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Jose de Leon

Publications and source records attributed to Jose de Leon.

At least 37 records · Page 2Linked to original sources
PubMed2005

A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors.

A meta-analysis of worldwide studies, found by a 10-year literature follow-up and/or by searching PubMed, was performed. Forty-two studies across 20 nations consistently demonstrated an association between schizophrenia and current smoking (weighted average odds ratio, OR=5.9; 95% confidence interval, CI 4.9--5.7). In 32 male studies across 18 nations, the weighted average OR was 7.2 (CI, 6.1--8.3). In 25 female studies across 15 nations, the weighted average OR was 3.3 (CI, 3.0--3.6). The association between schizophrenia and current smoking remained after using severe mentally ill controls (18 studies across 9 countries, weighted average OR was 1.9, CI 1.7--2.1) and controlling for other variables (3 studies, adjusted ORs ranged 2-3). Heavy smoking (6 studies across 4 countries, ORs ranged 1.9--6.4) and high nicotine dependence were more frequent in smokers with schizophrenia versus the general population. There was no consistent evidence that heavy smoking or high nicotine dependence was more frequent in smokers with schizophrenia versus severe mentally ill controls. Cessation rates were lower in schizophrenia smokers versus the general population. Schizophrenia patients had a higher prevalence of ever smoking than the general population (9 studies across 6 countries, weighted average OR=3.1, CI 2.4--3.8) and than severe mentally ill patients (5 studies across 5 countries, OR=2.0, CI 1.6--2.4). Moreover, in two studies adjusting for confounders schizophrenia patients had an increased risk of starting daily smoking than controls. Thus, people who are going to develop schizophrenia have risk factors that make them more vulnerable to start smoking.

Comorbidity↗
PubMed2005

Suicidal behavior in schizophrenia and depression: a comparison.

The aim of this study was to compare the frequencies and suicide attempt characteristics in patients with schizophrenia (N = 25) and major depression in absence of schizophrenia (N = 107). There were no significant differences in attempt methods, but attempters with schizophrenia reported a lower number of life events influencing the attempt (2.0 vs. 2.6), less influence of life events on the attempt (42% vs. 83%) and lower GAF scores (36 vs. 50). Schizophrenia was not associated with higher impulsivity scores but with significantly more lethal attempts (40% vs. 29%) and with a trend toward (p = 0.08) higher scores in aggressive behavior history.

Adult↗
PubMed2005

Smoking initiation and schizophrenia: a replication study in a Spanish sample.

In a prior US study, schizophrenia vulnerability was associated with higher risk of initiating daily smoking after 20 years of age. A survival analysis of onset age of daily smoking compared 290 controls with 250 consecutive DSM-IV schizophrenia patients from outpatient facilities at an urban catchment area in Spain. After controlling for gender and education, the cumulative hazard curves for smoking initiation age of controls and schizophrenia patients were significantly different. After age 20, smoking initiation rates were higher in all schizophrenia patients (and in 107 schizophrenia patients who started daily smoking at least 5 years before illness onset).

Adult↗
PubMed2005

Plasma clozapine concentration coefficients of variation in a long-term study.

Kurz et al. conducted the first study of the intra-individual variability of clozapine plasma concentrations but did not take into account the effect of smoking and co-medication. As patients were receiving varying doses, Kurz et al. standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients, the mean coefficient of variation (CV) was 53% (S.D. = 21). In this new study, plasma clozapine and norclozapine concentrations were measured every 2 weeks in 47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind clozapine trials under controlled conditions (stable smoking, limited co-medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day, the respective mean CVs for plasma clozapine concentrations were 23% (S.D. = 14), 19% (S.D.= 11) and 18% (S.D. = 8). For the combined concentrations of clozapine and norclozapine, the respective mean CVs were 20% (S.D. = 13), 16% (S.D. = 9) and 15% (S.D. = 7). Under 100 mg/day, the mean CV for clozapine concentrations was significantly higher for heavy smokers than non-heavy smokers (32%, S.D. = 3 vs. 19%, S.D. = 8) (p = 0.03). Studies of CVs in other environments are needed. Clozapine CVs may be important in order to understand the importance of variations around the therapeutic range and to interpret drug interactions above the usual noise of measuring plasma concentrations.

