The use of sertraline to treat an adolescent of dystonia comorbid with major depressive disorder with psychotic features.

Dystonia is characterized by sustained or intermittent involuntary muscle contractions. Psychiatric symptoms are essential non-motor features of dystonia, and higher risks of depressive and anxiety disorders have been reported. The precedence of psychiatric to motor symptoms in some patients and the dopaminergic and serotonergic system involvement in both the motor and psychiatric aspects suggest these psychiatric disorders may be intrinsic to the neurobiology of dystonia. Nevertheless, psychiatric comorbidities are often construed as secondary reactions to motor disabilities and the negative bio-psycho-social impacts of dystonia, leading to underdiagnosis and undertreatment. Research on antidepressant use in dystonia is scarce, especially in children and adolescents. This report presents a 17-year-old female with dystonia comorbid with depression with psychotic features, whose motor symptoms improved but psychiatric symptoms persisted with dopaminergic pharmacotherapy. Sertraline was finally added 5 years after the onset and successfully managed her psychotic depression without worsening motor symptoms. Early detection, prompt diagnosis, and timely holistic treatment with dopaminergic agents, antidepressants, and psychosocial interventions are critical for the mental health of dystonia patients.

Exposome of attention deficit hyperactivity disorder in Taiwanese children: exploring risks of endocrine-disrupting chemicals.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in ~7% of school-aged children. The role of endocrine-disrupting chemicals (EDC) and oxidative stress in ADHD etiology are not clear. OBJECTIVE: Assessment of the associations between simultaneous exposure to multiple compounds and ADHD in children. METHODS: The case-control study included 76 clinically diagnosed ADHD cases and 98 controls, aged 4-15 years old. Concentrations quartiles of urinary metabolites of acrylamide, acrolein, nonylphenol, phthalates, and organophosphate pesticides and biomarkers of oxidative stress were used to fit logistic regressions for each compound and weighted quantiles sum (WQS) regression for the mixture. RESULTS: Positive dose-response relationships with ADHD were observed for 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) (odds ratio(OR)Q4 = 3.73, 95%CI [1.32, 11.04], ptrend = 0.003), dimethyl phosphate (DMP) (ORQ4 = 4.04, 95%CI [1.34, 12.94], ptrend = 0.014) and diethyl phosphate (ORQ4 = 2.61, 95%CI = [0.93, 7.66], ptrend = 0.030), and for the mixture of compounds (ORWQS = 3.82, 95%CI = [1.78, 8.19]) with the main contributions from HNE-MA (28.9%) and DMP (18.4%). CONCLUSIONS: The dose-response relationship suggests enhanced susceptibility to EDC burden in children even at lower levels, whereas the main risk is likely from organophosphate pesticides. HNE-MA is recommended as a sensitive biomarker of lipid peroxidation in the further elucidation of the oxidative stress role in ADHD etiology.

The associations among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of paraoxonases in children with attention deficit/hyperactivity disorder.

This study will help to clarify the relationship between organophosphate pesticides (OPs) and attention deficit/hyperactivity disorder (ADHD) related to oxidative stress and paraoxonases (PON) polymorphisms to further characterize the gene-environment interaction. This case-control study enrolled 85 children with ADHD and 96 control subjects. Urinary OP levels were analyzed by using gas chromatography-mass spectrometry (GC-MS). Oxidative stress biomarkers, such as 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2-Gua), 8-iso-prostaglandin F2α (8-iso-PGF2α), and 4-hydroxy-2-nonenoic acid-mercapturic acid (HNE-MA), were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated to evaluate the additive interactions between OP exposure and PON genetic polymorphism on ADHD. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to OP exposure on ADHD. Children with ADHD had significantly higher DMP (238.95 nmol/g cre. vs. 164.83 nmol/g cre., p value = 0.01) and HNE-MA (30.75 µg/g cre. vs. 18.41 µg/g cre., p value<0.01) concentrations than control children. Children who carried the PON1 GG genotype (rs705379) had low urinary DMP levels, and the level increased with increasing numbers of allele variants. The risk for developing ADHD reached 2.06-fold (OR = 2.06, 95% CI:1.23-3.44) and 1.43-fold (OR = 1.45, 95% CI:1.04-2.03) when the DMP and HNE-MA levels increased by 1 natural log of the concentration, respectively. The estimated AP value was 0.66 (95% CI: 0.17-1.15), indicating that 66% of ADHD cases in DMP-exposed children with the PON1 CT/TT (rs705381) genotype were due to gene-environment interactions. No significant mediation of HNE-MA was observed between DMP exposure and the risk of ADHD. The estimated proportion mediated was only 7.0% (95% CI: -0.08-0.46). This research suggests the role of OP exposure in the occurrence of ADHD after adjusting for covariates.

