocrita, 'Symphyta' and 'Parasitica' are each demonstrably paraphyletic ; (2) we know too little about the inter-relationships of higher taxa within the Hymenoptera and next to nothing about the inter-generic or species-level relationships of the vast majority of Hymenoptera; (3) when alphabetically arranged, it is much simpler to find a name.Traditionally the ic e.g.,  so we doHymenoptera tree of life. The conclusions generally support the superfamily classification as summarised by Proctrotrupoidea has been successively chopped up since 1978 and I follow Proctotrupoidea by treating the Diaprioidea as a separate superfamily. Note that, although there are only two British families of Proctotrupoidea and one of Diaprioidea, these are more diverse in the wider world, with several extralimital families. However, Diaprioidea may be paraphyletic with respect to the Chalcidoidea and Mymarommatoidea. Recent studies have differed in suggesting that Ismarinae may , and other authors recognising a series of families (six in Britain). The first approach derives from the fact that bees are but one lineage of apoid wasps, equivalent to the Crabronidae or Sphecidae. The second approach emphasises the biological and phylogenetic distinctiveness of several clades of bees. I have followed the second approach, of dividing bees into several families, on the pragmatic grounds that this is the approach taken by There are two approaches to the classification of bees, with some authors recognising a single family, Hymenoptera and they have generally been very poorly defined.The family-level taxonomic ranks used here are Superfamily, Family, Subfamily and Tribe. Sub-tribes have not been included here; the use of sub-tribes is very inconsistent in http://iczn.org/node/40200).Various abbreviations are used in the checklist, relating to distribution, status, specimen depositories and nomenclature. Fuller explanations of nomenclatural terms and how they relate to the articles of the zoological code of nomenclature can be found in the International Code of Zoological Nomenclature  or identification in the British Isles uncertainmisident. has been misidentified as this namenomen dubium, a name of doubtful statusnom. dub. nomen oblitum, ‘forgotten name’, does not have priority over a younger namenom. ob. nomen novum, a replacement namenom. nov. nomen nudum, an unavailable name, with no type specimennom. nud. preocc. name preoccupied (junior homonym)status revocatus, revived status stat. rev. unavailable name unavailable under provisions of the ICZN codevar. variety, only available as a valid name under certain provisions of the ICZN codeCynipidae)-a- name based on agamic  generation (used in Cynipidae)-s- name based on sexual generation (used in


Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and have both performance and brain dysfunctions during motor response inhibition. Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders.We therefore used functional magnetic resonance imaging (fMRI) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders, as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine.Age-matched boys with ADHD (18), ASD (19) and healthy controls (25) were compared with fMRI during a stop task measuring motor inhibition. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomised design. Repeated measures analyses within patients assessed drug effects. To test for potential normalisation effects of brain dysfunctions, patients under each drug condition were compared to controls.Under placebo, relative to controls, ASD boys showed overactivation in left and right inferior frontal cortex (IFC), while ADHD boys showed disorder-specific underactivation in orbitofrontal cortex (OFC) and basal ganglia. Under fluoxetine, the prefrontal dysfunctions were no longer observed, due to inverse effects of fluoxetine on these activations: fluoxetine downregulated IFC and OFC activation in ASD but upregulated them in ADHD.The findings show that fluoxetine normalises frontal lobe dysfunctions in both disorders via inverse effects, downregulating abnormally increased frontal activation in ASD and upregulating abnormally decreased frontal activation in ADHD, potentially reflecting inverse baseline serotonin levels in both disorders.The online version of this article (doi:10.1007/s00213-014-3837-2) contains supplementary material, which is available to authorized users. It has been argued that inferior frontal activation during stop task performance may be confounded by the attentional oddball effect of the low frequency appearance of stop signals  Oldfield  25 cont participADHD boys had a clinical diagnosis of non-comorbid ADHD, inattentive/hyperactive-impulsive combined subtype, as assessed by an experienced child psychiatrist using the standardised Maudsley diagnostic interview that assesses ADHD according to DSM-IV criteria  Exclusion criteria for all were comorbidity with other psychiatric or neurological disorders and drug/alcohol dependency. Patients were recruited from local clinics and support groups.Patients were