Mei Hung Chi

Brain derived neurotrophic factor gene polymorphism (Val66Met) and short-term antidepressant response in major depressive disorder

BACKGROUNDS To determine the association between the brain derived neurotrophic factor (BDNF) Val66Met polymorphism and short-term antidepressant response in Taiwanese patients with major depressive disorder (MDD). METHODS We recruited 117 MDD patients who were randomized to fluoxetine or venlafaxine treatment and 106 controls. The association between genotypes and percentage changes in the Hamilton Rating Scale for Depression (HAM-D) scores over time was analyzed by repeated-measures ANOVA. The antidepressants were included in the model as covariates. RESULTS The frequency of the BDNF Val66Met polymorphisms was not significantly different between patient and control groups. Significantly changes in HAM-D scores were noted after 2 and 4 weeks of venlafaxine treatment among different genotypes. CONCLUSIONS Results suggest antidepressants acting through different mechanisms may affect the BDNF Val66Met polymorphism differently.

Oxytocin receptor gene rs53576 polymorphism modulates oxytocin–dopamine interaction and neuroticism traits—A SPECT study

Brain oxytocin and dopamine systems interact to modulate social cognitive behavior. Whether the interactions are modulated by oxytocin receptor (OXTR) gene variations remains unclear. Considering the dopamine transporter (DAT) availability as an endophenotype and the degree of dopamine-mediated neuroticism as a phenotype of the OXTR genotypes, the current molecular imaging study used [(99m)Tc]TRODAT-1 single photon emission computed tomography (SPECT) to measure the striatal DAT availability and the 57-item Maudsley Personality Inventory to measure neuroticism personality traits in healthy individuals to investigate (A) the correlation between the rs53576 (G/A) of OXTR and the striatal DAT availability, (B) the correlation between the peripheral oxytocin level and striatal DAT availability among different OXTR rs53576 (G/A) genotypes, and (C) whether neuroticism traits could be modified by oxytocin in certain OXTR rs53576 genotypes. The results showed that the striatal DAT availability in the AG+GG group was significantly lower than that in the AA group (2.08±0.47 vs. 1.90±0.32, p=0.04). Only individuals with one or two copies of the G allele of rs53576 showed a negative correlation between DAT availability and oxytocin level (r=-0.41, p=0.002). Furthermore, the oxytocin×DAT interaction was significantly correlated with the MPI neuroticism score in the AA group. Further analyses showed that the DAT availability was correlated with the neuroticism score only in the AA group with a low oxytocin level (r=0.74, p=0.002). The results indicated that the OXTR rs53576 is connected with the striatal DAT availability in vivo and modulates the interactions between the oxytocinergic and dopaminergic systems. Carriers with a specific rs53576 OXTR genotype may present a greater biological sensitivity as well as stress reactivity in terms of environmental adaptation.

The prevalence of metabolic syndrome in drug-naive bipolar II disorder patients before and after twelve week pharmacological intervention

BACKGROUND Accumulating evidence indicates a high prevalence rate of metabolic disturbance in bipolar disorder (BP) patients. However, the prevalence across BP subtypes has been investigated to a lesser degree. In the current study, we surveyed the prevalence of metabolic syndrome among drug-naïve bipolar II patients. Moreover, the effects of pharmacological treatment on metabolic indexes were also evaluated. METHODS This study recruited fifty-six drug-naïve BP II patients diagnosed according to the DSM-IV criteria. Among them, forty-four patients completed a 12-week pharmacological intervention with valproic acid, fluoxetine and lorazepam. Metabolic profiles and body mass index (BMI) were measured at baseline and 2 weeks, 8 weeks, and 12 weeks after receiving medication. RESULTS The mean age of the 56 patients was 30.3±11.1. Before receiving medication, 6.5% of the patients met the ATP III criterion for metabolic syndrome. Among the 44 patients who completed the 12-week pharmacological intervention, the prevalence of metabolic syndrome increased from 7% to 10%. Repeated measurements showed that the changes in metabolic indexes were not significant, with the exceptions of BMI, waist circumference, and buttock circumference. In addition, the interaction between the improvement of hypomanic symptoms and BMI change was significant. LIMITATIONS The study was limited by the follow-up duration and sample size. CONCLUSIONS In drug-naïve BP II patients, the prevalence of metabolic syndrome was significantly lower than that observed before in BP I patients. However, medications use was also associated with an increased risk of metabolic disturbance, although the impact was lesser. Clinical evidence suggests that metabolism and emotion homeostasis might share common mechanisms.