The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children.

OBJECTIVE: The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. METHODS: This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified. RESULTS: Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95µg/g cre. vs. 16.55µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24-0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13-1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12-65.04). CONCLUSION: This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected.

Comorbidity of Allergic and Autoimmune Diseases Among Patients With ADHD.

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.

Sugar-Sweetened Beverage Consumption Is Adversely Associated with Childhood Attention Deficit/Hyperactivity Disorder.

Attention deficit/hyperactivity disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Evidence of the negative effects of sugar-sweetened beverages (SSBs) on mental health has not been convincing, although a few studies have found an association between high SSB levels and attention problems in children. This study aimed to test the hypothesis that SSB consumption is associated with ADHD among children. Doctor-diagnosed ADHD cases (n = 173) and non-ADHD controls (n = 159) between age 4 to 15 were recruited. SSB consumption, socio-demographic and lifestyle characteristics of the children, as well as of their mothers' characteristics during pregnancy, were collected using a questionnaire. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. There was a dose-response relationship between SSB consumption and ADHD. After covariates were adjusted, children who consumed SSBs at moderate levels and high levels had 1.36 and 3.69 odds, respectively, of having ADHD, compared with those who did not consume SSBs (p for trend < 0.05). Similar results were obtained when females were excluded. Our findings highlighted the adverse correlation between SSB consumption and ADHD and indicated a dose-response effect even after covariates were adjusted.

Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study.

OBJECTIVE: Studies have suggested the association between autism spectrum disorder (ASD) and type 2 diabetes mellitus (DM)-related risk factors, such as obesity and dyslipidemia. However, the association between ASD and type 2 DM remains unknown. RESEARCH DESIGN AND METHODS: We used the Taiwan National Health Insurance Research Database for enrolling 6,122 adolescents and young adults with ASD and 24,488 age- and sex-matched control subjects between 2002 and 2009 and monitored them until the end of 2011. Participants who developed type 2 DM during the follow-up period were identified. RESULTS: Adolescents (hazard ratio [HR] 2.71 [95% CI 1.64-4.48]) and young adults (HR 5.31 [95% CI 2.85-9.90]) with ASD had a higher risk of developing type 2 DM than those without ASD, after adjustment for demographic data, atypical antipsychotics use, and medical comorbidities. Sensitivity analyses after excluding first year (HR 3.03 [95% CI 2.03-4.51]) and first 3-year (HR 2.62 [95% CI 1.62-4.23]) observation periods were consistent. Short-term (HR 1.97 [95% CI 1.20-3.23]) and long-term (HR 1.64 [95% CI 1.02-2.63]) use of atypical antipsychotics were associated with a higher likelihood of subsequent type 2 DM. CONCLUSIONS: Adolescents and young adults with ASD were more likely to develop type 2 DM during the follow-up. In addition, those with ASD using atypical antipsychotics exhibited a high risk. Therefore, further research is necessary to investigate the common pathophysiology of ASD and type 2 DM.

Structural and functional correlates of a quantitative autistic trait measured using the social responsive scale in neurotypical male adolescents.

Behaviors associated with autism spectrum disorder (ASD) have been suggested to be considered as quantitative traits. This study investigated the structural and functional correlates of autistic traits measured using the Social Responsiveness Scale (SRS) in neurotypical adolescents. Twenty-six neurotypical male adolescents (12-18 years old) were recruited for this study and underwent structural and resting functional magnetic resonance image scanning, and intelligence quotient and SRS evaluations. We used the automated surface-based method (FreeSurfer) to measure cortical thickness and seed-based functional connectivity (FC) analysis to derive the FC map of the dorsal anterior cingulate (dACC). Brain-wise regression analyses of cortical thickness and FC maps on SRS scores were performed using a general linear model. The results indicated that higher autistic trait ratings of total SRS scores were associated with a thinner cortex in the left insula, right insula, and right superior temporal gyrus. Furthermore, we observed that only higher scores of social awareness were correlated with increased FC between the dACC and right superior temporal gyrus and decreased FC between the dACC and right putamen and thalamus. These results indicated that a quantitative trait in social cognition is associated with structural and connectivity variations linked to ASD patients. Autism Res 2016, 9: 570-578. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Risk of bipolar disorder among adolescents with allergic rhinitis: A nationwide longitudinal study.