scanned twice in a double-blind, randomised, placebo-controlled design, using a Latin square randomization design for counter-balanced effects. Due to the half-life of fluoxetine (1–3 days) and its metabolite norfluoxetine (5–16 days) . The 8 min 49 s minute visual tracking stop task requires withholding of an already triggered motor response to a go stimulus when it is followed unpredictably by a stop signal  relative to go trials (80 %), which also activates IFC , calculated by subtracting the mean stop signal delay  from the mean reaction time (MRT) to go trials, i.e. MRT-SSD  as independent factor and drug condition (placebo/fluoxetine) as repeated measures were conducted to test for group by medication interaction effects on performance.Gradient-echo echoplanar MR imaging (EPI) data were acquired on a General Electric Signa 3T Horizon HDx system at the Centre for Neuroimaging Sciences, Institute of Psychiatry, King’s College London, UK. A semiautomated quality control procedure ensured consistent image quality. A quadrature birdcage headcoil was used for RF transmission and reception. In each of 28 non-contiguous planes parallel to the anterior-posterior commissure, 296 T2*-weighted MR images depicting BOLD contrast covering the whole brain were acquired with TE = 30 ms, TR = 1.8 s, flip angle = 75°, in-plane voxel-size = 3 mm, slice thickness = 5.5 mm and slice-skip = 0.5 mm. A whole-brain high-resolution structural scan (inversion recovery gradient echo planar image) on which to superimpose the individual activation maps, was also acquired in the inter-commissural plane with TE = 30 ms, TR = 3 s, flip angle = 90°, 43 slices, slice thickness = 3.0 mm, slice skip = 0.3 mm and in-plane voxel-size = 1.875 mm.All subjects performed three other fMRI tasks which are not reported here.http://www.brainmap.co.uk/) ) were conducted to identify the direction of the group differences.For between-group comparisons between controls and patients under either placebo or fluoxetine, one-way ANCOVA analyses with group as factor and rotational and translation movement in Euclidian 3-D space as covariate, were conducted using randomization-based tests for voxel or cluster-wise differences as described in detail elsewhere  were conducted to identify the direction of the interaction effects.A 2 × 2 ANCOVA  with rotational and translation movement as covariate was conducted using randomised-based testing for voxel or cluster-wise differences as described elsewhere  = 3; n.s.) but in IQ  = 10, p < 0.001) which was significantly lower in ADHD relative to control and ASD boys (p < 0.005), who did not differ. Given that ADHD children have typically lower IQ than their healthy peers  = 1.2; p = n.s.) nor fluoxetine  = 2.7, p = n.s.) nor were there any group or group by medication interaction effects for the within-patients analysis  < 1, p = n.s.). MANOVA showed a trend for a significant group effect for placebo ; p < 0.08), which was due to increased omission errors between controls and patients under placebo  = 4, p < 0.02). Post hoc analyses (corrected for multiple testing using least significance difference (LDS)) showed that this was due to ADHD boys having increased omission errors than both control (p < 0.05) and ASD boys (p < 0.01)  = 1.2, p = n.s.).As expected, all subjects achieved approximately 50 % probability of inhibition, suggesting the algorithm was successful and there were no differences between controls and patient groups in this measure for either placebo .Within the patient groups there were no significant group  or group by medication interaction effects  for any variables  = 0.02, p = n.s.).Given that ADHD patients performed the task twice, but controls only once, we also measured practice effects in the ADHD group using repeated measures d which is representative of movement in x, y and z. The formula was used to produce a d value for the maximum translation and maximum rotation of each participant.The Euclidean formula described below was used to produce a 3-D movement value known as F (df = 4118) = 2, p = 0.14) or maximum xyz translation (F(df = 4118) = 1, p = 0.58). Nevertheless, to eliminate any potential effects of non-significant variance in motion, these Euclidean motion parameters for maximum xyz translation and rotation were used as covariates in the fMRI analyses.Repeated measures ANOVAs showed no significant group by movement interaction effects in the Euclidean measures of maximum xyz rotation  reaching into putamen and globus pallidus and in left inferior parietal lobe (IPL). The hypothesised difference in right IFC was observed at a more lenient .05 Fig. , Table 3p < 0.005) and trend-wise compared to ADHD boys (p < 0.08). In left middle/IFC, ASD patients had significantly increased activation compared to both control and ADHD boys (p < 0.005) who activated this region during failed inhibition and had a trend-wise reduction relative to controls (p < 0.08). In left OFC/STL/basal ganglia both control and ASD boys, who did not differ from each other, showed increased activation relative to ADHD