Adults referred to a national ADHD clinic in Iceland: clinical characteristics and follow-up status.

OBJECTIVE: Evaluate adults referred to a national ADHD clinic, by comparing those diagnosed with those who were not, and those who screened negative and to evaluate changes among those diagnosed at follow-up. METHOD: Data obtained from 531 patients' medical records (49.7% males). One hundred thirty-six screened negative, 395 positive and 305 met diagnostic criteria for ADHD. Eighty-three of them were contacted by phone at follow-up. RESULTS: ADHD diagnosis was associated with lower educational status and more concerns expressed by parents and teachers during childhood. Participants not diagnosed with ADHD more often met diagnostic criteria for dysthymia, agoraphobia and generalized anxiety, and were more likely to be diagnosed with two or more comorbid disorders. At follow-up, all reported a significant reduction of ADHD symptoms, irrespective of medication, but the medicated participants reported fewer symptoms of inattention and better functioning in daily life. CONCLUSION: Adults referred to ADHD clinics may have multiple mental health problems, regardless of whether they receive ADHD diagnosis or not. This could have implications for differential diagnoses of ADHD in adults and emphasises the need to have appropriate treatment available for both groups. Psychoeducation about ADHD may be very helpful in decreasing anxiety and ADHD symptoms.

Psychiatric disorders in an urban sample of preschool children.

BACKGROUND: To increase limited epidemiological knowledge of early childhood psychopathology, a study of prevalence estimates and demographic correlates of psychiatric disorders was conducted in a sample of preschool children. METHODS: In a two-stage study, parents of 339 children aged 4-6 years who came for a medical check-up at three primary care centres in Reykjavik were invited to participate. First, the participants were screened with Brigance Screens and the Strengths and Difficulties Questionnaire (SDQ) for parents and teachers. Subsequently, the children were tested with a short version of Wechsler Preschool and Primary Scales of Intelligence - Revised and their parents were interviewed with the Schedule for Affective Disorders and Schizophrenia for School Aged Children Present and Lifetime Version. Weighted prevalence estimates were calculated and logistic regression was used to analyse the association between risk factors and psychiatric disorders. RESULTS: Of those invited to participate, 317 (93.5%) were included in the screening and of those, 131 received a full diagnostic assessment. The final study sample included 151 girls (47.6%) and 166 boys (52.4%) who represented 11.6% of the total birth cohort in Reykjavik. Weighted prevalence of DSM-IV psychiatric disorders was 10.1% (95% CI 6.7-13.5%) and 57/317 or 18.0% (95% CI 13.8-22.2%), including elimination disorders. Anxiety disorders (5.7%) and attention deficit hyperactivity disorder (3.8%) were the most common disorders in this preschool sample. Poor physical health of parents and higher education was associated with DSM-IV psychiatric disorders of the children. SDQ Total Difficulties score was associated with male gender and poor physical health of parents. CONCLUSIONS: This study indicates that psychiatric disorders in preschool children are common and may be correlated with parental health factors.

Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis.

BACKGROUND: Large, rare chromosomal deletions and duplications known as copy number variants (CNVs) have been implicated in neurodevelopmental disorders similar to attention-deficit hyperactivity disorder (ADHD). We aimed to establish whether burden of CNVs was increased in ADHD, and to investigate whether identified CNVs were enriched for loci previously identified in autism and schizophrenia. METHODS: We undertook a genome-wide analysis of CNVs in 410 children with ADHD and 1156 unrelated ethnically matched controls from the 1958 British Birth Cohort. Children of white UK origin, aged 5-17 years, who met diagnostic criteria for ADHD or hyperkinetic disorder, but not schizophrenia and autism, were recruited from community child psychiatry and paediatric outpatient clinics. Single nucleotide polymorphisms (SNPs) were genotyped in the ADHD and control groups with two arrays; CNV analysis was limited to SNPs common to both arrays and included only samples with high-quality data. CNVs in the ADHD group were validated with comparative genomic hybridisation. We assessed the genome-wide burden of large (>500 kb), rare (<1% population frequency) CNVs according to the average number of CNVs per sample, with significance assessed via permutation. Locus-specific tests of association were undertaken for test regions defined for all identified CNVs and for 20 loci implicated in autism or schizophrenia. Findings were replicated in 825 Icelandic patients with ADHD and 35,243 Icelandic controls. FINDINGS: Data for full analyses were available for 366 children with ADHD and 1047 controls. 57 large, rare CNVs were identified in children with ADHD and 78 in controls, showing a significantly increased rate of CNVs in ADHD (0·156 vs 0·075; p=8·9×10(-5)). This increased rate of CNVs was particularly high in those with intellectual disability (0·424; p=2·0×10(-6)), although there was also a significant excess in cases with no such disability (0·125, p=0·0077). An excess of chromosome 16p13.11 duplications was noted in the ADHD group (p=0·0008 after correction for multiple testing), a finding that was replicated in the Icelandic sample (p=0·031). CNVs identified in our ADHD cohort were significantly enriched for loci previously reported in both autism (p=0·0095) and schizophrenia (p=0·010). INTERPRETATION: Our findings provide genetic evidence of an increased rate of large CNVs in individuals with ADHD and suggest that ADHD is not purely a social construct. FUNDING: Action Research; Baily Thomas Charitable Trust; Wellcome Trust; UK Medical Research Council; European Union.