Adult↗
PubMed2005

Comparison of the Heavy Smoking Index and of the Fagerstrom Test for Nicotine Dependence in a sample of 749 cigarette smokers.

Nicotine Dependence (FTND) was administered to a sample of 749 adult smokers. The Heavy Smoking Index (HSI) which combines two items of the FTND (the number of cigarettes per day and the time of the first cigarette of the day) was compared to the FTND. A cut-off score equal or greater than 4 on the HSI detected a similar rate of nicotine dependence as a cut-off score equal or greater than 6 on the FTND. HSI had good sensitivity (79.5%) and specificity (96.5%). The concordance between the two instruments was high (Cohen's kappa=0.74). The HSI performed as well on men as on women. The HSI provides a good measure of high nicotine dependence, particularly appropriate for epidemiological surveys.

Adolescent↗
PubMed2005

High vulnerability to acute dystonic reactions: a case of antipsychotic exposure and uncontrolled seizure activity.

Antipsychotic-induced extrapyramidal side effects have a negative impact on treatment for mental illness. Acute dystonic reactions are uncomfortable and frightening to the patient, and often lead to early discontinuation of drug therapy and worsened long-term outcome. The lower propensity of the atypical antipsychotic agents to cause extrapyramidal symptoms (EPS) has been associated with multiple benefits, including improved adherence. The authors describe a 57-year-old male patient who was in the treatment refractory unit. This patient exhibited extreme sensitivity to antipsychotic agents, experiencing acute dystonic reactions with quetiapine and olanzapine, in addition to older typical antipsychotic agents. The patient has not experienced acute EPS since therapy with aripiprazole was initiated. Further complicating this patient's course is his unusual sensitivity to experiencing dystonic reactions. We have observed acute dystonias in the absence of antipsychotic treatment and in the context of seizure activity (or paroxysmal dyskinetic activity). The true etiology of the latter dystonic activity has not been completely determined due to the patient's unwillingness to cooperate with invasive testing. None of the gene variations tested (CYP2D6 phenotype, two dopamine D2 receptor variants and one D3 receptor variant) appeared to explain the patient's vulnerability to acute dystonic reactions.

Anticonvulsants↗
PubMed2005

A pilot genetic study of the continuum between compulsivity and impulsivity in females: the serotonin transporter promoter polymorphism.

According to some authors the obsessive-compulsive (OC) spectrum includes on one extreme, the Obsessive-Compulsive Disorder (OCD) and on the other extreme the most impulsive behaviors. This is a controversial idea and other authors define the OC spectrum in different ways. The serotonin transporter (5-HTT) gene is one of the main genes that control serotonergic function. A polymorphism in the promoter area of this gene classifies subjects with low expression as S individuals (s/s or s/l) and subjects with high expression as L individuals (l/l). This polymorphism was studied in female OCD patients (n = 24), non-impulsive controls (n = 112) and impulsive suicidal patients (n = 118) to support the OC spectrum hypothesis from a genetic perspective. A linear association exists among the serotonin transporter promoter functional genotypes (S versus L individuals) (chi2 linear by linear association = 8.9; df = 1; p = 0.003). The frequency of S individuals (s/l or s/s) was lowest in OCD (54%, 13/24); intermediate in non-impulsive controls (71%, 80/112) and highest in impulsive suicide attempters (82%, 96/117). More importantly, future studies need to consider that genetics may be related to behavioral dimensions (compulsivity to impulsivity) instead of to specific psychiatric disorders defined in clinical terms.

Adolescent↗
PubMed2005

Does clozapine decrease smoking?

