Qualitative analysis of verbal fluency in school-age children with high-functioning autism spectrum disorders. Associations with age and IQ.

This study analyzes performance on both a Semantic and a Letter verbal fluency (VF) task in school-age children with high-functioning autism spectrum disorder (HF-ASD) (n = 20) and without ASD (n = 20) and investigates the relationship between VF indicators and age, verbal and non-verbal IQ, ASD severity, and attention deficit hyperactivity disorder (ADHD) symptomatology. Furthermore, the Poor Lexical-Semantic Structure Model and the Slow-Retrieval Model are tested if they could account for semantic retrieval difficulties in children with HF-ASD. The HF-ASD group generated significantly fewer correct responses in both VF tasks in comparison to the control group. The type of task significantly affected performance and both groups showed higher word generativity on the Semantic task. The groups did not differ in clustering, switching, and errors. Age significantly correlated with the VF indicators in the ASD group, but in the control group, there was a significant negative correlation with the number of errors. Non-verbal and verbal IQ did not correlate with any VF indicators in both groups, while ASD severity and ADHD symptomatology correlated positively and significantly with error responses in the ASD group. The Slow-Retrieval Model explains VF difficulties in the HF-ASD group indicating that poorer word generativity can be attributed to slower retrieval of words from the semantic network.

Disentangling pediatric bipolar disorder and attention deficit-hyperactivity disorder: A neuropsychological approach.

The clinical and diagnostic debate circulating pediatric bipolar disorder (PBD) has been highlighted as one of the most controversial themes in child psychiatry. With atypical symptomatic expression, constituting its predominant diagnostic discrepancy, PBD is manifested through prolonged manic episodes and affective storms, lacking the symptomatic cycling and episodic nature presented in adult BD. Apart from its unique clinical presentation, the substantial symptomatic overlap with attention deficit hyperactivity disorder (ADHD) indicate an important diagnostic challenge in PBD. Specifically, both disorders share core characteristics such as irritability, hyperactivity, excessive talking and distractibility. Against this background of findings on the overlapping symptomatology between PBD and ADHD, current research guidelines highlight the need of exploring non-symptomatic markers as potential clinical phenotypes. Especially in disorders with distinctive biologic underpinnings, both clinicians and researchers have shown increased interest in establishing neuropsychological profiles. Recent neuropsychological studies indicated the distinct nature of neurocognitive deficits in PBD, describing impairments in various cognitive skills during acute episodes phases, while this severe deterioration of cognitive deficits appears to persist even during euthymic states. Regarding neuropsychological assessment in AHD, recent findings suggested dysfunctions in the domains of working memory, verbal memory and response inhibition. Furthermore, neuroimaging studies are fast becoming a key instrument to establish distinct neuropsychological profiles for PBD and ADHD. A large number of neuroimaging studies have indicated abnormalities in limbic, cortical and subcortical brain systems, while meta-analytic findings of voxel based morphometric studies highlight abnormalities in dorsolateral and lateral orbitofrontal-temporal areas in PBD. In recent neuroimaging findings with focus on neurocognitive performance during an emotional Stroop task, patients diagnosed with ADHD indicated activation on higher cortical centres associated with processing speed and significantly decreased role of sustained attention. Furthermore, these findings suggest emotional regulation and inhibitory control are moderately intercorrelated, adding more complexity to the theme of neurocognitive deficits in ADHD. These observations on the neurobiological mechanisms of cognitive impairments in PBD appear to provide robust evidence on a potential specific neuropsychological profile of PBD, the relationship between mood states and neuropsychological functioning, and the link between emotion generation and regulation in children with PBD.

[Βullying and the mental health of schoolchildren with special educational needs in primary education].

