chieh-liang Huang

• chief at TsaoTun Psychiatric Center

Background: Sleep difficulty is common in the current society. Poor sleep has a significant influence on health, social interactions and even mortality; therefore, maintaining good sleep is of prime importance. Cannabidiol (CBD), a cannabis-derived compound, is known for its medical significance with many positive effects in humans, including decre...

Background: The effects of methadone-induced severe prolongation of the corrected QT interval (QTc) and sudden cardiac death appear unpredictable and sex-dependent. Genetic polymorphisms in the nitric oxide synthase 1 adaptor protein (NOS1AP) have been implicated in QTc prolongation in general populations. We investigated whether common NOS1AP vari...

Study Objectives Lemborexant (LEM) is a dual orexin receptor antagonist approved for treating adults with insomnia. We analyzed the efficacy (subjective sleep outcomes) and safety of LEM over 12 months in the subgroup of Asian subjects from Study E2006-G000-303 (Study 303). Methods Study 303 was a 12-month, randomized, placebo-controlled (first 6...

Question Amphetamine use is a risk factor for psychosis, which imposes a substantial burden on society. We aimed to investigate the incidence of psychosis associated with illicit amphetamine use and whether rehabilitation treatments could influence the psychosis risk. Study selection and analysis A retrospective cohort study was conducted using th...

Road traffic under the influence of drugs is an important issue of public health and social safety. We aimed to investigate the temporal trends of road traffic accidents (RTAs) involving people who used illicit drugs. A population-based retrospective study was conducted using data from the Taiwan Illicit Drug Issue Database (TIDID) and traffic acci...

Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence....

Background: Ketamine has remained the most commonly used illicit drug among adolescents in Taiwan. A dual process model proposes that addictive behaviors develop in adolescents as a result of an imbalance between an appetitive, approach-oriented system (implicit and explicit attitudes) and a regulatory executive system (cool and hot executive func...

Over the past two decades, smartphones have become common, and the accompanying devices have also become much more popular and easily accessible worldwide. With the development of smartphones, accompanied by internet facilities, excessive smartphone use or smartphone addiction may cause sleep disturbance and daily dysfunction. This study proposed e...

Background The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration. Methods A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insura...

A correction to this paper has been published: https://doi.org/10.1007/s12325-021-01712-y

Addiction is characterized by drug-craving, compulsive drug-taking, and relapse, and results from the interaction between multiple genetic and environmental factors. Reward pathways play an important role in mediating drug-seeking and drug-taking behaviors, and relapse. The objective of this study was to identify heroin addicts who carry specific g...

Introduction: The health benefits of entering methadone maintenance treatment (MMT) for opioid-dependent persons may not be merely limited to therapy of opioid use disorder. We aimed to compare the healthcare utilization of MMT patients before and after MMT. Methods: A retrospective analysis was performed using the Taiwan Illicit Drug Issue Data...

Determining the clinically optimal dose in methadone maintenance therapy (MMT) is a time-consuming procedure, which considers clinical signs and symptoms. To perform a quantitative trait locus association for identifying genetic variants for MMT dosage that underlie heroin addiction and methadone metabolism and then integrate several genotypic and...

[This corrects the article DOI: 10.1155/2017/5642708.].

Opioid addiction is a major public health issue worldwide. Methadone maintenance treatment (MMT) is used to detoxify users of illicit opiates, but drug relapse is common and associated with poor quality of life (QoL). This study investigated the associations between the GRIN3A, GRM6, and TPH2 genetic variants and QoL in the MMT population. A total...

Genotype frequencies and score of each item of SF-36 of the participants. (PDF)

LD plot of SNPs in GRIN3A from CHB data in 1000 Genome project. (PDF)

LD plot of SNPs in GRM6 from CHB data in 1000 Genome project. (PDF)

SF-36 measurement model. (PDF)

Genotypes of TPH2, GRM6, GRIN3A in included participants. (PDF)

LD plot of SNPs in TPH2 from CHB data in 1000 Genome project. (PDF)

Table S1 Characteristics of two cohorts study subjects on MMT. Table S2 Primer list for SNP and qRT‐PCR. Table S3 The association of ERE‐SNPs in MMT Max.

