Huey-Ling Chiang

Association between symptoms and subtypes of attention-deficit hyperactivity disorder and sleep problems/disorders

This study aimed to investigate the association between attention‐deficit hyperactivity disorder (ADHD) symptoms and subtypes, and sleep schedules, daytime inadvertent napping, and sleep problems/disorders in children and adolescents with and without ADHD. The sample included 325 patients with ADHD, aged 10–17 years [male: 81.5%; combined type (ADHD‐C): 174; predominantly inattentive type (ADHD‐I): 130; predominantly hyperactive‐impulsive type (ADHD‐HI): 21], and 257 children and adolescents without lifetime ADHD (non‐ADHD). We conducted psychiatric interviews with the participants and their mothers before making the diagnoses of ADHD, other psychiatric disorders, and sleep problems or disorders. We also collected the medication treatment data and parent and teacher reports of ADHD symptoms. Multi‐level models were used for data analyses controlling for sex, age, psychiatric comorbidities, and treatment with methylphenidate. The ADHD‐C and ADHD‐I groups had more daytime inadvertent napping. In general, the three subtypes were associated with increased rates of sleep problems/disorders. Specifically, ADHD‐C rather than ADHD‐I was associated with circadian rhythm problems, sleep‐talking, nightmares (also ADHD‐HI), and ADHD‐I was associated with hypersomnia. The most‐related sleep schedules and problems for inattention and hyperactivity‐impulsivity were earlier bedtime, later rise time, longer nocturnal sleep, more frequent daytime napping, insomnia, sleep terrors, sleep‐talking, snoring, and bruxism across informants. The findings imply that in addition to the dichotomous approach of ADHD and considering the psychiatric comorbid conditions, ADHD subtypes and symptom dimensions need to be considered in clinical practice and in the research regarding the association between ADHD and sleep problems/disorders.

Association between early attention-deficit/hyperactivity symptoms and current verbal and visuo-spatial short-term memory

Deficits in short-term memory are common in adolescents with attention-deficit/hyperactivity disorder (ADHD), but their current ADHD symptoms cannot well predict their short-term performance. Taking a developmental perspective, we wanted to clarify the association between ADHD symptoms at early childhood and short-term memory in late childhood and adolescence. The participants included 401 patients with a clinical diagnosis of DSM-IV ADHD, 213 siblings, and 176 unaffected controls aged 8-17 years (mean age, 12.02 ± 2.24). All participants and their mothers were interviewed using the Chinese Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia to obtain information about ADHD symptoms and other psychiatric disorders retrospectively, at an earlier age first, then currently. The participants were assessed with the Wechsler Intelligence Scale for Children--3rd edition, including Digit Span, and the Spatial working memory task of the Cambridge Neuropsychological Test Automated Battery. Multi-level regression models were used for data analysis. Although crude analyses revealed that inattention, hyperactivity, and impulsivity symptoms significantly predicted deficits in short-term memory, only inattention symptoms had significant effects (all p<0.001) in a model that included all three ADHD symptoms. After further controlling for comorbidity, age of assessment, treatment with methylphenidate, and Full-scale IQ, the severity of childhood inattention symptoms was still significantly associated with worse verbal (p = 0.008) and spatial (p ranging from 0.017 to 0.002) short-term memory at the current assessment. Therefore, our findings suggest that earlier inattention symptoms are associated with impaired verbal and visuo-spatial short-term memory at a later development stage. Impaired short-term memory in adolescence can be detected earlier by screening for the severity of inattention in childhood.

Risk of depressive disorder following non-alcoholic cirrhosis: a nationwide population-based study.

Background & Aims To evaluate the risk of depressive disorders among non-alcoholic patients by using the Taiwan National Health Insurance Research Database (NHIRD). Methods We conducted a retrospective study of a matched cohort of 52 725 participants (10 545 non-alcoholic cirrhotic patients and 42 180 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 11 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in cirrhotic patients. Results During the 11-year follow-up period, 395 (3.75%) non-alcoholic cirrhotic patients and 1 183 (2.80%) control patients were diagnosed with depressive disorders. The incidence risk ratio of depressive disorders between non-alcoholic cirrhotic patients and control patients was 1.76 (95% CI, 1.57–1.98, P<.001). After adjusting for age, sex, and comorbidities, non-alcoholic cirrhotic patients were 1.75 times more likely to develop depressive disorders (95% CI, 1.56–1.96, P<.001) compared with the control patients. The hazard ratios for patients younger than 60 years old (1.31) and female (1.25) indicated that each is an independent risk factor for depressive disorders in non-alcoholic cirrhotic patients. Conclusions The likelihood of developing depressive disorders is greater among non-alcoholic cirrhotic patients than among patients without cirrhosis. Symptoms of depression should be sought in patients with cirrhosis.

