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Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data. © The Author(s) 2011.

Aim: To evaluate the prevalence of symptoms of posttraumatic stress disorder (PTSD), depression and anxiety among children and adolescents exposed to the 2007 fire disaster in Greece along with the relationships of these symptoms with disaster-related stressors and sociodemographic characteristics four months after the fire. Methodology: A sample of 343 youths aged 9-18 years from schools in an area severely affected by the fire completed self-reported questionnaires. The Children’s Post-Traumatic Stress Disorder-Reaction Index-Revised (CPTSD-RI-R), the Children’s Depression Inventory (CDI) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) were used to assess relative symptoms, while fire-related stressors were also examined in respondents. Results: The estimated prevalence rates of high levels of PTSD, depressive and anxiety symptoms four months after the disaster were approximately 45%, 34% and 32%, respectively. Staying without both parents after the fire was strongly associated with more PTSD symptoms, while housing adversity and loss of property were most strongly associated with elevated depressive symptoms. Life-threatening experience of a loved one and worry for a loved one predicted higher levels of PTSD symptomatology, whereas injury of a loved one was associated with high levels of depressive and anxiety symptoms. Conclusion: A significant proportion of children and adolescents exposed to 2007 Greek forest fires experienced mental health problems four months after the fire. Different types of stressors were associated with PTSD, depressive and anxiety symptoms. These findings highlight the importance of preventive and treatment mental health services in the aftermath of similar disasters.

Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings.

Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings. © 2011 Macmillan Publishers Limited All rights reserved.

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 3 10-28. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10-28 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. © The Author 2010. Published by Oxford University Press. All rights reserved.

The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours 1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable ( ∼90%)3, the underlying genetic determinants are still largely unknown.Hereweanalysed the genome-wide characteristics of rare (

Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 × 10-7). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

Purpose. The purpose of this study was to assess self-reported depressive and anxiety symptoms in adolescents with polycystic ovary syndrome (PCOS) and those with the rare Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKHS), compared with healthy adolescents. Material and methods. The participants were 49 adolescent girls, of whom 27 were patients with confirmed menstrual disorder, 22 with PCOS and 5 with MRKHS; and 22 were healthy eumenorrheic adolescents (control group) matched by age and school grade. The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-Gr) were used to measure depression and anxiety, respectively. Results. The results showed that it was 1.08 times more likely for the PCOS group (p=0.043) and 1.12 times more likely for the MRKHS group (p=0.039) to have higher scores than healthy adolescents on the anxiety scale. The MRKHS group was 1.40 times more likely to have a higher number of depressive symptoms (p=0.040) than the control group. Conclusions. These findings, although based on a small sample, suggest a relationship between PCOS and MRKHS and the presence of psychological problems, such as anxiety and depressive symptoms in adolescents. This study is among the first to examine psychological difficulties in adolescents with such a rare menstrual syndrome as MRKHS.

The objective of this study is to determine the level of depressive symptoms among a sample of Greek children aged 8-12 years, as measured by the Greek Children's Depression Inventory (CDI), as well as to examine CDI's psychometric properties. A nationwide school-based sample of 650 children was initially recruited and depressive symptoms were assessed with the CDI among 538 children who provided all relevant information. Statistical evaluation included assessment of CDI internal reliability, test-retest reliability, determination of age, gender and socioeconomic status (SES) effects. Based on the distributions of CDI scores observed in this normative sample, a recommended cutoff score, identifying a high probability of serious levels of depressive symptoms that need to be further evaluated, was defined. Internal reliability and test-retest reliability were satisfactory and the expected associations with age and gender were observed. High SES was correlated with significantly less depression symptoms. The prevalence of depressive risk, when the cutoff point of 19 or 13 was taken as threshold, was much lower than those obtained from studies in other countries. The cutoff point of 15, corresponding to 90th percentile of the present sample, may be used as a screening threshold for further assessment. The present results are encouraging providing evidence about the psychometric properties of the CDI and implications for child mental health promotion planning in Greece. Further validation of the CDI against other measures and psychiatric diagnoses is needed. © 2009 Springer-Verlag.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs. © 2007 Nature Publishing Group.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs. © 2007 Nature Publishing Group.

We report on a case of a 6-year-old female with partial trisomy 8p(21-23) associated with autism, mild dysmorphic features, and moderate learning disability. Although mental retardation is a common finding in patients with mosaic trisomy 8 or partial trisomy of various regions of chromosome 8, only two cases associated with autism have been reported so far. Also, in our case clinical manifestations were mild compared to other patients with duplication of the same region of chromosome 8. Although there has been no strong evidence for linkage on chromosome 8 in any of the genome-wide linkage studies so far, the possibility that this segment includes genes involved in the etiology of autism should be further explored. © Springer Science+Business Media, Inc. 2006.