The purpose of this study was to investigate the relationship between bullying and mental Health in schoolchildren with special educational needs (SEN). Random sampling was used to select two groups of children aged 11-12 years, attending the fifth and sixth grades of primary school and integration classes in urban and rural locations in Greece. The final sample comprised a group of 80 children with SEN and a control group of 81 children. The participants completed The Revised Olweus Bullying Victim Questionnaire and The Strengths and Difficulties Questionnaire (SDQ). The children in the SEN group scored significantly higher on both the "Victimization" dimension and the "Intimidation" dimension of the Olweus questionnaire than the children in the control group. On the SDQ, the SEN group scored significantly higher overall, and in the dimensions "Emotional Symptoms", "Hyperactivity" and "Peer Problems", and significantly lower in the dimension "Prο- social Behavior", indicating more mental health problems in comparison to the children in the control group. In addition, significant correlation was demonstrated between the dimensions "Victimization" and "Intimidation" of the Olweus questionnaire and almost all the SDQ dimensions. Multifactorial linear regression analysis showed that the SDQ scores were independently associated with the Olweus dimensions "Victimization" and "Bullying". In addition, higher scores in emotional symptoms and conduct problems were associated with higher scores in the dimensions 'Victimization' and Intimidation'. Higher scores in "Victimization" were recorded by children with SEN, but also by those who had not been born in Greece. Children with SEN and those with conduct problems scored higher in the dimension "Bullying" than children whose native language was not Greek. In conclusion, this study showed that in the fifth and sixth grades of primary school, a group of schoolchildren with SEN reported higher levels than a control group of victimization and bullying. These findings suggest that there is a great need for raising the awareness of this situation among the school staff through the provision of special training. Mental health preventive and promotive programs can enable school staff to identify students who are at higher risk of becoming victims of bullying and victimization. It is also recommended that children with SEN should be taught coping strategies against school bullying in the classroom and the wider school community.

[Mood disorders in childhood and adolescence: continuities and discontinuities to adulthood].

Studies in child and adolescent psychiatry show that both internalizing and externalizing problems tend to persist in adulthood, e.g. it has been found that almost 40% of the adolescents who were classified as deviant initially were still deviant 4 years later. In a more recent study, over a large period of 24 years, continuity of psychopathology was found from childhood into adulthood; anxious/ depressed and other problems in childhood were core predictors for adult psychopathology. Other studies also show that there is substantial continuity, morbidity, and potential mortality from suicide into adulthood in patients with adolescent-onset major depressive disorder. Formerly depressed adolescents are at higher risk for recurrence of major depressive disorder during young adulthood; more specifically, depressed adolescents are at 2-7 times increased odds of being depressed as adults, compared with non-depressed controls. In addition, recent studies indicate that symptoms of depression in adolescence strongly predict an episode of major depression, suicidal ideation and rates for treatment for depression in adulthood, even among adolescents without major depression. The Maudsley long-term follow-up of child and adolescent depression showed that adolescent depression carries an elevated risk of adult depression irrespective of comorbidity, and that comorbid conduct disorder in childhood is associated with raised rates of other psychiatric outcomes. Personality disorders, i.e. of dependent, antisocial, passive-aggressive, and histrionic type, may represent alternative pathways of continuity for major depressive disorder and other Axis I disorders across the child-adult transition. Bipolar disorder in childhood is often found to be associated with long delays to first treatment. Studies have shown that both childhood onset and treatment delay are associated with a persistently more adverse course of illness in adulthood. Earlier and more effective treatment of bipolar disorder in children and adolescents would result in a more benign illness and a better prognosis in adulthood. Lastly, parental depression is a strong and consistent risk factor for offspring major depression and anxiety disorder. When offspring mature into young adulthood, effects of parental depression and family discord persist. Because child and especially adolescent mood disorders are likely to continue into adulthood, early identification, assessment and treatment are warranted; capacity for treatment of children at earlier stages of risk and disorder needs to be developed in other public sectors, such as primary health care and schools. In addition, continuity of care from childhood and adolescence to adulthood is needed.

Psychiatric services and training for children and adolescents in Europe: results of a country survey.

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.

Posttraumatic stress reactions among children following the Athens earthquake of September 1999.

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.

Psychosocial adaptation of immigrant Greek children from the former Soviet Union.

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.

Surrogate antigen processing mediated by TAP-dependent antigenic peptide secretion.

