Attention-deficit/hyperactivity disorder and dopamine receptor D4 (DRD4) exon 3 variable number of tandem repeats (VNTR) 2-repeat allele.

To investigate the association of attention-deficit/hyperactivity disorder (ADHD) with the 48-base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT). The odds ratio (OR) (95% confidence interval) was 0.90 (0.64-1.3). The p-value was 0.6. Examining subgroups revealed nominally significant association of 2R with inattentive ADHD: OR = 0.33 (0.12-0.92) and p = 0.03. Because our study used TDT analysis, we meta-analyzed the association of 2R with ADHD in Asians (1329 patient alleles), revealing results similar to ours: OR = 0.97 (0.80-1.2) and p = 0.8. To examine the association of 2R with inattentive ADHD, we meta-analyzed all studies (regardless of analysis type or ethnicity, in order to increase statistical power): 702 patient alleles, 1420 control alleles, OR = 0.81 (0.57-1.1) and p = 0.2. Overall, there is no evidence of association between ADHD and the 2R allele, but the suggestive association with the inattentive type warrants further investigation.

Enhancing emotion recognition in young autistic children with or without attention-deficit/hyperactivity disorder in Hong Kong using a Chinese App version of The Transporters.

TRIAL REGISTRATION: This study was registered with the German Clinical Trials Register - Deutschen Register Klinischer Studien (DRKS) on 23 December 2018. The Trial Registration Number (TRN) is DRKS00016506. LAY ABSTRACT: The Transporters App is an intervention programme with 15 animated episodes that teach emotion recognition skills to autistic children between 4 and 6 years of age. Each episode contains a story depicting social interactions between characters in the form of a vehicle, with human faces grafted on to each of them. Each episode teaches a specific emotion in a story context. Autistic children watched at least three episodes at home for about 15 min daily for a month, with parental guidance. Its automated, home-based format is cost-saving and readily accessible. This study translated The Transporters to a Cantonese-Chinese version. Results showed a significant improvement in emotion recognition following viewing The Transporters in a group of Hong Kong Chinese autistic children, between 4 and 6 years of age, with and without attention-deficit/hyperactivity disorder (n = 48) relative to a control group (n = 24). A non-autistic group (n = 23) showed that the autistic children scored lower in emotion recognition pre-intervention. Post-intervention, the autistic children had improved in emotion recognition to the level of the non-autistic children. The autistic children in the intervention groups also generalized their learning to novel situations/characters not taught within The Transporters. There was no dosage effect, with the standard recommended number of episodes viewed being sufficient to achieve significant improvement. This study confirms the effectiveness of The Transporters for Chinese autistic children and contributes to the literature/practice by expanding the range of applicability of The Transporters to autistic children with attention-deficit/hyperactivity disorder, which is important given the high rate of co-occurrence between autism and attention-deficit/hyperactivity disorder.

A network analysis on the relationship between loneliness and schizotypy.

BACKGROUND: Schizotypy is a multidimensional personality trait related to the heightened risk for the development of schizophrenia spectrum disorders. While it has been suggested that loneliness may be associated with schizotypy in general, whether it relates to the specific schizotypal traits differentially remains unknown. Besides, as loneliness often co-occurs with depression and anxiety, it is important to delineate its relationship with schizotypy in consideration of these co-occurring emotional disturbances. METHODS: A demographically diverse sample of young people was obtained from multiple sources. The validated sample consisted of 2089 participants (68.4% female, age range: 18-30). The structural relationship between loneliness and schizotypy was modelled using a network analytic approach. The Gaussian graphical model with loneliness and nine schizotypal traits as nodes was first estimated without, and then with adjustment for the levels of depressive and anxiety symptoms. Edges were estimated as unique associations between nodes. RESULTS: 'Suspiciousness', 'odd beliefs or magical thinking', 'no close friends', 'constricted affect' and 'excessive social anxiety' were linked to loneliness directly. Loneliness was found to be more strongly associated with 'suspiciousness' and 'no close friends' than other schizotypal traits. After adjustment for the levels of depressive and anxiety symptoms, the above direct edges remained robust. LIMITATIONS: The use of cross-sectional data indicated only undirected associations between variables. CONCLUSIONS: Loneliness was more strongly linked to some schizotypal traits than others, with the relationships maintaining above and beyond the effects of anxiety and depression. These findings warrant further investigation of the specific relationships between loneliness and individual schizotypal traits.

