Tien-Yu Chen

Sex-specific association between nerve growth factor polymorphism and cardiac vagal modulation.

Objective Substantial research has shown that anxiety disorders are associated with decreased cardiac vagal tone, which is a known risk factor for cardiac vulnerability. A functional nerve growth factor (NGF) polymorphism (rs6330, c.104C > T, p.Ala35Val) has been associated with anxiety such that in males but not females, T-allele carriers exhibit higher levels of trait anxiety. Here we investigate whether the nonsynonymous NGF variant has an effect on cardiac autonomic control. Methods From 705 adults initially screened for medical and psychiatric illnesses, a final cohort of 580 healthy Han Chinese (352 men, 228 women; mean [standard deviation] age = 34.46 [8.45] years) was included in the NGF genotyping (C/C: 428% [73.8%] and T-allele carriers: 152% [26.2%]). Short-term heart rate variability was used to assess cardiac autonomic function. Results There were significant genotype-by-sex interaction effects (p < .05) on high-frequency power (HF) and root mean square of successive heartbeat interval differences (RMSSD), both indices of cardiac vagal control. Even after adjusting for possible confounders, men with any T allele showed lower HF and RMSSD compared with men with the C/C genotype. Women, however, showed an opposite but nonsignificant pattern. Conclusions The studied NGF polymorphism modulates autonomic outflow to the heart in a sex-dependent manner. The findings support the view that male T-allele carriers are at increased susceptibility for anxiety by association with low vagal activity and suggest a potential sex-specific genetic link between the highly comorbid anxiety disorders and cardiovascular diseases.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism affects sympathetic tone in a gender-specific way

The Val/Val genotype of the brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) has been reported to affect human anxiety-related phenotypes. Substantial research has demonstrated that anxiety is associated with sympathetic activation, while sex steroid hormones have been shown to exert differential actions in regulating BDNF expression. Thus, we examined whether the BDNF variant modulates autonomic function in a gender-dependent manner. From 708 adults initially screened for medical and psychiatric illnesses, a final cohort of 583 drug-free healthy Han Chinese (355 males, 228 females; age 34.43±8.42 years) was recruited for BDNF genotyping (Val/Val: 136, 23.3%, Val/Met: 294, 50.4%, and Met/Met: 153, 26.2%). Time- and frequency-domain analyses of heart rate variability (HRV) were used to assess autonomic outflow to the heart. Significant genotype-by-gender interaction effects were found on HRV indices. Even after adjusting for possible confounders, male participants bearing the Val/Val genotype had significant increases in low frequency (LF), LF% and LF/high frequency (HF) ratio, indicating altered sympathovagal balance with increased sympathetic modulation, compared to male Met/Met homozygotes. Females, however, showed an opposite but non-significant pattern. These results suggest that the studied BDNF polymorphism is associated with sympathetic control in a gender-specific way. The findings here support the view that male subjects with the Val/Val genotype have increased risk of anxiety by association with sympathetic activation.

Aripiprazole: A dopamine modulator that mimics methylphenidate in producing faster antidepressant effects

Up to 60% of depressed patients do not respond to two months of pharmacotherapy, and late treatment responses are often correlated with poor outcomes and may be characterized as treatment-resistant depression (TRD). Previous studies have noted that the addition of a psychostimulant such as methylphenidate to the therapeutic regimen of patients with TRD or those depressed patients with comorbid fatigue, advanced age, or a major medical illness showed significant improvement within two weeks. One explanation for the benefit of methylphenidate in treating TRD is that it enhances the level of dopamine in the brain. Adjunctive low dose aripiprazole in patients with TRD has also become a common intervention. Several studies have focused on aripiprazoles pharmacodynamic and pharmacokinetic profiles, but no definitive comments on its antidepressant effects. We hypothesize that a low dose of aripiprazole might play a role as a dopamine agonist similar to that of methylphenidate due to its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. In addition to its use in patients with TRD, adjunctive aripiprazole might work like methylphenidate in those depressed patients with fatigue, advanced age, or major illnesses. A new drug invention which combined an antidepressant with an adequate dose of aripiprazole should be considered. The neurobiological basis for this combination in treating TRD awaits further study.

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.

Advanced age is not a contraindication for liver resection in cases of large hepatocellular carcinoma

BACKGROUNDnThe role of surgery in the management of large hepatocellular carcinomas (HCCs) is controversial. Advanced age and comorbidities are taken into account when major surgery is considered.nnnPURPOSEnTo compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) for resectable HCC in patients aged 70 years or older.nnnPATIENTS AND MATERIALSnThis study included 70 patients aged 70 years or older treated for large HCCs (≥5 cm) between January 2007 and December 2012: 37 underwent LR and 33 underwent TACE. The outcomes of these patients were retrospectively analyzed. Univariate and multivariate Cox proportional hazard models were established. Kaplan-Meier survival curves were generated, and survival data were compared using the log-rank test.nnnRESULTSnHospital stay was significantly longer in the LR group than in the TACE group (10 days vs 8.5 days; P = 0.003). Treatment-related complications were more frequent in the TACE group, but this difference was not statistically significant. LR was associated with a better disease-free survival rate, median survival rate and cumulative overall survival rate.nnnCONCLUSIONnOur results showed that LR could be a safe and effective treatment option for HCC tumors ≥5 cm in patiets aged 70 years or older.