MHC class I proteins assemble with peptides in the ER. The peptides are predominantly generated from cytoplasmic proteins, probably by the action of the proteasome, a multicatalytic proteinase complex. Peptides are translocated into the ER by the transporters associated with antigen processing (TAP), and bind to the MHC class I molecules before transport to the cell surface. Here, we use a new functional assay to demonstrate that peptides derived from vesicular stomatitis virus nucleoprotein (VSV-N) antigen are actively secreted from cells. This secretion pathway is dependent on the expression of TAP transporters, but is independent of the MHC genotype of the donor cells. Furthermore, the expression and transport of MHC class I molecules is not required. This novel pathway is sensitive to the protein secretion inhibitors brefeldin A (BFA) and a temperature block at 21 degrees C, and is also inhibited by the metabolic poison, azide, and the protein synthesis inhibitor, emetine. These data support the existence of a novel form of peptide secretion that uses the TAP transporters, as opposed to the ER translocon, to gain access to the secretion pathway. Finally, we suggest that this release of peptides in the vicinity of uninfected cells, which we term surrogate antigen processing, could contribute to various immune and secretory phenomena.

The Leros PIKPA asylum. Deinstitutionalisation and rehabilitation project.

A three-year deinstitutionalisation and rehabilitation pilot intervention project was implemented at Leros PIKPA for people with severe learning disabilities. Initial conditions at the asylum were appalling. Residents suffered severe deprivation, extreme institutionalisation, and violation of basic human rights. Intervention involved professionals from different disciplines, and involved residents, their families, care staff, the institution, and the local community. As a result, resident care and adaptive behaviour has started to improve. Communication between residents and families has increased. Owing to training and sensitisation, care staff's poor resident-management practices and negative attitudes toward disabled people have changed. Living and hygienic conditions have been upgraded and building renovation is under way. Asylum administration and the local community have been sensitised to residents' needs. Eleven residents have moved to the project's pilot community home in Athens; two others now live with foster families. The results suggest that deinstitutionalisation and rehabilitation can be successfully initiated even in residential institutions of the severest kind.

The psychosocial dynamics of change at Leros PIKPA asylum.

The pilot intervention project at Leros PIKPA asylum was resisted at all levels of its implementation. Resistance ranged from implicit and passive to explicit and hostile. It took the form of strong rejective attitudes, defensiveness, and repressed emotions of guilt, shame and fear. It was apparent in efforts to delay, obstruct or reverse the progress of the project and undermine the work of intervention team members. It was evident in the interactions of the intervention team with all parties involved in implementing the project: medical professionals and welfare services, the state and local administrations, the central and local administrations of PIKPA staff, the local community, and the asylum residents' families and relatives. It is argued that this resistance to change is due to the interplay of cultural/attitudinal, psychodynamic and socio-economic factors that are not unique to Leros or Greece. The analysis of the psychosocial processes involved in resistance to changing the Leros PIKPA asylum may offer insights to the deinstitutionalisation of custodial settings in general.

Change in care staff's attitudes towards people with learning disabilities following intervention at the Leros PIKPA asylum.

The pilot intervention project at Leros PIKPA asylum sought to change the management of residents by decreasing care staff's tendency to view people with learning disabilities with attitudes of custodial segregation (e.g. "they should all live in institutions") and categorisation (e.g. "they are all alike"). To that end, staff were trained on the job in resident management and participated in seminars, sensitisation groups, clinical case presentations and visits to model rehabilitation units. To investigate whether staff attitudes towards people with learning disabilities had been influenced, staff members responded to a questionnaire of such attitudes, in March 1991 (initial assessment) and a year later (reassessment). Factor analyses of attitude ratings at initial assessment revealed a strong negative attitudinal construct, "Rejective and custodial segregation--Categorisation", according to which institutionalisation was the only appropriate type of care for people with learning disabilities, regardless of individual differences. At reassessment, however, this factor had split into two independent ones, "Rejective and custodial segregation" and "Categorisation", suggesting that the staff had understood that custodial care did not apply to all persons with learning disabilities indiscriminately. Reassessment factors further indicated that staff had comprehended the appropriateness of alternative care forms--community and home care. Analysis of Categorisation and Custodial segregation attitude ratings showed that only staff's tendency to view the disabled as "all alike" (Categorisation) had decreased at reassessment. The latter change and the structural change revealed by the factor analyses imply that staff's attitudes underwent a small but significant modification.