McEvoy et al.'s study in 1999, which used cotinine levels but had limited power, suggested that clozapine treatment may be associated with a mild smoking decrease (particularly when plasma clozapine levels are > 150 ng/ml). Some naturalistic studies also suggest that clozapine treatment may be associated with a mild smoking decrease. The present study included 38 schizophrenic daily smokers from a double-blind clozapine trial. Five analyses were tested for significant decreases in plasma cotinine levels from a haloperidol baseline to: (1) the end of clozapine trials regarding clozapine doses (100, 300 or 600 mg/day), (2) the end of the clozapine trial where the highest plasma clozapine level was achieved, (3) the end of the clozapine trial where a clozapine level in the 150-450 ng/ml range was achieved, (4) the end of the first clozapine trial regardless of clozapine dose, and (5) the end of the last clozapine trial in the study. The first and straightforward analysis by dose showed no clozapine effects on smoking. The second and the third analyses (an attempt to mimic the design by McEvoy et al. [McEvoy, J.P., Freudenreich, O., Wilson, W.H., 1999. Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol. Psychiat. 46, 125-129.]) also indicated that there was not a significant effect of clozapine on smoking. The fourth and five analyses were also negative. None of the five analyses in our clozapine trial demonstrated that clozapine had major effects on smoking. This study cannot rule out that in some subjects, clozapine treatment may be associated with a small decrease in smoking. New prospective longitudinal studies using repeated cotinine and clozapine levels are needed to explore whether clozapine may reduce smoking in some patients.

Adult↗
PubMed2005

A brief measure of high nicotine dependence for busy clinicians and large epidemiological surveys.

OBJECTIVE: It is important to perform a routine screening of nicotine dependence in psychiatric patients. The Fagerstrom Test for Nicotine Dependence (FTND) is a widely used six-item questionnaire. The Heavy Smoking Index (HSI) is a briefer measure including only two FTND items (time to first cigarette of day and number of daily cigarettes). In a prior study comparing HSI with FTND, a high HSI (score > or = 4) was a good and briefer alternative for detecting high nicotine dependence. The goals of this study were: (i) to compare the effectiveness of the HSI with the effectiveness of Items 1 and 4 alone for the screening of high nicotine dependence; (ii) to investigate the optimality of 4 as a cut-off score for the HSI so that the HSI can be used as a binary indicator of high nicotine dependence; and (iii) to compare the sensitivity and specificity of four indexes of high nicotine dependence, namely 'High HSI', 'Very Early Smoking', 'Heavy Smoking' and 'High in Either Item'. METHOD: The FTND was administered to 819 current daily smokers from a general population survey. As in a prior study, an FTND score > or = 6 was considered the reference or 'gold standard' test for detecting high nicotine dependence. Receiver-operating characteristic analyses were performed. RESULTS: This new study using more sophisticated statistical methodology verified that a cut-off of 4 for the HSI is appropriate and that the 'high' HSI has good sensitivity and specificity even across different population subclassifications. CONCLUSIONS: With four questions (smoking, daily smoking, time to first cigarette of day and number of daily cigarettes) and minimal calculations, it may be possible to screen whether a smoker has high nicotine dependence. If other studies in other populations and settings verify this finding, this brief measure might be an ideal screening instrument for busy clinicians, epidemiologists developing questionnaires for health surveys and psychiatric researchers.

Adolescent↗
PubMed2005

Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness.

This study tested the association between tardive dyskinesia (TD) and polymorphic variations in (a) 2 cytochrome P450 (CYP) genes (CYP2D6 or CYP3A5), (b) 2 DRD2 variants (Ser311Cys and -141C Ins/del) and the Ser9Gly DRD3 variants, (c) 2 glutathione S-transferases (GSTT1 and GSTM1), and (d) variations in the PgP gene, MDR1. The study sample included 516 severely mentally ill patients from Central Kentucky facilities. Logistic regression models that included clinical variables associated with TD were developed. Gene variants were added to these clinical models. The total sample included 31% (162/516) with TD where 30% (49/162) of those had severe TD. Polymorphisms in DRD2, MDR1, and GSTT1 were never significant. Two gene variants appeared to be significant after adding them to the clinical regression models: (1) Ser9Gly DRD3 polymorphism was associated with severe TD (odds ratio for patients with 1 mutant allele when compared with individuals with 2 wild types was 2.5, 95% confidence interval 1.1-5.6, whereas the odds ratio for patients with 2 mutant alleles when compared with individuals with 1 mutant was 2.8, 95% confidence interval 1.0-7.4), and (2) GSTM1 absence was associated with TD (odds ratio 1.7, 95% confidence interval 1.2-2.4) particularly in white women. The CYP2D6 and CYP3A5 absence showed potential for significant associations in larger samples, particularly in white men. New studies need to replicate whether these or other genes could be used conjointly with clinical variables to identify subjects at risk for TD in clinical settings.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions.