Methadone maintenance treatment (MMT) is the major tapering therapy for morphine addictive patients. There have gender differences reported in response to MMT. This study discovered that the estrogen-response element single nucleotide polymorphism (ERE-SNP; rs16974799, C/T) of cytochrome 2B6 gene (cyp2b6; methadone catabolic enzyme) responded diffe...

Human fibroblast-like synoviocytes (FLSs) play a role in joint synovial inflammation in rheumatoid arthritis (RA). Some evidence indicates that particulate matter (PM) in air pollution could contribute to the progression of RA. However, more research is needed to clarify this relationship. Up-regulation of cyclooxygenase (COX)-2 and its metabolite...

Methamphetamine (METH) is a major drug of abuse worldwide, and no efficient therapeutic strategies for treating METH addiction are currently available. Continuous METH use can cause behavioral upregulation or psychosis. The dopaminergic pathways, particularly the neural circuitry from the ventral tegmental area to the nucleus accumbens (NAc), have...

Background: Alcohol-related dementia (ARD) is a heterogeneous long-term cognitive problem that can develop in the course of alcoholism. Current understanding of ARD remains limited. Methods: We conducted a systematic review to synthesize available data on the epidemiology of ARD, through searching the relevant studies in the PubMed, PsycINFO, an...

The expression of the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells enables the attachment of leukocytes to the endothelium, which may lead to inflammation and the development of atherosclerosis. Magnolol is a major bioactive compound derived from the plant species Magnolia officinalis. In this study, we synthesi...

The opioid receptor, mu 1 (OPRM1) is a gene that encodes for the mu opioid receptor (MOR). The role of the MOR has been well characterized in both physiological and pharmacological animal studies. Its role in heroin-dependent patients under treatment with the synthetic opioid methadone, however, is unclear. Using a Taiwan methadone maintenance trea...

In this work we analyse data for 314 participants of a methadone study over 180 days. Dosages in milligram were converted for better interpretability to seven categories in which six categories have an ordinal scale for representing dosages and one category for missing dosages. We develop a dissimilarity measure and cluster the time series using “p...

Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the...

All haplotypes in association tests of individual haplotypes for plasma concentration of R-methadone. We list the chromosome, window, linkage disequilibrium (LD) block, and gene where the haplotypes are located. Haplotype frequencies and raw and adjusted p values of the significant haplotypes are provided in the final two columns. (DOCX)

Homozygosity check plot. The genome-wide homozygosity rate (i.e., one minus heterozygosity rate) and proportion of missing genotype (i.e., one minus genotyping call rate) of each individual are calculated and plotted based on autosomal SNPs. The two vertical reference lines are the mean homozygosity rate ± 3 standard deviations. Four individuals ar...

Principal component plot of allele frequency. Principal component plot of 344 MMT patients in Taiwan (MMT; pink color) and 210 independent individuals from the International HapMap II Project [53]. The HapMap II individuals consisted of 30 married African couples from Yoruba in Ibadan (YRI; green color), 30 married Caucasian couples of European-des...

Sliding-window genome-wide haplotype analysis of plasma concentration of R-EDDP and S-EDDP. Manhattan plot of genome-wide haplotype-based association test. The vertical axis is the raw p values of the omnibus haplotype tests (in a scale of -log10) and the horizontal axis is physical position of the initial SNP of a haplotype in different autosomes....

Distributions of windows with different sizes and distributions of LD blocks with different sizes. In terminology, the window width indicates the physical distance between the first and last SNPs in a window, and the window size indicates the number of SNPs in a window. For each window size of 2, 3, 4, 5, and 10 SNPs, the frequency of windows with...

Effect sizes of the significant haplotypes we identified. In accordance with the inclusion steps of haplotypes in each analysis of plasma concentration of R-methadone and S-methadone, we list the chromosome and linkage disequilibrium (LD) block where the haplotypes are located. Slope estimate and its standard error (s.e.) and the corresponding 95%...