Mortality among institutionalised people with learning disabilities in Greece: a 30-year survey at the Leros PIKPA asylum.

The life expectancy of institutionalised people with learning disabilities is shorter than that of the general population. Data on population dynamics in institutions for such people are vital for planning purposes. Mortality can be considered a crude measure of quality of health care. Mortality data on the 914 admissions to the Leros PIKPA asylum for children and young adults with learning disabilities and associated problems in the years 1961-91 were reviewed. The overall crude mortality rate was 59.2 deaths per 1000 person-years. Twenty-two per cent of the deaths occurred within a year after admission. Age-specific mortality rates were particularly high for those aged one to four years, and declined thereafter. Male residents had lower mortality than female residents in almost all of the age groups. Compared with sex- and age-specific mortality data for the general population of Greece, the observed rates were 20-150 times higher but still comparable to those reported for people with more severe learning disabilities in institutions in other countries. Lifetable analysis by length of stay showed that male residents had a statistically significant higher probability of survival than female residents, which could not be attributed to age-related differential mortality. Culture-specific differential admission criteria may account for the observed sex difference.

Comparison of cell lines deficient in antigen presentation reveals a functional role for TAP-1 alone in antigen processing.

Cytotoxic T lymphocytes (CTL) recognize antigenic peptides bound to major histocompatibility complex class I antigens on the cell surface of virus-infected cells. It is believed that the majority of peptides originate from cytoplasmic degradation of proteins assumed to be mediated by the "20S" proteasome. Cytosolic peptides are then translocated, presumably by transporters associated with antigen processing (TAP-1 and -2), into the lumen of the endoplasmic reticulum (ER) where binding and formation of the ternary complex between heavy chain, beta2-microglobulin (beta 2m) and peptide occurs. In this study, we have analyzed and compared the phenotype of two mutant cell lines, the thymoma cell line RMA-S and a small lung carcinoma cell line CMT.64, in order to address the mechanism that underlies the antigen processing deficiency of CMT.64 cells. Unlike RMA-S cells, vesicular stomatitis virus (VSV)-infected CMT.64 cells are not recognized by specific CTL. Interferon gamma (IFN-gamma) treatment of CMT.64 cells restores the ability of these cells to process and present VSV in the context of Kb. We show that although CMT.64 cells express a low level of beta 2m, the recognition of VSV-specific CTL is not restored by increasing the amount of beta 2m synthesized in CMT.64 cells. In addition, we find that CMT.64 cells express moderate levels of Kb heavy chain molecules, but most of it is unstable and rapidly degraded in the absence of IFN-gamma treatment. We infer that the antigen processing deficiency does not lie at the level of beta 2m or Kb production. We find also that the mRNAs for both TAP-1 and -2 are present in RMA and RMA-S cells but are absent in uninduced CMT.64 cells. Upon IFN-gamma induction, both mRNAs are highly expressed in CMT-64 cells. In addition, we find that the low molecular mass polypeptides 2 and 7, and additional components of the proteasome are induced by IFN-gamma in CMT-64 cells. Finally, introduction of the rat TAP-1 gene in CMT.64 cells restores CTL recognition of VSV-infected cells. These results indicate that a TAP-1 homodimer may translocate peptides in the ER and explain partially the CMT.64 defect and the RMA-S phenotype. These findings link a dysfunction in the transport and/or generation of antigenic peptides to the capacity of tumor cells to evade immunosurveillance and provide a unique model system to dissect this phenomenon.

IFN-gamma-induced recognition of the antigen-processing variant CMT.64 by cytolytic T cells can be replaced by sequential addition of beta 2 microglobulin and antigenic peptides.

