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Yuan-Hwa Chou,
Chih-Ken Chen,
Shyh-Jen Wang,
Shih-Jen Tsai,
Jiing-Feng Lirng,
Ying-Jay Liou,
Chun-Lung Lin,
Kai-Chun Yang,
Ming-Wei Lin,
Whai-Chin Lo,
Mei-Hsiu Liao,
Chia-Chieh Chen
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ABSTRACT: The S-allele of functional polymorphisms of the serotonin transporter (SERT) gene has been demonstrated to have lower transcriptional activity compared with the L-allele, which shows low expression of SERT in the brain. However, this finding cannot be consistently replicated in vivo. The aim of this study was to determine the availability of SERT based on SERT genotype. We also examined the relationship between brain-derived neurotrophic factor (BDNF) and the availability of SERT. Sixty-two healthy subjects were recruited. Each subject underwent single-photon emission computed tomography with I-ADAM (I-labeled 2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) for imaging SERT in the brain. The specific uptake ratio was measured, and venous blood was drawn when the subject underwent single-photon emission computed tomography to evaluate BDNF levels and SERT genotype. All subjects expressed SERT genotypes that were consistent with a biallelic model, and 26 subjects had SERT genotypes that were consistent with a triallelic model. No differences in specific uptake ratio were detected in the midbrain, putamen, caudate, and thalamus based on the SERT genotype using the biallelic and triallelic models. Interestingly, The Pearson correlation coefficient revealed a positive correlation between BDNF and SERT availability. In particular, this relationship was observed in homozygous S-allele expression and a genotype with low functional expression (SaSa/SaLg) in the biallelic and triallelic models of SERT genotypes, respectively. This finding might explain why the SS genotype of SERT did not increase the risk of major depressive disorder in Asian populations and implicate an important role of BDNF in the patients, who has the SS genotype of the SERT gene.
Journal of clinical psychopharmacology 04/2013; · 5.09 Impact Factor
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ABSTRACT: To study the impact of video game playing on the human brain, the effects of two video games playing on cerebral blood flow (CBF) in young adults were determined. Thirty healthy subjects comprising 18 males and 12 females who were familiar with video game playing were recruited. Each subject underwent three sessions of single photon emission computed tomography (SPECT) with a bolus injection of 20mCi (99m)Tc ECD IV to measure their CBF. The first measurement was performed as baseline, the second and third measurements were performed after playing two different video games for 30min, respectively. Statistic parametric mapping (SPM2) with Matlab 6.5 implemented on a personal computer was used for image analysis. CBF was significantly decreased in the prefrontal cortex and significantly increased in the temporal and occipital cortices after both video games playing. Furthermore, decreased CBF in the anterior cingulate cortex (ACC) which was significantly correlated with the number of killed characters was found after the violent game playing. The major finding of hypo-perfusion in prefrontal regions after video game playing is consistent with a previous study showing reduced or abnormal prefrontal cortex functions after video game playing. The second finding of decreased CBF in the ACC after playing the violent video game provides support for a previous hypothesis that the ACC might play a role in regulating violent behavior.
Psychiatry research. 11/2012;
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ABSTRACT: BACKGROUND: Aggression is frequently observed in patients diagnosed with bipolar disorder (BD). Previous studies found a negative association between aggression and serotoninergic function in patients with BD, as well as in healthy subjects. The objective of this study was to determine whether there is an association between aggression and the availability of the serotonin transporter (SERT) in euthymic BD II patients. METHODS: Thirty-eight age-matched healthy controls (HCs) and 24 BD II patients were recruited. BD II patients were under stable treatment in the euthymic state. The Overt Aggression Scale (OAS) was used for the assessment of aggression. Single photon emission computed tomography with (123)I-ADAM was used for SERT imaging. A specific uptake ratio, which represents availability, was the primary measured outcome. RESULTS: The total OAS scores, as well as the scores on all of the sub-items, were significantly higher in BD II patients than in the HCs group. There was no significant difference in SERT availability between BD II and HCs subjects in different brain regions. The Pearson's correlation between the total OAS scores and the sub-item aggression and SERT availability was significant. LIMITATION: The OAS was used for the assessment of the past week of the patients' condition and thus did not reflect their trait status. CONCLUSIONS: The higher total scores of OAS in euthymic BD II patients than in HCs support the idea that aggression might be a trait marker for BD. Although SERT availability in euthymic BD II patients and in HCs did not differ significantly, the correlation of SERT availability and total OAS provides the possible explanation of aggression in BD II.