boys who activated this area during failed inhibition (p < 0.005). Left IPL was significantly reduced in both patient groups relative to controls (p < 0.05), with ASD patients activating this area significantly more during failed inhibition than ADHD (p < 0.05).Post hoc analyses showed that the group effect in right IFC was due to significantly increased activation in ASD relative to control boys . No other correlations were significant.To test whether group effects were related to task performance, we correlated all clusters with SSRT and omission errors, since they were lower in ADHD relative to controls and ASD. The (reduced) activation in left OFC/basal ganglia in ADHD was significantly negatively correlated with omission errors (p < 0.0001). SMA proper was significantly more activated in patients, who did not differ relative to controls, who activated this region more during failed inhibition (p < 0.05). In bilateral IPL, controls and ASD boys had increased activation during successful inhibition relative to ADHD boys who activated this region more during failed inhibition (p < 0.05). In right IPL, ASD boys also had increased activation relative to controls (p < 0.05). In precuneus, ADHD boys showed significantly enhanced activation for successful inhibition relative to both ASD (p < 0.05) and controls who activated this region during failed inhibition and differed relative to ASD (p < 0.05). Correlations with behaviour showed that activation in pre-SMA/superior frontal cortex during successful inhibition was negatively correlated with SSRT in the ASD group . Activation in precuneus was negatively correlated with SSRT in the ADHD group .There were significant group differences in bilateral pre-SMA/superior frontal cortex, SMA proper, left IPL/middle temporal lobe, right IPL and precuneus Fig. , Table 3To establish whether the group differences between controls and patients under each drug condition  were significantly different, we directly compared the effect sizes (ES) of the group differences from the two case-control comparisons  = (es1 − es2)/sqrt(se12 + se22).When comparing two effect sizes, the z = −0.9, p = n.s.), right IFC  or the left inferior parietal activation clusters , suggesting that the normalisation effects in these clusters were not statistically significant.For the abnormalities in the ADHD patients, the effect sizes of the ADHD placebo-control contrast was not significantly different from the effect sizes of the ADHD fluoxetine-control comparison for left OFC  and right IFC , both of which were enhanced under placebo but normalised under fluoxetine, and for left inferior parietal lobe, which was significantly reduced in ASD relative to controls under placebo, but enhanced under fluoxetine . The findings show that all normalisation effects in these clusters were statistically significant.For the abnormalities in the ASD patients, however, the effect sizes for the ASD placebo-control contrast were significantly different from the effect sizes for the ASD fluoxetine-control contrast for left IFC . (2) Fluoxetine increased activation in left OFC/STL/putamen/globus pallidus in ADHD during successful inhibition relative to placebo, but reduced it in ASD (p < 0.05). (3) Both patient groups activated left IPL during failed inhibition under placebo, but ADHD boys activated this region more during failed inhibition and ASD boys more during successful inhibition under fluoxetine (p < 0.0001). (4) Right cerebellum activation was increased under fluoxetine in ADHD relative to placebo for successful inhibition, while ASD boys activated this area during failed inhibition under both placebo and fluoxetine (p < 0.05). (5) At a more lenient p < 0.05, relative to placebo, fluoxetine increased activation in the hypothesised right IFC during successful inhibition in ADHD and decreased it in ASD (p < 0.05)  Fluoxetine reduced pre-SMA activation in ADHD boys, whereas it increased it in ASD boys during successful inhibition ( 0.005).  Fluoxeti0.0001).  Right ceNo significant correlations with performance were observed. All findings remained when IQ was covaried for.The findings reveal opposite brain dysfunction patterns in inhibitory brain regions in ADHD and ASD as well as opposite disorder-dissociated modulation effects of fluoxetine on these neurofunctional abnormalities. Relative to controls, ADHD patients showed reduced left OFC/basal ganglia activation, whereas ASD patients showed enhanced bilateral ventrolateral prefrontal activation relative to ADHD and controls. Fluoxetine normalized these disorder-dissociated brain abnormalities relative to controls, via disorder-dissociated opposite effects within patients: fluoxetine enhanced the abnormally reduced OFC/basal ganglia activation in ADHD, but reduced it in ASD. In contrast, it reduced the abnormally enhanced IFC activation in ASD, but enhanced it in ADHD. However, rigorous testing for the significance of these normalisation effects showed that these were only significant for the abnormality clusters in ASD. Furthermore, fluoxetine also had opposite disorder-dissociated effects on other inhibition areas such as pre-SMA and cerebellum: these were, respectively, enhanced (SMA) and reduced (cerebellum) in ADHD with fluoxetine relative to placebo, but reduced (SMA) and enhanced (cerebellum) in ASD.The finding of disorder-specific increased activation in ASD relative to controls and ADHD in the left and right (trend-wise significant relative to ADHD) IFC extends our previous finding of increased left IFC activation in young adults with Asperger's syndrome during a go/no-go task Below is the link to the electronic supplementary material.


