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Background/purpose: The association between sex and diagnostic behavior of autism spectrum disorder (ASD), and the effects of comorbid mental retardation (MR) and attention-deficit hyperactivity disorder (ADHD), were explored. Methods: Based on the Taiwan Longitudinal Health Insurance Database (LHID)-2000 and data from 1996 through 2008, the cumulative incidence of ASD over time was compared between the sexes (both cohorts n = 38,117) using the log-rank test. The effects of comorbid MR and ADHD on the incidence of ASD were evaluated using Cox proportional hazard regression analysis. The age at first diagnosis of ASD in the two sexes was compared using the independent-sample t-test. Results: The incidence was higher in males than in females (0.0007 vs. 0.0002) across ages. Comorbid MR or ADHD increased the incidence of ASD in both sexes; comorbid MR or ADHD also decreased the male to female hazard ratio of ASD, with no significant differences in the incidence density of ASD between sexes. ADHD delayed diagnosis in both sexes (males: 6.61 vs 5.10, p

Objective Weight gain is an important risk factor for morbidity and mortality among patients with schizophrenia. We speculated that positive symptoms, related to dopaminergic hyperactivity and altered mesolimbic function, are associated with weight gain. Methods Twenty-two antipsychotic-naive, first-episode patients with schizophrenia were enrolled. The Positive and Negative Syndrome Scale was completed at enrollment and follow-up. Body mass index (BMI) was also measured. Results The increase in BMI, after 6.04 ± 2.16 years of follow-up, was associated with positive symptoms, but not negative symptoms, before treatment with antipsychotics in antipsychotic-naive patients with schizophrenia. Conclusion This finding implied that dopaminergic hyperactivity could be an important factor to predict the treatment outcome. Body weight control is important for the health management of patients with schizophrenia with more severe positive symptoms.

Aims The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics. Methods We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6–30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004–2012), Korea (2010–2016), Hong Kong (2001–2014) and the UK (1997–2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1–30 days, 30–90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia). Results We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20–1.38). The pooled IRR was 0.98 (0.90–1.06) for 1–30 days and 0.88 (0.76–1.02) for 31–90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74–4.64) for 1–30 days, 1.35 (0.74–2.47) for 31–90 days and 1.29 (0.98–1.70) for 90 + days. Conclusions Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.

Objective Previous animal studies have shown that the oxytocin system might affect glucose homeostasis through the hypothalamus-pituitary-adrenal (HPA) axis and peripheral organs. Moreover, whether the effect is stratified by the polymorphism of oxytocin receptor gene (OXTR) remains unclear. Methods In this study, we recruited 89 non-diabetic participants. Their plasma oxytocin and serum insulin profiles were obtained, and the polymorphism of OXTR rs53576 was genotyped. Results There were significant correlations between the oxytocin level and fasting glucose level (r = -0.29, P

Objective Altered event-related potential (ERP) performances have been noted in attention deficit hyperactivity disorder (ADHD) patients and reflect neurocognitive dysfunction. Whether these ERP alterations and correlated dysfunctions exist in healthy parents with ADHD offspring is worth exploring. Methods Thirteen healthy parents with ADHD offspring and thirteen healthy controls matched for age, sex and years of education were recruited. The auditory oddball paradigm was used to evaluate the P300 wave complex of the ERP, and the Wechsler Adult Intelligence Scale-Revised, Wisconsin Card Sorting Test, and continuous performance test were used to measure neurocognitive performance. Results Healthy parents with ADHD offspring had significantly longer auditory P300 latency at Fz than control group. However, no significant differences were found in cognitive performance. Conclusion The presence of a subtle alteration in electro-neurophysiological activity without explicit neurocognitive dysfunction suggests potential candidate of biological marker for parents with ADHD offspring.