Enhanced Bleeding Risk in an Elderly Dementia Patient Treated With Warfarin and Quetiapine

To the Editor: Quetiapine, a wellknown atypical antipsychotic, is approved for the treatment of schizophrenia and bipolar disorder. It is sometimes used off-label for dementia with severe psychotic symptoms. Warfarin, a highly effective oral anticoagulant, inhibits the extrinsic coagulant pathway and is used for the prevention of thromboembolic events. We present the case of an elderly man with dementia who had an enhanced bleeding tendency after warfarin was added to a therapeutic regimen of quetiapine.

Killing two birds with one stone: the potential role of aripiprazole for patients with comorbid major depressive disorder and nicotine dependence via altering brain activity in the anterior cingulate cortex.

The high comorbidity between major depressive disorder (MDD) and nicotine dependence (ND) is well recognized. Patients with comorbid MDD and ND often have increased suicidal risk and poor outcomes. A dysfunctional dopaminergic brain reward system might be a neurobiological link between MDD and ND. Aripiprazole has been considered as a dopamine stabilizer and was the first atypical antipsychotic agent approved by the US Food and Drug Administration as an adjunctive to the treatment of unipolar MDD. Bupropion is well known as a dual norepinephrine and dopamine reuptake inhibitor, and has been shown to be effective in smoking cessation. One reason bupropion is useful in treating ND is that it enhances the level of dopamine in the brain. Aripiprazole might act as a dopamine agonist similar to the way that bupropion does because of its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. Several recent studies have applied the unique pharmacodynamic characteristics of aripiprazole to treat patients with ND. Based on neuroimaging findings, aripiprazole can reduce substance cravings by altering brain activity, particularly in the brain regions of the anterior cingulate cortex. Therefore, we hypothesize that adjunctive aripiprazole with antidepressant may be an effective treatment for patients with MDD and ND comorbidity. A new drug invention that combines an antidepressant with an adequate dose of aripiprazole thus should be considered. The neurobiological basis for this combination to treat patients with MDD and ND comorbidity deserves further study.

Predictive Risk Factors for Fracture at Catheter of Totally Implantable Venous Access Devices via Subclavian Vein Insertion

Background: Fracture of totally implantable venous access devices (TIVAD) is a rare but potential serious complication. We aimed to explore the risk factors for fracture at catheter of TIVAD via subclavian vein insertion. Materials and Methods: From January 2008 to July 2010 the records of 34 patients with fractured TIVAD were retrospectively reviewed. The comparison group included 170 randomly selected cases (5 for every patient with a fractured catheter) from 3919 cases of TIVAD implantations without catheter fracture. Variables associated with catheter implantation and the relationship between the catheter and the clavicle were analyzed. Results: Statistical analysis revealed implantation method, duration of implantation, brand of device, and port-clavicle distance were predictive risk factors for catheter fracture on univariate analysis. Duration of implantation ＞200 days and port-clavicle distance ＜2.5 cm were independent risk factors for catheter fracture on multivariate analysis. Stratified analysis indicated that a port-clavicle distance ＜2.5 cm in patients with duration of TIVAD implantation ＞200 days was associated with a significantly increased risk of catheter fracture. Conclusions: We suggested that TIVAD with a port-clavicle distance ＜2.5 cm could be removed to prevent catheter fracture when the implantation duration is more than 200 days.

Reversible Godot Syndrome in an Elderly Patient With Frontal Lobe Meningioma.

Godot syndrome is the condition wherein the patient shows severe anxiety by repeatedly asking questions regarding an upcoming event. It occurs in around 1.6-4.6% of elderly patients with Alzheimers disease based on their decreased cognitive ability. Although Godot syndrome is rarely observed, it can become a major task for the caregivers. In addition, it is seldom reported in nondementia patients. We present a 74-year-old female with persistent Godot syndrome under treatment at the psychiatry outpatient clinic for 1 year. A meningioma over the patients frontal lobe was demonstrated by the neuroimaging study and her Godot syndrome subsided after removal of the mass lesion. Mrs. H was a 74-year-old female with type 2 diabetes mellitus and hypertensive cardiovascular disease under regular medical treatment. For 2 years, she showed symptoms of depressive mood, anxiety, poor sleeping quality and repeatedly asked the same questions about upcoming events. Because of the persistence of anxiety symptoms, her family brought her to the psychiatric outpatient department for evaluation. Under the diagnosis of elderly depression, she was treated with duloxetine, sulpride and hypnotics for 1 year. However, she still had refractory depression and anxiety. Due to her severe Godot syndrome of repeatedly asking the same things and making many phone calls to her family to confirm upcoming events, she was admitted to the psychiatric acute ward. After admission, several surveys were done. The possibility of vitamin B12 or folic acid deficiency, impaired thyroid function and infection that might cause symptoms mimicking cognition decline in dementia were excluded. None of the neurological signs as headache, nausea, unstable gaits and urinary incontinence were observed. Her Mini–Mental Status Examination score was 26, Clinical Dementia Rating score was 0.5, 17-item Hamilton Depression Rating scale score was 25 and Hamilton Anxiety Rating scale score was 29. Brain magnetic resonance imaging (MRI) revealed a welldefined homogeneous enhancing mass lesion about 46 65 31 mm in size at the central anterior frontal base, located at the extra-axial region and abutting the skull base. No ventriculomegaly was found (Figure). After surgical removal of the tumor, the final pathological report was a meningothelial meningioma, grade I. Follow-up brain MRI showed no recurrence. The Godot