Risk perception in paranoia and anxiety: Two investigations across clinical and non-clinical populations.

OBJECTIVES: It is common, among clinical and non-clinical populations alike, for paranoia and anxiety to co-occur. It has been suggested that anxiety and its related appraisal styles may contribute to development of paranoia. We aimed to evaluate different aspects of risk perception in relation to paranoia and anxiety and to identify specific aspects that may differentiate paranoia from anxiety. This paper consists of two inter-related studies. METHODS: Study 1 compared 30 patients with persecutory delusions, 21 patients with generalized anxiety disorder and 52 healthy controls. Study 2 compared 30 non-clinical individuals with high levels of paranoia and anxiety, 28 individuals with high anxiety only and 36 healthy controls. Within each study, the two symptomatic groups were matched on level of anxiety. Four dimensions of risk perception (i.e. likelihood, harm, controllability, and intentionality) were compared across groups, as measured by the locally validated Risk Perception Questionnaire. RESULTS: In both studies, the paranoia and the anxiety groups reported an elevated perceived likelihood of negative events than controls respectively. Only the paranoia groups reported an elevated perceived harm of neutral events than controls. In Study 2, the two at-risk groups attributed more harm and intentionality to negative events than controls. CONCLUSION: Although perception of negative events was characteristic in anxiety (with or without paranoia), a biased perception of neutral events as risky was unique to the addition of paranoia. Implications to the transdiagnostic and continual view of psychopathology, and mechanism-based interventions were discussed.

Paranoia and anxiety: A cluster analysis in a non-clinical sample and the relationship with worry processes.

BACKGROUND: Worry processes are implicated in paranoia and anxiety. However, clinical studies focused on patients with co-occurring paranoia and anxiety. As both paranoia and anxiety are distributed across clinical and non-clinical groups, an investigation on worry processes among non-clinical individuals will allow us to delineate the specific worry mechanisms in paranoia and anxiety respectively. AIMS: To identify clusters of non-clinical individuals who report varied levels of paranoia and anxiety, and to compare worry processes across clusters. METHOD: An online survey, consisting of self-report questionnaires on generalized anxiety, paranoia, and worry processes, was completed by 2796 undergraduate students. A multiple-step validity check procedure resulted in a subsample of 2291 students, upon which cluster analyses and multivariate analyses of variance were conducted. RESULTS: Four clusters of individuals were identified: (1) high paranoia/moderate anxiety, (2) average paranoia/high anxiety, (3) average paranoia/average anxiety, and (4) low paranoia/low anxiety. A unique cluster of individuals with high paranoia but low/average level of anxiety was not found. Cluster 1 reported a significantly higher intensity of day-to-day worries, a higher level of meta-worry, and more extreme meta-cognitive beliefs about worry than other clusters. CONCLUSIONS: Individuals with high paranoia tended to report anxiety as well, but not vice versa. Our findings supported a hierarchical structure of anxiety and paranoia. All worry processes were exacerbated in individuals with paranoia and anxiety than those with anxiety alone.

Children with a regular FP - do they have better health behaviours and psychosocial health?

