Smooth-pursuit eye movement dysfunction and liability for schizophrenia: implications for genetic modeling.

Forty-one nonpsychiatric subjects, 38 probands with schizophrenia, and 99 of their relatives were studied. Oculomotor functioning was bimodally distributed for probands and relatives. Oculomotor dysfunction was not present in all families with a schizophrenic proband. In those families in which it was present, there were significant phenotypic correlations between oculomotor functioning and schizophrenia-related characteristics. The patterns of familial resemblance in the families in whom oculomotor dysfunction was present were consistent with nonadditive genetic variance contributing both to oculomotor dysfunction and to the relationship between oculomotor dysfunction and clinical symptoms. These results suggest that schizophrenia may be etiologically heterogeneous and that oculomotor dysfunction may help to identify nonadditive genetic variance for this disorder.     

Hoarding in obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study

Hoarding behavior occurs frequently in obsessive-compulsive disorder (OCD). Results from previous studies suggest that individuals with OCD who have hoarding symptoms are clinically different than non-hoarders and may represent a distinct clinical group. In the present study, we compared 235 hoarding to 389 non-hoarding participants, all of whom had OCD, collected in the course of the OCD Collaborative Genetics Study. We found that, compared to non-hoarding individuals, hoarders were more likely to have symmetry obsessions and repeating, counting, and ordering compulsions; poorer insight; more severe illness; difficulty initiating or completing tasks; and indecision. Hoarders had a greater prevalence of social phobia and generalized anxiety disorder. Hoarders also had a greater prevalence of obsessive-compulsive and dependent personality disorders. Five personality traits were independently associated with hoarding: miserliness, preoccupation with details, difficulty making decisions, odd behavior or appearance, and magical thinking. Hoarding and indecision were more prevalent in the relatives of hoarding than of non-hoarding probands. Hoarding in relatives was associated with indecision in probands, independently of proband hoarding status. The findings suggest that hoarding behavior may help differentiate a distinct clinical subgroup of people with OCD and may aggregate in some OCD families. Indecision may be a risk factor for hoarding in these families.     

Evaluating the endophenotype model of ADHD neuropsychological deficit: results for parents and siblings of children with ADHD combined and inattentive subtypes

Neurogenetic models predict neuropsychological weaknesses in the relatives of children with attention-deficit/ hyperactivity disorder (ADHD). The authors examined executive and regulatory measures in 386 relatives (307 parents, 79 siblings) of children with ADHD combined type, ADHD inattentive type, and controls. Predicted deficits were seen on trailmaking (relatives of ADHD combined type only), stop-signal reaction times (relatives of girls only), and response variability (mothers only) but not on naming or output speed. Effects generally held, even with relatives' ADHD status controlled. A neuropsychologically impaired subgroup of children with ADHD had relatives with clear neuropsychological weaknesses. The authors conclude that a neurogenetic model of ADHD etiology is supportable only for a subset of executive functions and that neuropsychological heterogeneity warrants more examination in ADHD.     

PDD Symptoms in ADHD,an Independent Familial Trait?

The aims of this study were to investigate whether subtle PDD symptoms in the context of ADHD are transmitted in families independent of ADHD, and whether PDD symptom familiality is influenced by gender and age. The sample consisted of 256 sibling pairs with at least one child with ADHD and 147 healthy controls, aged 5–19 years. Children who fulfilled criteria for autistic disorder were excluded. The Children’s Social Behavior Questionnaire (CSBQ) was used to assess PDD symptoms. Probands, siblings, and controls were compared using analyses of variance. Sibling correlations were calculated for CSBQ scores after controlling for IQ, ADHD, and comorbid anxiety. In addition, we calculated cross-sibling cross-trait correlations. Both children with ADHD and their siblings had higher PDD levels than healthy controls. The sibling correlation was 0.28 for the CSBQ total scale, with the CSBQ stereotyped behavior subscale showing the strongest sibling correlation (r = 0.35). Sibling correlations remained similar in strength after controlling for IQ and ADHD, and were not confounded by comorbid anxiety. Sibling correlations were higher in female than in male probands. The social subscale showed stronger sibling correlations in elder than in younger sibling pairs. Cross-sibling cross-trait correlations for PDD and ADHD were weak and not-significant. The results confirm that children with ADHD have high levels of PDD symptoms, and further suggest that the familiality of subtle PDD symptoms in the context of ADHD is largely independent from ADHD familiality.     