Journal of affective disorders 11/2012; · 3.76 Impact Factor
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ABSTRACT: BACKGROUND: Studies have proposed that cognitive deficits are present in a variety of mood states in bipolar disorder (BD). The goal of this study was to find the cognitive deficits in euthymic BD patients and to further explore possible underlying mechanisms of the deficits. METHODS: Thirty-three healthy controls (HCs) and twenty-three euthymic BD type I patients were recruited. Single photon emission computed tomography (SPECT) with (123)I-ADAM was used to image the serotonin transporter (SERT). Ten milliliters of venous blood was drawn for the measurement of brain derived neurotrophic factor (BDNF). Cognitive functions were tested included attention, memory, and executive function. RESULTS: We found that the SERT availability in both the midbrain and striatal regions was decreased in the BD patients compared with the HCs; however, the BDNF were not different between the two groups. There was no correlation between the SERT availability and the BDNF. Interestingly, there were statistically significant differences in sub-items of the facial memory test and the Wisconsin Card Sorting Test between the BD patients and the HCs, which showed that there was a cognitive deficit in the BD patients. However, the overall deficits in cognition were not significantly correlated with the SERT availability or the BDNF. LIMITATION: The effect of medications on cognitive function and BDNF should be considered. CONCLUSIONS: We replicated previous findings that showed cognitive deficits in euthymic BD patients. However, the underlying mechanism of cognitive deficits in euthymic BD patients cannot be entirely explained by SERT and BDNF.
Journal of affective disorders 08/2012; · 3.76 Impact Factor
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ABSTRACT: Single photon emission computed tomography (SPECT) with Tc-99m TRODAT-1 as ligand can be used to evaluate striatal dopamine transporters (DAT) in young subjects. The purpose of this study was to evaluate the reproducibility of (99m)Tc-TRODAT-1 SPECT in DAT binding in healthy young men. Fourteen healthy young men were recruited. The test-retest studies were performed 1week apart. Specific uptake ratios (SUR) of the striatum (ST) and its subregions, the caudate (CA) and the putamen (PU), were measured using the occipital cortex as the reference tissue. The reliability of the two measurements between test and retest, showed significant correlations for the ST, CA and PU, was demonstrated by calculating the intraclass correlation coefficient (ICC). Thus, (99m)Tc-TRODAT-1 SPECT might provide a reproducible and reliable tool in clinical management of young patients with DAT-related disorders.
Psychiatry Research 04/2012; 201(3):222-5. · 2.52 Impact Factor
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Journal of clinical psychopharmacology 02/2012; 32(1):128. · 5.09 Impact Factor
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ABSTRACT: The goals of the meta-analysis were to investigate the overall effectiveness of cognitive behavioral group therapy (CBGT) for depression and relapse prevention in depression from 2000 to 2010, and to investigate how the variables (episode, residual symptoms, group size, control group, group manual, therapist experience, therapy frequency, session length, and take-home assignment) of a CBGT study could affect the effect size.
This study collected actual study designs sought of CBGT for depression published from 2000 to 2010. These studies were then cross-referenced using Medical Subject Headings (MeSH) with the following keywords: group therapy, cognitive therapy, cognitive behavioral therapy, cognitive behavioral group therapy, psychotherapy, depression, relapse, and recurrence. The quality of the studies was evaluated using Cochrane Collaboration Guidelines. The effect size of CBGT on depression and relapse prevention in depression used the formula devised by Hedges and Olkin (1985).
