Biomedical subjects

David C Henderson

Publications and source records attributed to David C Henderson.

At least 19 recordsLinked to original sources

PubMed2006

Elevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia.

The present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRP<or=0.50 mg/dl, normal CRP group, N=21) on the PANSS total score, negative symptom subscale score and general psychopathology subscale score. There was no significant difference between the two groups on the PANSS positive symptom subscale score. An inflammatory process, as reflected by elevated serum levels of CRP, might be associated with more severe psychopathology in a subgroup of patients with schizophrenia.

Adolescent↗

PubMed2006

Higher fasting serum insulin is associated with increased resting energy expenditure in nondiabetic schizophrenia patients.

BACKGROUND: Insulin has emerged as an important determinant of food intake, energy expenditure, and weight control. This study examined the relationship between fasting serum insulin level and resting energy expenditure (REE) in a cross-sectional sample of nondiabetic schizophrenia patients. METHODS: Subjects were recruited from an urban community mental health clinic. Each subject underwent a series of anthropometric measures and an indirect calorimetry measure. A fasting blood sample was taken for plasma glucose, serum insulin, and lipid profile. RESULTS: Seventy-one subjects (54 male, 17 female) were included in the study. There was a significant positive relationship between REE and fasting serum insulin level (r = .39, p = .001). Stepwise multiple regression analysis was performed with various characteristics such as age, race, antipsychotic agent used, fat-free mass, BMI, waist circumference, waist-hip ratio, physical activity level, and fasting serum insulin as candidate predictors for REE. Only fat-free mass and insulin were able to enter into the regression model, which indicates that higher fat-free mass and higher fasting serum insulin level predict increased REE. CONCLUSIONS: A higher fasting serum insulin level is associated with an increased REE, which may prevent further weight gain in nondiabetic patients with schizophrenia.

Adult↗

PubMed2006

Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia.

OBJECTIVE: Recent studies have suggested a beneficial role of insulin on brain function and psychological well-being. This study was undertaken to examine whether fasting serum insulin levels are associated with the psychopathology profile in a cross-sectional sample of acutely ill non-diabetic inpatients with schizophrenia. METHODS: Subjects were recruited from a county hospital. Each subject underwent a psychopathology assessment with the Positive and Negative Syndrome Scale (PANSS). A fasting blood sample was taken to measure serum insulin, plasma glucose and lipids. RESULTS: Twenty-six subjects (7 females, 19 males) were included in the study. Pearson correlation analysis showed significant inverse relationships between serum insulin level and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores (r=-0.41, p=0.037; r=-0.49, p=0.010; r=-0.45, p=0.023, respectively). However, there was no significant relationship between serum insulin level and PANSS-Negative Symptom subscale score (r=-0.13, p=0.53). Partial correlation analysis showed that the inverse relationships between serum insulin levels and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores became even stronger after controlling for potential confounding variables including age, gender, race, family history of mental illness, age of illness onset and body-mass index (BMI). CONCLUSIONS: Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia. It is speculated that insulin might improve clinical symptoms of schizophrenia by interacting with dopamine and other neurotransmitter systems.

Adult↗

PubMed2006

RAGGED SEEDLING2 is required for expression of KANADI2 and REVOLUTA homologues in the maize shoot apex.

The anatomy of ragged seedling2-R (rgd2-R) leaves is disorganized along the adaxial/abaxial axis. Mutant leaves often exhibit radial morphology but unlike similar mutants, rgd2-R radial leaves have no reduction of adaxial or abaxial identity. Previously, we proposed that RGD2 does not establish adaxial or abaxial fate but performs a signaling function during primordial leaf development. Here we describe genetic and molecular tests of our model for RGD2 function. Genetic analyses explored the phenotypic effects of rgd2-R on maize leaf mutations disrupting mediolateral and/or dorsiventral development. In situ hybridization and qRT-PCR analyses reveal that rgd2-R mutants show reduced accumulation of adaxial and abaxial molecular markers in the maize shoot apex. These data contribute to a revised model whereby RGD2 is required for normal accumulation of leaf patterning transcripts in the developing shoot. Molecular and genetic analyses suggest that RGD2 and LEAF BLADELESS1 share overlapping functions affecting shoot development in maize.