The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients.

BACKGROUND A reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose-insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients. METHODS This study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured. RESULTS Compared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8 μIU/mL vs. 5.1±4.2 μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059). LIMITATIONS The study was limited by the follow-up duration and lack of a placebo group. CONCLUSIONS Antidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.

Sex-specific associations between plasma oxytocin levels and schizotypal personality features in healthy individuals

OBJECTIVES Oxytocin (OT) has been shown to play a crucial role in the biology of social interaction. Sex differences associated with this neuropeptide system have been reported. OT may serves as an indicator of interpersonal stress, especially in women. The aim of this study was to investigate the sex-specific associations between plasma OT levels and schizotypal personality features, especially in interpersonal dimension, in healthy individuals. METHODS Ninety six healthy participants, including 41 males and 55 females, were recruited. Fasting blood samples were analyzed by enzyme immunoassay of OT. The Schizotypal Personality Questionnaire (SPQ) was administered. Mann-Whitney U test was used to test the difference between male and female. Spearmans ρ correlation analysis (two-tailed) was carried out to examine the association between OT level and SPQ score. RESULTS The results showed that OT level was significantly positively correlated with total score and interpersonal dysfunction dimensional scores of the SPQ only in females. CONCLUSIONS Although the causal relationship remains unclear, our findings provide further evidence to support the sexual dimorphic role of OT in interpersonal biology. Moreover, the effect of sex difference also is taken into consideration.

The readmission rate and medical cost of patients with schizophrenia after first hospitalization - A 10-year follow-up population-based study

BACKGROUND Hospital readmissions caused by relapse in patients with schizophrenia are associated with prognosis. Identifying individuals at high risk of readmission and providing interventions to lower the readmission rate are important. METHODS Patients with schizophrenia who were hospitalized for the first time were recruited from the National Health Insurance Research Database from 2001 to 2010 (n=808, mean age 28.9years) and compared with matched controls. Data on the demographics, cost, and utilization of medical resources of patients who were readmitted were compared with non-readmitted patients. The readmission time curve was analyzed by the Kaplan-Meier method. RESULT 570 (70.5%) patients were readmitted within 10years; the median time between admissions was 1.9years, and 25% of subjects were readmitted within 4months of the first hospitalization. There were no significant differences in age, gender, or length of hospitalization between the readmission and non-readmission groups. Taking into account all psychiatric medical services, the readmission group had a significantly higher mean frequency of care and a greater medical cost than the non-readmission group and matched controls. However, there were no significant differences with regard to non-psychiatric medical services. CONCLUSION Schizophrenia has a high rate of readmission and high medical cost in naturalistic settings. In addition to the traditional hospital-based treatment model for patients with schizophrenia, the development of an effective intervention program is important, especially in the early years of the disease.

Lower availability of striatal dopamine transporter in generalized anxiety disorder: A preliminary two-ligand SPECT study

Dopamine and serotonin have been indirectly found to be associated with generalized anxiety disorder (GAD). The aims of this study were to examine the availabilities of the striatal dopamine transporter (DAT) and the midbrain serotonin transporter (SERT) in patients with GAD. 12 patients with GAD and 12 sex-matched, age-matched, and smoking status-matched healthy controls were recruited. The availabilities of DAT and SERT were approximated using single-photon emission computed tomography, with [99mTc]TRODAT-1 and [123I]ADAM as the ligands. There were several missing data for six participants with GAD in the ADAM study because of a lack of the radioligand at the time of the experiment. The DAT availability in the striatum was significantly lower in the patients with GAD than in the healthy controls. However, the SERT availability did not differ between the two groups. The results with respect to the striatal DAT level suggested a potential role in the pathophysiology of GAD.