The study investigated the results of 32 studies on the effect of CBGT for depression. The CBGT had an immediate (g=-0.40) and continuous effect over 6 months (g=-0.38), but no continuous effect after 6 months (g=-0.06). The CBGT lowered the relapse rate of depression (RD = 0.16). Variables significantly different from each other in terms of immediate effect were: CBGT versus usual care, therapy sessions lasting longer than 1 hour, and take-home assignments. Preintervention severity of depression and patient turnover rate were found to be significantly related to the size of the immediate effect. The relapse rate after 6 months was significantly related only to "participants have no residual symptoms/participants did not mention residual symptoms."
Researchers and clinicians should take note that CBGT had a moderate effect on the level of depression and a small effect on the relapse rate of depression. The results of this study suggest that the patient should receive a course of therapy at least every 6 months.
Worldviews on Evidence-Based Nursing 02/2012; 9(1):2-17. · 1.24 Impact Factor
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ABSTRACT: Previous brain imaging studies have demonstrated a seasonal difference of serotonin transporter (SERT) binding in the human brain. However, the results were somewhat contradictory. We conducted test-retest study with single photon emission computed tomography (SPECT) with ¹²³I-ADAM as ligand in 28 healthy subjects. Ten of the subjects were studied within 1 month, whereas 18 were randomly assigned to be studied over a period of up to 1 year. The primary measure was the specific uptake ratio (SUR). Regions of interest included the midbrain, thalamus, putamen and caudate. The intra-class correlation coefficient (ICC) was 0.52-0.94 across different brain regions over 1 month, whereas the ICC was -0.24-0.63 over a 1-year period. The 1-month variability ranged from 6.5 ± 5.1% to 12.5 ± 10.6% across different brain regions, and the 1-year variability ranged from 16.5 ± 9.6% to 41.9 ± 35.5%. The Kruskal-Wallis test revealed a significant difference of variability across months. The Wilcoxon Signed Ranks Test showed the SUR between test-retest scans was of borderline significance. Curve fitting, using a 4th degree polynomial model, revealed a significant circadian correlation between the variability and interval of test-retest measurements. Our findings demonstrate the test-retest reproducibility of ¹²³I-ADAM in different time periods and suggest that circadian variation of SERT levels in the human brain might exist.
Psychiatry Research 11/2011; 194(3):224-9. · 2.52 Impact Factor
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ABSTRACT: Carbon monoxide poisoning (COP) after charcoal burning results in delayed neuropsychological sequelae (DNS), which show clinical resemblance to Parkinson's disease, without adequate predictors at present. This study examined the role of dopamine transporter (DAT) binding for the prediction of DNS. Twenty-seven suicide attempters with COP were recruited. Seven of them developed DNS, while the remainder did not. The striatal DAT binding was measured by single photon emission computed tomography with (99m)Tc-TRODAT. The specific uptake ratio was derived based on a ratio equilibrium model. Using a logistic regression model, multiple clinical variables were examined as potential predictors for DNS. COP patients with DNS had a lower binding on left striatal DAT binding than patients without DNS. Logistic regression analysis showed that a combination of initial loss of consciousness and lower left striatal DAT binding predicted the development of DNS. Our data indicate that the left striatal DAT binding could help to predict the development of DNS. This finding not only demonstrates the feasibility of brain imaging techniques for predicting the development of DNS but will also help clinicians to improve the quality of care for COP patients.
Psychiatry Research 10/2011; 194(3):219-23. · 2.52 Impact Factor
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ABSTRACT: Several previous studies, including a meta-analysis, reported no significant differences between various selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder. However, because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups, a head-to-head comparative study between SSRIs in different populations may be enlightening. We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded randomized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder. Fifty-one patients were randomly assigned to citalopram or sertraline treatment. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome. Efficacy and adverse effects were analyzed in an intent-to-treat population. Efficacy was analyzed using a last-observation-carried-forward method for early terminators. There were no significant differences in demographic characteristics at baseline. No significant differences were found in MADRS scores between citalopram and sertraline at baseline (36.6 ± 5.5 vs 38.2 ± 4.9; P = 0.322) or at the end of treatment (week 6; 10.8 ± 10.0 vs 16.7 ± 11.3; P = 0.082). However, MADRS scores in the citalopram group were significantly lower at week 1 (25.2 ± 8.5 vs 30.4 ± 6.1; P = 0.029) and week 3 (15.9 ± 10.0 vs 22.1 ± 8.7; P = 0.037). Overall, treatment-emergent adverse effects were reported by 14.3% and 28.6% of patients in the citalopram and sertraline groups, respectively. In conclusion, citalopram and sertraline were both efficacious and well tolerated. However, citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment, although the statistic was not significant.