Biomarkers↗

PubMed2006

Treatment of cardiac risk factors among patients with schizophrenia and diabetes.

OBJECTIVE: The appropriateness and effectiveness of the outpatient medical management of cardiac risk factors for patients with diabetes who had a diagnosis of schizophrenia or a related psychotic syndrome were examined. METHODS: In a cross-sectional analysis of 4,236 patients with diabetes, ICD-9 billing codes were used to identify 214 patients with schizophrenia or a schizophrenia-related syndrome. Measures of treatment appropriateness and effectiveness for the management of cardiac risk factors (control of blood sugar, blood pressure, and lipids) were assessed for this group and compared with measures from patients with diabetes but no severe mental illness (N = 3,594). Odds ratios were adjusted for between-group differences in gender, race, age, and clinic setting. RESULTS: There were no statistically significant between-group differences on any of the five measures of treatment appropriateness, indicating that patients with schizophrenia received a similar regimen of medical treatment for cardiac factors. However, two of the seven measures of treatment effectiveness indicated significant deficiencies, with fewer patients with schizophrenia meeting the clinical quality benchmarks for cholesterol and low-density lipoprotein control. This disparity may have been caused by factors other than the measured treatment appropriateness variables, including the prescription of older lipid-lowering agents and a higher rate of missed appointments in the group with schizophrenia. CONCLUSIONS: Effective lipid control may be more difficult to attain for at least some patients with schizophrenia. Given that population's high rates of cardiovascular mortality, additional research to clarify the barriers to effective lipid management is essential.

Aged↗

PubMed2006

Glucose metabolism in patients with schizophrenia treated with olanzapine or quetiapine: a frequently sampled intravenous glucose tolerance test and minimal model analysis.

OBJECTIVE: Clozapine and olanzapine treatment has been associated with insulin resistance in non-obese schizophrenia patients. Much less is known regarding other agents such as quetiapine. The objective of this study was to compare matched olanzapine- and quetiapine-treated schizophrenia patients and normal controls on measures of glucose metabolism. METHOD: A cross-sectional comparison of quetiapine-treated and olanzapine-treated non-obese (body mass index < 30.0 kg/m2) schizophrenia subjects (DSM-IV) with matched normal controls using a frequently sampled intravenous glucose tolerance test and nutritional assessment was conducted from April 2002 to October 2004. Data from 24 subjects were included in the analysis (7 quetiapine, 8 olanzapine, 9 normal controls). RESULTS: There was a significant difference among groups for fasting baseline plasma glucose concentrations (p = .02), with olanzapine greater than normal controls (p = .01). The insulin sensitivity index (SI) differed significantly among groups (p = .039); olanzapine subjects exhibited significant insulin resistance compared to normal controls (p = .01), but there was no significant difference for quetiapine versus olanzapine (p = .1) or quetiapine versus normal controls (p = .40). SI inversely correlated with quetiapine dose (p = .0001) and waist circumference (p = .03) in quetiapine-treated subjects. Insulin resistance calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) also differed significantly among groups (p = .03). The olanzapine group had a higher HOMA-IR level than normal controls (p = .01). There was a significant difference in glucose effectiveness (SG) among the groups (p = .049). SG was lower in the olanzapine group than in the quetiapine group (p = .03) and in the olanzapine group compared to normal controls (p = .049). CONCLUSIONS: Our findings are consistent with our previous report that nonobese olanzapine-treated subjects showed insulin resistance, measured by both HOMA-IR and SI, and reduction in SG. Studies that include larger samples, unmedicated patients, and varying durations of antipsychotic exposure are necessary to confirm these results.

Adult↗

PubMed2005

Added donepezil for stable schizophrenia: a double-blind, placebo-controlled trial.

