Wei Hung Chang

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.

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.

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.

The reductions in monetary cost and gains in productivity with methadone maintenance treatment: One year follow-up

While methadone maintenance treatment (MMT) is beneficial for heroin dependence, there is little information regarding the reductions in monetary cost and gains in productivity following MMT. The aim of this study was to evaluate the changes in the monetary cost of heroin addiction and productivity after one year of MMT. Twenty-nine participants from an MMT clinic were included. The monetary cost, productivity, quality of life (QOL) and mental health status were assessed at both baseline and one year follow-up. The average annual total cost was approximately US

Which demographic variables are necessary to correct in neuroimaging studies of serotonin transporter availability? A SPECT study with [123I]ADAM

26,485 (1.43 GDP per capita in 2010) at baseline, and decreased by 59.3% to US

Unaltered Dopamine Transporter Availability in Drug-Naive Patients with Schizophrenia after 6 Months of Antipsychotics Treatment: A Naturalistic Study

10,784 (0.58 GDP) at follow-up. The mean number of months of unemployment dropped from 6.03 to 2.79, the mean income increased to exceed the basic salary, but only reached 45.3% of the national average monthly earnings. The participants׳ mental health improved, but their QOL scores did not increase significantly. After one year of MMT, the monetary cost of heroin addiction fell, both the productivity and mental health of the participants׳ improved, but limited gains were seen with regard to their QOL.

Holistic Consideration of Patients with Schizophrenia to Improve Medication Adherence and Outcomes.

Previous studies have shown that many demographic variables influence serotonin transporter (SERT) availability as assessed by single photon emission computed tomography (SPECT). The aim of this study was to explore which demographic variables influenced the SERT availability most in a SPECT study with [(123)I]ADAM. Ninety-five healthy volunteers were recruited. Age, sex, smoking, alcohol intake, educational level, body mass index, seasonal change, and SERT availability were recorded and then analyzed by multivariate linear regression. Age was the only variable that was significantly associated with SERT availability (calculate: (midbrain-cerebellum)/cerebellum). Furthermore, the inverse correlation of age and SERT availability may be present only before the age of 47. Age should be a covariate in SERT-related neuroimaging analyses, particularly in participants under the age of 47 years.

Prefrontal cortex modulates the correlations between brain-derived neurotrophic factor level, serotonin, and the autonomic nervous system

Background Dopaminergic dysfunction, namely, dopamine transporter (DAT) availability variations in patients with drug-naive schizophrenia after long-term treatment, is still not well understood. The aims of the study were to explore (i) whether the DAT availability in patients with drug-naive schizophrenia differed after antipsychotic treatment and (ii) whether treatment with different generations of antipsychotics influenced the DAT availability after follow-up for 6 months. Methods Twenty-four first-episode, drug-naive patients with schizophrenia were divided into first- and second-generation antipsychotic groups naturalistically. After 6 months of follow-up, 7 patients who received first-generation antipsychotic treatment and 17 patients who received second-generation antipsychotic treatment completed the study. The patients underwent premedication and 6-month follow-up measurements using single-photon emission computed tomography with technetium Tc 99m (99mTc) TRODAT-1. Psychopathological evaluations and adverse effects were recorded using appropriate scales. Results Both of the treatment groups significantly improved according to Positive and Negative Symptoms Scale evaluation. However, no significant difference was noticed between the premedication and 6-month follow-up DAT scans. Nonsignificant differences existed even in the groups of different generations of antipsychotics. Conclusions Improvements in psychotic symptoms in patients with schizophrenia may not be influenced by DAT availability, even under treatment with different antipsychotics for a sufficient treatment period.

Dopamine transporter availability in drug-naïve patients with schizophrenia and later psychotic symptoms severity

Although several algorithms have been applied to treat patients with schizophrenia, their clinical use remains still limited, because most emphasize the prescription of antipsychotics. A new algorithm with a more holistic approach to treating patients with schizophrenia, to be used before applying traditional prescribing guidelines, was thus proposed by an expert team of Taiwanese psychiatrists. In this algorithm, several important treatment tasks/modalities are proposed, including long-acting injection anti-psychotics, shared decision-making, a case management system, compulsory treatment by law, community rehabilitation programs, the patients’ feeling about their health care professionals (patients’ behaviors) and their attitude/knowledge of their conditions/illness. This study proposes that evaluating the medication adherence of patients can be determined by two key domains, namely patients’ behaviors and attitudes. Based on different levels of their behaviors (X-axis) and attitude/knowledge (Y-axis), it is possible to categorize patients with schizophrenia into six subgroups, for which various different interventions, including the use of antipsychotics, could be applied and integrated. Further research is needed to assess the applicability of this treatment algorithm in clinical settings.

Coexisting geriatric anxiety and depressive disorders may increase the risk of ischemic heart disease mortality—a nationwide longitudinal cohort study

Top-down regulation in the human brain and anatomical connections between the prefrontal cortex (PFC) and specific catecholamine-related regions have been well-studied. However, the way in which the PFC modulates downstream neuro-networks in terms of serotonin and the autonomic nervous system (ANS) by variation in the level of brain-derived neurotrophic factor (BDNF) is still unclear. We recruited sixty-seven healthy subjects. Serotonin transporter (SERT) availability was examined by SPECT with [123I]ADAM analysis; heart rate variability (HRV) testing was performed, and the BDNF level was measured. The Wisconsin card-sorting test (WCST), which assesses PFC activation, was also conducted. The interactions of BDNF level and SERT availability were significant in relation to the HRV indexes of low frequency, high frequency, total power, and mean heart rate range. Moderate to significant positive correlations between SERT availability and the above-mentioned HRV indexes existed only in subjects with a low BDNF level. Furthermore, in the low BDNF level group, only those with high WCST perseveration errors or low category completions exhibited significant positive correlations between SERT availability and HRV indexes. A lower BDNF level and poorer PFC function might modulate the synergistic effects of serotonergic and ANS systems in order to maintain brain physiological and psychological homeostasis.