Objective Loneliness is a specific risk factor for depressive symptoms and suicidal behavior. The present study examined whether the serum oxytocin level would interact with social support and buffers loneliness and hypothalamic-pituitary-adrenal (HPA)-axis activity in drug-naive patients with major depressive disorder (MDD). Methods Twenty-six patients with MDD (male:female = 3:23; mean age, 45.54 ± 12.97 years) were recruited. The 17-item Hamilton Depression Rating Scale, UCLA Loneliness Scale and self-reported Measurement of Support Function Questionnaire were administered. Serum oxytocin and cortisol levels were assessed using a commercial immunoassay kits. Results In MDD patients, a negative association was found between degrees of social support and loneliness (β= -0.39, p = 0.04). The interaction between social support and serum oxytocin level was negatively associated with loneliness (β= -0.50, p = 0.017) and serum cortisol level (β= -0.55, p = 0.020) after adjusting for age. Follow-up analyses showed that the association between higher social support and lower loneliness was observed only in the higher-oxytocin group (r = -0.75, p = 0.003) but not in the lower group (r = -0.19, p = 0.53). The significance remained after further adjusting for sex and depression severity. Conclusion Low oxytocin level is a vulnerability factor for the buffering effect of social support for loneliness and aberrant HPA-axis activity in MDD patients.

Studies on the cholesterol‐serotonin hypothesis and its link to mood disorders are scarce. In addition, little is known about the association between cholesterol and the effects of tryptophan depletion (TD). The aim of the present study was to investigate the association between plasma cholesterol and changes in heart rate variability (HRV), an important marker of depression and anxiety, after TD. The plasma cholesterol levels of 28 healthy participants were noted, and their HRVs were measured by spectrum analysis. TD was carried out on testing day, and participants provided blood samples just before and 5 hours for tryptophan level after TD. HRV was measured again after TD. An association was found between plasma cholesterol levels and the change in HRV. Decreased high frequency HRV was marginally associated with lower levels of high‐density lipoprotein cholesterol, while increased low frequency HRV was significantly associated with lower levels of total and low‐density lipoprotein cholesterol. Our findings indicate that low cholesterol levels may play parts of role in the mechanism of the deactivation of parasympathetic, and activation of sympathetic, functions induced by altered serotonergic function.

Objective The present study aimed to detect differences in the reward response between adults with attention deficit hyperactivity disorder (ADHD) and healthy controls (HCs) using functional magnetic resonance imaging (fMRI). Methods The Iowa gambling task (IGT) was designed to explore participants’ reward-related decision-making in relation to selections during risky behaviors. Twenty adults with ADHD and 20 HCs were enrolled. fMRI with a modified IGT was performed. Results The adults with ADHD showed a poorer performance in terms of avoidance during risky behaviors. The fMRI results indicated that the adults with ADHD had significantly lower orbitofrontal cortex (OFC) activation. A positive correlation between performance in the IGT and brain activation in the OFC was detected. Conclusions The results suggested that the adults with ADHD exhibited abnormal OFC responses during decision-making. Significance To the best of our knowledge, this is the first study to use fMRI to collect brain activation data while performing the IGT in adults with ADHD. Our findings suggest that deficits in reward processing in ADHD are still present during adulthood.