No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder.

The Autism Genome Project (AGP) Consortium recently reported genome-wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case-control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non-centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case-control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta-analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944-1.133), with a P-value of 0.5 for ASD and OR of 0.99 (95% CI 0.88-1.11) with P-value = 0.85 for the Autism (A) sub-group. Therefore, this study does not provide support for the reported association between rs4141463 and autism.

Validity of K-SADS-PL (Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime Version) depression diagnoses in an adolescent clinical population.

BACKGROUND: Validity studies of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) interview are modest in number given the international acceptance and extensive use of this instrument in epidemiological and treatment research. The results are somewhat mixed and limited, particularly for adolescent depression. AIMS: The objective of this study was to assess the convergent-divergent validity of the screen criteria and depression diagnoses (major depressive episode) generated with the diagnostic interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). METHODS: Participants were 86 consecutively admitted inpatients aged 12-17 years and their parents. Both convergent and divergent validity of the depression diagnoses were assessed against 11 standard self-report or parent-report rating scales, all of which had been translated, adapted and in most cases validated in Iceland. A total of 25 subscales were included in calculations. RESULTS: Convergent validity was confirmed, with adolescents who screened positive or met criteria for major depressive episode scoring higher than other patients did on scales assessing depressive symptoms. However, divergent validity was only partially supported in this highly comorbid inpatient sample. Severity based on number of diagnostic criteria met had a generally substantial correlation with the rating scales. CONCLUSIONS: This study provides a substantial additional amount of convergent-divergent validity data related to this extensively used diagnostic instrument.

Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5-BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10-21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.

An Icelandic version of the Kiddie-SADS-PL: translation, cross-cultural adaptation and inter-rater reliability.

The development of structured diagnostic instruments has been an important step for research in child and adolescent psychiatry, but the adequacy of a diagnostic instrument in a given culture does not guarantee its reliability or validity in another population. The objective of the study was to describe the process of cross-cultural adaptation into Icelandic of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (Kiddie-SADS-PL) and to test the inter-rater reliability of the adapted version. To attain cross-cultural equivalency, five important dimensions were addressed: semantic, technical, content, criterion and conceptual. The adapted Icelandic version was introduced into an inpatient clinical setting, and inter-rater reliability was estimated both at the symptom and diagnoses level, for the most frequent diagnostic categories in both international diagnostic classification systems (DSM-IV and ICD-10). The cross-cultural adaptation has provided an Icelandic version allowing similar understanding among different raters and has achieved acceptable cross-cultural equivalence. This initial study confirmed the quality of the translation and adaptation of Kiddie-SADS-PL and constitutes the first step of a larger validation study of the Icelandic version of the instrument.

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.

Electroencephalography as a clinical tool for diagnosing and monitoring attention deficit hyperactivity disorder: a cross-sectional study.

OBJECTIVES: The aim of this study was to develop and test, for the first time, a multivariate diagnostic classifier of attention deficit hyperactivity disorder (ADHD) based on EEG coherence measures and chronological age. SETTING: The participants were recruited in two specialised centres and three schools in Reykjavik. PARTICIPANTS: The data are from a large cross-sectional cohort of 310 patients with ADHD and 351 controls, covering an age range from 5.8 to 14 years. ADHD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria using the K-SADS-PL semistructured interview. Participants in the control group were reported to be free of any mental or developmental disorders by their parents and had a score of less than 1.5 SDs above the age-appropriate norm on the ADHD Rating Scale-IV. Other than moderate or severe intellectual disability, no additional exclusion criteria were applied in order that the cohort reflected the typical cross section of patients with ADHD. RESULTS: Diagnostic classifiers were developed using statistical pattern recognition for the entire age range and for specific age ranges and were tested using cross-validation and by application to a separate cohort of recordings not used in the development process. The age-specific classification approach was more accurate (76% accuracy in the independent test cohort; 81% cross-validation accuracy) than the age-independent version (76%; 73%). Chronological age was found to be an important classification feature. CONCLUSIONS: The novel application of EEG-based classification methods presented here can offer significant benefit to the clinician by improving both the accuracy of initial diagnosis and ongoing monitoring of children and adolescents with ADHD. The most accurate possible diagnosis at a single point in time can be obtained by the age-specific classifiers, but the age-independent classifiers are also useful as they enable longitudinal monitoring of brain function.

Autism Diagnostic Interview-Revised and the Childhood Autism Rating Scale: convergence and discrepancy in diagnosing autism.

The agreement between the Autism Diagnostic Interview-Revised (ADI-R) and the Childhood Autism Rating Scale (CARS) was investigated in the diagnostic assessment of 54 children aged 22-114 months referred for possible autism. The observed agreement between the two systems was 66.7% (Cohen's kappa = .40) when the ADI-R definition for autism was applied (i.e., scores reaching cutoff in three domains on the ADI-R), but increased considerably with less stringent criteria; that is, scores reaching cutoffs in two domains and in one domain on the ADI-R. As predicted, the CARS identified more cases of autism than the ADI-R. Children classified as autistic according to both instruments had significantly lower IQ/DQ and more severe autistic symptomatology than those classified with the CARS only.