BACKGROUND: Smoking may have a beneficial effect on either schizophrenic symptoms or antipsychotic side-effects, but studies are hampered by the lack of control of confounding factors. AIMS: To explore the self-medication hypothesis in a large sample of stable out-patients with schizophrenia. METHOD: Symptoms, assessed with the Positive and Negative Syndrome Scale (PANSS), and number of hospitalisations were compared in 250 out-patients with DSM-IV schizophrenia classified into three categories: highly dependent smokers, mildly dependent smokers and non-smokers. Log-linear analysis was used to control for potential confounding and interacting variables. RESULTS: High PANSS total scores and positive symptoms were less frequent in mildly dependent smokers than in non-smokers or highly dependent smokers. The highly dependent smokers had the worst outcome. CONCLUSIONS: The data do not generally support the self-medication hypothesis but rather suggest a complex interaction between nicotine dependence and nicotine dependence and schizophrenic symptoms.

Adult↗
PubMed2005

The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation.

OBJECTIVE: The cytochrome P450 2D6 (CYP2D6) enzyme metabolizes risperidone. CYP2D6 poor metabolizers have no CYP2D6 activity (7% of whites and 1%-2% of other races). This study tested whether the CYP2D6 poor metabolizer phenotype was associated with adverse drug reactions (ADRs) and discontinuation due to ADRs. METHOD: Adult inpatients and outpatients were recruited from July 2000 to March 2003 including (1) 325 who were stabilized on risperidone therapy and classified as either expressing moderate-to-marked ADRs (22%, 73/325) or not (78%, 252/325) and (2) 212 who discontinued risperidone and were classified as discontinued due to ADRs (38%, 81/212) or for other reasons (62%, 131/212). Genetic tests were performed by allele-specific polymerase chain reaction and/or by the AmpliChip CYP450 microarray system for up to 34 separate CYP2D6 alleles. Two logistic regression models with dependent variables (moderate-to-marked ADRs while taking risperidone and risperidone discontinuation due to ADRs) were evaluated with respect to the CYP2D6 phenotype. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) for the CYP2D6 poor metabolizer phenotype in the univariate analyses and after correcting for clinical variables were (1) OR = 3.1 (CI = 1.4 to 7.0) and 3.4 (CI = 1.5 to 8.0) for moderate-to-marked ADRs on risperidone and (2) OR = 3.0 (CI = 0.85 to 10.6) and 6.0 (CI = 1.4 to 25.4) for discontinuation due to ADRs. CONCLUSIONS: The CYP2D6 poor metabolizer phenotype appears to be associated with risperidone ADRs and discontinuation due to ADRs; however, this finding requires further study in larger patient populations. The CYP3A5 and p-glycoprotein exon 21 and 26 genotypes were not significantly associated with risperidone response.

Adult↗
PubMed2005

Obesity and associated complications in patients with severe mental illnesses: a cross-sectional survey.

BACKGROUND: This naturalistic cross-sectional survey of patients with severe mental illnesses explores the association between important variables and obesity, extreme obesity, diabetes mellitus type 2, hypertension, and hyperlipidemia in the clinical environment. METHOD: Weight and height were obtained from 560 patients with severe mental illnesses (including DSM-IV schizophrenia, schizoaffective disorder, bipolar disorder, and major depressive disorder) at central Kentucky inpatient and outpatient facilities to estimate their body mass index (BMI). Chart diagnoses of diabetes mellitus, hypertension, and hyperlipidemia were obtained. RESULTS: When comparing the patients with severe mental illnesses with Kentucky adults from the general population, the odds ratio (OR) of obesity (BMI > or = 30 kg/m(2)) was 2.6 (95% confidence interval [CI] = 2.2 to 3.0), and the OR of diabetes mellitus was 2.9 (95% CI = 2.3 to 3.6). Female gender, African American race, early start of psychiatric medication, and long psychiatric medication duration were significantly associated with obesity. Current alcohol and nicotine use exhibited significant ORs of obesity lower than 1, particularly in males. Obesity was closely associated with hypertension, type 2 diabetes mellitus, and hyperlipidemia. These complications were closely associated with each other and may indicate a further progression of obesity after aging. CONCLUSIONS: These results suggest a complex pattern of variables that may influence the development of obesity and its complications in patients with severe mental illnesses, but they need replication. The major factors associated with obesity appear to be a long-term illness or treatment duration and substance use. The former may be more important in females, while the latter may be more important in males. Clinical diagnoses (schizophrenic or mood disorders) or current treatment did not appear to be fundamental factors.

