Ju-Wei Hsu

Attention deficit hyperactivity disorder, tic disorder, and allergy: is there a link? A nationwide population-based study

BACKGROUND Attention deficit hyperactivity disorder (ADHD) and tic disorder usually co-occur in the same individuals, but the underlying mechanisms remain unclear. Previous evidence has shown that a frequent coexistence of allergic diseases was noted in patients with ADHD or tic disorder. We attempted to investigate the possible link among ADHD, tic disorder, and various allergic diseases. METHODS Utilizing the Taiwan National Health Insurance Research Database from 1996 to 2010, 5,811 patients with ADHD alone, 1,816 patients with tic disorder alone, and 349 patients with dual diagnoses of ADHD and tic disorder were identified and compared with age-/gender-matched controls (1:4) in an investigation of the association among ADHD, tic disorder, and allergic diseases. RESULTS Patients with dual diagnoses of ADHD and tic disorder had a significantly higher prevalence of allergic diseases and psychiatric comorbidities, including allergic rhinitis (43% vs. 28.4% vs. 33.6% vs. 19.7%, p < 0.001), asthma (27.5% vs. 17.2% vs. 18.2% vs. 11.9%, p < 0.001), atopic dermatitis (10.6% vs. 8.4% vs. 7.0 vs. 5.9%, p < 0.001), allergic conjunctivitis (55.6% vs. 34.7% vs. 43.5% vs. 26.3%, p < 0.001), obsessive compulsive disorder (4.0% vs. 1.3% vs. 2.0% vs. 0.1%, p < 0.001), and anxiety disorder (22.1% vs. 18.0% vs. 6.0% vs. 0.5%, p < 0.001) than the ADHD alone group, the tic alone group, and the control group. Furthermore, ADHD patients with more allergic diseases (≥ 3 comorbidities: OR: 3.73, 95% CI: 2.65~5.25; 2 comorbidities: OR: 2.52, 95% CI: 1.82~3.47; 1 comorbidity: OR: 1.87, 95% CI: 1.41~2.49) exhibited an increased risk of tic disorder compared with ADHD patients without allergic disease. CONCLUSION   A significant association among ADHD, tic disorder, and allergic diseases was noted in our study. The results may inspire further studies to clarify the underlying mechanisms and help us understand more about the complex etiology of ADHD, tic disorder, and their co-occurrence.

Association between psychiatric disorders and iron deficiency anemia among children and adolescents: a nationwide population-based study.

BackgroundA great deal of evidence has shown that iron is an important component in cognitive, sensorimotor, and social-emotional development and functioning, because the development of central nervous system processes is highly dependent on iron-containing enzymes and proteins. Deficiency of iron in early life may increase the risk of psychiatric morbidity.MethodsUtilizing the National Health Insurance Database from 1996 to 2008, children and adolescents with a diagnosis of IDA were identified and compared with age and gender-matched controls (1:4) in an investigation of the increased risk of psychiatric disorders.ResultsA total of 2957 patients with IDA, with an increased risk of unipolar depressive disorder (OR = 2.34, 95% CI = 1.58 ~ 3.46), bipolar disorder (OR = 5.78, 95% CI = 2.23 ~ 15.05), anxiety disorder (OR = 2.17, 95% CI = 1.49 ~ 3.16), autism spectrum disorder (OR = 3.08, 95% CI = 1.79 ~ 5.28), attention deficit hyperactivity disorder (OR = 1.67, 95% CI = 1.29 ~ 2.17), tic disorder (OR = 1.70, 95% CI = 1.03 ~ 2.78), developmental delay (OR = 2.45, 95% CI = 2.00 ~ 3.00), and mental retardation (OR = 2.70, 95% CI = 2.00 ~ 3.65), were identified. A gender effect was noted, in that only female patients with IDA had an increased OR of bipolar disorder (OR = 5.56, 95% CI = 1.98 ~ 15.70) and tic disorder (OR = 2.95, 95% CI = 1.27 ~ 6.86).ConclusionIron deficiency increased the risk of psychiatric disorders, including mood disorders, autism spectrum disorder, attention deficit hyperactivity disorder, and developmental disorders. Further study is required to clarify the mechanism in the association between IDA and psychiatric disorder.

