Progress in neuro-psychopharmacology & biological psychiatry, Jan 15, 2011
Interactions between smoking and movement disorders include the contrasting associations of more ... more Interactions between smoking and movement disorders include the contrasting associations of more cigarette smoking with reductions in Parkinson's disease and increases in tardive dyskinesia (TD) symptoms. Here we examine the relationship between smoking and TD in a large sample of inpatients with schizophrenia. We used cross-sectional naturalistic methods to analyze the prevalence and severity of neuroleptic-induced TD in relation to cigarette smoking among 764 male chronic and medicated inpatients meeting DSM-IV criteria for schizophrenia. We administered a detailed questionnaire including general information, medical and psychological conditions, and smoking behaviors. We evaluated TD severity using the abnormal involuntary movement scale (AIMS) and psychopathology using the Positive and Negative Syndrome Scale (PANSS). The main statistical analyses used cross-tabulations for the prevalence of TD by smoking and multivariate regression analyses for continuous measures (AIMS and...
The physiological and psychological responses to drug cue exposure have been assessed in substanc... more The physiological and psychological responses to drug cue exposure have been assessed in substance abusers. However, there is no study to demonstrate whether the responses to drug cue exposure are diurnal dependence. The present study was to examine whether there was a variation in drug-related cue reactivity across the diurnal cycle among recently abstinent opiate addicts. Four groups of 20 abstinent heroin dependent patients (n=80) were exposed to both neutral and drug-related videos at four separate times during the day: 8:00, 12:00, 16:00, and 20:00 h. Physiological and psychological responses, including heart rate, blood pressure, heroin craving, and subjective anxiety were assessed before and after each cue exposure. Drug cue significantly increased craving ratings compared to neutral cues across all the four separate times of day. Drug cue-induced craving was greater in the morning (8:00 am) than noon (12:00 pm), but was similar to evening assessments (8 pm). Drug cues also significantly increased anxiety, which positively correlated with cue-induced craving. Drug cues increased heart rate, systolic and diastolic blood pressures, which were not correlated with cue-induced craving or anxiety. However, no time effects were found on the three physiological measures. Cue-induced craving could be profoundly affected by the time points of cue exposure, using cue-reactivity paradigm. The relative sensitivity of morning and evening assessments of drug craving suggests a need for replication and further research on mechanisms contributing to these diurnal variations.
Pharmacotherapy trials for cocaine abuse among methadone-maintained patients have typically repor... more Pharmacotherapy trials for cocaine abuse among methadone-maintained patients have typically reported negative findings as well as high rates of cocaine use during the trial. The contribution of motivational factors to these results is a potentially important, underinvestigated area. This article points out that some methadone-maintained patients may enter a trial for cocaine abuse with little desire for treatment, motivated primarily
Under normal physiological conditions, free-radical-induced oxidative stress is combated by a com... more Under normal physiological conditions, free-radical-induced oxidative stress is combated by a complex antioxidant defense system (Lohr, 1991; Lohr and Browning, 1995; Yao et al., 2001). A major contribution to the total antioxidant capacity comes from antioxidant molecules in plasma. There are several antioxidant molecules in plasma, such as albumin, uric acid and ascorbic acid which account for >85% of the total antioxidant capacity in human plasma (Yao et al., 1998), as well as other antioxidants in blood, e.g., bilirubin, a-tocopherol and b-carotene (Yao et al., 2000; Reddy et al., 2003). Although measuring levels of specific antioxidant molecules can yield valuable information, determination of total antioxidant status (TAS) provides an index of the sum of activities of all antioxidants (Yao et al., 1998). Excessive free radical production leading to increased oxidative stress may be involved in the development of tardive dyskinesia (TD) (Lohr et al., 2003). Studies have shown increased membrane lipid peroxidation and impairment in antioxidant enzyme activity in animal model of TD (Naidu et al., 2003) and in TD patients (Lohr et al., 2003). In our recent study, we reported that patients with TD had lower plasma superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities, but higher plasma levels of malondialdehyde (MDA), a marker of lipid peroxidation (Zhang et al., 2003, 2007), suggesting that oxidative stress is involved in the pathophysiology of TD. However, studies to date have generally been exploratory. Further elucidation of the role of free radicals and antioxidants in TD and its treatment will require systematic investigation. To our knowledge, there is no published study to investigate the total antioxidant capacity in TD. The purposes of the study therefore were to investigate: (1) whether plasma TAS was altered in TD patients; (2) whether there was a relationship between the altered TAS and dyskinetic movements of TD patients. All inpatients satisfied DSM-IV criteria for schizophrenia. TDwas diagnosed using the criteria of Schooler and Kane (1982). The patients with TD (n 1⁄4 38) and those without TD (n 1⁄4 40) were selected from among the inpatients of Beijing Hui-Long-Guan hospital. All patients had been receiving stable dose of oral neuroleptic medications for at least 12 months. Healthy Han Chinese control subjects (n 1⁄4 50) were selectively recruited from the local community, and matched for age and gender. All subjects were Han Chinese from Beijing area. All subjects gave written informed consent approved by the institutional Review Board of the hospital. Fasting plasma TAS was measured using spectrophotometric method in duplicate by using a commercially available kit in all subject samples. Assessments included the abnormal involuntary
Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates... more Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n=57), risperidone (n=23) or typical antipsychotics (n=44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.
Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 wee... more Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Consulting and Clinical Psychology, 1998
In response to a need to match drug users to the most appropriate and cost-effective level of car... more In response to a need to match drug users to the most appropriate and cost-effective level of care, it was hypothesized the socially anxious methadone-maintained patients would attain greater benefit from coping skills training provided in the context of a low-intensity enhanced standard methadone maintenance intervention (E-STD) than in the context of a high-intensity, socially demanding day treatment program (DTP). Social anxiety was assessed in 307 methadone-maintained patients using the Social Anxiety and Distress Scale prior to randomization to either E-STD or DTP. The hypothesis was supported: Socially anxious patients were drug free longer during treatment, were more likely to be abstinent at treatment completion, and had greater reductions in HIV risk behaviors if assigned to the lower intensity intervention, which was provided at 1/3 the cost of the DTP.
Weight gain is a problem commonly encountered with antipsychotic treatment and has become more ap... more Weight gain is a problem commonly encountered with antipsychotic treatment and has become more apparent with increasing use of the newer atypical antipsychotics. The adipocyte-derived hormone, leptin, has been associated with body weight and energy homeostasis, and abnormal regulation of leptin could play a role in weight gain induced by antipsychotics. We investigated whether a leptin gene promoter variant affected weight gain after long-term treatment with clozapine in chronic schizophrenia. Leptin G2548A polymorphism was genotyped in 102 Chinese Han inpatients with chronic schizophrenia treated with clozapine. Weight gains, expressed as change in body mass index (BMI), were monitored after long-term clozapine treatment. We found a significant relationship between the 3 leptin G/A genotypes and mean BMI gain (F(2,99) = 3.35, P = 0.039, r(2) = 0.09). Moreover, genotype had a strong effect on BMI gain in male (P = 0.004, r(2) = 0.16), but not in female patients (P > 0.05). Thus, variation in the leptin gene may be a risk factor for weight gain in male patients with schizophrenia on long-term clozapine treatment.
Free radical-mediated pathology has been implicated in the development of tardive dyskinesia (TD)... more Free radical-mediated pathology has been implicated in the development of tardive dyskinesia (TD). Antioxidant defense system alterations and increased lipid peroxidation have been postulated as a possible mechanism for neuronal damage associated with TD. However, the relationship between antioxidant enzymes, lipid peroxidation products, and the severity of TD symptoms has not been determined within a single patient group. Plasma levels of malondialdehyde (MDA), a marker of lipid peroxidation, superoxide dismutase, glutathione peroxidase, and catalase were examined in 80 patients with schizophrenia (DSM-IV criteria) and TD (Schooler-Kane criteria) and 45 schizophrenia patients without TD. Results were compared to those of 50 age-, sex-, and smoking status-matched controls. Tardive dyskinesia severity was assessed using the Abnormal Involuntary Movement Scale, and patient psychopathology was assessed using the Positive and Negative Syndrome Scale. Patients with TD had lower plasma superoxide dismutase, glutathione peroxidase, and catalase levels but higher MDA levels than those without TD. In the patients with TD, MDA levels were positively correlated with Abnormal Involuntary Movement Scale total score and with Positive and Negative Syndrome Scale negative subscore. Superoxide dismutase and catalase activities were inversely correlated with MDA levels. Our data support the hypothesis that oxidative stress is involved in the patho-physiology of TD. These data also suggest a relationship between oxidative stress and the severity of dyskinesia in TD patients. Increased lipid peroxidation may likely be a result of decreased endogenous antioxidant enzyme activities in TD.