Journal of clinical psychopharmacology 08/2011; 31(5):577-81. · 5.09 Impact Factor
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Lei Zhang,
Tung-Ping Su,
Kwang Choi,
Webster Maree,
Cheng-Ta Li,
Ming-Yi Chung,
Ying-Sheue Chen,
Ya-Mei Bai, Yuan-Hwa Chou,
Jeffery L Barker,
James E Barrett,
Xiao Xia Li,
He Li,
David M Benedek,
Robert Ursano
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ABSTRACT: Although suicide represents 1.8% of the global burden of disease, there are few objective assays for suicide risk. Being associated with depressive disorders, which have a high risk of suicide, the proteins P11, P2RX7, and S100β may be biomarkers for a suicidal disposition. We measured levels of p11 and P2RX7 mRNA in peripheral blood mononuclear cells (PBMCs) of 26 psychiatric patients (11 suicide attempters, 15 suicide non-attempters) with post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), and 14 normal controls, using quantitative real-time PCR. We also conducted a meta-analysis of microarray data of p11, P2RX7 and S100β from post-mortem prefrontal cortex (PFC) of patients who committed suicide (n = 56) and non-suicide controls (n = 61). We found that PBMC p11 mRNA levels were significantly lower in suicide attempters and higher in suicide non-attempters, when compared to normal controls. The PFC p11 mRNA levels in suicide completers were also lower than non-suicide controls (adjusted p = 0.007). Unlike p11, PBMC P2RX7 mRNA levels were significantly lower than normal controls in all patients including suicide attempters, suicide non-attempters, and suicide completers. In addition, levels of S100β in PFC did not differ between suicide completers and non-suicide controls. These results suggest that PBMC p11 mRNA levels may be a potential adjunctive biomarker for the assessment of suicide risk in mental disorders and warrants a larger translational study to determine its clinical utility.
Journal of psychiatric research 04/2011; 45(4):435-41. · 3.72 Impact Factor
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ABSTRACT: 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.
NeuroImage 02/2011; 56(3):1526-30. · 5.89 Impact Factor
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Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2011; 35(1):278-9. · 3.25 Impact Factor
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ABSTRACT: Marked increases in the incidence of charcoal burning suicide have contributed to Taiwan's rising suicide rate in the past decade. To assess possible opportunities for intervention, we have compared survivors of suicide attempts by charcoal burning with people who ingested poisons.
We interviewed a consecutive series of suicide attempters by charcoal burning (n=37) and self-poisoning (n=38) admitted to Taipei Veterans General Hospital (TVGH) between January 2009 and March 2010. Interviews included the Structured Clinical Interview of DSMIV (SCID) and Beck Suicide Intent Scale.
Compared to people who ingested medicines/poisons, charcoal burning suicide attempters were less likely to have a pre-existing physical illness or contact with psychiatric services prior to the attempt and more likely to be employed. Charcoal burning suicide attempters had higher levels of suicide intent (mean score 20.1) compared to people ingesting poisons (mean score 13.5) (p<0.001) and were considerably more likely to report that their choice of method was influenced by the media (87% vs. 8%), particularly the portrayal of the method as a peaceful way of dying. Charcoal burning suicides were less impulsive.
The study sample was limited to a single hospital.
Survivors of suicide attempts by charcoal burning have high levels of intent and low levels of psychiatric contact indicating they may be more difficult to prevent than suicides by self-poisoning. Encouraging responsible media reporting of suicide and restricting the availability of charcoal may be the most promising approaches to preventing these deaths.
