Yi-Wei Yeh

Association study of catechol‐O‐methyltransferase gene polymorphisms with schizophrenia and psychopathological symptoms in Han Chinese

Although dysfunction of catechol‐O‐methyltransferase (COMT)‐mediated dopamine transmission is implicated in the etiology of schizophrenia, the human COMT gene has not been associated consistently with schizophrenia. The purpose of this study was to investigate whether the COMT gene is associated with the development of schizophrenia and whether the polymorphisms of this gene influence the psychopathological symptoms in patients with schizophrenia. Fourteen polymorphisms of the COMT gene were analyzed in a case–control study of 876 Han Chinese individuals (434 patients and 442 controls). All participants were screened using a Chinese version of the modified Schedule for Affective Disorders and Schizophrenia‐Lifetime Version (SADS‐L) and all patients met the criteria for schizophrenia. Furthermore, pretreatment of psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) in a subset of 224 hospitalized schizophrenia patients, who were drug‐naÏve or drug‐free, to examine the association between clinical symptomatology and COMT polymorphisms. No significant differences in allele or genotype frequencies were observed between schizophrenia patients and controls, for all variants investigated. Haplotype analysis showed that three haplotype blocks of the COMT gene were not associated with the development of schizophrenia. Moreover, these COMT polymorphisms did not influence the PANSS scores of schizophrenia patients. This study suggests that the COMT gene may not contribute to the risk of schizophrenia and to the psychopathological symptoms of schizophrenia among Han Chinese.

DRD3 variation associates with early-onset heroin dependence, but not specific personality traits

Dopamine D3 receptor-mediated pathways are involved in the mechanism of addiction, and genetic factors play a role in the vulnerability to heroin dependence. The aim of this study was to examine whether the corresponding gene, DRD3, is associated with the development of heroin dependence and specific personality traits in HD patients. Eight polymorphisms in DRD3 were analyzed in 1067 unrelated Han Chinese subjects (566 heroin dependence patients and 501 controls). All participants were screened using the same assessment tool and all patients met the criteria for heroin dependence. A Tridimensional Personality Questionnaire was used to assess personality traits in 276 heroin dependence patients. In addition, heroin dependence patients were divided into 4 clinical subgroups based on age-of-onset and family history of substance abuse, to reduce the clinical heterogeneity. The rs6280 and rs9825563 variants showed association with the development of early-onset heroin dependence. The GTA haplotype frequency in the block (rs324029, rs6280, rs9825563) was significantly associated with early-onset heroin dependence (p=0.003). However, these significant associations were weaker after Bonferronis correction. In addition, these DRD3 polymorphisms did not influence novelty seeking and harm avoidance scores in HD patients. DRD3 is possibly a genetic factor in the development of early-onset heroin dependence, but is not associated with specific personality traits in these patients among the Han Chinese population.

A shift toward T helper 2 responses and an increase in modulators of innate immunity in depressed patients treated with escitalopram

Depression is hypothesized to involve inflammatory processes, and identifying the key cytokines targeted by antidepressant drugs is critical for tailoring treatment to specific cases. However, investigating a limited number of cytokines at one time cannot provide a broad picture of antidepressant-associated immunomodulation. Cytokines act in a network where one could demonstrate pleiotropism, redundancy, synergy, and antagonism with other cytokine functions. This study was aimed at determining whether escitalopram functions as an anti-inflammatory agent and, if so, how it influences cytokine networks. A total of 24 healthy controls and 26 patients with clinical depression requiring inpatient treatment were recruited. A multiplex assay, an efficient tool to simultaneously measure 27 cytokines, was applied in patients with depression before and after 4-week escitalopram treatment. Healthy controls did not take escitalopram and completed cytokine analyses once. We demonstrated that escitalopram increased the levels of interleukin (IL)-1 receptor antagonist and IL-2. Moreover, escitalopram contributed to a shift toward T helper 2 responses and an increase in modulators of innate immunity, leading to a decrease of immune system activation, both innate and adaptive. We suggest that escitalopram modulates the balance of IL-1 and IL-1 receptor antagonist and improves the function and number of T regulatory cells. However, diverse conclusions could be drawn if only a few cytokines were assessed or different significance levels were used. Further studies should investigate a wide range of cytokines in a reliable and valid way, which is key to disentangling the effects of different antidepressants on inflammatory processes.

Neither single-marker nor haplotype analyses support an association between the dopamine transporter gene and heroin dependence in Han Chinese.