The authors examined cocaine use in 110 opioid‐dependent cocaine users during a 24‐week, randomiz... more The authors examined cocaine use in 110 opioid‐dependent cocaine users during a 24‐week, randomized, double‐blind clinical trial in which patients were maintained daily on one of the following: 2 mg of buprenorphine, 6 mg of buprenorphine, 35 mg of methadone, or 65 mg of methadone. During the 24‐week trial, cocaine use, as measured by urinalysis and self‐reports, did not differ across medication groups, although opiate use decreased significantly in the methadone groups relative to the buprenorphine groups. These results suggest that buprenorphine, at doses up to 6 mg/day, is not more effective than methadone in decreasing cocaine use in opioid‐dependent cocaine users. (American Journal on Addictions 1994; 3:43–48)
Progress in neuro-psychopharmacology & biological psychiatry, Jan 13, 2018
We attempted to replicate the efficacy of minocycline, a second-generation tetracycline, as adjun... more We attempted to replicate the efficacy of minocycline, a second-generation tetracycline, as adjunctive therapy for the negative symptoms of schizophrenia, and to investigate its association with pro-inflammatory cytokine levels. Seventy-five schizophrenia patients with negative symptoms entered a 3-month, double blind, randomized, placebo-controlled clinical trial. Subjects were assigned low dose (100 mg per day) or high dose minocycline (200 mg per day) or placebo combined with risperidone. The outcomes used the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS)-negative subscale. We assessed three pro-inflammatory cytokines in serum: interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Subjects receiving high dose minocycline not only had greater improvements on the SANS total scores and PANSS negative subscale scores (P < 0.01), but also had greater reductions in IL-1β and IL-6 serum levels (P ...
Progress in neuro-psychopharmacology & biological psychiatry, Jan 15, 2011
Interactions between smoking and movement disorders include the contrasting associations of more ... more Interactions between smoking and movement disorders include the contrasting associations of more cigarette smoking with reductions in Parkinson's disease and increases in tardive dyskinesia (TD) symptoms. Here we examine the relationship between smoking and TD in a large sample of inpatients with schizophrenia. We used cross-sectional naturalistic methods to analyze the prevalence and severity of neuroleptic-induced TD in relation to cigarette smoking among 764 male chronic and medicated inpatients meeting DSM-IV criteria for schizophrenia. We administered a detailed questionnaire including general information, medical and psychological conditions, and smoking behaviors. We evaluated TD severity using the abnormal involuntary movement scale (AIMS) and psychopathology using the Positive and Negative Syndrome Scale (PANSS). The main statistical analyses used cross-tabulations for the prevalence of TD by smoking and multivariate regression analyses for continuous measures (AIMS and...
The physiological and psychological responses to drug cue exposure have been assessed in substanc... more The physiological and psychological responses to drug cue exposure have been assessed in substance abusers. However, there is no study to demonstrate whether the responses to drug cue exposure are diurnal dependence. The present study was to examine whether there was a variation in drug-related cue reactivity across the diurnal cycle among recently abstinent opiate addicts. Four groups of 20 abstinent heroin dependent patients (n=80) were exposed to both neutral and drug-related videos at four separate times during the day: 8:00, 12:00, 16:00, and 20:00 h. Physiological and psychological responses, including heart rate, blood pressure, heroin craving, and subjective anxiety were assessed before and after each cue exposure. Drug cue significantly increased craving ratings compared to neutral cues across all the four separate times of day. Drug cue-induced craving was greater in the morning (8:00 am) than noon (12:00 pm), but was similar to evening assessments (8 pm). Drug cues also significantly increased anxiety, which positively correlated with cue-induced craving. Drug cues increased heart rate, systolic and diastolic blood pressures, which were not correlated with cue-induced craving or anxiety. However, no time effects were found on the three physiological measures. Cue-induced craving could be profoundly affected by the time points of cue exposure, using cue-reactivity paradigm. The relative sensitivity of morning and evening assessments of drug craving suggests a need for replication and further research on mechanisms contributing to these diurnal variations.
