Ying-Sheue Chen

Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study

BACKGROUND People with major depressive disorder who fail to respond to adequate trials of antidepressant treatment may harbour hidden bipolar disorder. AIMS We aimed to compare the rates of a change in diagnosis to bipolar disorder among people with major depressive disorder with stratified responses to antidepressants during an 8-year follow-up period. METHOD Information on individuals with major depressive disorder identified during 2000 (cohort 2000, n = 1485) and 2003 (cohort 2003, n = 2459) were collected from a nationally representative cohort of 1,000,000 health service users in Taiwan. Participants responding well to antidepressants were compared with those showing poor responses to adequate trials of antidepressants. RESULTS In 7.6-12.1% of those with a diagnosis of unipolar major depressive disorder this diagnosis was subsequently changed to bipolar disorder, with a mean time to change of 1.89-2.98 years. Difficult-to-treat participants presented higher rates of change to a bipolar diagnosis (25.6% in cohort 2000; 26.6% in cohort 2003) than easy-to-treat participants (8.8-8.9% in cohort 2000; 6.8-8.6% in cohort 2003; P<0.0001). Regression analysis showed that the variable most strongly associated with the change in diagnosis was antidepressant use history. The difficult-to-treat participants were associated most with diagnostic changing (cohort 2000: odds ratio (OR) = 1.88 (95% CI 1.12-3.16); cohort 2003: OR = 4.94 (95% CI 2.81-8.68)). CONCLUSIONS This is the first large-scale study to report an association between antidepressant response history and subsequent change in diagnosis from major depressive disorder to bipolar disorder. Our findings support the view that a history of poor response to antidepressants in unipolar depression could be a useful predictor for bipolar diathesis.

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.

Levels of the potential biomarker p11 in peripheral blood cells distinguish patients with PTSD from those with other major psychiatric disorders

Posttraumatic stress disorder (PTSD) is a severely debilitating anxiety disorder. Over 80% of patients with PTSD also exhibit other psychiatric condition, such as bipolar disorder (BP) or major depression (MDD). Previously, it has been found that p11 mRNA expression was significantly changed in post mortem cortex of patients with PTSD and depression. We hypothesize that p11 mRNA levels in the peripheral blood cells will be a potential biomarker for PTSD with heterogeneity in terms of type of trauma, time since trauma and duration of illness. We examined the peripheral blood mononuclear cell (PBMC) P11 mRNA of patients with PTSD (n=13), major depressive disorder (MDD, n=16), bipolar disorder (BP, n=24), and schizophrenia (SCZ, n=12) or controls (n=14) using quantitative real-time PCR and the circulating levels of cortisol in blood plasma and saliva of PTSD using radioimmunoassay kit CORT-CT2. The Hamilton Rating Scale for Depression (HAMD) and Anxiety (HARS), the Chinese version of the Davidson Trauma Scale-Frequency (CDTS-F) and the Chinese version of the Davidson Trauma Scale-Severity (CDTS-S), and Impact of Event Scale-Revised (IES-R) were administered. We found that patients with PTSD had lower levels of p11 mRNA than control subjects, while those with MDD, BP and SCZ had significantly higher p11 levels than the controls. P11 mRNA levels were positively correlated with the scores of HAMD (r=0.62, p<0.05), CDTS-F (r=0.71, p<0.05) and CDTS-S (r=0.62, p<0.05), while they did not correlate with scores of HARS and IES-R. Basal levels of plasma and salivary cortisol of PTSD patients were not statistically different from those of controls. Our findings suggest that PBMC p11 mRNA expression levels may serve as a potential biomarker to distinguish PTSD from BP, MDD and SCZ.

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.

Comorbidity of Allergic and Autoimmune Diseases Among Patients With ADHD: A Nationwide Population-Based Study

Objective: Patients with ADHD have been suggested to have increased risks of allergic diseases but without consistent results, and limited studies about the association between ADHD and autoimmune diseases were noted in the literature. Method: Utilizing the Taiwan National Health Insurance Research Database, ADHD patients were identified and compared with age- and gender-matched controls (1:4). Results: In all, 8,201 participants were identified as having ADHD, and an increased prevalence of allergic diseases, including asthma (odds ratio [OR] = 1.53), allergic rhinitis (OR = 1.59), atopic dermatitis (OR = 1.53), and urticaria (OR = 1.39), compared with the control group. Although the comorbidity of autoimmune diseases with ADHD was low, ADHD patients had a significantly greater prevalence of ankylosing spondylitis (OR = 2.78), ulcerative colitis (OR = 2.31), and autoimmune thyroid disease (OR = 2.53) than the controls. Conclusion: Our results supported the association between ADHD and allergic/autoimmune diseases. The further studies will be required to clarify the underlying mechanisms.

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 stroke among patients with post-traumatic stress disorder: nationwide longitudinal study

BACKGROUND Previous evidence has shown positive associations between post-traumatic stress disorder (PTSD) and hypertension, dyslipidaemia and diabetes mellitus, which are all risk factors for stroke, but the role of PTSD in the subsequent development of stroke is still unknown. AIMS To investigate the temporal association between PTSD and the development of stroke. METHOD Identified from the Taiwan National Health Insurance Research Database, 5217 individuals aged ≥18 years, with PTSD but with no history of stroke, and 20 868 age- and gender-matched controls were enrolled between 2002 and 2009, and followed up until the end of 2011 to identify the development of stroke. RESULTS Individuals with PTSD had an increased risk of developing any stroke (hazard ratio (HR) 3.37, 95% CI 2.44-4.67) and ischaemic stroke (HR = 3.47, 95% CI 2.23-5.39) after adjusting for demographic data and medical comorbidities. Sensitivity tests showed consistent findings (any stroke HR = 3.02, 95% CI 2.13-4.28; ischaemic stroke HR = 2.89, 95% CI 1.79-4.66) after excluding the first year of observation. CONCLUSIONS Individuals with PTSD have an increased risk of developing any stroke and ischaemic stroke. Further studies are required to investigate the underlying mechanisms.

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.