Kao Chin Chen

A study on the sleep quality of incoming university students.

This study was designed to examine the prevalence and the risk factors of poor sleep quality in 4318 incoming university students in Taiwan. The test battery comprised a self-administered structured questionnaire, including items related to personal medical history and lifestyle habits, the Measurement of Support Functions (MSF), Pittsburgh Sleep Quality Index (PSQI), Chinese Internet Addiction Scale-Revision (CIAS-R), neuroticism subscale of the Maudsley Personality Inventory (MPI), and the 12-item Chinese Health Questionnaire (CHQ-12). Of the total study population, 2360 students (54.7%) were classified into the poor sleep quality group, as defined by a PSQI score ≥6. Based on the results of multivariate logistic regression analysis, poor sleep quality was significantly associated with undergraduate students, female gender, skipping breakfast, tea drinking, a higher tendency toward internet addition, poor social support, higher neuroticism, and higher CHQ scores. Poor sleep quality is prevalent among incoming university students in Taiwan, and more work is needed on the identification of the factors influencing poor sleep, and in providing systematic education in the importance of sleep and time management skills to university students.

A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

Background: Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Methods: Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Results: After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. Conclusions: We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT.

Availability of dopamine and serotonin transporters in opioid-dependent users—a two-isotope SPECT study

Rationale and objectiveThe aims of this study were to examine the differences between 32 opioid-dependent users treated with a very low dose of methadone or undergoing methadone-free abstinence and 32 controls.MethodsSPECT analysis using [99mTc] TRODAT-1 to assess striatal dopamine transporter (DAT) availability and [123I] ADAM to assess midbrain serotonin transporter (SERT) availability were performed.ResultsLower striatal DAT and midbrain SERT availabilities were noted in low-dose methadone users. History of metamphatamine use was associated with the lower striatal DAT. The striatal DAT of methadone-free abstainers was also lower than controls. The midbrain SERT availability tended to be higher in the methadone-free abstainers than the low-dose methadone users. The severity of depressive symptoms was negatively correlated with midbrain SERT availability in the opioid users.ConclusionThe availability of striatal DAT tended to be, and the availability of midbrain SERT was, lower in the opioid users. History of metamphatamine use may confound the difference in straital DAT between controls and opioid users, as midbrain SERT and depressive symptoms are also associated with opioid use and abstinence.

Distribution volume ratio of serotonin and dopamine transporters in euthymic patients with a history of major depression — a dual-isotope SPECT study

Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depression who are in a depressed state in comparison with healthy controls. The aim of this study was to examine the distribution volume ratios (DVRs) of SERT and DAT in drug-free and euthymic patients with a history of major depression. Subjects comprised 13 patients with a history of major depression and 26 sex- and age-matched healthy controls. The euthymic state of depression was defined as a score of 7 or less on the Hamilton Depression Rating Scale. The DVRs of SERT and DAT were approximated using SPECT, with [(123)I] 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) and [(99m)Tc] TRODAT-1 as the ligands, respectively. There were no significant differences in the DVRs of SERT or DAT between healthy subjects and euthymic patients with a history of major depression; hence, the SERT and DAT DVRs may not therefore be trait markers for patients with major depression, which helps us to understand more about the pathophysiology of depression.

The differential levels of inflammatory cytokines and bdnf among bipolar spectrum disorders

Objective: Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder. To investigate biological markers of cytokines and brain-derived neurotrophic factor between bipolar I, bipolar II, and other specified bipolar disorder with short duration hypomania may support the association with inflammatory dysregulation and bipolar disorder and, more specifically, provide evidence for other specified bipolar disorder with short duration hypomania patients were similar to bipolar II disorder patients from a biological marker perspective. Methods: We enrolled patients with bipolar I disorder (n=234), bipolar II disorder (n=260), other specified bipolar disorder with short duration hypomania (n=243), and healthy controls (n=140). Their clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokine (tumor necrosis factor-α, C-reactive protein, transforming growth factor-β1, and interleukin-8) and brain-derived neurotrophic factor levels were measured in each group. Multivariate analysis of covariance and linear regression controlled for possible confounders were used to compare cytokine and brain-derived neurotrophic factor levels among the groups. Results: Multivariate analysis of covariance adjusted for age and sex and a main effect of diagnosis was significant (P<.001). Three of the 5 measured biomarkers (tumor necrosis factor-α, transforming growth factor-β1, and interleukin-8) were significantly (P=.006, .01, and <.001) higher in all bipolar disorder patients than in controls. Moreover, covarying for multiple associated confounders showed that bipolar I disorder patients had significantly higher IL-8 levels than did bipolar II disorder and other specified bipolar disorder with short duration hypomania patients in multivariate analysis of covariance (P=.03) and linear regression (P=.02) analyses. Biomarkers differences between bipolar II disorder and other specified bipolar disorder with short duration hypomania patients were nonsignificant. Conclusion: The immunological disturbance along the bipolar spectrum was most severe in bipolar I disorder patients. Other specified bipolar disorder with short duration hypomania patients and bipolar II disorder patients did not differ in these biological markers.

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.