Results of a meta-analysis by combining p-values at the discovery and replication stages. We list the chromosome (Chrom.), linkage disequilibrium (LD) block, and significant haplotypes followed by their p-values according to the urine morphine test (UMT): UMT = All, Negative, and Positive. (DOCX)

Sex check plots. The homozygosity intensities of each individual are calculated and plotted based on 12,531 SNPs on chromosome X using software LOHAS. Five individuals exhibited a homozygosity pattern of X chromosome(s) inconsistent to their self-reported gender: (A) Individual 206–055: the self-report gender is “female” but the pattern of homozygo...

Analysis flow of the replication study. (A) Flow of all statistical analyses. (B) Flow of quality control. (TIF)

Gene structure and LD plot of 15 SNPs from the present genome-wide pharmacogenomic study and our previous candidate gene study of CYP2B6. In the top panel, coding regions on CYP2B6 are displayed by green rectangles. In the bottom panel, pairwise LD of 15 SNPs on CYP2B6 was measured by D’ [27]. SNPs with a strong LD were framed in a black inverse di...

All haplotypes in association tests of individual haplotypes for plasma concentration of S-methadone. We list the chromosome, window, linkage disequilibrium (LD) block, and gene where the haplotypes are located. Haplotype frequencies and raw and adjusted p values of the significant haplotypes are provided in the final two columns. (DOCX)

Descriptive statistics of three covariates and two quantitative traits. The number of individuals and means ± standard deviations (SD) of covariates and quantitative traits are provided by gender. In the final column, p values of the Kolmogorov-Smirnov Good-of-Fit tests for normality for the pre- and post-transformation data of four quantitative tr...

Two outlier individuals (217–024 and 301–156) who carried multiple excessive runs of homozygosity on multiple chromosomes. (A) Principal component plot of homozygosity intensity identified two outlier MMT patients (217–024 and 301–156) who carried multiple excessive runs of homozygosity on multiple chromosomes. (B) For patient 217–024, chromosome-w...

Genome-wide single-locus association test for plasma concentration of S-methadone, R-EDDP, and S-EDDP. Manhattan plot of genome-wide single-locus association test. The vertical axis indicates the raw p values of the association tests (in a scale of -log10). The horizontal axis is physical position of a SNP on different autosomes. Each point indicat...

Haplotype frequencies and p-values of the significant haplotypes, identified by our genome-wide pharmacogenomic study, at the discovery and replication stages. We list the chromosome (Chrom.), linkage disequilibrium (LD) block, and significant haplotypes followed by their haplotype frequencies (HF) and raw p-values (P) at discovery stage and replic...

Distributions of the raw data and transformed data of four quantitative traits. The subfigures in the diagonal show the histograms of the four quantitative traits (R-methadone, S-methadone, R-EDDP, and S-EDDP). The subfigures in the upper diagonal part are the pairwise scatterplots of the four quantitative traits. The subfigures in the lower diagon...

Gene expression for CYP2B6, SPON1, and GSG1L in different tissues. The gene expression plots were generated from the Genotype-Tissue Expression (GTEx) Project [54] (http://www.gtexportal.org/home/). In each bar chart, the height of a bar indicates gene-level RPKM (i.e., reads per kilobase per million reads) values, from RNA sequencing experiments....

Regional association plot and LD plot of the imputation region. Regional association plot and LD plot on the flanking region of rs17180299. In the regional association plot, the vertical axis is the raw p values of the association tests (in a scale of -log10) and the horizontal axis is physical position of SNPs (in unit of kb). Raw p values of sing...

Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence,...

Aims: Betel-quid (BQ) contains biologically psychoactive ingredients; however, data are limited concerning the symptoms and syndrome of BQ dependence among chewers. The aims of this study were to evaluate the ingredients-associated BQ dependence syndrome and country-specific chewing features and behaviour for BQ dependence among chewers from six A...

Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (S...

Whether genetic factors affect social cognition, particularly emotion management, requires elucidation. This study investigates whether social cognition varies with genetic variations of COMT and tryptophan hydroxylase-2 (TPH2), which modulate dopamine and serotonin neurotransmissions respectively, and thereby emotion regulation. NIMH-recommended "...

