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1.  Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia 
What is already known about this subject
Plasma concentrations of clozapine (CLZ) and its active metabolite vary considerably at a given dosage.A number of patient-related factors have been reported to increase the variability of plasma CLZ concentrations, with gender, age and smoking behaviour representing some of the more important contributing variablesHowever, results of previous studies concerning these factors have been inconsistent and most studies were conducted in western populations.
What this study adds
Using this ethnically unique, relatively large sample, we replicated some findings in western populations, including large interindividual variability of plasma CLZ concentrations, significant effects of gender on plasma CLZ concentrations.Female patients had significantly higher levels than males and no significant differences in plasma CLZ concentrations were observed between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher.
Aim
To study the relationship between age, gender, cigarette smoking and plasma concentrations of clozapine (CLZ) and its metabolite, norclozapine (NCLZ) in Chinese patients with schizophrenia.
Methods
Data from a therapeutic drug monitoring programme were analysed retrospectively. One hundred and ninety-three Chinese inpatients with schizophrenia were assessed using clinical data forms. Steady-state plasma concentrations of CLZ and NCLZ were assayed using high-performance liquid chromatography. Comparisons of dosage and plasma CLZ concentrations were undertaken between males (n = 116) and females (n = 77), younger (≤40 years, n = 82) and older patients (>40 years, n = 111) and current male smokers (n = 50) and nonsmokers (n = 66).
Results
(i) Plasma CLZ concentrations demonstrated large interindividual variability, up to eightfold at a given dose; (ii) there were significant effects of gender on plasma CLZ concentrations (relative to dose per kg of body weight) with female patients having significantly higher concentrations than males (30.09 ± 24.86 vs. 19.87 ± 3.55 ng ml−1 mg−1 day−1 kg−1; P < 0.001); (iii) there were no significant differences in plasma CLZ concentrations between those patients ≤40 years old and those >40 years; and (iv) there were no significant differences in plasma CLZ concentrations between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher.
Conclusions
Plasma CLZ concentrations vary up to eightfold in Chinese patients. Among the patient-related factors investigated, only gender was significant in affecting CLZ concentrations in Chinese patients with schizophrenia, with female patients having higher levels.
doi:10.1111/j.1365-2125.2007.02852.x
PMCID: PMC2000616  PMID: 17298477
Chinese race; clozapine; gender; patient-related variables; plasma levels; schizophrenia
2.  QT Interval Prolongation Associated with Intramuscular Ziprasidone in Chinese Patients: A Case Report and a Comprehensive Literature Review with Meta-Analysis 
Case Reports in Psychiatry  2014;2014:489493.
Intramuscular (IM) ziprasidone has been associated with QTc interval prolongations in patients with preexisting risk factors. A 23-year-old male Chinese schizophrenia patient experienced an increase of QTc interval of 83 milliseconds (ms) after receiving 20 mg IM ziprasidone (baseline and increased QT/QTc were, respectively, 384/418 and 450/501). This was rated as a probable adverse drug reaction (ADR) by the Liverpool ADR causality assessment tool. A systematic review including all types of trials reporting the effect of IM ziprasidone on the QTc interval prolongation identified 19 trials with a total of 1428 patients. Mean QTc change from baseline to end of each study was −3.7 to 12.8 ms after IM ziprasidone. Four randomized trials (3 of 4 published in Chinese) were used to calculate a meta-analysis of QTc interval prolongation which showed no significant differences between IM ziprasidone and IM haloperidol groups (risk ratio 0.49 to 4.31, 95% confidence interval 0.09 to 19.68, P = 0.06 to 0.41). However, our review included two cases of patients who experienced symptoms probably related to QTc prolongation after IM ziprasidone. Thus, careful screening and close monitoring, including baseline ECG, should be considered in patients receiving IM ziprasidone for the first time.
doi:10.1155/2014/489493
PMCID: PMC4235192  PMID: 25530900
3.  Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia 
Human genetics  2011;130(5):635-643.