Striatal dopamine transporter availability in drug-naive patients with schizophrenia: A case-control SPECT study with [99mTc]-TRODAT-1 and a meta-analysis

Central dopaminergic hyperactivity has been one of the main hypotheses of the pathophysiology of schizophrenia since the 1970s. Excess dopamine (DA) neurotransmission in the striatum is hypothesized to alter the processing of information and result in psychotic symptoms in schizophrenia. Single photon emission computerized tomography (SPECT) provides in vivo indices of DA neurotransmission. Our study aimed to compare dopamine transporter (DAT) availability between drug-naive patients with schizophrenia and controls using SPECT. DAT availability through [(99m)Tc]-TRODAT-1 SPECT was compared between 47 drug-naive patients with recent-onset schizophrenia and 112 healthy controls. We also conducted a random-effects meta-analysis of the available literature synthesizing the results of 6 comparable published articles as well as our current data. The mean specific striatal binding showed a statistical trend for a reduction among the patients compared with controls (estimated difference = 0.071; 95% CI -0.01, 0.15; P = .08). There was an effect of gender, whereby females had a higher ratio of specific striatal binding than males. Age was negatively correlated with the ratio of specific striatal binding, both in patients and controls. The meta-analysis provided a pooled standardized effect size (Cohens d) of -0.07 (95% CI -0.31, 0.18; P = .60) for the patient vs control comparison in TRODAT binding, with no evidence of heterogeneity between studies or publication bias. Our findings suggest that striatal DAT levels are not altered in the early stages of schizophrenia before medication is introduced. We identified gender differences and aging effects that could have significance for future studies.

Effects of C825T polymorphism of the GNB3 gene on availability of dopamine transporter in healthy volunteers - A SPECT study

Striatal dopaminergic activity is significantly correlated with various cognitive activities, mood regulation, and even metabolic homeostasis, and is modulated by the dopamine transporter (DAT). The availability of DAT could be regulated by presynaptic autoreceptors, which are G-protein coupled receptors; however, whether functional variations in the common downstream signaling molecule, G-protein, could cause individual differences in presynaptic transporter availability remains unclear. To investigate this relationship, the DAT availability in seventy-eight healthy subjects was approximated using single photon emission computed tomography (SPECT) with [(99m)Tc] TRODAT-1, a radio-labeled form of tropan derivative for the selective labeling of DAT. The C825T single nucleotide polymorphism (SNP) (rs5443) of the beta subunit of the G-protein second messenger (GNβ3) gene was genotyped, and analysis of variance showed a significant difference in striatal DAT when referenced to the entire occipital lobe among the three genotypes. Post hoc independent t tests were also performed, and showed that the striatal DAT availability of the CC genotype was higher than that of the other two genotypes. These results indicated that genetic variation in the common downstream signaling molecule of the dopamine autoreceptor could affect the functional status of the striatal dopamine system. These results together with the known role of the GNβ3 gene might provide further evidence to support the common effect of the striatal dopamine system on mood and metabolic regulation.

Sunshine-exposure variation of human striatal dopamine D2/D3 receptor availability in healthy volunteers

BACKGROUNDnIn addition to the serotonergic system, the central dopaminergic system has been reported to be correlated with seasonality. The aim of this study was to explore the difference in striatal dopamine D(2)/D(3) receptor availability between healthy volunteers who had a high-sunshine exposure and those who had a low exposure.nnnMETHODSnSixty-eight participants were enrolled, and those in the upper and lower quartiles in terms of sunshine exposure were categorized into high- (n = 17) and low-sunshine-exposure (n = 18) subgroups. Single photon emission computed tomography with [(123)I] iodo-benzamide was used to measure striatal dopamine D(2)/D(3) receptor availability.nnnRESULTSnStriatal dopamine D(2)/D(3) receptor availability was significantly greater in the subjects with high-sunshine exposure than in those with low-sunshine exposure (F = 7.97, p = 0.01) after controlling for age, sex, and smoking status.nnnLIMITATIONSnDifferent subjects were examined at different time points in our study. In addition, the sex and tobacco use distributions differed between groups.nnnCONCLUSIONnThe central dopaminergic system may play a role in the neurobiological characteristics of sunshine-exposure variation.

Schizotypy trait and striatal dopamine receptors in healthy volunteers.

Individuals with schizotypal features exhibit cognitive, perceptual and social deficits that are similar to but less prominent than those seen in patients with schizophrenia. Dopaminergic hyperactivity in the striatum has been related to the positive symptoms of schizophrenia, and brain-imaging studies of dopamine uptake in the striatum are thought to be linked to the pathophysiological mechanisms underlying schizophrenia. The aim of this study was to investigate whether the increased availability of striatal dopamine (DA) D(2/3) receptors is related to elevated levels of schizotypal features in healthy individuals. The Schizotypal Personality Questionnaire (SPQ) was administered to 55 healthy volunteers. The availability of their striatal DA D(2/3) receptors was analysed using [(123)I] iodobenzamide single photon emission computed tomography (SPECT). Although the SPQ total scores showed no correlation with the availability of total (left and right) striatal DA D(2) receptors, the SPQ disorganised subscale scores were positively correlated with the availability of right striatal DA D(2/3) receptors. Our findings demonstrated that the availability of striatal DA D(2/3) receptors may be associated with schizotypal features in healthy volunteers.