Malnutrition in children under five years remains a significant problem in Bangladesh, despite substantial socio-economic progress and a decade of interventions aimed at improving it. Although several studies have been conducted to identify the important risk factors of malnutrition, none of them assess the role of low birth weight (LBW) despite its high prevalence (36%). This study examines the association between LBW and malnutrition using data from the Bangladesh Demographic and Health Survey (BDHS) 2011 and provides practical guidelines for improving nutritional status of children.Malnutrition in children is measured in terms of their height-for-age, weight-for-height, and weight-for-age. Children whose Z-scores for either of these indices are below two standard deviations (–2SD) from median of WHO’s reference population are considered as stunted, wasted or underweight, respectively. The association between malnutrition and LBW was investigated by calculating adjusted risk-ratio (RR), which controls for potential confounders such as child’s age and sex, mother’s education and height, length of preceding-birth-interval, access to food, area of residence, household socio-economic status. Adjusted RR was calculated using both Cochran-Mantel-Haenszel approach and multivariable logistic regression models controlling for confounder.The prevalence of malnutrition was markedly higher in children with LBW than those with normal birth-weights . While controlling for the known risk factors, children with LBW had significantly increased risk of becoming malnourished compared to their counter part with RR 1.23 (95% CI:1.16–1.30), 1.71 (95% CI:1.53–1.92) and 1.47 (95% CI: 1.38–1.56) for stunting, wasting and underweight, respectively. The observed associations were not modified by factors known to reduce the prevalence of malnutrition, such as higher education of mother, better household socio-economic conditions and longer birth-interval.Higher education of mother, better household socio-economic conditions and prolonged birth intervals alone are not sufficient in bringing about substantial reductions in prevalence of child malnutrition in Bangladesh. Targeted interventions should be designed to reduce prevalence of LBW in addition to improving mother’s education and other socio-demographic conditions. Malnutrition is considered as one of the major causes of morbidity and mortality in children under five years of age ,2. It haReducing the burden of malnutrition in children under five years is now one of the major concerns of the government and many international agencies in Bangladesh. Therefore, it is essential to identify the factors associated with malnutrition in children under five so that stakeholders can implement evidence-based policy to improve nutrition status. Identifying these factors and providing practical guidelines to improve nutrition has become one of the main challenges for public health researchers . StudiesLBW is reported in many studies –30 as a Data on child nutrition has been extracted from the database of the Bangladesh Demographic Health Survey (BDHS) 2011 conducted between November 2010 and April 2011. The BDHS is a nationally representative sample survey that has been carried out every two years since 1993 through the collaborative efforts of the National Institute of Population Research and Training (NIPORT),ICF International (USA), and Mitra and Associates under the world-wide demographic and health survey program (DHS). BDHS is a retrospective study based on two stage stratified-cluster sampling design where each of the seven adminstrative divisions was treated as strata. From each stratum the primary sampling units called PSUs  were randomly selected at the first stage and households were then randomly selected from each PSU at the second stage. The survey collects health and reproductive history of both men and women of reproductive age. In particular, it collects information on childhood mortality, maternal and child health, nutrition, breast feeding practice and knowledge and attitude regarding HIV/AIDS. Nutrition information has been collected for all living children of age up to 5 years at the time of interview by recording their anthropometric measurements. Children with twin or multiple birth history were excluded from the analysis to avoid correlation in data from multiple births. Therefore, this study is based on 7530 living children of age under five years who have anthropometric