Mental health budgets, services and programs are seldom commensurate with mental health needs in the countries, particularly of population groups whose voice in advocacy is weak. In this inquiry we explored the adequacy of mental health care resources available for the young in Europe. To achieve this objective this survey investigated a few variables (e. g., number of services, degree of coverage, trained personnel) that were used as gross indicators of the discrimination suffered by this health sector. We sent a short postal questionnaire to the mental health focal points of the 51 countries included in the World Health Organization European Region. Thirty six countries (70.5%) responded. The results showed that the degree of coverage and quality of services for the young were generally worse in comparison with those for adults, including for serious disorders. A lack of both specialized and in-training personnel was identified. The exposure of general practitioners and pediatricians to psychiatry for the young was limited. Generally, the lower the income level of the country the worse the situation. Our mapping confirmed findings of previous inquiries. European child psychiatry leaders had raised a set of recommendations to improve the current situation; their implementation can now benefit from novel strategies adopted by the World Health Organization to advance mental health worldwide.

The mental health needs of adults with learning disabilities have not been adequately addressed in many European countries. Although carers can play a significant role in identification and referral, they usually lack the expertise necessary to identify signs of mental disorders. This study evaluated a care staff training programme aiming at improving awareness on issues of dual diagnosis in a group of 36 care staff from residential and community centres in Greece. Training was based on the British Mental Health in Learning Disabilities Training Pack and the PAS-ADD Checklist. The overwhelming majority of staff were very satisfied with training. Staff from institutional work settings, with no previous training on dual diagnosis and with a lower level of education, benefited to a significant degree. Changes occurred mostly in their knowledge and attitudes rather than practice. Supervised practical training is vital to transfer, strengthen and maintain positive changes at work. © 2004 Sage Publications.

The objective of the present study was to assess symptoms of posttraumatic stress disorder (PTSD), depression and anxiety among children 6 months after they had been exposed to an earthquake (EQ) affecting the northwestern suburbs of Athens in September 1999. A total of 115 children attending two elementary schools located at the epicentre of the EQ were assessed. A group of 48 children not affected by the EQ attending a school not affected by the EQ were used as controls. The children and their parents completed a number of questionnaires. Overall, there was a high rate (78%) of severe to mild PTSD symptoms in the EQ exposed group. Additionally, a substantial proportion of these children scored above criteria (32%) for depression compared to the control group (12.5%). Severe or moderate symptoms of PTSD were associated with high scores of depression (p=0.002). The relationship between PTSD symptoms and anxiety was limited to the “avoidance” factor of the anxiety questionnaire (p=0.029). Those who were most likely to be affected were children alone at the time of the EQ, and children who sustained injuries. In summary, countries where EQs are frequent should be prepared to offer psychological support to a substantial proportion of children presenting with PTSD and depressive symptoms and should educate and prepare children to cope with these events.

Background: The objective of this study was to assess psychiatric disorders in, and the psychosocial adaptation and academic performance of, children of immigrant families of Greek origin from countries of the former Soviet Union. Method: At a preliminary stage, all immigrant children (276) aged 8-12 years attending 22 schools in a working-class suburb of Athens were assessed by their teachers in terms of behaviour and academic performance. They and their families had migrated to Greece within the previous three years. A matching control group of native children (251) attending the same schools and classes was also assessed. For an in-depth assessment of psychopathology and social adaptation, 65 immigrant and 41 native children were randomly selected from the two larger groups and were further assessed. Results: No statistically significant differences were observed between the immigrant and native children in terms of psychopathology and social adaptation, although a few differences were observed in subscales. However, there were significant differences between the groups in academic performance, that of the immigrant group being poorer, particularly in language-related areas (p < 0.01). In the light of these results, language enrichment classes are suggested for immigrant children who need them.

Background. Psychological stress is associated with physical illnesses like asthma or infections. For an infant, situations perceived as stressful are highly dependent on the relationship with the caregiver. Constantly poor mother-infant interaction increases the child's vulnerability to stressful conditions and experiences. The aim of the study was to investigate the impact of the quality of early mother-infant interaction on the subsequent physical health of the child. Poor mother-infant interaction was hypothesized to be associated with chronic or recurrent health problems in the child. Participants. Fifty-seven mother-infant dyads from families at risk of psychosocial problems and 63 from non-risk families, altogether 120 dyads, participated in the study. Families were drawn from normal population, from well-baby clinics in the city of Tampere, Finland. Infants were full-term and healthy, families with severe risks like psychotic illnesses of the parents or a history of child protection concerns were excluded from the study. Methods. After the initial interview with the mother, the mother-infant interaction was videotaped when the infants were 8-11 weeks of age and the interaction was assessed using the Global Rating Scale for Mother-Infant Interaction (Murray et al. 1996a). After the 2-year follow-up mothers were interviewed again and the health problems of the child were elicited. Results. Poor dyadic mother-infant interaction and infant's poor interactive behaviour assessed at two months were separately associated with the physical health of the child during the two-year follow-up. After adjusting for other factors in the logistic regression analysis infant's poor interactive behaviour remained as a significant predictor of chronic or recurrent health problems in the child. Infant's health problems at the time of the initial interview and day care centre attendance were also significant predictors. Conclusions. The results suggest that interactional issues between a mother and her infant are related to the child's subsequent physical health. Children with recurrent or chronic health problems may have relationship difficulties with which they need help. Also, early avoidant behaviour of the infant should be regarded as an indicator of the infant's distress with possibly adverse outcomes in the child's physical health, among other consequences.