Understanding the relations among gender,disinhibition, and disruptive behavior in adolescents

This study examined whether disinhibition shows similar relations with attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) symptomatology among male and female adolescents. The mixed-incentive or punishment condition of Newman's go/no-go task was administered to 172 adolescents. As expected, ADHD symptoms in boys and girls were predictive of disinhibition (i.e., commission errors) in the mixed-incentive but not punishment condition. Also consistent with expectations, CD symptoms in boys were predictive of disinhibition in the mixed-incentive but not punishment condition. In contrast, CD symptoms in girls were not predictive of disinhibition in either condition. These findings are discussed in terms of implications for understanding sex differences in the etiology of ADHD and CD.     

Family handedness as a predictor of mental rotation ability among minority girls in a math-science training program.

Right-handed girls from nonright-handed families outperformed the other groups of minority adolescent girls enrolled in a science and technology program on a test of mental rotation ability. This target group excelled over right-handed girls with all right-handed relatives and nonright-handers. The pattern of group differences in mental rotation ability found here is consistent with those found for women with math-science training at the college level. The minority boys in the program outperformed the girls as a whole, but did not differ significantly from the right-handed girls with nonright-handed relatives. The present findings provide further support for the generality of Annett's genetic theory of handedness and brain organization, and for the interaction of genetic and environmental factors in accounting for individual differences in mental rotation ability.     

Cognitive Load Differentially Impacts Response Control in Girls and Boys with ADHD

Children with attention-deficit hyperactivity disorder (ADHD) consistently show impaired response control, including deficits in response inhibition and increased intrasubject variability (ISV) compared to typically-developing (TD) children. However, significantly less research has examined factors that may influence response control in individuals with ADHD, such as task or participant characteristics. The current study extends the literature by examining the impact of increasing cognitive demands on response control in a large sample of 81children with ADHD (40 girls) and 100 TD children (47 girls), ages 8–12 years. Participants completed a simple Go/No-Go (GNG) task with minimal cognitive demands, and a complex GNG task with increased cognitive load. Results showed that increasing cognitive load differentially impacted response control (commission error rate and tau, an ex-Gaussian measure of ISV) for girls, but not boys, with ADHD compared to same-sex TD children. Specifically, a sexually dimorphic pattern emerged such that boys with ADHD demonstrated higher commission error rate and tau on both the simple and complex GNG tasks as compared to TD boys, whereas girls with ADHD did not differ from TD girls on the simple GNG task, but showed higher commission error rate and tau on the complex GNG task. These findings suggest that task complexity influences response control in children with ADHD in a sexually dimorphic manner. The findings have substantive implications for the pathophysiology of ADHD in boys versus girls with ADHD.     

A Grammatical Specific Language Impairment in Children: An Autosomal Dominant Inheritance?

The aim of this study is to provide further characterization of a subgroup of so-called “Grammatical specific language-impaired (SLI)” children. The Grammatical SLI children have a persistent and disproportionate impairment in grammatical comprehension and expression of language. Previous research has indicated that their language impairment may be characterized by a domain-specific and modular language deficit. This study provides an initial investigation as to whether there is a genetic basis underlying their disorder as has been found for other forms of SLI and for SLI in general. The incidence of familial aggregation of language impairment was investigated in 12 Grammatical SLI children (aged 9:3 to 12:10). A familial language impairment (LI) history was classified as positive if one or more of the probands' relatives had a history of a speech/language or reading/writing problem which required speech therapy or any other form of remedial help. Case history information provided an initial indication that the Grammatical SLI children had a significantly higher incidence of a positive familial LI history than could be expected by chance. A questionnaire provided evidence of a positive LI history in the first-degree relatives of the SLI probands and 49 normally developing control probands. The SLI probands had a clearly and significantly higher incidence of a positive familial LI history than the control probands (77.8 vs. 28.5%, respectively). The results are consistent with a genetic basis underlying Grammatical SLI. The pattern of impairment in the SLI probands' relatives is consistent with an autosomal dominant genetic inheritance. In contrast to the control probands, the SLI probands' impaired relatives did not show a male gender bias. Thus, the gene does not appear to be sex-linked. The data indicate that further research is warranted to investigate the nature of the LI in the relatives of the Grammatical SLI probands and the genetic characteristics of this subgroup. The implications for the biological, domain-specific, and modular bases to language are discussed.     