Use of Radioactive Iodine for Thyroid Cancer and Risk of Second Primary Malignancy: A Nationwide Population-Based Study.

BACKGROUND Radioactive iodine (RAI) is widely used for the treatment of thyroid cancers. However, information on associations between RAI dose and second primary malignancy (SPM) is lacking. METHODS Patients without antecedent cancer age 20 years or older and newly diagnosed with thyroid cancer were recruited from the Taiwan National Health Insurance database between 1997 and 2010. Standardized incidence ratios (SIRs) for the cancers were calculated to compare the incidence of thyroid cancer with the general population. The association between RAI dosage and cancer development was estimated using time-dependent Cox regression analysis. All statistical tests were two-sided. RESULTS A total of 692 cases of SPM were identified among 20 235 patients with thyroid cancer. Regarding the latter, 79.7% of the patients were women, the median age was 46 years, and the follow-up period included 134 178 person-years. The SIR for any SPM was 1.41 (95% confidence interval [CI] = 1.31 to 1.52). A statistically significantly higher SIR was observed in leukemia (2.74), non-Hodgkins lymphoma (2.38), prostate (2.30), lung and mediastinum (1.93), pancreas (1.83), kidney (1.81), breast (1.48), and colon-rectum (1.31) cancers. Cumulative RAI dose (per 30 mCi increase) conferred a strong risk for SPM (adjusted hazard ratio [aHR] = 1.01, 95% CI = 1.01 to 1.02, P < .001) and leukemia (aHR = 1.03, 95% CI = 1.02 to 1.04, P < .001) occurrences. A cumulative RAI dose greater than 150 mCi possessed a statistically significant risk for all cancer combined (aHR = 1.30) and leukemia (aHR = 6.03). CONCLUSIONS An increased risk of SPM was observed for thyroid cancer patients, especially with cumulative RAI doses over 150 mCi.

Associations of symptoms and subtypes of attention-deficit hyperactivity disorder with visuospatial planning ability in youth

Little is known about which ADHD core symptom or subtype is most associated with visuospatial planning deficit. This issue was investigated in a sample of 408 youths with current DSM-IV diagnosis of ADHD, and 332 youths without lifetime ADHD, aged 8-17 years (mean age 12.02±2.24). All the participants and their mothers were interviewed using the Chinese Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia to obtain information about ADHD symptoms and diagnosis and other psychiatric disorders. In addition to clinical assessments, the participants were assessed with the WISC-III and the Stocking of Cambridge task of the Cambridge Neuropsychological Test Automated Battery. Multi-level regression models were used for data analysis. The results showed that univariate analyses revealed that inattention, hyperactivity, and impulsivity were significantly associated with visuospatial planning, and the magnitude of such association was amplified with increased task difficulties. Only inattention independently predicted visuospatial planning in a model that included all three ADHD symptoms. After further controlling for comorbidity, age of assessment, treatment with methylphenidate, and Full-scale IQ, inattention was still independently associated with visuospatial planning indexed by mean moves needed to solve problems. In subtype comparison, participants with combined subtype and those with prominently inattentive subtype, rather than prominently hyperactivity/impulsivity subtype, had poorer visuospatial planning performance. Our findings indicate that inattention is independently associated with impaired visuospatial planning, and dimensional approach retains the important distinction among ADHD symptoms than subtype approach in understanding the neuropsychological functioning of ADHD.

Different neural substrates for executive functions in youths with ADHD: a diffusion spectrum imaging tractography study.

BACKGROUND The relationship between white-matter tracts and executive functions (EF) in attention deficit hyperactivity disorder (ADHD) has not been well studied and previous studies mainly focused on frontostriatal (FS) tracts. The authors explored the microstructural property of several fibre tracts hypothesized to be involved in EF, to correlate their microstructural property with EF, and to explore whether such associations differ between ADHD and typically developing (TD) youths. METHOD We assessed 45 youths with ADHD and 45 individually matched TD youths with a computerized test battery for multiple dimensions of EF. From magnetic resonance imaging, FS tract, superior longitudinal fasciculus (SLF), arcuate fasciculus (AF) and cingulum bundle (CB) were reconstructed by diffusion spectrum imaging tractography. The generalized fractional anisotropy (GFA) values of white-matter tracts were computed to present microstructural property of each tract. RESULTS We found lower GFA in the left FS tract, left SLF, left AF and right CB, and poorer performance in set-shifting, sustained attention, cognitive inhibition and visuospatial planning in ADHD than TD. The ADHD and TD groups demonstrated different association patterns between EF and fibre tract microstructural property. Most of the EF were associated with microstructural integrity of the FS tract and CB in TD youths, while with that of the FS tract, SLF and AF in youths with ADHD. CONCLUSIONS Our findings support that the SLF, AF and CB also involve in a wide range of EF and that the main fibre tracts involved in EF are different in youths with ADHD.