The number of children in Europe with significant psychologic and social problems is large and increasing. This article describes an innovative crosscultural method of working with families to promote the psychosocial well being of children and prevent the development of psychologic and social problems. A study designed to evaluate the effects of the service is also presented. Primary health care workers in five European countries have been trained to conduct promotional interviews with all prospective mothers in their area one month before and one month after birth. They have also been taught to work with mothers identified as in need of support as a parent by using a specific counselling model to try to prevent the onset of child mental health difficulties. Effects of the intervention on children's psychologic development and family adaptation are being evaluated at two years in comparison with matched groups not receiving the intervention. © 2002 Michigan Association for Infant Mental Health.

This article presents a school-based, peer-led programme aiming at smoking prevention among Greek adolescents. The intervention was based on the social influence approach, and utilized 28 students personal sensitization for the development of audio-visual material, which was presented to the remaining students of the two experimental schools (n = 440). The effectiveness of the intervention was assessed by means of experimental and control (n = 217) students' completion of a questionnaire prior to, immediately after and 3 months after the intervention. The Repeated Measures Analysis of Variance (MANOVAR) showed declines in the experimental group's smoking behaviour and intention to smoke immediately after, but not 3 months after the intervention, and more lasting changes in this group's knowledge of addiction and anti-smoking attitude. These effects were not observed for the control group. Programme evaluation and the implementation of health education programmes in the Greek school curriculum are discussed in the light of these findings.

The aim of the present paper is to describe and compare services for adults with intellectual disability (ID) and mental health needs in five European countries: Austria, England, Greece, Ireland and Spain. A framework and structure for collecting information about service provision was designed. This information was collected through a mixture of interviews with service providers, questionnaires and a review of the research literature within each country. Information was collected on historical context, policy, legislation, assessment, treatment and the structure of services for people with ID and mental health problems. Overall, the needs of those with additional mental health needs have not been specifically addressed at a national level with perhaps the exception of England and Ireland, although there are still gaps in services in these nations. Normalization has been adopted in each of the five countries, and there are moves toward deinstitutionalization, integration and inclusion. Families and self-advocacy groups have grown. The pace of this change varies between and even within countries. The main findings of the study include: unclear policy, trends for legislative changes, increased prevalence of mental health problems, inadequate generic service provision, a need for specialist mental health services, a need for improved interconnections of services, and a need for training developments. Policy and legislation in the five European countries under consideration tend to separate the disability aspects of people with ID from their mental health needs. Consequently, the service needs of this group remain largely invisible. This might be a direct reflection of policy clarity and legislation, or could be the result of a failure to implement existing guidelines. This has a detrimental effect on the lives of people with ID, and their families and carers.

The paper presents results from the implementation and evaluation of a EU/WHO multi-centre programme on the promotion of children's psychosocial development through primary health care services. The aims of the study were to develop methods for use by primary health care workers in their contact with families on issues pertaining to healthy psychosocial development in the first two years of life, to develop a training programme for primary health care workers to implement in their contact with the families, to evaluate the effectiveness of the programme and to promote the implementation of the developed intervention techniques through the network of primary health care services. © 2000, MCB UP Limited

Greece joined the European Community in 1981 and, three years later, the Commission of the European Communities provided financial and technical assistance under EEC Regulation 815/84 for the modernisation of the traditional psychiatric care system, with the emphasis on decentralisation of mental health services and the development of community-based services, as well as on deinstutionalization of long-stay patients and improvement of conditions in public mental hospitals. Over the last 11 years, the implementation of the EEG Reg. 815/84 programme contributed to a significant shift towards extramural care and rehabilitation. The role of the large mental hospitals has gradually been diminished and a large number of long-stay patients have been deinstitutionalised. It is commonly accepted that the EEC-funded psychiatric reform programme, despite inadequacies and constraints, had an impact on the changing mental health scene in Greece. (C) 1999 Editions scientifiques et medicales Elsevier SAS.