Katerina Papanikolaou

A genomewide screen for autism: Strong evidence for linkage to chromosomes 2q, 7q, and 16p

Autism is characterized by impairments in reciprocal communication and social interaction and by repetitive and stereotyped patterns of activities and interests. Evidence for a strong underlying genetic predisposition comes from twin and family studies, although susceptibility genes have not yet been identified. A whole-genome screen for linkage, using 83 sib pairs with autism, has been completed, and 119 markers have been genotyped in 13 candidate regions in a further 69 sib pairs. The addition of new families and markers provides further support for previous reports of linkages on chromosomes 7q and 16p. Two new regions of linkage have also been identified on chromosomes 2q and 17q. The most significant finding was a multipoint maximum LOD score (MLS) of 3.74 at marker D2S2188 on chromosome 2; this MLS increased to 4.80 when only sib pairs fulfilling strict diagnostic criteria were included. The susceptibility region on chromosome 7 was the next most significant, generating a multipoint MLS of 3.20 at marker D7S477. Chromosome 16 generated a multipoint MLS of 2.93 at D16S3102, whereas chromosome 17 generated a multipoint MLS of 2.34 at HTTINT2. With the addition of new families, there was no increased allele sharing at a number of other loci originally showing some evidence of linkage. These results support the continuing collection of multiplex sib-pair families to identify autism-susceptibility genes.

Variable Expression of the Autism Broader Phenotype: Findings from Extended Pedigrees

Factors influencing the rate, form, and severity of phenotypic expression among relatives of autistic probands are examined. Family history data on 3095 first- and second-degree relatives and cousins from 149 families with a child with autism and 36 families with a child with Down syndrome are studied. The results provide further evidence of an increased risk among autism relatives for the broadly defined autism phenotype. Of proband characteristics, severity of autism and obstetric optimality were confirmed as being related to familial loading for probands with speech. There was little variation in loading among probands lacking speech. The type of phenotypic profile reported in relatives appeared little influenced by characteristics of the relative or the proband, except for variation by degree of relative, parental status of relative, and perhaps probands birth optimality score. Phenotypic rates among parents suggested reduced fitness for the severest and more communication-related forms of expression but not for the more mild and social forms of expression. Patterns of expression within the families did not support a simple X-linked nor an imprinted X-linked mode of inheritance. The basis for sex differences in rates of expression is discussed.

Association Between Family Divorce and Children's BMI and Meal Patterns: The GENDAI Study

The aim of this work was to explore the associations between family factors, including divorce, and childrens overweight as well as eating and physical activity patterns in a population‐based sample of healthy school‐aged children. In this cross‐sectional study, 1,138 children (53% girls; age: 11.2 ± 0.7 years) from elementary schools in the Attica region participated. Their parents provided sociodemographic information, including their marital status. Overweight status classification was based on weight and height measurements and BMI evaluation. Children completed a physical activity checklist and a questionnaire on meal patterns and eating behaviors. The Eating Style score was calculated: the higher the score, the more frequent a child was engaged in less‐structured feeding practices promoting food intake for reasons other than hunger. Analysis revealed significant association between family divorce and childrens overweight: compared with children of married parents, those of divorced had significantly higher BMI levels (20.0 ± 3.6 kg/m2 vs. 21.3 ± 3.4 kg/m2, respectively, P = 0.007). Controlling for socioeconomic and physical activity factors, divorce remains a significant predictor of a higher BMI, along with older age, higher fathers and mothers BMI, less children in the family, and more minutes of daily screen time. Children who had experienced a divorce in their family also reported higher Eating Style score, even after adjusting for potential confounders. In conclusion, in this sample of fifth and sixth graders, unfavorable family circumstances have been associated with childrens overweight, as well as with aspects of their eating behavior, namely eating style in relation to conditions around food consumption and hunger, independent of other socioeconomic factors.

A Family Genetic Study of Autism Associated with Profound Mental Retardation

We sought to determine if the family loading for either the broader autism phenotype or for cognitive impairment differed according to whether or not autism was accompanied by severe mental retardation. The sample comprised 47 probands with autism meeting ICD-10 criteria, as assessed by the Autism Diagnostic Interview and the Autism Diagnostic Observation Schedule. Family history interview and findings were compared with those for the higher IQ autism and Down syndrome samples in the Bolton et al. (1994) study. The familial loading for autism and for the broader phenotype was closely comparable to that in the study of higher IQ autism, and different from that for Down syndrome. The family loading for scholastic achievement difficulties was slightly, but significantly, higher when autism was accompanied by severe retardation.

Using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic for the Diagnosis of Autism Spectrum Disorders in a Greek Sample with a Wide Range of Intellectual Abilities

We studied the interrelationship between the Autism Diagnostic Observation Schedule-Generic (ADOS-G), the Autism Diagnostic Interview-Revised (ADI-R) and DSM-IV clinical diagnosis, in a Greek sample of 77 children and adolescents, referred for the assessment of a possible pervasive developmental disorder (PDD) and presenting a wide range of cognitive abilities. The agreement of the ADOS-G and the ADI-R with the clinical diagnosis was estimated as satisfactory and moderate, respectively, while both instruments presented with excellent sensitivity for the diagnosis of autistic disorder along with satisfactory specificity. ADOS-G/ADI-R agreement was estimated as fair. Our results confirm the discriminant validity of ADI-R and ADOS-G in diagnosing pervasive developmental disorders in children and adolescents with a wide range of intellectual abilities.