Dopamine β-hydroxylase (DβH) catalyzes the conversion of dopamine to norepinephrine. DβH enters the plasma after vesicular release from sympathetic neurons and the adrenal medulla. Plasma DβH activity (pDβH) varies widely among individuals, and genetic inheritance regulates that variation. Linkage studies suggested strong linkage of pDβH to ABO on 9q34, and positive evidence for linkage to the complement fixation locus on 19p13.2-13.3. Subsequent association studies strongly supported DBH, which maps adjacent to ABO, as the locus regulating a large proportion of the heritable variation in pDβH. Prior studies have suggested that variation in pDβH, or genetic variants at DβH, associate with differences in expression of psychotic symptoms in patients with schizophrenia and other idiopathic or drug-induced brain disorders, suggesting that DBH might be a genetic modifier of psychotic symptoms. As a first step toward investigating that hypothesis, we performed linkage analysis on pDβH in patients with schizophrenia and their relatives. The results strongly confirm linkage of markers at DBH to pDβH under several models (maximum multipoint LOD score, 6.33), but find no evidence to support linkage anywhere on chromosome 19. Accounting for the contributions to the linkage signal of three SNPs at DBH, rs1611115, rs1611122, and rs6271 reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Analysis of markers genome-wide uncovered positive evidence for linkage between markers at chromosome 20p12 (multi-point LOD = 3.1 at 27.2 cM). The present results provide the first direct evidence for linkage between DBH and pDβH, suggest that rs1611115, rs1611122, rs6271 and additional unidentified variants at or near DBH contribute to the genetic regulation of pDβH, and suggest that a locus near 20p12 also influences pDβH.
doi:10.1007/s00439-011-0989-6
PMCID: PMC3193571  PMID: 21509519
4.  Substance Use Disorders Assessed using the Kreek-McHugh-Schluger-Kellogg (KMSK) Scale in an Urban Low-Income and Predominantly African-American Sample of Primary Care Patients 
The Kreek–McHugh–Schluger–Kellogg (KMSK) scale was developed to quantify self-exposure to opiates, cocaine, alcohol, and tobacco. The original study was limited by a relatively small sample that was not representative of general clinical populations, and did not include marijuana exposure. For the current study, participants were recruited from primary-care outpatient clinics in an urban public hospital. The primary measure was the KMSK scale. The Structured Interview for Diagnosis for DSM-IV (SCID) was used as the “gold standard” for substance dependence diagnoses, and the results of KMSK assessments were evaluated using Receiver Operator Characteristic (ROC) analysis. The sample (N=439) was predominantly African-American (90.6%), with mean age (± SD) of 43.1±12.8 yrs. ROC analyses found that the optimal cutoff scores for alcohol dependence were the same as suggested previously (11), while they were lower for cocaine dependence (10 vs. 11) and opiate dependence (4 vs. 9). The analysis suggested a cutoff score for marijuana of 8. The KMSK performed well in the current study as a brief tool for evaluating dependence on alcohol, cocaine, marijuana and opiates in this nonpsychiatric clinic sample of predominantly poor urban African Americans.
doi:10.1111/j.1521-0391.2011.00121.x
PMCID: PMC3076102  PMID: 21477058
5.  Genotype-controlled analysis of serum dopamine β-hydroxylase activity in civilian Post-traumatic Stress Disorder 
Background
Norepinephrine (NE) plays a central role in post-traumatic stress disorder (PTSD). Dopamine β-hydroxylase (DβH) converts dopamine (DA) to NE and its activity varies widely across individuals. Mustapic et al. (2007) reported a PTSD-associated deficit in serum DβH activity (sDβH) in a genotype-controlled analysis of combat veterans. We tested whether such a deficit would occur in a sample of civilians.
Methods
The severity of current adult PTSD symptoms and current DSM-IV diagnosis of PTSD were determined by the PTSD Symptom Scale (PSS). Adulthood trauma exposure was assessed using the Traumatic Experience Inventory (TEI). sDβH was assayed by HPLC with electrochemical detection and genotypes were determined using the Taqman® platform.