BACKGROUND: Previous studies have suggested an immunological dysfunction in bipolar disorder, but none has investigated the temporal association between allergic rhinitis (AR) and bipolar disorder. METHODS: Using Taiwan National Health Insurance Research Database, 9506 adolescents aged 12-18 years with allergic rhinitis were enrolled between 2000 and 2008 and compared to 38,024 age-and gender-matched (1:4) control groups. Subjects of bipolar disorder that occurred up to the end of follow-up (December 31, 2011) were identified. RESULTS: Adolescents with AR had a significantly higher incidence of developing bipolar disorder (0.77 vs. 0.18 per 1000 person-years, p<0.001) during the follow-up period than the controls. Adolescents with AR had an increased risk (hazard ratio [HR]: 4.62, 95% confidence interval [CI]: 3.17-6.75) of developing bipolar disorder in their later life compared to the control group after adjusting for demographic data and comorbid allergic diseases. DISCUSSION: This is the first study showing a temporal association between AR and bipolar disorder, in that patients who had AR in adolescence exhibited an increased risk of developing bipolar disorder in later life. Further study would be required to investigate the underlying mechanism about this association.

Acute exacerbation of psychiatric symptoms during influenza treatment with oseltamivir in chronic schizophrenia.

Influenza treatment and prophylaxis with oseltamivir are critically important in reducing the morbidity and mortality of patients in chronic psychiatric facilities. Abnormal behavior, delusions, perceptual disturbances, mania, and depression have all been reported as oseltamivir-related psychiatric side effects. We hereby report two chronic schizophrenia patients in Taiwan manifesting psychiatric instability who were being treated with oseltamivir for suspected influenza infection, and further discuss other potential contributing factors. The possibility that oseltamivir can cause psychotic or affective symptoms suggests that additional caution is necessary for its use in patients with an established psychiatric diagnosis.

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.

OBJECTIVES: 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. METHODS: Using the Taiwan National Health Insurance Research Database, 58,023 subjects < 30 years of age who had major depression with (n = 1,193) or without (n = 56,830) ADHD comorbidity between the years 2000 and 2008 were enrolled in our study. Subjects who developed bipolar disorder during the follow-up to the end of 2011 were identified. RESULTS: Adolescents and young adults who had major depression with ADHD comorbidity had an increased incidence of subsequent bipolar disorder (18.9% versus 11.2%, p < 0.001) compared to those without ADHD. Cox regression analysis showed that ADHD comorbidity was an independent risk factor (hazard ratio = 1.50, 95% confidence interval 1.30-1.72) predicting subsequent bipolar disorder among those with major depression, adjusting for demographic data and psychiatric comorbidities. CONCLUSIONS: Patients with comorbid diagnoses of major depression and ADHD had an increased risk of diagnostic conversion to bipolar disorder compared to those who had major depression alone. Further studies would be required to validate this finding and to investigate the possible underlying mechanisms.

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 narcolepsy and schizophrenia in an adolescent patient.

A 13-year-old boy suffered from hypersomnia, fragmented nighttime sleep, and cataplexy since age 10 years, and then developed prominent psychotic symptoms (i.e., auditory and visual hallucination, hallucinatory behavior, delusions of reference, and misidentification) that occurred persistently during the wakeful and consciously clear period when he was aged 12 years. The child underwent additional medical evaluation and testing, and comorbidity of narcolepsy and schizophrenia was diagnosed. The child's psychotic symptoms and narcolepsy improved significantly upon treatment with methylphenidate 30 mg, olanzapine 25 mg, and haloperidol 10 mg. In this case, the child's symptomology of narcolepsy and schizophrenia and the dilemma of the use of antipsychotics and psychostimulants are representative examples of the diagnostic and therapeutic challenges in adolescent psychiatry.

Risk of epilepsy among patients with atopic dermatitis: a nationwide longitudinal study.

OBJECTIVE: Both atopic dermatitis and epilepsy have been regarded as chronic inflammatory diseases. However, their association has yet to be investigated. METHODS: Using the Taiwan National Health Insurance Research Database, 35,312 patients with atopic dermatitis but without a history of epilepsy, and 35,312 age-/gender-matched controls were enrolled between 1998 and 2008, and followed to the end of 2011 to identify the development of epilepsy. RESULTS: Subjects with atopic dermatitis had a higher incidence of developing epilepsy (0.94 vs. 0.27/1,000 person-years, p < 0.001) than the control group. The Cox regression model showed that atopic dermatitis increased the risk of developing epilepsy (hazard ratio [HR] 2.91, 95% confidence interval [CI] 2.23-3.82) after adjusting for demographic data and medical comorbidities. Sensitivity tests showed consistent findings (HR 2.32, 95% CI 1.68-2.96) after excluding the first year of observation. In addition, asthma (HR 1.34, 95% CI 1.04-1.72) and allergic rhinitis (HR 1.34, 95% CI 1.04-1.73) were related to the risk of epilepsy. SIGNIFICANCE: Subjects with atopic dermatitis were associated with an increased risk of developing epilepsy in later life. Further studies would be needed to investigate the underlying mechanisms.