A Validation Study of the Chinese Version of the Athens Insomnia Scale

Objectives: To establish the validity of the Chinese version of the Athens Insomnia Scale (CAIS) and the diagnostic cutoff scores for insomnia. Methods: Two hundred and eighty-three subjects, consisting of 65 psychiatric outpatients and 218 non-clinical samples, completed the CAIS. The ICD-10 ”nonorganic insomnia” was the diagnostic standard of insomnia, and the Insomnia Self-assessment Inventory (ISAI) was used as the external validator. Both the 8-item scale (CAIS-8) and the brief version containing the first 5 items (CAIS-5) were analyzed. Results: In both versions, the Cronbachs α of internal consistency reached 0.82-0.84. Correlation coefficients of test-retest reliability were 0.84-0.86. The correlation coefficients between the CAIS and ISAI were 0.72-0.76. The CAIS-8 demonstrated two components in factor analysis: items 1 to 5 (nighttime symptoms) and items 6 to 8 (daytime symptoms). The suggested cutoff points for insomnia among this ethnic Chinese population are 8 for the CAIS-8 (AUC=0.89, p＜0.01) and 5 for the CAIS-5 (AUC=0.90, p＜0.01), respectively. Conclusion: The CAIS-8 and CAIS-5 are fair tools in screening and making insomnia diagnoses in clinical practice, and have satisfactory reliability and validity.

A haplotype of the norepinephrine transporter gene (SLC6A2) is associated with visual memory in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common heritable childhood-onset psychiatric disorder with impaired visual memory. Based on the evidence from treatment effect of atomoxetine, which interacts directly with the norepinephrine transporter, on visual memory in children with ADHD, this study examined the linkage disequilibrium structure of the norepinephrine transporter gene (SLC6A2) and the association between SLC6A2 and ADHD and visual memory, a promising endophenotype for ADHD. This family-based association sample consisted of 382 probands with DSM-IV ADHD and their family members (n=1298 in total) of Han Chinese in Taiwan. Visual memory was assessed by the Pattern Recognition Memory (PRM) and Spatial Recognition Memory (SRM) tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB). We screened 21 polymorphisms across SLC6A2 and used the Family-Based Association Test (FBAT) to test the associations of SLC6A2 polymorphisms with ADHD and the PRM and SRM measures. In haplotype analyses, a haplotype rs36011 (T)/rs1566652 (G) was significantly associated with ADHD (minimal p=0.045) after adjustment for multiple testing. In quantitative analyses, this TG haplotype also demonstrated significant associations with visual memory measures, including mean latency of correct responses in PRM (minimal p=0.019), total correct responses in PRM (minimal p=0.018), and total correct responses in SRM (minimal p=0.015). Our novel finding of the haplotype rs36011 (T)/rs1566652 (G) as a novel genetic marker involved in both ADHD disease susceptibility and visual memory suggests that allelic variations in SLC6A2 could provide insight into the pathways leading from genotype to phenotype of ADHD.

The Association between Pubertal Development and Emotional/Behavioral Problems, Substance Use, and Suicidality among Adolescents

Objectives: Advanced pubertal stage and pubertal timing are among the risk factors of several emotional/behavioral problems in White populations. But little is known about such relationship in ethnic Chinese population. We cross-section-ally and prospectively examined the relationship between adolescent pubertal stage and mental health, focusing on emotional/behavioral problems, habitual use of substances and suicidality. Methods: With randomized multi-stage sampling method, we chose 1,388 7th graders, aged 13 to 14 years. Students completed the Pubertal Developmental Scale, Youth Self Report and questions about habitual substance use; their parents completed the Child Behavior Checklist and questions about habitual substance use. One year later, the same subjects repeated same questionnaires for comparison. Results: Totally 1,220 7th graders (604 boys, 49.5%) gave complete information. We followed up half of those students one year later. Of 593 8th graders, 488 (242 boys, 49.6%) and their parents completed the assessment. Our results showed that for both assessments in one year apart, most of the severity of the behavioral/emotional problems and rates of habitual use of substances and suicidality did not differ significantly among students in the five pubertal stages. Conclusion: This study did not support an association between pubertal staging and a wide range of emotional/behavioral problems, habitual use of substances and suicidality in Taiwanese adolescents. We suggest that future investigations on this topic need to include psychiatric interviews and objective assessments of pubertal development.

Disorder-Specific Alteration in White Matter Structural Property in Adults With Autism Spectrum Disorder Relative to Adults With ADHD and Adult Controls.

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are not only often comorbid but also overlapped in behavioral and cognitive abnormalities. Little is known about whether these shared phenotypes are based on common or different underlying neuropathologies. Therefore, this study aims to examine the disorder‐specific alterations in white matter (WM) structural property.