Pharmacotherapy trials for cocaine abuse among methadone-maintained patients have typically repor... more Pharmacotherapy trials for cocaine abuse among methadone-maintained patients have typically reported negative findings as well as high rates of cocaine use during the trial. The contribution of motivational factors to these results is a potentially important, underinvestigated area. This article points out that some methadone-maintained patients may enter a trial for cocaine abuse with little desire for treatment, motivated primarily
Under normal physiological conditions, free-radical-induced oxidative stress is combated by a com... more Under normal physiological conditions, free-radical-induced oxidative stress is combated by a complex antioxidant defense system (Lohr, 1991; Lohr and Browning, 1995; Yao et al., 2001). A major contribution to the total antioxidant capacity comes from antioxidant molecules in plasma. There are several antioxidant molecules in plasma, such as albumin, uric acid and ascorbic acid which account for >85% of the total antioxidant capacity in human plasma (Yao et al., 1998), as well as other antioxidants in blood, e.g., bilirubin, a-tocopherol and b-carotene (Yao et al., 2000; Reddy et al., 2003). Although measuring levels of specific antioxidant molecules can yield valuable information, determination of total antioxidant status (TAS) provides an index of the sum of activities of all antioxidants (Yao et al., 1998). Excessive free radical production leading to increased oxidative stress may be involved in the development of tardive dyskinesia (TD) (Lohr et al., 2003). Studies have shown increased membrane lipid peroxidation and impairment in antioxidant enzyme activity in animal model of TD (Naidu et al., 2003) and in TD patients (Lohr et al., 2003). In our recent study, we reported that patients with TD had lower plasma superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities, but higher plasma levels of malondialdehyde (MDA), a marker of lipid peroxidation (Zhang et al., 2003, 2007), suggesting that oxidative stress is involved in the pathophysiology of TD. However, studies to date have generally been exploratory. Further elucidation of the role of free radicals and antioxidants in TD and its treatment will require systematic investigation. To our knowledge, there is no published study to investigate the total antioxidant capacity in TD. The purposes of the study therefore were to investigate: (1) whether plasma TAS was altered in TD patients; (2) whether there was a relationship between the altered TAS and dyskinetic movements of TD patients. All inpatients satisfied DSM-IV criteria for schizophrenia. TDwas diagnosed using the criteria of Schooler and Kane (1982). The patients with TD (n 1⁄4 38) and those without TD (n 1⁄4 40) were selected from among the inpatients of Beijing Hui-Long-Guan hospital. All patients had been receiving stable dose of oral neuroleptic medications for at least 12 months. Healthy Han Chinese control subjects (n 1⁄4 50) were selectively recruited from the local community, and matched for age and gender. All subjects were Han Chinese from Beijing area. All subjects gave written informed consent approved by the institutional Review Board of the hospital. Fasting plasma TAS was measured using spectrophotometric method in duplicate by using a commercially available kit in all subject samples. Assessments included the abnormal involuntary
Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates... more Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n=57), risperidone (n=23) or typical antipsychotics (n=44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.
Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 wee... more Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Consulting and Clinical Psychology, 1998
In response to a need to match drug users to the most appropriate and cost-effective level of car... more In response to a need to match drug users to the most appropriate and cost-effective level of care, it was hypothesized the socially anxious methadone-maintained patients would attain greater benefit from coping skills training provided in the context of a low-intensity enhanced standard methadone maintenance intervention (E-STD) than in the context of a high-intensity, socially demanding day treatment program (DTP). Social anxiety was assessed in 307 methadone-maintained patients using the Social Anxiety and Distress Scale prior to randomization to either E-STD or DTP. The hypothesis was supported: Socially anxious patients were drug free longer during treatment, were more likely to be abstinent at treatment completion, and had greater reductions in HIV risk behaviors if assigned to the lower intensity intervention, which was provided at 1/3 the cost of the DTP.