Adult↗
PubMed2005

Variables associated with alcohol, drug, and daily smoking cessation in patients with severe mental illnesses.

BACKGROUND: Co-occurrence of substance use disorders and severe mental illnesses (SMIs) is a major U.S. public health issue, although the role of tobacco is usually neglected. This study explored variables associated with alcohol, drug, and smoking cessation in a naturalistic setting. METHOD: Logistic regression was used to study variables associated with cessation of alcohol and drug use disorder and daily smoking in 560 SMI inpatients and outpatients from central Kentucky facilities. Patients with a lifetime history of alcohol or drug use disorder were considered to be in cessation if they had not suffered from abuse or dependence during the last year. Alcohol and drug use disorder diagnoses were determined using the Clinician Rating of Alcohol and Drug Use Disorder. Patients were recruited from July 2000 to March 2003. RESULTS: The cessation rates for alcohol and drug use disorders were, respectively, 44% (95% CI = 39% to 49%) and 46% (CI = 40% to 51%); these were higher than the daily cigarette smoking cessation rate of 10% (CI = 7% to 13%). Drug use disorders (p < or = .02), outpatient status (p < .001), and having a medical complication of obesity (diabetes mellitus, hypertension, or hyperlipidemia; p < .001) were significantly associated with alcohol cessation. Alcohol use disorder (p < .001), starting treatment with psychiatric medications after 33 years of age (p < .001), taking these medications for 14 years or more (p = .02), schizophrenia diagnosis (p < .001), outpatient status (p = .03), and obesity (p = .04) were significantly associated with drug cessation. Cessation of daily smoking was associated with hypertension (p = .02), late start of treatment with psychiatric medications (> 33 years old; p = .01), and lack of lifetime drug abuse (p < .001). CONCLUSIONS: These results are limited by the cross-sectional and naturalistic design but suggest that public health experts, researchers, and clinicians need to mindfully address smoking cessation in patients with SMIs. Clinicians may want to consider that medical illnesses may motivate patients with SMIs to stop substance abuse and that patients with SMIs who abuse both alcohol and drugs rarely stop abusing just one of them.

Adult↗
PubMed2004

Suicide attempts and impulsivity.

Impulsivity in suicidal behavior can describe the attempt (state) or the attempter (trait). There are no studies simultaneously measuring attempt impulsivity and attempter impulsivity in representative samples of suicide attempts. A one-year study of 278 suicide attempts in a general hospital tested the continuous versus dichotomous relationship between attempter impulsivity (Barratt Impulsiveness Scale) and attempt impulsivity (low scores in the planning subscale of Beck's Suicidal Intent Scale). Attempter impulsivity was not a good predictor of attempt impulsivity independently of how both dimensions were measured (continuous or dichotomous ways). Impulsive attempts were associated with low lethality and lack of depression. Opportunities for prevention of suicide attempts in major depression and some personality traits may exist but require attentive monitoring of suicidal ideation and intent.

Adjustment Disorders↗
PubMed2004

Lack of association between the serotonin transporter promoter gene polymorphism and impulsivity or aggressive behavior among suicide attempters and healthy volunteers.

The association between a polymorphism in the promoter area of the serotonin transporter (17q11.1-q12) with impulsivity and history of aggressive behavior was studied in a Spanish general hospital. Subjects comprised 216 suicide attempters (152 women and 64 men) and 223 control blood donors (124 women and 99 men). They were classified as S individuals (s/s or s/l) with low expression of the serotonin transporter, and L individuals (l/l) with high expression. The genotype was not associated with high levels of impulsivity (measured with the Barratt Impulsiveness Scale) or history of aggressive behavior (measured with the Brown-Goodwin scale). This lack of association did not appear to be explained by lack of statistical power. High scores on the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Aggressive Behavior Scale were associated with being an attempter, male gender and borderline personality disorder. While our Spanish suicide attempters and published US suicide attempters have similar BIS scores, our Spanish suicide attempters have significantly lower aggressive behavior scores. If cross-cultural differences in aggressive behavior scores are definitively established, country norms for aggressive behavior scales will need to be developed to compare genetic studies in different countries.

Adult↗