Asthma and attention‐deficit/hyperactivity disorder: a nationwide population‐based prospective cohort study

BACKGROUND Previous cross-sectional studies have suggested an association between asthma and attention-deficit/hyperactivity disorder (ADHD), but the temporal relationship was not determined. Using a nationwide population-based prospective case-control cohort study (1:4, age-/gender-matched), we hypothesized that asthma in infanthood or early childhood would increase the risk of ADHD in later life. METHODS In all, 2,294 children with asthma and 9,176 controls aged between 0 and 3 years in 2000 were included in our study. Cases of ADHD that occurred to the end of follow-up (31 December 2010) were identified. RESULTS Children with asthma had a higher incidence of developing ADHD (7% vs. 4.6%, p < .001) than control cohort during the follow-up period. After adjusting for age at enrollment, gender, level of urbanization, and comorbid allergic diseases (allergic rhinitis and atopic dermatitis), children with asthma had an elevated risk (HR: 1.31, 95% CI: 1.07-1.59) of developing ADHD compared with control group. DISCUSSION Our prospective study supported a temporal relationship between asthma and ADHD. Asthma in very early life increased the risk of developing ADHD during the school years. Further studies are required to investigate whether the prompt treatment of asthma and comorbid allergic diseases could prevent the development of ADHD or decrease ADHD symptoms.

Is atopy in early childhood a risk factor for ADHD and ASD? A longitudinal study

OBJECTIVE Previous studies have found a temporal concordance in the increased prevalence of atopic diathesis/atopic diseases, attention-deficit hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD) worldwide. But, the temporal association among these 3 distinct diseases is unknown. METHOD 14,812 atopic subjects diagnosed with any atopic disease (asthma, atopic dermatitis, allergic rhinitis, or allergic conjunctivitis) before the age of 3 (atopic cohort) and 6944 non-atopic subjects with no lifetime atopic disease (non-atopic cohort), born between 1997 and 2000, were enrolled and followed to December 31, 2010 to identify the development of ADHD and ASD. RESULTS The presence of any atopic disease in early childhood increased the risk of developing ADHD (hazard ratio [HR]: 1.97) and ASD (HR: 3.40) in later life. Greater numbers of atopic comorbidities (4 comorbidities: ADHD: HR: 2.53; ASD: HR: 4.29) were significantly related to a greater risk of developing ADHD and ASD. DISCUSSION Atopic diathesis in early childhood elevated the risk of developing ADHD and ASD in later life, with the dose-dependent relationship of more atopic comorbidities with a greater likelihood of ADHD and ASD.

Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study.

BACKGROUND Previous cross-sectional studies have suggested a comorbid association between atopic dermatitis (AD) and depressive disorder as well as anxiety disorders, but the temporal relationship was not determined. METHODS Using the Taiwan National Health Insurance Research Database, 8208 AD patients aged 12 and older without psychiatric history and age-/sex-matched (1:1) controls between 1998 and 2008 were enrolled in our study and followed to the end of 2011. Subjects who developed major depression, any depressive disorder, and anxiety disorders during the follow-up were identified. RESULTS The Cox regression analysis after adjusting for demographic data and atopic comorbidities demonstrated that patients with AD had an elevated risk of developing major depression (hazard ratio [HR]: 6.56, 95% confidence interval [CI]: 3.64-11.84), any depressive disorder (HR: 5.44, 95% CI: 3.99-7.44), and anxiety disorders (HR: 3.57, 95% CI: 2.55-4.98). Stratified by age group, both adolescents and adults with AD were prone to developing major depression (HR: 4.26, 95% CI: 1.39-13.13; HR: 7.56, 95% CI: 3.75-15.23), any depressive disorder (HR: 4.38, 95% CI: 2.09-9.18; HR: 5.66, 95% CI: 4.01-7.99), and anxiety disorders (HR: 5.40, 95% CI: 2.02-14.39; HR: 3.36, 95% CI: 2.38-4.80). CONCLUSIONS AD in both adolescence and adulthood increased the risk of developing major depression, any depressive disorder, and anxiety disorders in later life. Further studies would be required to clarify the possible underlying mechanism between AD and depression as well as anxiety disorders.

Allergic rhinitis in adolescence increases the risk of depression in later life: A nationwide population-based prospective cohort study

BACKGROUND Many cross-sectional studies have suggested an association between allergic rhinitis (AR) and depression, but the timing relationship was not determined. Using a nationwide population-based prospective cohort study (1:4, age-/gender-matched), we hypothesized that AR in adolescence would increase the risk of depression in later life. METHODS In all, 1673 adolescents aged 12-15 that had AR between 1996 and 2000 were recruited for our study. Cases of major depressive disorder and any depressive disorder that occurred to the end of follow-up (December 31, 2010) were identified. RESULT Adolescents with AR had a higher prevalence of major depression (2.5% vs. 1.2%, p<0.001) and any depressive disorder (4.9% vs. 2.8%, p<0.001) and an earlier onset of major depression (19.31 ± 2.91 vs. 20.43 ± 2.71 years, p=0.038) and any depressive disorder (19.35 ± 2.63 vs. 20.43 ± 2.62 years, p=0.002) compared with the controls. The Cox regression model showed that adolescents with AR had increased HRs of major depression (HR: 1.59, 95% CI: 1.02-2.50) and any depressive disorder (HR: 1.42, 95% CI: 1.04-1.93) after controlling residence location and comorbid allergic diseases. LIMITATIONS The prevalence of depressive disorder may be underestimated because only those who had medicine-seeking behaviors were enrolled. CONCLUSIONS This first cohort case-control study showed an association between AR in early adolescence and depression in late adolescence and early adulthood. Our results suggested that allergic responses played important roles in the development of depression.

Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study

BACKGROUNDS Several cross-sectional studies suggested a link between endometriosis and mood disorders. However, the temporal association between endometriosis and mood disorders (depression and anxiety disorders) is still unclear. METHODS Using the Taiwan National Health Insurance Research Database, 10,439 women with endometriosis and 10,439 (1:1) age-/sex-matched controls between 1998 and 2009 were enrolled, and followed up to the end of 2011. Those who developed depression or anxiety disorders during the follow-up were identified. RESULTS Women with endometriosis had an increased risk of developing major depression (hazard ratio [HR]: 1.56, 95% confidence interval [CI]:1.24-1.97), any depressive disorder (HR: 1.44, 95% CI: 1.25-1.65), and anxiety disorders (HR: 1.44, 95% CI: 1.22-1.70) in later life compared to those without endometriosis. Stratified by age group, women with endometriosis aged <40 years and those aged ≧40 years were both prone to developing major depression (HR: 1.52, 95% CI: 1.15-1.99; HR: 1.69, 95% CI: 1.09-2.62), any depressive disorder (HR: 1.43, 95% CI: 1.21-1.69; HR: 1.45, 95% CI: 1.13-1.56), and anxiety disorders (HR: 1.39, 95% CI: 1.14-1.71; HR: 1.53, 95% CI: 1.15-2.04). LIMITATION the incidence of depression and anxiety disorders may be underestimated since only those who sought medical consultation and help would be enrolled in our study. CONCLUSION Endometriosis was associated with an elevated likelihood of developing depression and anxiety disorders. Further studies may be required to investigate the underlying pathophysiology between endometriosis and both depression and anxiety disorders.

No Evidence for Association of Alpha 1a Adrenoceptor Gene Polymorphism and Clozapine-Induced Urinary Incontinence

Clozapine is an effective atypical antipsychotic that has high affinity for many neurotransmitter receptors. Among the adverse effects of clozapine, urinary incontinence is commonly found and is suggested to be caused by α-adrenergic blockade. We tested the hypothesis that clozapine-induced urinary incontinence is related to a genetic variant of the α1a-adrenoceptor. We also tested whether the α1a-receptor gene confers susceptibility to schizophrenic disorders. Our result indicated that the α1a-adrenoceptor gene polymorphism investigated plays no major role in the pathogenesis of schizophrenia or in clozapine-induced urinary incontinence. Considering the superior effects of clozapine and its potent adrenergic antagonistic effects, it is of interest to investigate the association between this polymorphism and the treatment response.

Bidirectional Association Between Depression and Fibromyalgia Syndrome: A Nationwide Longitudinal Study

Several cross-sectional studies have reported a common comorbidity between depression and fibromyalgia syndrome (FMS). However, a bidirectional temporal association between these 2 distinct diseases has rarely been investigated. Using the Taiwan National Health Insurance Research Database, 25,969 patients with FMS and without any psychiatric disorder and 17,142 patients with depression and without FMS between 2000 and 2008 were enrolled and separately compared with age- and sex-matched (1:4) control groups. Patients with FMS who developed a new-onset depression and those with depression who developed new-onset FMS were identified during follow-up (to the end of 2011). The conditional Cox regression analyses, after adjustment for demographic data and medical comorbidities, showed that the patients with FMS were associated with an increased risk (hazard ratio [HR] 7.46, 95% confidence interval [CI] 6.77-8.22) of subsequent depression and that those with depression were associated with an increased risk (HR 6.28, 95% CI 5.67-6.96) of subsequent FMS. Our results supported a bidirectional temporal association between depression and FMS. Each disease occurring first may increase the risk of the other subsequently. Further study may be necessary to determine the underlying mechanism between depression and FMS and to clarify whether a prompt intervention for depression or FMS may decrease the risk of the other later in life. Perspective: Our study supported a bidirectional temporal association between depression and FMS such that each disease occurring first may increase the risk of the other subsequently. This result may imply a shared pathophysiology between FMS and depression, but further investigation is needed.

Comorbidity of ADHD and subsequent bipolar disorder among adolescents and young adults with major depression: a nationwide longitudinal study

Previous studies have found that attention‐deficit hyperactivity disorder (ADHD) in childhood and adolescence is associated with an increased risk of major depression and bipolar disorder in later life. However, the effect of ADHD comorbidity on the diagnostic conversion to bipolar disorder among patients with major depression is still uncertain.