RATIONALE: Schizophrenia is a disorder with cognitive deficits that could stem from cholinergic dysfunction. OBJECTIVES: Our aim was to examine if donepezil administered to stable, medicated outpatients with schizophrenia improves cognition and psychopathology. METHODS: We conducted a double-blind placebo-controlled trial of donepezil up to 10 mg/day added for 8 weeks to ongoing antipsychotic treatment in 36 typical community-treated schizophrenia patients not selected for cognitive impairment. RESULTS: Donepezil did not improve measures of cognition or psychopathology. It was well tolerated. CONCLUSION: Consistent with other studies, addition of donepezil to stable patients with schizophrenia did not improve cognition or measures of psychopathology. This result does not support the hypothesis that residual symptoms and cognitive problems result from a cholinergic deficit that can be remedied by an acetylcholinesterase inhibitor. A donepezil add-on strategy might make sense in selected schizophrenia cases where a pathological process is known to affect cholinergic neurons (e.g., history of head injury or comorbid dementia).

Capsules↗

PubMed2005

Radial leaves of the maize mutant ragged seedling2 retain dorsiventral anatomy.

ragged seedling2 (rgd2) is a novel, recessive mutation affecting lateral organ development in maize. The mutant phenotype of homozygous rgd2-R leaves is variable. Mild leaf phenotypes have a reduced midrib and may be moderately narrow and furcated; severe Rgd2-R(-) leaves are filamentous or even radial. Despite their radial morphology, severe Rgd2-R(-) mutant leaves develop distinct adaxial and abaxial anatomical features. Although Rgd2-R(-) mutants exhibit no reduction in adaxial or abaxial cell types, areas of epidermal cell swapping may occur that are associated with misaligned vascular bundles and outgrowths of ectopic margins. Scanning electron microscopy of young primordia and analyses of leaf developmental-marker gene expression in mutant apices reveal that RGD2 functions during recruitment of leaf founder cells and during expansive growth of leaf primordia. Overall, these phenotypes suggest that development is uncoordinated in Rgd2-R(-) mutant leaves, so that leaf components and tissues may develop quasi-independently. Models whereby RGD2 is required for developmental signaling during the initiation, anatomical patterning, and lateral expansion of maize leaves are discussed.

Gene Expression Regulation, Developmental↗

PubMed2005

Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis.

BACKGROUND: While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes. OBJECTIVE: To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test. DESIGN: A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis. SETTING: Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center. Patients Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis. MAIN OUTCOME MEASURES: Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness. RESULTS: The mean +/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +/- 28.9 months (clozapine), 29.5 +/- 17.5 months (olanzapine), and 40.9 +/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F(33) = 3.35; P = .047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33) = 2.32; P = .03) and olanzapine and risperidone (t(33) = 2.15; P = .04). There was a significant difference in insulin sensitivity index among groups (F(33) = 10.66; P<.001) (clozapine olanzapine>risperidone) (clozapine vs risperidone, t(33) = 2.94; P = .006; olanzapine vs risperidone, t(33) = 2.42; P = .02). There was a significant difference among groups in glucose effectiveness (F(30) = 4.18; P = .02) (clozapine<olanzapine<risperidone) with significant differences between clozapine and risperidone (t(30) = -2.59; P = .02) and olanzapine and risperidone (t(30) = -2.34, P = .03). CONCLUSIONS: Both nonobese clozapine- and olanzapine-treated groups displayed significant insulin resistance and impairment of glucose effectiveness compared with risperidone-treated subjects. Patients taking clozapine and olanzapine must be examined for insulin resistance and its consequences.

Adult↗

PubMed2005

A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia.

The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia. Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers, enrolled in a 12-week group cognitive behavioral therapy intervention, and randomly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo. Fifty-three adults, 25 on bupropion and 28 on placebo, were randomized, completed at least 1 postbaseline assessment and were included in the analysis. The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date (week 4) and at the end of the intervention (week 12). Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date (36% [9/25] vs. 7% [2/28], P = 0.016) and at end of the intervention (16% [4/25] vs. 0%, P = 0.043). Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence (weeks 8-12) (16% [4/25] vs. 0%, P = 0.043) and a longer duration of abstinence (4.2 [3.2] weeks vs. 1.8 [0.96] weeks, t = 2.30, P = 0.037). The effect of bupropion did not persist after discontinuation of treatment. Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms. We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia. The relapse rate is high after treatment discontinuation.