Efficacy of antidepressants in child and adolescent depression: a meta-analytic study

Summary.Objectives: To examine whether antidepressant drugs are superior to placebo in the treatment of juvenile depression. Method: Extensive literature search was done to retrieve all randomised controlled and all uncontrolled trials describing children and adolescents with a diagnosis of depression who underwent any antidepressant drug treatment. In order to combine results, separate analyses using random effect models were conducted first for controlled and then for both controlled and open studies. Results: 18 controlled and 23 open trials were submitted to meta-analysis. Tricyclics showed no significant benefit over placebo. Odds ratios for SSRIs were 1.84 (95% CI 1.35–2.50) for controlled and 1.83 (95% CI 1.40–2.40) for controlled and uncontrolled studies suggesting a significant benefit over placebo. Combining all antidepressants also gave confidence interval excluding the value one. Conclusions: Despite some promising data concerning the use of SSRIs in the treatment of adolescent depression, caution is warranted until the long-term safety of these agents can be demonstrated. Insufficient data are available to judge even the short term merits of these agents in prepubertal children. There is no evidence to support the use of tricyclics in this population.

Circadian cortisol profiles, anxiety and depressive symptomatology, and body mass index in a clinical population of obese children

Obesity is highly co-morbid with anxiety and/or depression in children, conditions that may further worsen the metabolic and cardiovascular risks for obese individuals. Dysregulation of the hypothalamic–pituitary–adrenal axis is involved in the pathophysiology of anxiety disorders, depression, and obesity, and diverse cortisol concentrations may be found in obese children, depending on their degree of psychological distress. The aim of this study was to examine cortisol profiles among obese children with or without symptoms of anxiety and depression. A group of 128 children (53% females; mean age ± SD: 11.2 ± 2.2 years) derived from a pediatric obesity clinic were studied. Anxiety and depressive symptomatology were assessed with appropriate instruments. Morning serum and five diurnal salivary cortisol concentrations were measured. Obese children were 3.1/2.3 times more likely to report state and trait anxiety, respectively, and 3.6 times more likely to report depressive symptoms than children of the same age group, from a contemporary Greek sample. Trait anxiety and noon salivary cortisol concentrations were significantly positively correlated (p = 0.002). Overall, salivary cortisol concentrations were increased in children with anxiety or depression symptomatology compared to obese children without any affective morbidity (p = 0.02) and to those with anxiety and depression co-morbidity (p = 0.02). In conclusion, in obese children, emotional distress expressed by symptoms of anxiety and/or depression is associated with circadian cortisol profiles reflecting a potential pathway for further morbidity. Longitudinal studies may reveal a role of cortisol in linking obesity, anxiety, and depression to the development of further psychological and physical morbidity.

Comorbid attention-deficit/hyperactivity disorder in adult psychiatric outpatients with depressive or anxiety disorders

Abstract Background. There are very few studies reporting on the prevalence and the contribution of not previously diagnosed ADHD in the clinical picture of other psychiatric disorders. The aim of our study is to determine the prevalence and clinical correlates of comorbid attention deficit/hyperactivity disorder (ADHD) in adult psychiatric outpatients with depressive or anxiety disorders. Methods. During a 6-month period, 114 outpatients with depressive or anxiety disorders were evaluated for ADHD diagnosis. Assessment included interviews with both patient and relatives/friends and the use of a daily diary. Moreover, the patients completed the self-report scales Beck Depression Inventory (BDI), Spielbergers Anxiety Inventory (STAI), and the Symptom Checklist-90-R Rating Scale (SCL-90-R). Results. A total of 22 out of 114 patients (19.3%) received an ADHD diagnosis for the first time in their life. Comorbid ADHD compared to non ADHD patients scored significantly higher (p < 0.05) for depression (BDI), state and trait anxiety (STAI) and in the following SCL-90-R factors: Positive Symptoms Distressing Index, Positive Symptoms Index, Somatization, Obsessive Compulsive, Depression, Anxiety, and Hostility. Conclusions. ADHD might go unrecognized among psychiatric outpatients. Patients with depressive or anxiety disorder reporting more severe symptomatology should be carefully screened for possible comorbid adult ADHD.

Parental readiness to implement life-style behaviour changes in relation to children's excess weight.

The aim if this study is to evaluate parental readiness to implement changes in specific life‐style behaviours for preventing or reducing obesity in children.

New Interview and Observation Measures of the Broader Autism Phenotype: Impressions of Interviewee Measure.

A 20 item observational measure of social functioning, the Impression of Interviewee rating scale, is one of three measures devised to assess the broader autism phenotype. The sample studied included families containing at least two individuals with autism spectrum disorder; observations were undertaken by the researcher who interviewed the subject. An exploratory factor analysis suggested a single factor was most appropriate (Cronbach’s α of 0.78). There was a modest but significant retest correlation of 0.42. Correlations between live ratings and blind consensus ratings of vignettes were high (0.93). Correlations with the interview measures were moderate but statistically significant. In conclusion, the observational scale provides a promising start but further work is required before general use can be recommended.