Lamprini Psychogiou

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.

Paternal psychiatric disorders and children's psychosocial development

Psychiatric disorders of parents are associated with an increased risk of psychological and developmental difficulties in their children. Most research has focused on mothers, neglecting psychiatric disorders affecting fathers. We review findings on paternal psychiatric disorders and their effect on childrens psychosocial development. Most psychiatric disorders that affect fathers are associated with an increased risk of behavioural and emotional difficulties in their children, similar in magnitude to that due to maternal psychiatric disorders. Some findings indicate that boys are at greater risk than girls, and that paternal disorders, compared with maternal disorders, might be associated with an increased risk of behavioural rather than emotional problems. Improved paternal mental health is likely to improve childrens wellbeing and life course.

Autism symptoms in Attention-Deficit/Hyperactivity Disorder: A Familial trait which Correlates with Conduct, Oppositional Defiant, Language and Motor Disorders

It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes; Class 1(31%) had few autism symptoms and low comorbidity; Classes 2–4 were intermediate; Class 5(7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders.

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.

Autism symptoms in Attention-Deficit/Hyperactivity Disorder: a familial trait which correlates with conduct, oppositional defiant, language and motor disorders.

It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes; Class 1(31%) had few autism symptoms and low comorbidity; Classes 2–4 were intermediate; Class 5(7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders.

Delay Aversion in Attention Deficit/Hyperactivity Disorder: an empirical investigation of the broader phenotype.

BACKGROUND Delay-related motivational processes are impaired in children with Attention Deficit/Hyperactivity Disorder (ADHD). Here we explore the impact of ADHD on the performance of three putative indices of Delay Aversion (DAv): (i) the choice for immediate over delayed reward; (ii) slower reaction times following delay; and (iii) increased delay-related frustration-to see whether these tap into a common DAv construct that differentiates ADHD cases from controls and shows evidence of familiality. METHOD Seventy seven male and female individuals (age range 6-17) with a research diagnosis combined type ADHD, 65 of their siblings unaffected by ADHD and 50 non-ADHD controls completed three delay tasks. RESULTS As predicted the size of the correlation between tasks was small but a common latent component was apparent. Children with ADHD differed from controls on all tasks (d=.4-.7) and on an overall DAv index (d=.9): The battery as a whole demonstrated moderate sensitivity and specificity. In general, deficits were equally marked in childhood and adolescence and were independent of comorbid ODD. IQ moderated the effect on the MIDA. Scores on the DAv factor co-segregated within ADHD families. DISCUSSION There is value in exploring the broader DAv phenotype in ADHD. The results illustrate the power of multivariate approaches to endophenotypes. By highlighting the significant, but limited, role of DAv in ADHD these results are consistent with recent accounts that emphasize neuropsychological heterogeneity.

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.

Depression in fathers in the postnatal period: assessment of the Edinburgh Postnatal Depression Scale as a screening measure.

Background Postnatal depression commonly affects women after the birth of a child, and is associated with an increased risk of adverse outcomes for their children. A wide variety of measures have been used to screen for depression in the postnatal period but little research has investigated such measures with men. However depression can also affect men at this time, and this is associated with an independently increased risk of adverse child outcomes. The present study aimed to determine whether a reliable cut off point for the Edinburgh Postnatal Depression Scale (EPDS) can be established to screen fathers. Method A sample of fathers was sent the EPDS at 7 weeks after the birth of their child. A structured clinical interview was conducted with 192 men to determine whether they were suffering from depression. Results Fathers with depression scored significantly higher on the EPDS than non-depressed fathers. A score of greater than 10 was found to be the optimal cut off point for screening for depression, with a sensitivity of 89.5% and a specificity of 78.2%. Limitations The relatively modest participation rate means the results may not be fully generalisable to the whole population. Conclusion The EPDS is shown to have reasonable sensitivity and specificity at a cut off score of over 10. The study shows that it is possible to screen fathers for depression in the postnatal period and it may be valuable to administer this measure to new fathers.

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.