Adult↗

PubMed2005

Building primary care practitioners' attitudes and confidence in mental health skills in a post-conflict society: a Cambodian example.

Our program attempted to integrate community mental health in primary care settings in Cambodia and to evaluate the effects of training on local providers. The training program underwent an extensive evaluation to determine its impact on the mental health knowledge, confidence in performing medical and psychiatric procedures, skills and attitudes of its trainees. One hundred four Cambodian primary care practitioners (PCPs) were trained in a primary care setting in Siem Reap, Cambodia, over a 2-year period. There was a significant improvement in PCPs' confidence in all clusters of medical and psychiatric procedures (counseling, medical evaluation, prescribing medications, psychiatric diagnosis, assessing risk for violence, traditional treatments, and treating trauma victims) comparing baseline to posttraining and baseline to 2-year follow-up (p < 0.05). Only confidence in prescribing psychotropic medications improved from posttraining to 2-year follow-up. This study supports the feasibility of training PCPs in a culturally effective manner in a postconflict society.

Adult↗

PubMed2005

A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain.

OBJECTIVE: Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder. METHOD: Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of >/=30 kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification. RESULTS: The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group. CONCLUSIONS: Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.

Adult↗

PubMed2005

Medical morbidity and mortality in schizophrenia: guidelines for psychiatrists.

BACKGROUND: Medical morbidity and mortality rates remain elevated in schizophrenia patients compared with the general population, in part due to potentially reversible medical risk factors. Psychiatrists should address this problem by adopting established strategies for prevention and intervention. METHOD: The literature on modifiable medical risk factors relevant to individuals with schizophrenia and corresponding guidelines for prevention and treatment established by expert consensus panels were reviewed. RESULTS: Schizophrenia patients are at elevated risk for cardiovascular disease due to high rates of cigarette smoking and, increasingly, due to obesity, diabetes, and hypertriglyceridemia. Rates of human immunodeficiency virus infection and infectious hepatitis are also higher in schizophrenia patients. Interventions that have reduced medical morbidity in the general population can be adopted to reduce premature mortality in individuals with schizophrenia. CONCLUSIONS: Patients with schizophrenia have high rates of potentially reversible medical morbidity. Implementation of practice guidelines for identifying and modifying risk factors could substantially improve the health of patients with schizophrenia.

Adult↗

PubMed2005

Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: results of a 10-year naturalistic study.

OBJECTIVE: The goal of this 10-year naturalistic study was to examine, in clozapine-treated patients, the change in cardiovascular risk factors following clozapine initiation and the mortality estimates from cardiovascular disease. METHOD: Data were collected from medical records from January 1992 to December 2003 and included age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation for clozapine-treated patients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Clozapine dosage and laboratory results were recorded at 12-month intervals. RESULTS: At the time of clozapine initiation, the mean +/-?SD age of the 96 patients studied was 36.5 +/- 7.9 years; 28% (N = 27) were women. The Kaplan-Meier estimate for 10-year mortality from cardiovascular disease was 9%. African American and Hispanic American patients exhibited elevated risk of cardiovascular disease-related mortality (odds ratio [OR] = 7.2, p = .09; OR = 11.3, p = .04, respectively) compared to white patients. Body mass index (BMI) significantly increased the odds ratio of mortality (OR = 1.2, p < .01). The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43%, and Hispanic American (OR = 4.3, p = .027) and African American (OR = 11.5, p = .0001) patients showed elevated risks of developing diabetes mellitus compared to white patients. Additionally, BMI (OR = 1.11, p = .0006), total cholesterol level (OR = 1.006, p = .04), and serum triglyceride level (OR = 1.002, p = .04) modestly increased the odds ratio for the development of diabetes mellitus. CONCLUSIONS: These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia.

Adult↗

PubMed2005

Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia.