Journal of affective disorders 01/2011; 131(1-3):402-7. · 3.76 Impact Factor
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ABSTRACT: The objective of this study was to use a mixture of Poisson (MOP) model expectation maximum (EM) algorithm for segmenting microPET images. Simulated rat phantoms with partial volume effect and different noise levels were generated to evaluate the performance of the method. The partial volume correction was performed using an EM deblurring method before the segmentation. The EM-MOP outperforms the EM-MOP in terms of the estimated spatial accuracy, quantitative accuracy, robustness and computing efficiency. To conclude, the proposed EM-MOP method is a reliable and accurate approach for estimating uptake levels and spatial distributions across target tissues in microPET (11)C-raclopride imaging studies.
Computerized medical imaging and graphics: the official journal of the Computerized Medical Imaging Society 01/2011; 35(5):417-26. · 1.04 Impact Factor
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The primary care companion to CNS disorders. 01/2011; 13(1).
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Comp. Med. Imag. and Graph. 01/2011; 35:417-426.
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ABSTRACT: Co-registration of brain SPECT and MR images has been used extensively in clinical applications. The complementary features of two major co-registration methods--surface- and mutual-information-based (MI-based)--motivated us to study a hybrid-based scheme that uses the surface-based method to achieve a quick alignment, followed by the MI-based method for fine tuning. Computer simulations were conducted to evaluate the accuracy and robustness of surface-, MI-, and hybrid-based registration methods by designing different levels of noise and mismatch in the registration experiments. Results demonstrated that the hybrid surface-MI-based scheme outperforms both the surface- and MI-based methods in providing superior accuracy and success rates. Specifically, the translational and rotational errors were no more than 1 mm and 2°, respectively, with consistent success rates over 98%. Besides, the hybrid-based method saved 12-53% of the computation efforts, compared with using the MI-based method alone. We recommend the use of hybrid-based method when the orientational differences between the floating and reference images exceed 10°.
Medical & Biological Engineering 12/2010; 49(6):671-85. · 1.76 Impact Factor
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Psychosomatics 11/2010; 51(6):536-7. · 2.12 Impact Factor
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ABSTRACT: Silymarin and silibinin are bioactive components isolated from Silybum marianum. They have been reported to exhibit anti-oxidative and anti-inflammatory effects. Many studies revealed that drugs with potent anti-inflammatory potential can protect animals against inflammation-associated neurodegenerative disease, e.g., stroke. In this current work we established an animal model of acute ischemic stroke injury by inducing cerebral ischemic/reperfusion (CI/R) in rats to elucidate whether silymarin or silibinin can protect animals from CI/R injury. Pretreatment with silymarin, but not silibinin, dose-dependently (1-10μg/kg, i.v.) reduced CI/R-induced brain infarction by 16-40% and improved neurological deficits in rats with a stroke. Elevated pathophysiological biomarkers for CI/R-induced brain injury, including lipid peroxidation, protein nitrosylation, and oxidative stress, were all reduced by silymarin. In addition, expression of inflammation-associated proteins (e.g., inducible nitric oxide synthase, cyclooxygenase-2 and myeloperoxidase), and transcriptional factors (e.g., nuclear factor (NF)-kappa B and signal transducer and activator of transcription (STAT)-1), as well as production of proinflammatory cytokine (e.g., interleukin-1β and tumor necrosis factor-α) was all significantly prevented by silymarin. Furthermore, an in vitro study on microglial BV2 cells showed that silymarin could inhibit nitric oxide and superoxide anion production, possibly by interfering with NF-κB nuclear translocation/activation. Likewise, silymarin pretreatment also inhibited IκB-α degradation and NF-κB nuclear translocation in brain tissues of ischemic rats. Our results reveal that silymarin, but not its active component silibinin, protected rats against CI/R-induced stroke injury by amelioration of the oxidative and nitrosative stresses and inflammation-mediated tissue injury through impeding the activation of proinflammatory transcription factors (e.g., NF-κB and STAT-1) in the upregulation of proinflammatory proteins and cytokines in stroke-damaged sites. In conclusion, silymarin displays beneficial effects of preventing inflammation-related neurodegenerative disease, e.g., stroke, which needs further investigation and clinical evidences.
Phytomedicine: international journal of phytotherapy and phytopharmacology 10/2010; 17(12):963-73. · 2.17 Impact Factor