Background: Antidepressants, aiming at monoaminergic neurotransmission, exhibit delayed onset of action, limited efficacy, and poor compliance. Glutamatergic neurotransmission is involved in depression. However, it is unclear whether enhancement of the N-methyl-D-aspartate (NMDA) subtype glutamate receptor can be a treatment for depression. Metho...

Methadone is a widely used substitution therapy for opioid addiction. Large inter-individual variability has been observed in methadone maintenance dosages and P-glycoprotein (P-gp) was considered to be one of the major contributors. To investigate the mechanism of P-gp's interaction with methadone, as well as the effect of genetic variants on the...

Background: The functional outcome of schizophrenia is affected by multiple factors such as cognitive function and clinical symptoms. The complex relationship among cognitive function (both neuro- and social-cognitions), clinical symptoms, and functional outcome remains unclear. The current study employed structural equation modeling (SEM) to exam...

To test whether the genetic polymorphisms within the gene encoding the UGT2B7 gene may have an impact on methadone treatment. Twelve SNPs in UGT2B7 were selected. 366 methadone maintenance treatment patients in Taiwan were recruited and genotyped. In a genotype recessive model, rs6600879, rs6600880, rs4554144, rs11940316, rs7438135, rs7662029, rs76...

Facial emotion perception is a major social skill, but its molecular signal pathway remains unclear. The MET/AKT cascade affects neurodevelopment in general populations and face recognition in patients with autism. This study explores the possible role of MET/AKT cascade in facial emotion perception. One hundred and eighty two unrelated healthy vol...

Linkage disequilibrium (D′) for the MET SNPs was computed using Haploview 4.2. (TIF)

Demographics, facial emotion perception, composite cognition*, and MET SNPs and haplotypes, AKT SNP, and MET/AKT variants in the 149 patients who also received thorough cognitive assessments. (DOC)

Allele frequencies of MET SNPs and AKT SNP. (DOC)

Methadone, a synthetic racemic opioid that primarily works as a μ-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic poly...

Methadone is associated with QTc prolongation and sudden death in susceptible patients. We sought to investigate whether there is a gender-based difference in susceptibility to methadone-associated QTc prolongation in heroin-dependent patients receiving a low-dose treatment regimen. A cross-sectional assessment of dose and gender effects was perfor...

The present study explored the integrative effect of genes encoding methadone pharmacokinetic and pharmacodynamic pathways on methadone maintenance doses in Han Chinese Patients. Genomic DNA was extracted from 321 opioid-dependent patients and 202 healthy controls, and realtime-PCR and PCR-RFLP were conducted to determine the genotypes. Pair-wise c...

Methadone maintenance therapy is one of the standard treatments for heroin addiction. The isozyme CYP3A4 of the CYP system is one of the metabolic enzymes, as well as CYP2B6, responsible for the metabolism of methadone. The aim of the present study is to evaluate the potential use of genetic polymorphisms in CYP3A4 as biomarkers for the prediction...

Methadone is a racemic compound composed of the R-form and S-form enantiomers. The drug is usually used in maintenance therapy for the heroin-addicted patients. In our previous study, we found that the cytochrome P-450 (CYP) isozyme 2B6 preferentially metabolizes the S-methadone enantiomer. We thus tested whether CYP2B6 gene polymorphisms had any i...

Heroin addicts often combined the use of alcohol as a multiple drug abusers. The use of alcohol may create hepatic toxicity, increase the severity of withdrawal and side effects, and cause difficulty in methadone dosage regimen while under the treatment. In order to decipher the role of alcohol elimination process in these patients under methadone...

Methadone and QT Prolongation. Background: Methadone is associated with QTc prolongation and sudden death in susceptible patients.We sought to investigate whether there is a gender-based difference in susceptibility to methadone-associated QTc prolongation in heroin-dependent patients receiving a low-dose treatment regimen. Methods: A cross-section...

Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an important role in cytokine-induced depression and sickness behavior. Patients with chronic hepatitis C viral infection (n = 132) were assessed to examine the effects of seven single nucleotide polymorph...

