Vaheshta Sethna

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder : association signals in DRD4, DAT1 and 16 other genes

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

PTSD and depression in refugee children - Associations with pre-migration trauma and post-migration stress

This paper describes the effect of pre-migration and post-migration experiences on the mental health of a sample of 40 refugee children aged 8–16 who lived in London with at least one parent or a refugee relative. Children’s post-traumatic stress disorder (PTSD) and depression symptoms were assessed with standardised self-report measures (Impact of Event Scale and Depression Self-Rating Scale for Children, respectively). Information regarding past and present experiences were gathered during an interview with parents. There was a significant correlation between the number of pre-migration traumas experienced by the families and the children’s PTSD scores. There was also a significant correlation between the families’ number of post-migration stresses and children’s depression scores. Higher PTSD scores were significantly associated with the pre-migration experience of violent death of family members and the post-migration experience of an insecure asylum status. Higher depression scores were significantly associated with insecure asylum status and severe financial difficulties. The clinical implications of these findings are discussed.

DSM-IV Combined Type ADHD Shows Familial Association With Sibling Trait Scores: A Sampling Strategy For QTL Linkage

Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM‐IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, underscoring the applicability of quantitative dimensional approaches. To investigate the appropriateness of QTL approaches, we tested the familial association between 894 probands with a research diagnosis of DSM‐IV ADHD combined type and continuous trait measures among 1,135 of their siblings unselected for phenotype. The sibling recurrence rate for ADHD combined subtype was 12.7%, yielding a sibling recurrence risk ratio (λsib) of 9.0. Estimated sibling correlations around 0.2–0.3 are similar to those estimated from the analysis of fraternal twins in population twin samples. We further show that there are no threshold effects on the sibling risk for ADHD among the ADHD probands; and that both affected and unaffected siblings contributed to the association with ADHD trait scores. In conclusion, these data confirm the main requirement for QTL mapping of ADHD by demonstrating that narrowly defined DSM‐IV combined type probands show familial association with dimensional ADHD symptom scores amongst their siblings.

Do early father-infant interactions predict the onset of externalising behaviours in young children? Findings from a longitudinal cohort study

Background Factors related to parents and parenting capacities are important predictors of the development of behavioural problems in children. Recently, there has been an increasing research focus in this field on the earliest years of life, however, relatively few studies have addressed the role of fathers, despite this appearing to be particularly pertinent to child behavioural development. This study aimed to examine whether father–infant interactions at age 3 months independently predicted child behavioural problems at 1 year of age. Method A sample of 192 families was recruited from two maternity units in the United Kingdom. Father–infant interactions were assessed in the family home and coded using the Global Rating Scales. Child behaviour problems were assessed by maternal report. Hierarchical and logistic regression analyses were used to examine associations between father–infant interaction and the development of behavioural problems. Results Disengaged and remote interactions between fathers and their infants were found to predict externalising behavioural problems at the age of 1 year. The children of the most disengaged fathers had an increased risk of developing early externalising behavioural problems [disengaged (nonintrusive) interactions – adjusted Odds Ratio 5.33 (95% Confidence Interval; 1.39, 20.40): remote interactions adj. OR 3.32 (0.92, 12.05)] Conclusions Disengaged interactions of fathers with their infants, as early as the third month of life, predict early behavioural problems in children. These interactions may be critical factors to address, from a very early age in the child’s life, and offer a potential opportunity for preventive intervention.

Paternal depression: an examination of its links with father, child and family functioning in the postnatal period

Background: Maternal depression is common and is known to affect both maternal and child health. One of the mechanisms by which maternal depression exerts its effects on child health is through an increased rate of parental disharmony. Fathers also experience depression, but the impact of this on family functioning has been less studied. The aim of this study was to investigate the association between paternal depressive disorder and family and child functioning, in the first 3 months of a childs life. Methods: A controlled study comparing individual and familial outcomes in fathers with (n=54) and without diagnosed depressive disorder (n=99). Parental couple functioning and child temperament were assessed by both paternal and maternal report. Results: Depression in fathers is associated with an increased risk of disharmony in partner relationships, reported by both fathers and their partners, controlling for maternal depression. Few differences in infants reported temperament were found in the early postnatal period. Conclusions: These findings emphasize the importance of considering the potential for men, as well as women, to experience depression in the postnatal period. Paternal symptoms hold the potential to impact upon fathers, their partners, and their children. Depression and Anxiety, 2011.

