Chin-Bin Yeh

Assessment of symptom exacerbations in a longitudinal study of children with Tourette's syndrome or obsessive-compulsive disorder.

OBJECTIVESnThe severity of tic and obsessive-compulsive (OC) symptoms varies over time. Consequently, how do we, as clinicians, know when a change in symptom severity occurs that falls outside of the normal range of fluctuation? The goal of this study was to describe the level of symptom severity fluctuation over time and to establish an objective, prospective, and quantitative method for identifying symptom exacerbations in children with Tourettes syndrome, obsessive-compulsive disorder (OCD), or both. A second major aim was to assess whether fluctuations in tic and OC symptom severity covaried with one another.nnnMETHODnMonthly consecutive Yale Global Tic Severity Scale and Childrens Yale-Brown Obsessive Compulsive Scale scores were prospectively obtained in 64 children diagnosed with Tourettes syndrome and/or OCD for periods ranging from 3 to 39 months. Exacerbation thresholds were estimated by using state-of-the-art bootstrap methods. These thresholds were then independently evaluated by asking two expert clinicians to identify, retrospectively, clinically significant exacerbations based on a review of all available clinical and research records.nnnRESULTSnThe severity of tic and OC symptoms displayed a high degree of intrasubject variability. Exacerbation thresholds, which incorporated the change score from the previous month and the current symptom score, provided the best agreement with those of expert clinicians. When both tic and OC symptoms were present, they showed a significant degree of covariation.nnnCONCLUSIONSnEvidence-based treatments are coming of age. The use of valid, clinician-rated severity scales will likely become a standard part of clinical practice. Bootstrapping methods may provide a quantitative and convenient way to obtain clinically valid thresholds to assess tic and OC symptom exacerbations. This method has the potential to be applied to other symptom domains where exacerbation thresholds are needed.

Characteristics of acute stress symptoms and nitric oxide concentration in young rescue workers in Taiwan

Disaster workers as well as victims are at increased risk for acute stress disorder (ASD). The present study was undertaken to study the course of the stress response in a group 187 young, male military personnel who served as rescue workers for 3 days after an earthquake in central Taiwan. A control group of 83 young, male military personnel who remained on the base was also studied. The initial evaluation took place within 16 days of the earthquake. Participants were interviewed using the Mini International Neuropsychological Interview. Thirty-one individuals met DSM-IV criteria for ASD at the initial evaluation. These 31 individuals were interviewed a second time 1 month after the earthquake. Plasma samples were also collected and assayed for nitric oxide (NO). The point prevalence rates of ASD 2 weeks after the earthquake in the initial evaluation were 9 and 16% in the rescue worker and control groups, respectively. At 1 month, the prevalence was substantially lower, in the range of 2-3%. Significant inverse correlations were observed between severity of stress symptoms and the plasma concentration of NO in the rescue worker group (r=-0.36 to -0.64, n=17, P<0.05). We conclude that young military personnel without formal training in rescue operations are at risk for ASD, but their risk appears to be no higher than that in a similarly composed control group of young military personnel. Longitudinal studies with plasma measures of NO are needed to clarify its potential role in the development and course of ASD and related syndromes.

Effect of valproate on plasma levels of interleukin-6 in healthy male humans.