data available. Further details may be found in the report on BDHS 2011 .The Eithics committee at NIPORT, Mitra and Associates, and ICF international approved a waiver from eithical approval for this retrospective study. As the de-identified data for this study came from the secondary sources, this study does not require eithical approval.The dependent variable of this study is malnutritonal status  in children under-five years that is measured using three different anthropometric indices called stunting (lowheightforage), wasting (low weight for height) and underweight (low weight for age). Each of these indices are expressed as the number of standard deviation (SD) units (Z-score) from the median of the reference population for which the 2006 WHO  Child Growth Standards were calculated ,32. WHO Birth weight is considered to be the main independent variable or risk factor of interest because the focus of this study is to assess the association between LBW and malnutrition. The BDHS including all DHS in developing countries retrospectively collect information on baby’s size at birth based on mother’s perception as proxy of birth weight by asking question “was the newborn very large, larger than average, average, smaller than average or very small?” This is because majority of births in Bangladesh, like other developing countries, occur at home without proper measurement of birth weight. Actual weight at birth was possble to obtain only for 38% births in 2011 survey. However, the birth weight was reported more often by mothers with higher education and better socio-economic condition and who delivered birth at health facility. Therefore, including birth weight particularly low birth weight in the analysis would introduce selection bias due to such socio-economic differences.Some recent studies –35 conduIt is a well known fact that child malnutrition is the outcome of multiple factors. Hence, in addition to LBW, several other independent variables have been considered following relevant literature ,19,27. TTo explore the relationship between LBW and malnutrition, risk ratio (RR) of malnutrition comparing children having LBW with those having normal birth weights was calculated from 2x2 table consisting of one of the malnutrition indicators in the column and birth weight status in the row. However, the true relationship between malnutrition and LBW may be distorted by other risk factors associated with both LBW and malnutrition (confounding). To mitigate the influence of a given risk factor or confounder, the association between LBW and malnutrition was assessed separately at each level of that confounder . This provides RRs with 95% confidence interval for each level of the confounder. The adjusted RR was then calculated as the weighted average of stratum-specific risk ratios (Cochran-Mantel-Haenszel approach) controlling for the confounder. In the next step significance of interactions was assessed by fitting logistic regression models with log link function containing an interaction term for LBW and the confounder and their corresponding main effects. Separate models were estimated for each of the dependent variables stunting, wasting and underweight that collectively reflect malnutritional status. Finally, the relationship between LBW and child malnutrition was assessed in a multivariate setting by controlling for all possible confounders and significant interactions in a multivariable regression model.The risk factors ‘child age’ and ‘mother’s height’ were considered as continuous variables in the multivariable model to allow for their full variation. However, these variables were treated as categorical in 2x2 table analysis to make them interpretable. The linearity of the continuous risk factors was examined by including their quadratic terms in the model and found linear relationship with the risk of malnutrition.As the dataset used in the study is extracted from a multistage cluster survey, all the statistical analyses were conducted allowing for the design effect of complex survey to provide precise confidence interval for RR. Analyses were conducted using a combination of packages “svy”, “epitab” and “binreg” in Stata version 12.It is evident from data that a higher percentage of children with LBW are malnourished compared to those with normal birth weights. For example, among the children with LBW, 50.9% are stunted, 24.6% are wasted, and 52.1% are underweight compared to 38.6%, 13.9% and 32.6%, respectively in the case of children with normal birth weights (results not shown). These prevalences are still markedly high among children with LBW compared to those with normal birth weights at each level of the confounder in stratified analysis , 1.53 (95% CI: 1.44–1.63), and 1.53 (95% CI: 1.44–1.63) for stunting, wasting and underweight, respectively. Similarly, a significantly increased risk of malnutrition  is observed among children with LBW at all levels of the risk factor socio-economic status. The RR is also significantly greater than one indicating that LBW is associated with malnutrition even