Mother-Child Relationship in Youths with Attention-Deficit Hyperactivity Disorder and their Siblings

Despite impaired mother-child interactions noted in youth with attention-deficit/hyperactivity disorder (ADHD), there is no such information for their siblings. This study aimed to test whether the affected and unaffected siblings, like youth with ADHD, also encountered impaired mothering and mother-child relationships as compared to typically developing youth (TD). The sample consisted of 122 probands (107 males, 87.7 %), aged 10–16, with DSM-IV ADHD, 44 affected (26 males, 59.1 %) and 78 unaffected (28 males, 35.9 %) siblings, and 122 TD youth. Both participants and their mothers received psychiatric interviews (K-SADS-E) about the participants and reported maternal parenting style, mother-child interactions and child behavioral problems at home. Based on both reports, probands with ADHD and affected siblings (only youth report) had more impaired relationships, more behavioral problems at home, and less perceived family support than unaffected siblings and TD youth. Probands with ADHD had higher maternal authoritarian control than unaffected siblings. The findings suggest that impaired mothering, mother-child interactions, and family support are related to the presence of ADHD diagnosis in both probands and their affected siblings.     

Validity of self-report and informant rating scales of adult ADHD symptoms in comparison with a semistructured diagnostic interview

In a study of ADHD symptoms in the relatives of probands diagnosed with ADHD, the validity of self-reported and informant-reported symptoms in childhood and adulthood was investigated with a semistructured diagnostic interview, the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) adapted for adults, as a criterion. The participating relatives were 80 women and 46 men aged 17 to 77. Rating scales based on the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) were completed by participants and informants. Internal consistency of the scales and interrater reliabilities of the diagnostic interview were satisfactory. Correlations between ratings across sources of information supported convergent and divergent validity. Self-report scales and informant scales predicted interview-based diagnoses in childhood and adulthood with adequate sensitivities and specificities. It was concluded that the rating scales have good psychometric properties, at least in at-risk populations.     

Sex differences in school-aged children with pervasive attention deficit hyperactivity disorder

This study investigated 54 children (37 boys and 17 girls) with cross-situational attention deficit hyperactivity disorder (ADHD) to determine whether there are sex differences in the expression of either the primary or secondary symptomatology of ADHD. Results indicated that the male and female ADHD groups were strikingly similar on all measures of primary (impulsivity, inattention, and overactivity) and secondary (learning problems, externalizing symptoms, internalizing symptoms, peer relationship difficulties, and self-perceptions) symptomatology included in this study. The lack of significant sex differences conflicts with prior reports in the literature, and these conflicting results are discussed in terms of differences in inclusion criteria. Implications for understanding the long-term outcome of ADHD in girls are also discussed.     

Is the Positive Illusory Bias Illusory? Examining Discrepant Self-Perceptions of Competence in Girls with ADHD

It has been claimed that excessively positive self-perceptions of competence are a key risk factor for concurrent and subsequent impairments in youth with attention-deficit/ hyperactivity disorder (ADHD). We examined whether girls with ADHD demonstrate positive illusory self-perceptions in scholastic competence, social acceptance, and behavioral conduct domains. We then tested, across a five-year longitudinal span, whether (a) such self-perceptions versus (b) the constituent informant ratings or test scores were more strongly predictive of adolescent impairment and positive adjustment. Participants included an ethnically diverse sample of 140 girls with ADHD and 88 comparison girls, aged 6-12 at baseline (M?=?9.0, SD?=?1.7). Girls with ADHD rated themselves as more positive than indicated by external ratings, but these self-reports were still in a negative direction (comparison girls rated themselves as less positive than these indicators). ADHD subtypes were not related to discrepancy scores. Higher rates of depression symptoms were associated with attenuated discrepancy scores. Crucially, measures of actual competence were more strongly associated with adolescent impairment and positive adjustment than were "illusory" self-perceptions for girls with ADHD. Our findings challenge the view that, at least in girls with ADHD, overly positive and "illusory" appraisals of competence are strongly associated with future impairment and adjustment. The key psychometric point is that, in difference or discrepancy scores, the individual components of such scores should be separately examined.     