PURPOSE: To investigate the association between use of methylphenidate and risk of myocardial infarction among Asians. METHODS: We conducted a multinational self-controlled case series study using nationwide healthcare databases of South Korea (2002-2018), Taiwan (2004-2015), and Hong Kong (2001-2016). Of patients with myocardial infarction who were also prescribed methylphenidate within the observation period, methylphenidate use was classified into four mutually exclusive periods by each person-day: exposed (exposed to methylphenidate), pre-exposure (prior to the first methylphenidate prescription), washout (after the end of methylphenidate treatment), and baseline (unexposed to methylphenidate). Risk of myocardial infarction among the three periods of methylphenidate use was compared to the baseline period using conditional Poisson regression analysis to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: We identified 2104, 484, and 30 patients from South Korea, Taiwan, and Hong Kong, respectively. Risk of myocardial infarction was the highest during the pre-exposure period in all three populations: South Korea, pre-exposure (IRR 3.17, 95% CI 3.04-3.32), exposed (1.05, 1.00-1.11), washout (1.92, 1.80-2.04); Taiwan, pre-exposure (1.97, 1.78-2.17), exposed (0.72, 0.65-0.80), washout (0.56, 0.46-0.68); Hong Kong, pre-exposure (18.09, 8.19-39.96), exposed (9.32, 3.44-25.28), washout (7.69, 1.72-34.41). Following stratification for age and sex, the trends remained analogous to the main findings across all three populations. CONCLUSIONS: Although a positive association between initiating methylphenidate and the onset of myocardial infarction was observed, the risk was the highest in the period before its initiation. Thus, this multinational study suggests there was no causal relationship between methylphenidate and myocardial infarction among Asians.

Patients with schizophrenia could have a higher risk of mortality. We compared the risk of mortality and the years of potential life lost (YPLL) associated with various causes of death between patients with schizophrenia and the general population. A total of 4,298 patients with schizophrenia were included. The cohort was linked to the Taiwan Death Register between 1998 and 2010 using personal identification numbers, which showed 367 patients with schizophrenia had died by the end of 2010. The standard mortality ratios (SMRs) and YPLL were analyzed by age, sex and cause of death. The overall SMR was significantly higher in patients with schizophrenia. Suicide had the most significantly greater SMR, and the SMRs for physical illnesses, accidents and injuries were all significantly greater in patients with schizophrenia. Suicide had the largest YPLL/deaths among all causes of mortality in patients with schizophrenia. Suicide had the most significantly greater risk of mortality among patients with schizophrenia as compared with the general population. Patients with schizophrenia are highly vulnerable in terms of increased mortality and require special attention.

Objective: Communication skills are important, but the evaluation of these skills in the medical curriculum remains inconsistent. The aim of this study was to explore the relationship between the communication skills scores of junior medical students following curricula with different module evaluations and the clinical interview performance of the same students in a psychiatry department in their fifth year. Design: Prospective evaluation of communication and clinical interview skills. Setting: Medical school and psychiatry department inpatient setting. Method: The communication skills scores of 208 medical students in their second year (between 2009 and 2011) and their performance in interviews with patients in a psychiatry department in their fifth year (between 2012 and 2014) were assessed. Initial assessment was undertaken on the basis of problem-based learning (PBL) performance, evaluation of performance during conversation with patients, a related oral presentation and written report, students’ self-rating and a peer rating. Extra marks were given if students completed an optional special report inspired by the curriculum. To assess the interview performance of fifth-year medical students, the mini-Clinical Evaluation Exercise (mini-CEX) was used, together with weekly case-based discussions and the observation of a clinical interview with a real patient. Results: Tutors’ evaluations of the junior medical students’ performance during role-play ( ρ = .22, p = .001), its related reciprocal assessment ( ρ = .18, p = .010) and an extra-effort task ( ρ = .18, p = .009) as part of the communication skills curriculum were significantly correlated with the students’ later performance in a clinical interview with a patient. Conclusion: Observation of student interactions and motivations along with reciprocal peer evaluations offer better measures of communication skills in medical education than are oral presentations, self-ratings and conversations with real patients.

ObjectivePrevious studies have indicated that there is dopamine transporter (DAT) dysregulation and P300 abnormality in adults with attention-deficit hyperactivity disorder (ADHD); however, the correlations among the three have not been fully explored.MethodsA total of 11 adults (9 males and 2 females) with ADHD and 11 age-, sex-, and education-level-matched controls were recruited. We explored differences in DAT availability using single-photon emission computed tomography and P300 wave of event-related potentials between the two groups. The correlation between DAT availability and P300 performance was also examined.ResultsDAT availability in the basal ganglia, caudate nucleus, and putamen was significantly lower in the ADHD group. Adults with ADHD had lower auditory P300 amplitudes at the Pz and Cz sites, as well as longer Fz latency than controls. DAT availability was negatively correlated to P300 latency at Pz and Fz.ConclusionsAdults with ADHD had both abnormal DAT availability and P300 amplitude, suggesting that ADHD is linked to dysfunction of the central dopaminergic system and poor cognitive processes related to response selection and execution.