Valproate exerts many biochemical and physiological effects and may have a modulating effect on the immune system. The present study aimed to determine whether there is a treatment effect of valproate on plasma levels of the pro-inflammatory cytokine, interleukin (IL)-6, in healthy male humans. Plasma levels of IL-6 were measured in 10 healthy male humans before and after 7 days of treatment with 1000u2009mg per day of valproate (i.e. 500u2009mg in the morning and 500u2009mg in the evening). All the healthy subjects had no past or current psychiatric disorder. They reported to the outpatient clinic at 09.00u2009h for baseline sampling. Subsequently, they were commenced on valproate 1000u2009mg per day for 7 days. They took the last dose of valproate at 22.00u2009h on the day 7, and post-treatment blood sampling for plasma levels of IL-6 was carried out on day 8. An additional blood sample was also taken from each subject at the same time to measure plasma levels of valproic acid for drug compliance. We found a significant increase in plasma levels of IL-6 after the 7 days of valproate treatment in healthy male subjects. Furthermore, there was a significant positive correlation between the changes in plasma IL-6 and blood levels of valproic acid. The findings of this study are consistent with previous studies on subjects with epilepsy, suggesting a modulating effect of valproate on the pro-inflammatory cytokine IL-6 in humans. However, studies with a larger number of participants and employing a double-blind, placebo-control group are required to confirm the findings, and also the levels of other cytokines should be measured to generalize the effect to the immune system.

Combination treatment of clozapine and topiramate in resistant rapid-cycling bipolar disorder.

Several open-label studies or case reports have suggested the effectiveness of clozapine or topiramate in the treatment of resistant rapid-cycling bipolar patients, but none of these publications report the long-term effectiveness of these two agents in combination. The authors present a 38-year-old woman with a 22-year history of rapid-cycling bipolar I disorder who failed to respond satisfactorily to various somatic therapies, including combination therapy for complex regimens and a course of bilateral electroconvulsive therapy, but finally responded well to a combination treatment of clozapine and topiramate. Such a combination therapy led the patient to a complete remission for more than 3 years without inducing side effects such as weight gain, hyperglycemia, type II diabetes mellitus, or hyperlipidemia. In addition, she had a weight loss of 12 kg over the past 3 years. This case suggests that the combination treatment of clozapine and topiramate can be safe and effective in some resistant rapid-cycling bipolar patients.

Risk of Dementia in Adults With ADHD: A Nationwide, Population-Based Cohort Study in Taiwan

Objective:This study aimed to investigate the association between adults with ADHD and the risk of developing dementia. Method: Utilizing National Health Insurance Research Database of Taiwan, ADHD patients were identified and compared with age- and gender-matched controls (1:3). Results: Of the study participants, 37 (5.48%) developed dementia compared with 81 (4.0%) in the control group. Cox proportional hazards regression analysis revealed that the study participants were more likely to develop dementia. The crude hazard ratio (HR) is 3.418 (95% confidence interval [CI] = [2.289, 5.106], p < .001), and adjusted HR is 4.008 (95% CI = [2.526, 6.361], p < .001) in risk of developing dementia after adjusted for age, gender, comorbidities, geographical area of residence, urbanization level of residence, and monthly income. Conclusion: Adults with ADHD have a 3.4-fold risk of developing dementia, and other large or national data sets should be explored to support the current findings.