Comparison of antidepressant efficacy-related SNPs among Taiwanese and four populations in the HapMap database

The genetic influence of single nucleotide polymorphisms (SNPs) on antidepressant efficacy has been previously demonstrated. To evaluate whether there are ethnic differences, we compared the allele frequencies of antidepressant efficacy-related SNPs between the Taiwanese population and four other populations in the HapMap database. We recruited 198 Taiwanese major depression patients and 106 Taiwanese controls. A panel of possible relevant SNPs (in brain-derived neurotrophic factor, 5-hydroxytryptamine receptor 2A, interleukin 1 beta, and G-protein beta 3 subunit genes) was selected for comparisons of allele frequencies using the χ(2) test. Our results suggested no difference between Taiwanese patients and controls, but there were significant differences among Taiwanese controls and the other four ethnic groups in brain-derived neurotrophic factor, 5-hydroxytryptamine receptor 2A, interleukin 1 beta and G-protein beta 3 subunit genes. We conclude that there are ethnic differences in the allele frequencies of antidepressant efficacy-related SNPs, and that the degree of variations is consistent with geographic distances. Further investigation is required to verify the attribution of genetic differences to ethnic-specific antidepressant responses.

A comparison of the effectiveness of risperidone, haloperidol and flupentixol long-acting injections in patients with schizophrenia--A nationwide study.

BACKGROUND Risperidone long-acting injection (RLAI), the first licensed, long-acting second-generation antipsychotic (SGA), has not yet been studied in terms of its effectiveness compared with first-generation antipsychotic (FGA) LAIs. METHODS The differences in the effectiveness of RLAI and two other FGA LAIs, haloperidol and flupentixol, were assessed by conducting a one-year pre-post study based on the Taiwanese National Health Insurance Research Database. Effectiveness was defined as reduced medical care utilization and relapse prevention. RESULTS A decreased number of relapses were identified in the haloperidol injection group in the post-LAI period than in the pre-LAI period (Wilcoxon signed rank test, p<0.05). The RLAI group had the largest number of acute admissions and relapses, the longest duration of admission (Wilcoxon signed rank test, p<0.005), and the lowest utilization of anticholinergic agents, such as benzodiazepine (BZD) and SGAs (except oral risperidone), among all of the LAI groups in the post-LAI period. CONCLUSIONS According to the results of this observational study, we suggest that the effectiveness of RLAI is not superior to that of FGA (haloperidol or flupentixol) LAIs, but that RLAI might have fewer adverse effects.

Factors Related to Self-Reported Attention Deficit Among Incoming University Students

Objective: This study was designed to explore physical, social/behavioral, and mental health factors among incoming university students with elevated self-reported ADHD symptoms. Method: A total of 5,240 incoming university students were recruited. The test battery included the ADHD Self-Report Scale, the Measurement of Support Functions, the Chinese Internet Addiction Scale–Revision, Quality of Life assessment, the Brief Symptoms Rating Scale, and the 10-item Social Desirability Scale. Results: ADHD symptoms were elevated in 8.6% of the sample. Only individuals with a lower social desirability score, however, were recruited for further analysis. Significant influential factors for higher self-reported levels for ADHD symptoms included greater suicidal ideation and emotional disturbance, as well as a higher Internet addiction tendency, lower levels of social support, and a greater amount of exercise. Conclusion: Given the elevated prevalence of self-reported ADHD symptoms among this sample of university students, screening for these kinds of problems to detect early challenges before students fail in college as well as identify youth with undiagnosed ADHD should be considered.