It has been proposed that the dopaminergic system and heritability may play roles in attention deficit/hyperactivity disorder (ADHD). We assessed the performance of healthy parents of children with ADHD in the finger tapping test (FTT) in this study, which is a reliable test and sensitive to central dopamine activity. A total of 16 parents of children with ADHD and 32 controls were enrolled. The FTT was conducted. The 16 healthy parents of children with ADHD exhibited a significantly poorer performance in the FTT, using the nondominant hand, than the 32 healthy controls. This finding indicated that poor motor function could be a potential characteristic in parents of offspring with ADHD.

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.

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 28.9 years) 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 10 years; the median time between admissions was 1.9 years, and 25% of subjects were readmitted within 4 months 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.

Research into the association between heart rate variability (HRV) and cognitive function is scarce, particularly with regard to gender differences. HRV in 182 healthy volunteers was assessed by the root mean square of the successive difference (RMSSD) and spectrum analysis, while the Wechsler Memory Scale-Revised (WMS-R) was used to determine memory function. Robust and significant associations were found to exist between HRV (RMSSD and high-frequency HRV) and domains of the WMS-R in females. Caution should therefore be taken to control for gender when conducting studies on the relationships between HRV and cognitive variables.

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.

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.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.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, p0.05). The RLAI group had the largest number of acute admissions and relapses, the longest duration of admission (Wilcoxon signed rank test, p0.005), 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.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.

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.

Summary 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.

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. Spearman's 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.

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-naive bipolar II patients. Moreover, the effects of pharmacological treatment on metabolic indexes were also evaluated. Methods This study recruited fifty-six drug-naive 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-naive 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.

Objective: ADHD is the most prevalent neurodevelopmental disorder. It is highly heritable and multifactorial, but the definitive causes remain unknown. Abnormal dopamine transporter (DAT) availability has been reported, but the data are inconsistent. The aim of this study was to examine whether DAT availability differs between healthy parents with and without ADHD offspring. Method: Eleven healthy parents with ADHD offspring and 11 age- and sex-matched healthy controls without ADHD offspring were recruited. The availability of DAT was approximated using single-photon emission computed tomography, with [99mTc] TRODAT-1 as the ligand. Results: DAT availability in the basal ganglia, caudate nucleus, and putamen was significantly lower in the parents with ADHD offspring than in the healthy controls without ADHD offspring. Conclusion: The results suggest that ADHD could be heritable via abnormal DAT activities.

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.

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.

In this study, the role of brain derived neurotrophic factor (BDNF) in stress resilience was investigated. With a focus on healthy subjects, we explored whether plasma BDNF levels are correlated with the dexamethasone suppression test (DST) and subjectively perceived social support status. Moreover, we examined the possible interacting effect of DST status and perceived social support on BDNF levels. Seventy-two healthy volunteers, 44 females and 28 males, were recruited from the community and completed the perceived routine support subscale of Measurement of Support Function (PRS_MSF) questionnaire. Plasma BDNF levels and DST suppression rate with the low dose DST were measured. There was a significant positive correlation between BDNF and DST suppression rate in the female subjects. This was also true for the plasma BDNF levels and PRS_MSF in the female subjects. The positive correlation between BDNF and PRS_MSF was significant only in female subjects with low DST suppression rates. Plasma BDNF levels were associated with stress resilience in a sex-specific manner. Subjects' belief in social support might buffer the biological stress reactions. Differences in social perception and the biological stress response between men and women merits further investigation.