Chronic inflammatory demyelinating polyneuropathy associated with manic symptoms.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease involving cellular and humoral immunity. It is characterized by progressive symmetrical weakness or sensory loss in both proximal and distal muscles developing over a more than 8-week period (Vallat et al., 2010). Neuropsychiatric disorders related to CIDP rarely occur. Here, we report a case of CIDP with manic symptoms. A 66-year-old man was referred to our hospital with progressive weakness and numbness in all limbs over the past 2 years. One year prior to presentation, he developed irritable and labile mood and manic symptoms, including exaggerated sense of self-confidence, talkativeness, spending sprees, insomnia and increased energy. Laboratory investigation showed increased erythrocyte sedimentation rate (ESR: 39 mm/h). The nerve conduction velocity showed prolonged distal latency, a slowing of the conduction velocity and prolonged F-wave latency of the median, ulnar and peroneal nerves. Although he refused lumbar puncture, cerebrospinal fluid (CSF) studies are not mandatory according to the Inflammatory Neuropathy Cause and Treatment criteria for CIDP. A clinical diagnosis of CIDP was made. Intravenous methylprednisolone was given for 4 days and then shifted to oral prednisolone. His muscle weakness gradually improved after 1 week of steroid therapy. The mood symptoms improved with the initial Young Mania Rating Scale (YMRS) 22 and decreased to 13 after 3 weeks of steroid treatment. To our knowledge, no cases of bipolar disorder associated with CIDP have been previously documented. In acute inflammatory demyelinating polyneuropathy (AIDP), brief reactive psychosis, anxiety, depressive episodes and rapid eye movement (REM) sleep abnormalities were observed (Chan and Gold, 2007). The possible mechanism includes potential central nervous system (CNS) targets of the disease shown by lower CSF hypocretin-1 levels, inflammation and microglial activation in CNS, and proinflammatory cytokine-induced neurotransmitter dysfunction (Chan and Gold, 2007). Several reports have shown subclinical involvement and demyelination of the central pathways (Chan and Gold, 2007; Vallat et al., 2010). This is similar to another chronic inflammatory demyelinating disorder, multiple sclerosis (MS), which affects the CNS and could increase rates of depression and bipolar disorder that might be related to oxidative stress, autoimmunity and demyelination (Carta et al., 2014). Immune-mediated inflammation and cytokines may influence brain circuits as observed in MS and AIDP, and steroid treatment was effective for both CIDP and mania-like episode in our patient, suggesting that his manic symptoms could relate to the immunopathogenesis of CIDP. In conclusion, we report the first case of mania-like episode associated with CIDP. More studies are needed to clarify the associations between CIDP and manic-like episode.

Aripiprazole-related hyponatremia and consequent valproic acid–related hyperammonemia in one patient:

Australian & New Zealand Journal of Psychiatry, 51(3) patients with schizophrenia, but these blood levels also significantly increased side-effect burden. Therefore, when psychiatrists are faced with clozapine non-responsive patients with schizophrenia, the first suggested step would be to measure clozapine serum levels, aiming for between 350 and 400 μg/mL (Spina et al., 2000), if clozapine side effects can be tolerated. This would be a recommended strategy before adding a second antipsychotic medication. TDM is particularly important in differentiating between psychotic symptoms due to either breakthrough psychosis or non-compliance with clozapine. Break-through psychosis due to non-response at maintenance clozapine doses will possibly require an increased dose of clozapine, while non-compliance to clozapine will generally require reinitiation of the usual maintenance clozapine dose. At this stage, beyond clozapine, there is only limited evidence for regular TDM for other second-generation antipsychotic medication (Lopez and Kane, 2013).

Risk of psychiatric disorders in overactive bladder syndrome: a nationwide cohort study in Taiwan

Population-based cohort study investigating the risk of depression and other psychiatric disorders for patients with overactive bladder (OAB) syndrome is unavailable. This study investigated the subsequent risk of psychiatric disorders among patients with OAB in an Asian population. Using data from the National Health Insurance Research Database of Taiwan, we established a cohort with 811 patients in an exposed group with OAB between January 1, 2000 and December 31, 2000, and a non-exposed group, without OAB, of 2433 patients without OAB matched by age and year of diagnosis. The occurrence of psychiatric disorders and Cox regression model measured adjusted HRs (aHR) were monitored until the end of 2013. The overall incidence of psychiatric disorders was 41.7% higher in the exposed group with OAB than in the non-exposed group without OAB (14.2% vs 10.1%, p<0.001), with an aHR of 1.34 (95% CI 1.12 to 1.80, p<0.001) for the OAB cohort. OAB was associated with the increased risk of dementia, anxiety, depressive, sleep, and psychotic disorders, with aHRs as 1.53 (p=0.040), 1.61 (p<0.001), 2.10 (p<0.001), 1.43 (p<0.001), and 2.49 (p=0.002), respectively. The risk of psychiatric disorders, including depression and anxiety, is significantly higher in patients with OAB than in those without OAB. Evaluation of psychiatric status in patients with OAB is strongly recommended.