Uptake of Cardiac Screening and Genetic Testing Among Hypertrophic and Dilated Cardiomyopathy Families

Cardiomyopathy is a genetically and clinically heterogeneous, life threatening disease which affects people of all ages. Recent guidelines provide recommendations for cardiac screening and genetic testing in at-risk relatives, but the uptake and impact of these measures in the United States is unknown. This is a single institution retrospective study that characterizes the uptake of cardiac screening and genetic testing for relatives of a cohort of 57 probands with hypertrophic (HCM) and dilated cardiomyopathy (DCM) who underwent both clinical evaluation and genetic testing. Cardiac screening was indicated for 302 relatives. One hundred and seventy-three (57 %) completed cardiac screening. Forty of the 57 probands were mutation positive and genetic testing was indicated for 213 relatives. Eighty-four (39 %) completed genetic testing. The uptake of cardiac surveillance was greater than the uptake of genetic testing (p?<?0.0001) among relatives of mutation positive probands. Within the group of at-risk, asymptomatic relatives of probands, cardiac screening and genetic testing were positive in 25 % and 40 % of cases, respectively. These data demonstrate the important role and utility of cascade cardiac screening and genetic testing in the care of patients and families with HCM or DCM. The approach to cardiac screening and genetic testing should be family-specific and requires expertise in the genetics of cardiomyopathy.     

Retrospective ratings of ADHD symptoms made at young adulthood by clinic-referred boys with ADHD-related problems, their brothers without ADHD, and control participants

Retrospective childhood attention-deficit/hyperactivity disorder (ADHD) symptoms are required to diagnosis adult ADHD, but the validity of self-rated symptoms across time is questionable. Here, boys with ADHD-related problems, their brothers without ADHD, and former schoolmates rated themselves during young adulthood for ages 9, 14, and 19. Brothers rated probands retrospectively at the same ages. The young adults referred as children for ADHD (a) acknowledged childhood symptoms; (b) described improvement over time; (c) did not differ from brothers or controls on most self-ratings of young adult symptoms; (d) rated themselves as more symptomatic at age 9, but less symptomatic at age 19, than their brothers rated them; and (e) agreed only to some degree with brothers' ratings of probands' aggression (median correlation = .22). Probands' ratings showed limited agreement with judges' symptom ratings (median correlation = .16) and young adult follow-up examiners' ratings (median correlation = .14). These findings are not accounted for solely by changes in informants, nor by the course of ADHD psychopathology. They suggest some stability but limited internal consistency and validity for retrospective ADHD ratings by probands and brothers.     

Greater delay discounting among girls,but not boys,with ADHD correlates with cognitive control

Cognitive neuroscience models suggest both reward valuation and cognitive control contribute to reward-based decision-making. The current study examined the relationship between cognitive control and delay discounting (i.e., choosing smaller, immediate over larger, delayed rewards) in a large sample of boys and girls diagnosed with attention-deficit/hyperactivity disorder (ADHD; N = 95) and typically developing control children (TD; N = 59). Specifically, we examined performance on multiple measures of cognitive control (i.e., Go/No-Go task, Stop Signal task, and Spatial Span task) and delay discounting (i.e., Classic Delay Discounting and Real-Time Delay Discounting tasks), as well as the relationship between these measures. Results indicated that sex moderated the effects of group on task performance. Specifically, girls with ADHD, but not boys with the disorder, exhibited atypical delay discounting of real-time rewards. Results from correlational analyses indicated that delay discounting and cognitive control were not significantly correlated in the overall sample. Multiple regression analyses demonstrated that among girls with ADHD poorer spatial working memory and inhibitory control predicted greater real-time discounting. Collectively, findings provide support for distinct patterns of cognitive control and delay discounting among school-aged girls and boys with ADHD. Additionally, findings suggest that among girls with ADHD, those who exhibit relatively poor working memory and inhibitory control might be a particularly vulnerable subgroup with the greatest propensity to exhibit maladaptive decision-making.     

Diagnosis of Fabry Disease via Analysis of Family History

Fabry disease is an X-linked lysosomal storage condition caused by a deficiency of α-galactosidase A. In order to determine the average number of family members who are diagnosed with Fabry disease following the diagnosis of a proband, four lysosomal storage disease centers across the United States reviewed the completed pedigrees of their Fabry disease patients. In addition, data from three Fabry disease families from other centers were submitted by patients directly. The pedigree review found 74 probands (54 males and 20 females) who had 357 diagnosed family members, of which 223 were female (60.5%) and 146 were male (39.5%). Analysis found that, on average, there were five family members diagnosed with Fabry disease for every proband. Now that enzyme replacement therapy (ERT) is available for the treatment of Fabry disease, this finding emphasizes the need for all health care professionals to ensure a detailed pedigree has been constructed for each patient affected by Fabry disease and to encourage testing and evaluation of all at-risk family members.     