BACKGROUND: Adults who receive care from family physicians (FPs) are healthier than those who do not, but not much is known about the health behaviours and psychosocial health of children who have FPs. OBJECTIVE: This study aims to test the hypothesis that children who have a regular FP have better health behaviours and psychosocial health than children who do not have a regular FP. METHODS: The health behaviours and psychosocial wellbeing of 7057 children in Hong Kong were measured by the Youth Risk Behaviour Survey and the 'anxious/depressed', 'somatic complaints' and 'aggressive behaviours' domains of the Children Behaviour Checklist (CBCL). RESULTS: Good health and hygiene behaviours were significantly more prevalent in children who had a regular FP. Children who did not have a regular FP had statistically significant higher scores in all three main domains of the CBCL. Children with a regular FP had higher odds ratios for various hygiene and health behaviours after adjusting for socioeconomic status. DISCUSSION: The findings highlight the potential role of FPs in promoting health, hygiene, and wellbeing in children.

Family-based association study of DRD4 gene in methylphenidate-responded Attention Deficit/Hyperactivity Disorder.

The 48-basepair (48-bp) variable number tandem repeat (VNTR) polymorphism in exon 3 of the dopamine receptor D4 gene (DRD4) is implicated in the etiology of attention-deficit/ hyperactivity disorder (ADHD). In particular, ADHD in European-ancestry population is associated with an increased prevalence of the 7-repeat (7R) allele of the exon 3 VNTR. However, it is intriguing to note that the 7R allele has been found to be of very low prevalence in the Chinese general population. In a previous case-control study, our research team had found that the 7R allele was similarly absent in Chinese ADHD children in Hong Kong. Instead, there was an increased prevalence of the 2R allele in Chinese ADHD children. Interestingly, in Asian samples, the 2R allele had been found to be an evolutionary derivative of the 7R allele with equivalent biochemical functionality. So, the finding of an association between ADHD and 2R allele in Chinese population does not exactly contradict the original 7R allele finding in European-ancestry population. However, given the potential pitfall of population stratification in the previous case-control design, this current study tested the 2R allele and ADHD association using a methodologically more rigorous family-based approach on 33 Chinese ADHD probands who had favorable clinical responses to stimulant medication (methylphenidate). Haplotype Relative Risk (HRR) analysis and Transmission Disequilibrium Test (TDT) both showed a significant preferential transmission of the 2R allele from the biological parents to ADHD probands (pone-tailed = 0.038, OR = 2.04; pone-tailed = 0.048, OR = 2.29, respectively). A second hypothesis speculates that it is the deviation, including 7R and 2R alleles, from the conserved ancestral 4R allele which confers risk to ADHD. Thus, a preferential transmission of non-4R alleles, against the 4R allele, from biological parents to their ADHD probands is predicted. Both HRR analysis and TDT confirmed such prediction (pone-tailed = 0.029, OR = 2.07; pone-tailed = 0.032, OR = 2.43, respectively). This study re-confirmed the original finding of a previous study that in Chinese population, the 2R allele of the DRD4 exon 3 VNTR was related to ADHD. This endorses the general thesis that DRD4 exon 3 VNTR polymorphism is related to ADHD, despite that the exact length or number of repeats of the associated alleles varies across ethnicity. This in turn supports the dopamine dysregulation theory of ADHD.

Diagnostic yield of array CGH in patients with autism spectrum disorder in Hong Kong.

BACKGROUND: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNV) and it is advocated to be the first tier genetic testing for patients with autism spectrum disorder (ASD). In this regard, diagnostic yield of array comparative genomic hybridization (CGH) for ASD patients is determined in a cohort of Chinese patients in Hong Kong. METHODS: A combined adult and paediatric cohort of 68 Chinese ASD patients (41 patients in adult group and 27 patients in paediatric group). The genomic DNA extracted from blood samples were analysed by array CGH using NimbleGen CGX-135K oligonucleotide array. RESULTS: We identified 15 CNV and eight of them were clinically significant. The overall diagnostic yield was 11.8 %. Five clinically significant CNV were detected in the adult group and three were in the paediatric group, providing diagnostic yields of 12.2 and 11.1 % respectively. The most frequently detected CNV was 16p13.11 duplications which were present in 4 patients (5.9 % of the cohort). CONCLUSIONS: In this study, a satisfactory diagnostic yield of array CGH was demonstrated in a Chinese ASD patient cohort which supported the clinical usefulness of array CGH as the first line testing of ASD in Hong Kong.