after taking into account the effect of socio-economic status  remains statistically significant with RR values of 1.23 (95% CI: 1.16–1.30), 1.71 (95% CI: 1.53–1.92) and 1.47 (95% CI: 1.38–1.56) being observed for stunting, wasting and underweight, respectively. Similar findings are observed when the association between LBW and child’s BMI-for-age is investigated (results not shown). Further investigation is also conducted by fitting multivariable linear regression to the continuous Z-score for each of the malnutrition indicators instead of their binary outcome and found similar results (not shown).This study has examined the association between LBW and malnutrition among children under five years in Bangladesh while adjusting for other known risk factors. In the literature, mother’s education, socio-economic status and length of preceding birth interval are well established risk factors of child malnutrition yet the link between LBW and child malnutrition in Bangladesh has not been thoroughly studied. In this paper, a detailed analysis using retrospective data has been conducted to investigate how and to what extent LBW is associated with the nutritional status of children under five years of age. Such association studies reveal whether there is a systematic variation in the prevalence of LBW among malnouished and healthy children. This in turn may be useful in generating hypotheses and designing future studies that investigate whether LBW has a causal effect on malnutrition.This study has found a very strong positive association between LBW and malnutrition among children under age five in Bangladesh. For example, the risk of being underweight during the early years of childhood was found to be 47% higher in children with LBW than in children with normal birth weights even after controlling for other factors in a multivariable model. Thus, it appears that babies who are underweight at birth have a tendency to remain underweight during their early childhood. The observed association between birth weight and malnutrition is consistent with the findings of other studies ,26,36–40On the other hand, the link between LBW and child malnutrition could possibly be described by the increased vulnerability of children with LBW to infections, such as, diarrheal and lower respiratory infections and the increased risk of complications including sleep apnea, jaundice, anemia, chronic lung disorders, fatigue and loss of appetite compared to children with normal birth weights ,42–44. GHowever, perhaps the most interesting finding of this study is that the well known risk factors for child malnutrition, such as, mother’s education, length of preceding birth interval and socio-economic conditiondid notmodify the association between LBW andmalnutrition. The implications of this finding are important. This suggests that once a baby is born underweight, the risk of becoming malnourished during the first five years of life is higher compared to a baby of normal birth weight even if the mother is educated, household socio-economic conditions are good, and the preceding birth interval is long. This may be one explanation as to why prevalence of malnutrition has remained high in Bangladesh during the last decade despite marked improvements with respect to each of these factors over the same period.Based on the results of the current investigation, it is our opinion that a reasonable prescription for addressing the child malnutrition problem in Bangladesh would be to reduce the prevalence of LBW in addition to spacing births and improving mother’s education and socio-economic well-being. Since child malnutrition has its origins in the foetal period , favorabAs discussed in the medical literature, the main reason for LBW in developing countries is intra-uterine growth retardation (IUGR) ,30. A baUnfortunately, the percentage of women in Bangladesh seeking health care during pregnancy from trained health care providers is still below 50% , which iIn conclusion, this study has provided evidence of a strong link between LBW and child malnutrition. This link is crucial to the formulation of successful interventions aimed at reducing the prevalence of child malnutrition. For a quick improvement in nutritional status of children under five in Bangladesh, it is very urgent to undertake targeted interventions aimed at reducing prevalence of children with LBW in addition to improving women’s education and other socio-demographic conditions.One caveat regarding measurement of the main exposure variable LBW should be mentioned. Since the BDHS 2011 collected information retrospectively, actual birth weight measurements were unavailable, so that LBW was defined based on mother’s perception of the size of child at birth. Underreporting is therefore expected since most mothers would be able to recall whether the baby was underweight only if the baby was very small in size (i.e. << 2500gm). Thus, the prevalence of LBW was found to be 16.7% in our study, which is much lower than 35.6% obtained by the 2004 National Low Birth Weight Survey  that mea