The present study describes the functional nature of the MHC class I determinants expressed in CMT.64 cells and was undertaken to define and further analyze the deficiency in the cell line CMT.64 in the hope of elucidating the relative functional importance of constituent parameters in the recognition of these cells by CTL. We show that induction of Kb in CMT.64 cells with IFN-gamma results in molecules capable of presenting VSV epitopes to the appropriate CTL. However, cells untreated with IFN-gamma and infected with VSV are not recognized by VSV-specific CTL. This study reveals that beta 2 m3 is synthesized in limiting amounts in uninduced CMT.64 and becomes highly expressed after IFN-gamma induction. Thus, the limiting amount of beta 2 m expressed in uninduced cells may partially explain the inability of the cells to present viral components of CTL recognition. This concept is reinforced by the experiments identifying two functional effects upon the addition of immunogenic peptides to uninduced CMT.64 cells: at high peptide concentrations in excess of 5 nM, CMT.64 cells are recognized efficiently after 5 min of incubation; at the limiting peptide concentration of 500 pM, uninduced CMT.64 cells are only recognized providing beta 2m is added before or simultaneously with the antigenic peptide. BFA, an inhibitor of protein transport, and emetine, an inhibitor of protein synthesis, were used to show that at high peptide concentrations, 25 microM, recognition takes place after the peptide has stabilized the limited amount of newly arriving MHC/beta 2m complexes, devoid of peptides, at the cell surface of uninduced CMT.64 cells. These experiments thereby exclude the possibility that peptides are taken up into CMT.64 cells for assembly, transport and surface expression of functional MHC/beta 2m/peptide complexes. In summary, our data expands previous research showing the importance of exogenous beta 2m in sensitizing cells for CTL recognition with peptides added exogenously. These functional experiments also imply that the concentration of endogenous beta 2m may regulate the amount of MHC class I expressed at the cell surface and receptive to exogenous peptides. Finally, the phenotype of CMT.64 cells we describe provides evidence of the complexity of the Ag-presenting capacity of this cell line not previously identified in other studies on these cells, thus revising our understanding of the Ag-processing deficiency in these cells.

Differential recruitment of viral and allo-epitopes into the MHC class I antigen processing pathway of a novel mutant of Ltk- cells. HSV/MHC class I restriction/immune recognition/antigen processing/antigen presentation/influenza virus.

It is generally thought that the Ag processing pathways for endogenously synthesized proteins are the same for allo and viral Ag processing. However, this view does not take into consideration the diversity of specialized maturation and assembly pathways for viruses. In particular, viral assembly that takes place within intracellular membranes may require unique Ag processing steps. In this study we sought to assess this possibility. Hence, we describe the CTL response against a murine Ltk- cell derivative, gro29, which was previously shown to be defective in the propagation of herpes simplex virus type 1 (HSV-1). In HSV-1-infected gro29 cells, viral polypeptides are synthesized in normal amounts and viral assembly takes place. However, transport of the assembled particles is defective in these cells, resulting in the accumulation of noninfectious virus in cytoplasmic vesicles, and a reduction in the release of viral particles by at least 2000-fold. We show that the rate of transport of individual endogenous proteins through the organelles of the secretory pathway is also impaired, but only by roughly 50%, suggesting that the defect in this cell line affects the transport of particles to a greater extent than the transport of individual proteins. It is also shown that allogeneic and influenza A- specific CTL responses are indistinguishable between gro29 and Ltk- cells, as is the response against target cells pretreated with a influenza A derived synthetic peptide. By contrast, HSV-1-infected gro29 cells are approximately eightfold less sensitive than infected Ltk- cells to lysis by HSV-1-specific CTL. This illustrates that in contrast to the allogeneic and influenza specific responses, the recruitment of herpes virus-specific Ag into the Ag-processing pathway is dependent on a cellular function that is also required for viral maturation and egress. We believe that this is the first demonstration of this phenomenon.

Demonstration of MHC class II-restricted cytotoxic T lymphocytes in mice against herpes simplex virus.

In humans CD4+ major histocompatibility complex (MHC) class II-restricted T cells dominate cytotoxic T-lymphocyte (CTL) responses to herpes simplex virus (HSV), whereas in the mouse only CD8+ MHC class I-restricted CTL have been reported. In this study, we demonstrate that a minor fraction (around 30%) of the response in draining lymph nodes of acute local HSV infections is attributable to CD4+ CTL mice. Such CTL were identified on the basis of antiserum inhibition studies, negative depletion approaches, as well as their differing antigen processing requirements to CD8+ MHC class I-restricted CTL. A possible role for CD4+ CTL as immunoregulators in local infections is discussed briefly.