OBJECTIVE: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation. METHOD: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function. RESULTS: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT. CONCLUSION: We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention.

Adult↗

PubMed2005

Schizophrenia and comorbid metabolic disorders.

Comorbid metabolic disorders in patients with schizophrenia are underrecognized by many health care professionals and patients. That lack of awareness can contribute to serious morbidity and mortality in patients with schizophrenia. Patients with schizophrenia may be at greater risk for metabolic disorders such as insulin resistance, lipid abnormalities, and weight gain. In addition, although the use of atypical antipsychotics in the treatment of schizophrenia offers many positive benefits and may reduce some of the factors related to the morbidity and mortality of the disorder, these drugs appear to be associated with varying degrees of comorbid metabolic disorders, such as metabolic syndrome, and more serious consequences, such as cardiovascular disease. Recent consensus guidelines recommend that metabolic risks be considered when initiating therapy with atypical antipsychotics. Thus, baseline screening and routine monitoring of patient weight, fasting lipid profile, and fasting plasma glucose are essential. In addition, optimal treatment for patients with schizophrenia and comorbid metabolic disorders is best achieved when all parties involved with patient care (mental health and medical community, caregiver/family, and patient) communicate and work together. With proper awareness and cooperation on the part of the medical community, caregivers, and patients, the detrimental consequences that may result from the metabolic disorders addressed in this article can be at least partially offset.

Antipsychotic Agents↗

PubMed2004

A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients.

RATIONALE: D-Cycloserine, a partial agonist at the glycine site of the N-methyl-D-aspartate receptor, has demonstrated inconsistent efficacy for negative and cognitive symptoms of schizophrenia. The strongest evidence for efficacy has come from studies using D-cycloserine at a dose of 50 mg/day added to conventional antipsychotics in trials of 8 weeks duration or less. OBJECTIVE: To assess the efficacy for negative symptoms and cognitive impairment of D-cycloserine augmentation of conventional antipsychotics in a 6-month trial. METHODS: Fifty-five schizophrenia patients with prominent negative symptoms, treated with conventional antipsychotics, were randomly assigned to treatment with D-cycloserine 50 mg/day or placebo for 6 months in a double-blind, parallel group design. RESULTS: Twenty-six subjects completed the 6-month trial; drop-out rates did not differ between treatment groups. D-Cycloserine treatment did not differ from placebo treatment on any primary outcome measure at 8 or 24 weeks, including response of negative symptoms and performance on a cognitive battery. Serum D-cycloserine concentrations did not correlate with response of negative symptoms. CONCLUSION: D-Cycloserine did not exhibit therapeutic effects in this trial, possibly reflecting the high drop-out rate, a narrow range of therapeutic serum concentrations, a modest magnitude of therapeutic effect for the selected outcome measures, or loss of efficacy over time. Because D-cycloserine is a partial agonist with relatively low affinity for the glycine site, the magnitude of potential therapeutic effect may be smaller than that achieved by the higher-affinity full agonists, glycine and D-serine.

Adult↗

PubMed2004

Folate, homocysteine, and negative symptoms in schizophrenia.

OBJECTIVE: Because glutamate carboxypeptidase II (GCPII) regulates both folate absorption and activation of N-methyl-d-aspartic acid receptors, the authors examined relationships between serum folate concentrations and clinical symptoms in schizophrenia patients. METHOD: For 91 outpatients with schizophrenia, clinical assessments were performed and serum folate, homocysteine, B(12), glycine, and serine concentrations were measured. RESULTS: Serum folate concentrations were significantly lower than in a representative sample from the Framingham Offspring Study. Folate concentration correlated inversely with the Scale for Assessment of Negative Symptoms total score and was lower in patients with the deficit syndrome than in nondeficit patients. Homocysteine concentration correlated with the severity of extrapyramidal symptoms. CONCLUSIONS: These findings could reflect several possible mechanisms, including low dietary intake of folate, low GCPII activity, cigarette smoking, and the involvement of folate in the synthesis of neurotransmitters. Additional studies are needed to clarify these findings.

Adult↗