Much evidence suggests that dysfunction of dopamine transporter‐mediated dopamine transmission may be involved in the pathophysiology of substance abuse and dependence. The aim of this study was to examine whether the dopamine transporter gene (DAT1; SLC6A3) is associated with the development of heroin dependence (HD) and whether DAT1 influences personality traits in patients with HD. Polymorphisms of DAT1 were analyzed in a case–control study of 1046 Han Chinese (615 patients and 431 controls). All participants were screened using a Chinese version of the modified Schedule of Affective Disorder and Schizophrenia‐Lifetime and all patients met the criteria for HD. Furthermore, a Chinese version of the Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits in the patient group and examine the association between their personality traits and DAT1 polymorphisms. Of the patient group, 271 completed the TPQ. No statistically significant differences in allele or genotype frequencies of all investigated variants between HD patients and controls were observed. In haplotype analyses, four haplotype blocks of DAT1 were not associated with the development of HD. These DAT1 polymorphisms did not influence novelty seeking and harm avoidance scores in HD patients. This study suggests that the DAT1 gene may not contribute to the risk of HD and specific personality traits in HD among the Han Chinese population.

New Onset Somnambulism Associated With Different Dosage of Mirtazapine: A Case Report

Somnambulism consists of variously complex behaviors that may result in harm to self or to others. Many different medications have been reported to induce somnambulism, and a few of them are newer antidepressants. A 40-year-old woman with history of major depression who experienced new onset somnambulism for successive 3 nights, whereas the antidepressant mirtazapine was increased from 30 to 45 mg/d. The notable and complex sleepwalking symptoms terminated dramatically on the first night after withdrawal of mirtazapine. There is clearly a cause-and-effect relationship between the treatment of higher-dosage mirtazapine and development of somnambulism. It might be related to the different affinities to 5-hydroxytryptamine 2 (5-HT(2)) and H(1) receptors at different dosages of mirtazapine, which explain the patient experiencing sleepwalking episodes exclusively at higher doses of mirtazapine. Clinical physicians should be aware of this adverse effect and taper or discontinue the regimen if sleepwalking develops.

Urinary tract infection complicated by urine retention presenting as pseudocyesis in a schizophrenic patient

Pseudocyesis is a rare condition wherein a nonpregnant woman shows signs and symptoms of pregnancy, such as abdominal enlargement, breast enlargement, pigmentation, cessation of menses, subjective sensation of fetal movement and labor pains at the expected delivery date. In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, it is classified as a somatoform disorder, characterized by a false belief of being pregnant that is associated with objective signs of pregnancy. We report the case of a middle-aged female schizophrenic patient who developed pseudocyesis secondary to a urinary tract infection complicated by acute urine retention. The patient accepted that she had pseudocyesis after the causative medical condition resolved.

Reduced striatal dopamine transporter density associated with working memory deficits in opioid-dependent male subjects: a SPECT study

Research on the effects of repeated opioid use on striatal dopamine transporters has yielded inconsistent results, possibly confounded by a history of methamphetamine or methadone exposure in opioid‐dependent individuals. Previous studies have shown that striatal dopamine transporter density is positively correlated with the cognitive performance of healthy volunteers. This study aimed to investigate changes in striatal dopamine transporter density and their functional significance in opioid‐dependent individuals. Single‐photon emission computed tomography with [99mTc]TRODAT‐1 as a ligand was used to measure striatal dopamine transporter levels in 20 opioid‐dependent individuals and 20 age‐ and sex‐matched healthy controls. Opioid‐dependent individuals had no history of methamphetamine or methadone use. The Wisconsin Card Sorting Test (WCST) was performed to assess neurocognitive function. We found that compared with healthy controls, opioid‐dependent individuals showed a significant reduction in striatal dopamine transporter density. They also showed poorer performance on the WCST in terms of the trials administered, total errors, perseverative responses, perseverative errors, and non‐perseverative errors. Striatal dopamine transporter levels negatively correlated with non‐perseverative errors not only in opioid‐dependent individuals but also in healthy controls. These findings suggest that in human, repeated opioid exposure reduces striatal dopamine transporter density, which can be associated with non‐perseverative errors. Non‐perseverative errors may be one of the more sensitive parameters in WCST to identify working memory deficits associated with striatal dopamine transporter reduction. Moreover, we suggest that whether opioid‐associated neurotoxicity is reversible depends on the brain region.

A possible association of the norepinephrine transporter gene in the development of heroin dependence in Han Chinese.