Weight gain is a problem commonly encountered with antipsychotic treatment and has become more ap... more Weight gain is a problem commonly encountered with antipsychotic treatment and has become more apparent with increasing use of the newer atypical antipsychotics. The adipocyte-derived hormone, leptin, has been associated with body weight and energy homeostasis, and abnormal regulation of leptin could play a role in weight gain induced by antipsychotics. We investigated whether a leptin gene promoter variant affected weight gain after long-term treatment with clozapine in chronic schizophrenia. Leptin G2548A polymorphism was genotyped in 102 Chinese Han inpatients with chronic schizophrenia treated with clozapine. Weight gains, expressed as change in body mass index (BMI), were monitored after long-term clozapine treatment. We found a significant relationship between the 3 leptin G/A genotypes and mean BMI gain (F(2,99) = 3.35, P = 0.039, r(2) = 0.09). Moreover, genotype had a strong effect on BMI gain in male (P = 0.004, r(2) = 0.16), but not in female patients (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). Thus, variation in the leptin gene may be a risk factor for weight gain in male patients with schizophrenia on long-term clozapine treatment.
Free radical-mediated pathology has been implicated in the development of tardive dyskinesia (TD)... more Free radical-mediated pathology has been implicated in the development of tardive dyskinesia (TD). Antioxidant defense system alterations and increased lipid peroxidation have been postulated as a possible mechanism for neuronal damage associated with TD. However, the relationship between antioxidant enzymes, lipid peroxidation products, and the severity of TD symptoms has not been determined within a single patient group. Plasma levels of malondialdehyde (MDA), a marker of lipid peroxidation, superoxide dismutase, glutathione peroxidase, and catalase were examined in 80 patients with schizophrenia (DSM-IV criteria) and TD (Schooler-Kane criteria) and 45 schizophrenia patients without TD. Results were compared to those of 50 age-, sex-, and smoking status-matched controls. Tardive dyskinesia severity was assessed using the Abnormal Involuntary Movement Scale, and patient psychopathology was assessed using the Positive and Negative Syndrome Scale. Patients with TD had lower plasma superoxide dismutase, glutathione peroxidase, and catalase levels but higher MDA levels than those without TD. In the patients with TD, MDA levels were positively correlated with Abnormal Involuntary Movement Scale total score and with Positive and Negative Syndrome Scale negative subscore. Superoxide dismutase and catalase activities were inversely correlated with MDA levels. Our data support the hypothesis that oxidative stress is involved in the patho-physiology of TD. These data also suggest a relationship between oxidative stress and the severity of dyskinesia in TD patients. Increased lipid peroxidation may likely be a result of decreased endogenous antioxidant enzyme activities in TD.
The authors examined cocaine use in 110 opioid‐dependent cocaine users during a 24‐week, randomiz... more The authors examined cocaine use in 110 opioid‐dependent cocaine users during a 24‐week, randomized, double‐blind clinical trial in which patients were maintained daily on one of the following: 2 mg of buprenorphine, 6 mg of buprenorphine, 35 mg of methadone, or 65 mg of methadone. During the 24‐week trial, cocaine use, as measured by urinalysis and self‐reports, did not differ across medication groups, although opiate use decreased significantly in the methadone groups relative to the buprenorphine groups. These results suggest that buprenorphine, at doses up to 6 mg/day, is not more effective than methadone in decreasing cocaine use in opioid‐dependent cocaine users. (American Journal on Addictions 1994; 3:43–48)
Progress in neuro-psychopharmacology & biological psychiatry, Jan 13, 2018
We attempted to replicate the efficacy of minocycline, a second-generation tetracycline, as adjun... more We attempted to replicate the efficacy of minocycline, a second-generation tetracycline, as adjunctive therapy for the negative symptoms of schizophrenia, and to investigate its association with pro-inflammatory cytokine levels. Seventy-five schizophrenia patients with negative symptoms entered a 3-month, double blind, randomized, placebo-controlled clinical trial. Subjects were assigned low dose (100 mg per day) or high dose minocycline (200 mg per day) or placebo combined with risperidone. The outcomes used the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS)-negative subscale. We assessed three pro-inflammatory cytokines in serum: interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Subjects receiving high dose minocycline not only had greater improvements on the SANS total scores and PANSS negative subscale scores (P < 0.01), but also had greater reductions in IL-1β and IL-6 serum levels (P ...
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