Dimensions of Delusions and Attribution Biases along the Continuum of Psychosis.

This study compared delusional dimensions and attribution biases along the continuum of psychosis. Participants completed questionnaires on delusion-like beliefs and attributions. Although patients with first-episode psychosis (N = 70) endorsed fewer delusion-like beliefs than non-clinical individuals with psychotic-like experiences (N = 12), they scored highest on delusional conviction, distress and preoccupation, followed by non-clinical individuals with psychotic-like experiences, and then healthy controls (N = 642). Self-serving bias was found in patients and non-clinical individuals with psychotic-like experiences, but not in healthy controls. Personalizing bias for negative events was not significantly different across the three groups. When compared with healthy controls, non-clinical individuals with psychotic-like experiences had an exaggerated self-serving bias, but were not more marked in personalizing bias. Self-serving bias and personalizing bias were both associated with delusional dimensions. However, the association between self-serving bias and number of delusion-like beliefs was stronger among patients than non-clinical participants. Future research could investigate the extent to which self-serving bias, in combination with an appraisal of delusional ideation as convincing, distress, and preoccupying, contributes to the development of clinical delusions.

Clinical utility of the Chinese Strengths and Weaknesses of ADHD-Symptoms and Normal-Behaviors questionnaire (SWAN) when compared with DISC-IV.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing child and adolescent psychiatric disorder. Early identification and prompt treatment are essential. Rating scales are commonly used by clinicians and researchers to assess ADHD children. OBJECTIVE: In the current study, we aimed to examine the clinical utility of the Chinese version of the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviors (SWAN) questionnaire. We validated its subscale scores against the Diagnostic Interview Schedule for Children Version IV (DISC-IV) and looked into its ability to identify ADHD in a psychiatric clinic setting. We also tested age and gender effects on SWAN scores. Specific subscale cutoff scores of SWAN were subsequently determined. METHOD: A total of 290 children aged 6-12 years old studying in local mainstream primary schools were recruited from a clinic setting and interviewed with the parent version of DISC-IV. Their parents and teachers completed the corresponding version of SWAN. RESULTS: Both parent and teacher versions of SWAN were found to have good concurrent validity with DISC-IV. It could identify ADHD well in a clinic sample. Gender-specific cutoff scores were determined. Sensitivities and specificities were found to be satisfactory. SWAN was also found to perform equally well in identifying ADHD in those with and without comorbid Autistic Spectrum Disorder. CONCLUSION: SWAN was proven to be a useful tool to aid the assessment of ADHD in a clinic sample.

Test-retest reliability of the Chinese version of the Diagnostic Interview Schedule for Children-Version 4 (DISC-IV).

BACKGROUND: Despite the huge youth population, there is a lack of psychiatric diagnostic instruments with reported psychometric properties in Chinese. This study reports the development of the Chinese version of DISC-IV and examines its test-retest reliability. METHOD: Seventy-eight parents and 79 youths (mean age 13.1 years) attending child psychiatric clinics were interviewed twice using the Chinese DISC-IV (Diagnostic Interview Schedule for Children-IV) about 22 days apart. RESULTS: The kappa coefficients were good to excellent for obsessive compulsive disorder (OCD) (both youth (Y) and parent (P) versions), major depressive disorder (MDD) (P), attention deficit hyperactivity disorder (ADHD) (P); fair for anxiety disorder (P), oppositional defiant disorder (ODD) (P, Y), MDD (Y); but poor for anxiety disorder (Y) and ADHD (Y). Parent informants had better test-retest reliability than youth informants. CONCLUSIONS: The Chinese DISC-IV had comparable test-retest reliability with the original English version.