Ya-Mei Bai

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

BACKGROUNDnPeople with major depressive disorder who fail to respond to adequate trials of antidepressant treatment may harbour hidden bipolar disorder.nnnAIMSnWe 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.nnnMETHODnInformation 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.nnnRESULTSnIn 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)).nnnCONCLUSIONSnThis 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.

The association between online gaming, social phobia, and depression: an internet survey

BackgroundOnline gaming technology has developed rapidly within the past decade, and its related problems have received increasing attention. However, there are few studies on the psychiatric symptoms associated with excessive use of online games. The aim of this study is to investigate the characteristics of online gamers, and the association between online gaming hours, social phobia, and depression using an internet survey.MethodsAn online questionnaire was designed and posted on a popular online game websites, inviting the online gamers to participate the survey. The content of the questionnaire included demographic data, profiles of internet usage and online gaming, and self-rating scales of Depression and Somatic Symptoms Scale (DSSS), Social Phobia Inventory (SPIN), and Chen Internet Addiction Scale (CIAS).ResultsA total of 722 online gamers with a mean age of 21.8u2009±u20094.9u2009years completed the online survey within one month. 601 (83.2%) participants were male, and 121 (16.8%) were female. The mean weekly online gaming time was 28.2u2009±u200919.7 hours, which positively associated with history of online gaming (ru2009=u20090.245, pu2009<u20090.001), total DSSS (ru2009=u20090.210, pu2009<u20090.001), SPIN (ru2009=u20090.150, pu2009<u20090.001), and CIAS (ru2009=u20090.290, pu2009<u20090.001) scores. The female players had a shorter history of online gaming (6.0u2009±u20093.1 vs. 7.2u2009±u20093.6u2009years, pu2009=u20090.001) and shorter weekly online gaming hours (23.2u2009±u200917.0 vs. 29.2u2009±u200920.2 hours, pu2009=u20090.002), but had higher DSSS (13.0u2009±u20099.3 vs. 10.9u2009±u20099.7, pu2009=u20090.032) and SPIN (22.8u2009±u200914.3 vs. 19.6u2009±u200913.5, pu2009=u20090.019) scores than the male players. The linear regression model showed that higher DSSS scores were associated with female gender, higher SPIN scores, higher CIAS scores, and longer weekly online gaming hours, with controlling for age and years of education.ConclusionThe online gamers with longer weekly gaming hours tended to have a longer history of online gaming, and more severe depressive, social phobic, and internet addiction symptoms. Female online gamers had fewer weekly online gaming hours and a shorter previous online gaming history, but tended to have more severe somatic, pain, and social phobic symptoms. The predictors for depression were higher social phobic symptom, higher internet addiction symptoms, longer online gaming hours, and female gender.

Antidepressant mechanism of add-on repetitive transcranial magnetic stimulation in medication-resistant depression using cerebral glucose metabolism

BACKGROUNDnAdd-on repetitive transcranial magnetic stimulation (rTMS) is effective in treating medication-resistant depression (MRD), but little is known about the rTMS antidepressant mechanism and pathophysiology underlying MRD.nnnMETHODSnTwenty MRD patients received 2 weeks of navigated add-on rTMS to the left dorsolateral prefrontal cortex (DLPFC). Treatment response was defined as a ≥50% decrease in HDRS after treatment. Cerebral glucose metabolism was measured from all MRD patients twice, before and 3 months after rTMS, and from 20 healthy controls once at baseline.nnnRESULTSnAt baseline, MRD subjects presented significant hypometabolism at the bilateral DLPFC and anterior cingulum, as well as hypermetabolism at several limbic and subcortical regions compared to the controls. Higher metabolism at the medial PFC and rostral anterior cingulum, and lower metabolism at the limbic structures, including the left parahippocampus and fusiform gyrus, predicted a response to rTMS. After successful rTMS treatment, the abnormally elevated metabolism in the left middle temporal cortex and fusiform gyrus decreased significantly, suggesting a reversal of metabolic imbalances. However, the overall metabolic pattern was still abnormal, even after their depression was under control. In contrast, the non-responders showed a worsening pattern of increased metabolism in the bilateral temporal cortex and fusiform gyrus.nnnCONCLUSIONSnThe antidepressant mechanism of add-on rTMS may be reflected as suppression of hyperactivity in the left temporal cortex and fusiform gyrus, perhaps through enhancing the function of the medial prefrontal cortex and anterior cingulum. The limbic-cortical dysregulation of glucose metabolism might be a trait of an underlying mechanism of MRD.

Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study

Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation (P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness.

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

BACKGROUNDnAttention 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.nnnMETHODSnUtilizing 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.nnnRESULTSnPatients 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.nnnCONCLUSIONnu2002 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 (ORu2009=u20092.34, 95% CIu2009=u20091.58u2009~u20093.46), bipolar disorder (ORu2009=u20095.78, 95% CIu2009=u20092.23u2009~u200915.05), anxiety disorder (ORu2009=u20092.17, 95% CIu2009=u20091.49u2009~u20093.16), autism spectrum disorder (ORu2009=u20093.08, 95% CIu2009=u20091.79u2009~u20095.28), attention deficit hyperactivity disorder (ORu2009=u20091.67, 95% CIu2009=u20091.29u2009~u20092.17), tic disorder (ORu2009=u20091.70, 95% CIu2009=u20091.03u2009~u20092.78), developmental delay (ORu2009=u20092.45, 95% CIu2009=u20092.00u2009~u20093.00), and mental retardation (ORu2009=u20092.70, 95% CIu2009=u20092.00u2009~u20093.65), were identified. A gender effect was noted, in that only female patients with IDA had an increased OR of bipolar disorder (ORu2009=u20095.56, 95% CIu2009=u20091.98u2009~u200915.70) and tic disorder (ORu2009=u20092.95, 95% CIu2009=u20091.27u2009~u20096.86).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.

Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics

The use of atypical antipsychotics (AAPs) is associated with increasing the risk of the metabolic syndrome (MetS), which is an important risk factor for cardiovascular disease and diabetes. Two insulin-induced gene (INSIG) isoforms, designated INSIG-1 and INSIG-2 encode two proteins that mediate feedback control of lipid metabolism. In this genetic case–control study, we investigated whether the common variants in INSIG1 and INSIG2 genes were associated with MetS in schizophrenic patients treated with atypical antipsychctics. The study included 456 schizophrenia patients treated with clozapine (n=171), olanzapine (n=91) and risperidone (n=194), for an average of 45.5±27.6 months. The prevalence of MetS among all subjects was 22.8% (104/456). Two single-nucleotide polymorphisms (SNPs) of the INSIG1 gene and seven SNPs of the INSIG2 gene were chosen as haplotype-tagging SNPs. In single-marker-based analysis, the INSIG2 rs11123469-C homozygous genotype was found to be more frequent in the patients with MetS than those without MetS (P=0.001). In addition, haplotype analysis showed that the C-C-C haplotype of rs11123469-rs10185316- rs1559509 of the INSIG2 gene significantly increased the risk of MetS (P=0.0023). No significant associations were found between polymorphisms of INSIG1 gene and MetS, however, INSIG1 and INSIG2 interactions were found in the significant 3-locus and 4-locus gene–gene interaction models (P=0.003 and 0.012, respectively). The results suggest that the INSIG2 gene may be associated with MetS in patients treated with AAPs independently or in an interactive manner with INSIG1.

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

BACKGROUNDnPrevious 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.nnnMETHODSnIn 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.nnnRESULTSnChildren 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.nnnDISCUSSIONnOur 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.

Higher risk of developing major depression and bipolar disorder in later life among adolescents with asthma: A nationwide prospective study

OBJECTIVEnPrevious studies have suggested an immunological dysfunction in mood disorders, but rarely have investigated the temporal association between allergic diseases and mood disorders. Using the Taiwan National Health Insurance Research Database, we attempted to investigate the association between asthma in early adolescence and the risk of unipolar depression and bipolar disorder in later life.nnnMETHODSnIn all, 1453 adolescents with asthma aged between 10 and 15 years and 5812 age-/gender-matched controls were selected in 1998-2000. Subjects with unipolar depression and bipolar disorder that occurred up to the end of follow-up (December 31 2010) were identified.nnnRESULTSnAdolescents with asthma had a higher incidence of major depression (2.8% vs. 1.1%, pxa0<xa00.001), any depressive disorder (6.1% vs. 2.6%, pxa0<xa00.001), and bipolar disorder (1.0% vs. 0.3%, pxa0<xa00.001) than the control group. Cox regression analysis showed that asthma in early adolescence was associated with an increased risk of developing major depression (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.14-2.89), any depressive disorder (HR: 1.74, 95% CI: 1.27-2.37), and bipolar disorder (HR: 2.27, 95% CI: 1.01-5.07), after adjusting for demographic data and comorbid allergic diseases.nnnDISCUSSIONnAdolescents with asthma had an elevated risk of developing mood disorders in later life. Further studies would be required to investigate the underlying mechanisms for this comorbid association and elucidate whether prompt intervention for asthma would decrease the risk of developing mood disorders.

Risk of developing diabetes mellitus and hyperlipidemia among patients with bipolar disorder, major depressive disorder, and schizophrenia: A 10-year nationwide population-based prospective cohort study

BACKGROUNDnThe high comorbidity of metabolic side effects with severe mental disorders (SMDs), including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia, had gained much attention, because the excess mortality of these patients is mainly due to physical illness. However, most of these studies were with cross-sectional study design, the time course of metabolic side effects and SMD cannot be elucidated without a cohort study.nnnMETHODnUsing a nationwide database with a large sample size and a matched control cohort study design, we enrolled patients with SMDs but without diagnoses of and medications for DM and hyperlipidemia from 1996 to 2000, and followed them to the end of 2010. We compared them with age and gender-matched controls (1:4) for the incidence of DM and hyperlipidemia.nnnRESULTSnThe identified cases were 367 patients with BD, 417 patients with MDD, and 1993 patients with schizophrenia, with average age of 45.3 ± 14.0, 46.5 ± 13.7, and 45.9 ± 12.3, respectively. The patients with BD and schizophrenia had increased risk of initiation of anti-diabetic medications (10.1% vs. 6.3%, p=0.012; 13.3% vs. 7.2% p<0.001; respectively), and anti-hyperlipidemia medications (15.8% vs.10.5%, p=0.004; 14.2% vs.12.1%, p=0.005; respectively) than the controls. After controlling age, gender, urbanization, and income, the Cox regression model showed significantly increased risk of initiation of anti-diabetic medications among patients with BD (hazard ratio (HR) of 1.702, 95% confidence interval (CI): 1.155-2.507) and schizophrenia (HR of1.793, 95% CI: 1.532-2.098). Increased risk of initiation of anti-hyperlipidemia medications was also noted among patients with BD (HR of 1.506, 95% CI: 1.107-2.047) and schizophrenia (HR of 1.154, 95% CI: 1.002-1.329). The patients with MDD did not show increased risk of initiation of these medications than the controls.nnnCONCLUSIONSnThis first 10-year nationwide population-based prospective matched control cohort study showed increased risks of initiation of anti-diabetic and anti-hyperlipidemia medications among patients with BD and schizophrenia. No significant increased risk was noted among the patients with MDD.