This study aimed to assess whether there is a bidirectional association between autism spectrum disorder (ASD) and epilepsy in child and adolescent patients. The National Health Insurance Research Database of Taiwan was used to conduct two cohort studies of patients who were under 18 years of age during the period 1997-2008. Cohort 1 comprised patients with newly diagnosed ASD but excluded those diagnosed with epilepsy prior to ASD. A non-ASD comparison group was matched to each case in terms of age and sex. Cohort 2 comprised patients with newly diagnosed epilepsy but excluded those diagnosed with ASD prior to epilepsy. A non-epilepsy comparison group was matched to each case in terms of age and sex. We calculated the incidence of epilepsy in patients with ASD and hazard ratio (HR) to estimate the risk of epilepsy in association with ASD in cohort 1, and the reverse in cohort 2. In cohort 1, the incidence of epilepsy was 13.7 in the ASD group and 1.3 in the non-ASD group (per 1000 person-years). The adjusted HR for epilepsy was 8.4 (95 % CI 5.5-12.7) in the ASD group when compared with the non-ASD group. In cohort 2, the incidence of ASD was 3.4 in the epilepsy group and 0.3 in the non-epilepsy group (per 1000 person-years). The adjusted HR for ASD was 8.4 (95 % CI 6.2-11.4) in the epilepsy group when compared with the non-epilepsy group. A bidirectional association was, therefore, found to exist between ASD and epilepsy. These findings implicate that ASD and epilepsy probably share common risk factors. However, further studies are required to reveal more detail on the mechanism of this bidirectional association.

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 [Tc]TRODAT-1 and [I]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.

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.

The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited. Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results. The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found. The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin.

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-naive major depressive disorder (MDD) patients. Methods This study included 104 healthy controls and 50 drug-naive 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.

Levels of inflammatory markers have been found to be significantly associated with major depressive disorder (MDD) and cognitive impairment. The aim of this study was to investigate whether the level of C-reactive protein (CRP) is correlated with depressive mood and cognitive impairment in MDD patients. In 149 subjects with MDD, the 21-item Hamilton Rating Scale for Depression (HAM-D), Continuous Performance Test (CPT), Finger-Tapping Test (FTT), and Wisconsin Card-Sorting Test (WCST) were administered before and after antidepressant treatment. Besides, the level of CRP was measured. After 6weeks of treatment, the total HAM-D scores decreased significantly. In addition, the subjects' performance in the masked CPT and the WCST with completed categories significantly improved (p

Tryptophan hydroxylase 1 (TPH1), which encodes the rate-limiting enzyme tryptophan hydroxylase in the biosynthesis of serotonin, is a candidate gene in the development and treatment response of major depressive disorder (MDD); however, its actual role is uncertain. We aimed to compare the allele frequencies of TPH1 in MDD patients and healthy controls in Taiwan, and also to investigate the association between TPH1 A218C and treatment response to either fluoxetine or venlafaxine in a Taiwanese population with MDD. One hundred five healthy controls and 115 outpatients diagnosed with MDD were recruited and genotyped for the TPH1 218A/C (rs1800532) polymorphism. Patients were randomized into either the fluoxetine or venlafaxine treatment group. The 21-item Hamilton rating scale for depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. The TPH1 218A/C allele frequencies differed significantly between healthy controls and MDD patients in Taiwan, with a higher prevalence of the A allele in the patient group (p = 0.025). The odds ratio of the A allele to the C allele was 0.507 for the subjects with MDD. There was no significant correlation between the percentage change in HAM-D score and either TPH1 218A/C genotype or TPH1 allele frequencies. This study indicated that the TPH1 218A/C genotype and allele frequencies differed between the Taiwanese healthy controls and MDD patients but could not be used to predict treatment outcome in Taiwanese MDD patients. Further research with larger sample sizes is needed to confirm the role of TPH1 218A/C.