Results
Two hundred and twenty seven African American (AA) subjects were enrolled in this study, with a mean age (± SD) of 42.9 (±12.9) years. We found a strong association between rs1611115 genotype and sDβH (p<0.0001). After controlling for adulthood trauma exposure, there were no significant differences of sDβH between subjects who met a PTSD diagnosis and those who did not (p>0.05) in any genotype group. No significant correlations were found between sDβH and PTSD severity, but sDβH significantly associated with the status of comorbid depression based on the cutoff of HAMD (p=0.014) in subjects with PTSD.
Conclusions
We have replicated in this sample the prior finding that DBH rs1611115 genotype strongly associates with sDβH. No associations between sDβH and PTSD diagnosis or symptom severity in this civilian sample.
doi:10.1016/j.pnpbp.2010.07.002
PMCID: PMC2974949  PMID: 20621148
post-traumatic stress disorder; serum dopamine β-hydroxylase; genotype; depression; civilian trauma; association
6.  Transient Cocaine-Associated Behavioral Symptoms Rated with a New Instrument, the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP) 
Chronic use of cocaine is associated with a variety of behavioral symptoms. The current report describes the assessment of cocaine-related behavioral symptoms (CRB) using the Scale for Assessment of Positive Symptoms of Cocaine-Induced Psychosis (SAPS-CIP). The CRB section, one of the three domains in the SAPS-CIP, consists of sub-domains, including Aggressive/Agitated Behavior, Repetitive/Stereotyped Behavior, Unusual Social or Sexual Behavior. Severity scores are assigned according to operational criteria, and range from 0 (not present) to 5 (severe). We interviewed 261 unrelated cocaine-abusing adults using the SAPS-CIP, and 243 of them met criteria for inclusion in the study. The proportion of subjects endorsing different classes of CRBs varied across categories, with 109 of 243 (44.9%) subjects reporting aggressive and agitated behaviors, 180 subjects (74.1%) repetitive/stereotyped behaviors, and 192 (79.0%) unusual social/sexual behaviors. A substantial minority of the subjects (10.3-25.1%) reported that they experienced marked-to-severe behavioral symptoms associated with cocaine use. The proportions of subjects endorsing CRB did not differ by ethnic/racial group or by sex. Correlations among the different domains of CRB were strong, but behaviors rated in the CRB section were less well correlated with psychotic symptoms, which were rated in the hallucination and delusion sections of the instrument. A variety of CRBs are common in cocaine-dependent subjects, and many of these are highly intercorrelated. CRBs also correlate with hallucinations and delusions induced by cocaine, but to a lesser degree. Our findings suggest that there may be some common vulnerability factors that contribute to both cocaine-induced psychosis and CRBs.
doi:10.3109/10550490903077937
PMCID: PMC2878659  PMID: 19874151
7.  Substance Use Disorders Assessed Using the Kreek–McHugh–Schluger–Kellogg (KMSK) Scale in an Urban Low-Income and Predominantly African American Sample of Primary Care Patients 
The Kreek–McHugh–Schluger–Kellogg (KMSK) scale was developed to quantify self-exposure to opiates, cocaine, alcohol, and tobacco. The original study was limited by a relatively small sample that was not representative of general clinical populations, and did not include marijuana exposure. For the current study, participants were recruited from primary care outpatient clinics in an urban public hospital. The primary measure was the KMSK scale. The Structured Interview for Diagnosis for DSM-IV (SCID) was used as the “gold standard” for substance dependence diagnoses, and the results of KMSK assessments were evaluated using receiver operator characteristic (ROC) analysis. The sample (n = 439) was predominantly African American (90.6%), with mean age (±SD) of 43.1 ± 12.8 years. ROC analyses found that the optimal cutoff scores for alcohol dependence were the same as suggested previously (11), while they were lower for cocaine dependence (10 vs. 11) and opiate dependence (4 vs. 9). The analysis suggested a cutoff score of 8 for marijuana. The KMSK performed well in the current study as a brief tool for evaluating dependence on alcohol, cocaine, marijuana, and opiates in this nonpsychiatric clinic sample of predominantly poor urban African Americans. (Am J Addict 2011;20:292–299)
doi:10.1111/j.1521-0391.2011.00121.x
PMCID: PMC3076102  PMID: 21477058

Results 1-7 (7)