Sex differences in genetic and environmental influences on DSM-III-R attention-deficit/hyperactivity disorder

Approximately 5% of children are affected by attention-deficit/hyperactivity disorder (ADHD), and more boys are affected than girls. This study examined the magnitude of genetic and environmental influences on ADHD and several questions regarding sex differences in its prevalence and liability. The participants were 2,391 twin and sibling pairs from Australia, ages 3-18. ADHD symptoms in the general population were highly heritable (h2 = .85-.90), as were deviant ADHD scores in the selected population. The magnitude of familial influences was similar for boys and girls, although there were shared environmental influences on ADHD in girls but not boys and dominance genetic influences on ADHD in boys but not girls. Specific genetic and environmental influences were highly similar for boys and girls. Evidence supported the polygenic multiple threshold model rather than the constitutional variability model of sex differences in ADHD.     

Facilitating Family Communication About Predictive Genetic Testing: Probands’ Perceptions

The responsibility of informing relatives that predictive genetic testing is available often falls to the proband. Support is required during this process, however the perceived utility of genetic counseling and other strategies to facilitate communication have not been explored. We investigated the experiences of 12 individuals with hereditary nonpolyposis colorectal cancer (HNPCC) in a semistructured telephone interview. Respondents informed their immediate family about the availability of genetic testing, however many more-distant relatives were not directly informed. Respondents were mostly satisfied with the way they told family members about testing and had mixed views about the usefulness of genetic counseling. Gender differences were observed, with most men expressing a need for guidance or support in communicating to relatives. Letters and booklets were thought to enhance the quality of information but the provision of further aids is unlikely to increase the number of relatives made aware of predictive testing by the proband.     

The attributions of children with Attention-Deficit/ Hyperactivity Disorder for their problem behaviors

This study investigated the attributions children with ADHD make about their most problematic symptoms. Children were interviewed to determine the degree to which they felt their behavior was controllable, stable, global, and stigmatizing; and about the locus of the cause of their behavior. Participants were 16 children with ADHD (10 boys, 6 girls), and 16 children without ADHD (9 boys, 7 girls), ages 7 to 13. The present study demonstrated that children with ADHD viewed their most problematic behaviors as less within their control and more global across situations than children without ADHD. Children with ADHD were more likely than children without ADHD to view their most problematic behavior as always having been present, but were no more likely to view their most problematic behavior as persisting into the future. No significant group differences emerged on the locus of causality dimension. With regards to stigmatization, girls without ADHD reported that their behaviors can bother their teachers, parents, and peers, whereas girls and boys with ADHD did not perceive their behavior as bothersome.     

Observed classroom behavior of children with ADHD: relationship to gender and comorbidity

Examined hypothesized gender and comorbidity differences in the observed classroom behavior of children with attention deficit hyperactivity disorder (ADHD). The behavior of 403 boys and 99 girls with ADHD, ages 7–10, was compared (a) to observed, sex-specific classroom behavior norms, (b) by sex, and (c) by comorbid subgroups. Boys and girls with ADHD deviated significantly from classroom norms on 15/16 and 13/16 categories, respectively. Compared to comparison girls, girls with ADHD had relatively high rates of verbal aggression to children. Boys with ADHD engaged in more rule-breaking and externalizing behaviors than did girls with ADHD, but the sexes did not differ on more neutral, unobtrusive behaviors. The sex differences are consistent with notions of why girls with ADHD are identified and referred later than boys. Contrary to hypothesis, the presence of comorbid anxiety disorder (ANX) was not associated with behavioral suppression; yet, as hypothesized, children with a comorbid disruptive behavior disorder (DBD) had higher rates of rule-breaking, and impulsive and aggressive behavior, than did children with ADHD alone and those with ADHD+ANX. Elevated rates of ADHD behaviors were also observed in children with comorbid DBD, indicating that these behaviors are truly present and suggesting that reports of higher ADHD ratings in this subgroup are not simply a consequence of negative halo effects and rater biases.