The elucidation of genotype-phenotype relationships in psychiatric research is at an early stage. V-akt murine thymoma viral oncogene homolog 1 (AKT1) is a serine/threonine kinase known as protein kinase B. Emerging studies have implicated the role of AKT1 in pathogenesis of schizophrenia; however, the findings have not been consistent. This study...

Perinatal depression is common, and treatment remains challenging. Depression has been reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs). A profound decrease of omega-3 PUFAs in the mother during pregnancy is associated with the higher demand of fetal development and might precipitate the occurrence of de...

Background: Perinatal depression is common, and treatment remains challenging. Depression has been reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs). A pro- found decrease of omega-3 PUFAs in the mother during pregnancy is associated with the higher demand of fetal development and might precipitate the oc...

Polymorphisms of the gene encoding the regulator of G-protein signaling subtype 4 (RGS4) are associated with schizophrenia. This study aims to investigate the association of 4 RGS4 polymorphisms (single nucleotide polymorphisms [SNPs] 1, 4, 7, and 18), implicated in previous studies, with baseline symptoms and treatment response to risperidone in p...

The Val158Met polymorphism of the catechol-O-methyltransferase gene has been demonstrated to be associated with prefrontal executive function explaining 4% of variance in perseverative errors on the Wisconsin Card Sorting Test (WCST). Studies suggest that dopamine D(1) and D(3) and serotonin 5-HT(2A) and 5-HT(6) receptors may also be involved in pr...

Small molecules that enhance the N-methyl-D-aspartate (NMDA) neurotransmission have been shown to be beneficial as adjuvant therapy for schizophrenia. Among these compounds, sarcosine (a glycine transporter-I inhibitor), when added to an existing regimen of antipsychotic drugs, has shown its efficacy for both chronically stable and acutely ill pati...

Objective: Validating self-reported questionnaires to detect depression during pregnancy, compared to depression during postpartum, has gained much less attention. Furthermore, it is unknown whether it is appropriate to use the same cutoff point to detect depression on different trimesters of pregnancy. The aims of this study, conducted in pregnan...

Researchers, by studying first-generation antipsychotics, have established an early prediction model, which had a favorable specificity but a low sensitivity. This study aims to optimize early prediction of treatment response for schizophrenia using a novel statistic method that can be done even under the Microsoft Excel system of a personal comput...

Agonists at the N-methyl-D-aspartate (NMDA)-glycine site (D-serine, glycine, D-alanine and D-cycloserine) and glycine transporter-1 (GlyT-1) inhibitor (N-methylglycine, or called sarcosine) both improve the symptoms of stable chronic schizophrenia patients receiving concurrent antipsychotics. Previous studies, however, found no advantage of D-serin...

A serious side effect of atypical antipsychotics is increased body weight, which leads to further morbidity and nonadherence to medication. It has been suggested that both genetic and nongenetic variables may influence antipsychotics-related weight gain. This study aimed to simultaneously explore the effects of multiple candidate genes and environm...

The present study examined the relationship between the Lie scale scores and striatal D(2)/D(3) receptor availability with respect to the cerebellum in 42 healthy community volunteers in Taiwan using single photon emission computed tomography (SPECT) with [(123)I]iodo-benzoaminde (IBZM). Even after controlling of age and educational level, subjects...

Although generalized anxiety disorder (GAD) is associated with significant occupational disability, it has, however, received little attention with regard to adjustment to illness. Subjects included 102 chronic dialysis (CD) patients, 58 kidney transplant (KT) patients, and 42 GAD patients. The evaluations included the Psychosocial Adjustment to Ph...

There is strong evidence to suggest that genetic variation plays an important role in inter-individual differences in medication response and toxicity. Most of the previous pharmacogenetic studies, however, cannot be reconfirmed. Of note, drug efficacy or side effects depend not only on genetic factors but also on nongenetic factors, such as illnes...

The monitoring of patients, by themselves and their caregivers, is very important in the prophylaxis of bipolar disorder. This study aimed to develop a Chinese-language version of an instrument for assessment of manic and depressive symptoms by patients and their families. Fifty-eight inpatients and outpatients with a DSM-IV (Diagnostic and Statist...