Objective Noradrenergic pathways have been suggested to play a crucial role in the motivation–reward system of heroin dependence (HD), but so far, the role of the human norepinephrine transporter (NET; SLC6A2) gene in the pathogenesis of HD has never been investigated. The purpose of this study was to examine whether the NET gene is associated with the development of HD, and whether the NET gene influences specific personality traits. Methods Twelve single-nucleotide polymorphisms of the NET gene were analyzed in a case–control study of 965 Han Chinese participants (603 patients and 362 controls). All participants were screened using a Chinese version of the modified Schedule of Affective Disorder and Schizophrenia-Lifetime and all patients met the criteria for HD. A Chinese version of the Tridimensional Personality Questionnaire was used to assess personality traits and examine the association between specific personality traits and NET polymorphisms. Results No statistically significant differences in allele or genotype frequencies were observed in any of the investigated NET variants between HD patients and controls. After logistic regression analyses, no statistically significant effect of NET variants in the development of HD was found. In haplotype analysis, the frequency of AATA haplotype in rs1532701-rs40434-rs13333066-rs187714 was significantly different between HD patients and controls. These NET polymorphisms did not influence novelty seeking and harm avoidance scores. Conclusion This study suggests that the NET gene may be associated with the development of HD, but not associated with specific personality traits among Han Chinese.

Effects of a selective educational system on fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents in Taiwan

Objective The aim of the study reported here was to clarify the effects of academic pressure on fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents in Taiwan. Methods This cross-sectional study enrolled 757 senior high school adolescents who were classified into four groups: Grade 1 (n=261), Grade 2 (n=228), Grade 3T (n=199; Grade 3 students who had another college entrance test to take), and Grade 3S (n=69; Grade 3 students who had succeeded in their college application). Fatigue, sleep quality, daytime sleepiness, and depression were assessed using the Chinese version of the Multidimensional Fatigue Symptom Inventory – Short Form, Pittsburgh Sleep Quality Index-Taiwan Form, the Chinese version of the Epworth Sleepiness Scale, and the Chinese version of the Beck Depression Inventory®-II (BDI-II), respectively. Results Physical, emotional, and mental fatigue scores were all higher in higher-grade groups. The Grade 3T (test) students had the worst fatigue severity, and the Grade 3S (success) students had the least fatigue severity. More than half of the students (60.9%) went to bed after 12 am, and they had on average 6.0 hours of sleep per night. More than 30% of the students in Grade 2 (37.3%) and Grades 3T/S (30.2%/30.4%) possibly had daily sleepiness problems. The students in Grade 3T had the worst BDI-II score (13.27±9.24), and the Grade 3S students had a much lower BDI-II score (7.91±6.13). Conclusion Relatively high proportions of fatigue, sleep problems, daytime sleepiness, and depression among senior high school adolescents were found in our study. The severities of fatigue, sleep problems, and depression were significantly diminished in the group under less academic stress (Grade 3S). Our findings may increase the understanding of the mental health of senior high school students under academic pressure in Taiwan. Further large sample size and population-based study should be done for better understanding about this topic.

Adjunctive Use of Methylphenidate in the Treatment of Psychotic Unipolar Depression

Adjunctive use of methylphenidate, a central stimulant, has been considered as a potential therapeutic choice for patients with refractory unipolar depression, geriatric depression, bipolar depression, and depression secondary to a medical illness. We present a case of psychotic unipolar depression in which the patient responded significantly to the adjunctive use of methylphenidate. A 45-year-old woman had melancholic depressive symptoms and mood incongruent psychotic features during her second episode of unipolar depression. She attempted suicide by hanging herself and was forcibly hospitalized. She was initially treated with venlafaxine (262.5 mg/d), olanzapine (20 mg/d), and benzodiazepines. However, she responded unsatisfactorily to the combination treatment. Because her family refused electroconvulsive treatment, we added methylphenidate to her medications for adjunctive use. The dose of methylphenidate was started at a dose of 5 mg/d. It was not until the patient received 30 mg/d of methylphenidate that her persistent psychosis and severe depression were substantially improved. She tolerated her medications well and did not report any side effects. She was discharged in a stable condition 2 weeks after the adjunctive use of methylphenidate. The patients methylphenidate was gradually tapered and finally discontinued. To date, she remains well and is regularly followed up at our outpatient clinic. Our case suggests that adjunctive use of methylphenidate can be a therapeutic option in treating some patients with psychotic unipolar depression who do not adequately respond to the combination treatment of an antidepressant and an atypical antipsychotic. Further controlled studies are warranted to verify this.