A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband–sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, ∼95 cM) and Dutch (LOD>1, ∼100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

Paternal Depression in the Postnatal Period and Early Father–Infant Interactions

SYNOPSIS Objective. Paternal depressive disorder is associated with adverse effects on child development. One possible mechanism for this is through the effects of the disorder on parenting capacities. The link between paternal depression and father–infant interactions was investigated at three-months postpartum. Design. Major depressive disorder was assessed in N = 192 fathers using a structured clinical interview (SCID). Altogether, 54 fathers met criteria for depression, and 99 fathers were categorized as non-depressed. Observational assessments of face-to-face father–infant interactions were conducted in an infant-seat setting and a floor-mat setting. Associations between paternal depression and father–infant interactions were analyzed. Results. Paternal depression is associated with more withdrawn parental behavior in interactions on the floor-mat. There were few other differences in observed interaction between depressed and non-depressed fathers. Conclusions. Fathers with depression may be more withdrawn, displaying less verbal and behavioral stimulation during interactions with their young infants. They may initiate a pattern of parenting that remains compromised, potentially affecting their children’s development.

Intergenerational transmission of parenting: findings from a UK longitudinal study

Background: The quality of parenting is associated with a wide range of child and adult outcomes, and there is evidence to suggest that some aspects of parenting show patterns of intergenerational transmission. This study aimed to determine whether such intergenerational transmission occurs in mothers and fathers in a UK birth cohort. Methods: The study sample consisted of 146 mothers and 146 fathers who were recruited from maternity wards in England and followed up for 24 months [‘Generation 2’ (G2)]. Perceptions of their own parenting [by ‘Generation1’ (G1)] were assessed from G2 parents at 12 months using the Parental Bonding Instrument (PBI). G2 parents were filmed interacting with their ‘Generation 3’ (G3) children at 24 months. Results: We found that G1 mothers’ ‘affection’ was associated with positive parenting behaviour in the G2 fathers (‘positive responsiveness’ β = 0.19, P = 0.04 and ‘cognitive stimulation’ β = 0.26, P < 0.01). G1 mothers’ ‘control’ was associated with negative parenting behaviour in G2 mothers (decreased ‘engagement’ β = −0.19, P = 0.04), and negative parenting behaviour in G2 fathers (increased ‘control’ β = 0.18, P = 0.05). None of the G1 fathers’ parenting variables were significantly associated with G2 parenting. Conclusions: There is evidence of intergenerational transmission of parenting behaviour in this highly educated UK cohort, with reported parenting of grandmothers associated with observed parenting in both mothers and fathers. No association was seen with reported parenting of grandfathers. This raises the possibility that parenting interventions may have benefits that are realised across generations.

Atypical processing of voice sounds in infants at risk for autism spectrum disorder

Adults diagnosed with autism spectrum disorder (ASD) show a reduced sensitivity (degree of selective response) to social stimuli such as human voices. In order to determine whether this reduced sensitivity is a consequence of years of poor social interaction and communication or is present prior to significant experience, we used functional MRI to examine cortical sensitivity to auditory stimuli in infants at high familial risk for later emerging ASD (HR group, N = 15), and compared this to infants with no family history of ASD (LR group, N = 18). The infants (aged between 4 and 7 months) were presented with voice and environmental sounds while asleep in the scanner and their behaviour was also examined in the context of observed parent–infant interaction. Whereas LR infants showed early specialisation for human voice processing in right temporal and medial frontal regions, the HR infants did not. Similarly, LR infants showed stronger sensitivity than HR infants to sad vocalisations in the right fusiform gyrus and left hippocampus. Also, in the HR group only, there was an association between each infants degree of engagement during social interaction and the degree of voice sensitivity in key cortical regions. These results suggest that at least some infants at high-risk for ASD have atypical neural responses to human voice with and without emotional valence. Further exploration of the relationship between behaviour during social interaction and voice processing may help better understand the mechanisms that lead to different outcomes in at risk populations.

Expressed emotion as an assessment of family environment with mothers and fathers of 1-year-old children

BACKGROUND High levels of expressed emotion (EE) in parents have been found to put children at risk for emotional and behavioural problems. However, the majority of existing studies have focused on mothers of school-aged children and adolescents rather than younger children, and have only rarely included fathers. METHODS The present study examined the reliability of EE in mothers and fathers of 1-year old children. It also investigated whether depression and marital problems in the postnatal period predicted EE toward the child at 12 months. EE was assessed with the Preschool Five Minute Speech Sample in 163 families. RESULTS The rater-interrater and code-recode reliability was high for most EE dimensions. Mothers and fathers were found to display quite similar EE scores. Regression analyses showed that depression and couple relationship significantly predicted EE in mothers, but not fathers. CONCLUSIONS The findings suggest that EE provides a reliable and useful assessment of the family environment in families of young children.