Amy Harrington

Elevated levels of adiponectin and other cytokines in drug naïve, first episode schizophrenia patients with normal weight☆

OBJECTIVE The study was to examine the levels of adiponectin (APN) and other cytokines, and body metabolism in drug naïve, first episode schizophrenia patients with normal weight. METHODS Ninety-six drug naïve, first episode schizophrenia patients with normal weight (SZ group), 60 healthy individuals with normal weight (control group), and 60 overweight or obese but otherwise healthy individuals (obesity group) were enrolled in the study. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and APN were measured using enzyme linked immunosorbent assay (ELISA). Glucose oxidase was used to measure plasma glucose level. Lipid levels were measured using the enzymatic colorimetric method. RESULTS Serum levels of IL-1β, IL-6 and TNF-α in both the SZ group and the obesity group were significantly higher than those in the control group (ps<0.001). There were no significant differences between the SZ group and the obesity group on those cytokines (ps>0.05). In addition, the levels of APN were significantly higher in the SZ group (p<0.001), and significantly lower in the obesity group (p<0.01) compared with the control group. Further, there were significant positive relationships between levels of APN and levels of other cytokines within the SZ group (ps<0.05); in contrast, there were significant negative relationships between levels of APN and levels of other cytokines within the obesity group (ps<0.05). Fasting serum levels of glucose, LDL, triglycerides and total cholesterol were significantly higher, and fasting serum levels of HDL were significantly lower in the obesity group compared with the other two groups (ps<0.01). There were no significant differences in any of the metabolic parameters between the control group and the SZ group (ps>0.05). CONCLUSIONS Drug naïve, first episode schizophrenia patients with normal weight seem to present an up-regulated inflammatory status as reflected by elevated levels of IL-1β, IL-6, and TNF-α. APN may play a unique pro-inflammatory role in this patient population. Implications of the findings in relation to the pathogenesis of schizophrenia and the vulnerability for metabolic problems were discussed.

Activation of Th17 cells in drug naïve, first episode schizophrenia.

OBJECTIVE The present study was to examine the role of pro-inflammatory T helper 17 (Th17) cells in drug naïve, first episode schizophrenia. METHOD Patients with normal weight, drug naïve, first episode schizophrenia and healthy controls were enrolled in the study. Flow cytometric analysis was performed to analyze the proportion of Th17 cells among the CD4(+) T cells. Plasma levels of interleukin-17 (IL-17), interferon-γ (IFN-γ) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). All measures were repeated for the patient group after 4 weeks of risperidone treatment. RESULTS Sixty-nine patients with normal weight, drug naïve, first episode schizophrenia and 60 healthy controls were enrolled. At baseline, the patient group hadz significantly higher proportions of Th17 cells and plasma levels of IFN-γ and IL-6 compared with the control group (ps<0.01). Within the patient group, there were significant positive relationships between the proportion of Th17 cells, plasma levels of IL-17, IFN-γ, IL-6 and the PANSS total score after controlling for potential confounding variables (ps<0.05). After 4weeks of risperidone treatment, the proportion of Th17 cells decreased significantly (p <0.001), and there was a significant positive relationship between the PANSS total score change rate and the change in proportion of Th17 cells (p = 0.039). CONCLUSIONS Patients with normal weight, drug naïve, first episode schizophrenia present activation of Th17 cells, which might be associated with therapeutic response after risperidone treatment.

Decreased cortical thickness in drug naïve first episode schizophrenia: In relation to serum levels of BDNF

This study was to examine cortical thickness in drug naïve, first episode schizophrenia patients, and to explore its relationship with serum levels of brain-derived neurotrophic factor (BDNF). Forty-five drug naive schizophrenia patients and 28 healthy controls were enrolled in the study. Freesurfer was used to parcellate cortical regions, and vertex-wise group analysis was used for whole brain cortical thickness. The clusters for the brain regions that demonstrated group differences were extracted, and the mean values of thickness were calculated. Serum levels of BDNF were measured using enzyme-linked immunosorbent assay (ELISA). After controlling for age and gender, significantly thinner cortical thickness was found in left insula and superior temporal gyrus in the patient group compared with the healthy control group (HC group) (ps < 0.001). Lower serum levels of BDNF were also found in the patient group compared with the HC group (p = 0.001). Correlation analysis showed a significant positive relationship between thickness of left insula and serum levels of BDNF within the HC group (r = 0.396, p = 0.037) but there was no such relationship within the patient group (r = 0.035, p = 0.819). Cortical thinning is present in drug naïve, first episode schizophrenia patients, indicating neurodevelopmental abnormalities at the onset of schizophrenia. Left insula might be an imaging biomarker in detecting the impaired protective role of neurotrophic factor for the brain development in schizophrenia.

Prolactin serum levels correlate with inflammatory status in drug-naïve first-episode schizophrenia

Abstract Objectives. The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naïve, first-episode schizophrenia patients with normal weight. Methods. Patients with normal weight, drug-naïve, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Results. Sixty patients with normal weight, drug-naïve, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1β, IL-6 and TNF-α compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1β, IL-6 and TNF-α within the schizophrenia group. Within the schizophrenia group, TNF-α was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. Conclusions. Patients with normal weight, drug-naïve, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.

Hippocampal volume reduction in female but not male recent abstinent methamphetamine users

Growing evidence suggests abnormalities in brain morphology including hippocampal structure in patients with methamphetamine (MA) dependence. This study was performed to examine hippocampal volume in abstinent MA users, and to further explore its relationship with cognitive function. 30 abstinent MA users (20 males and 10 females) with average 5.52 months of duration of abstinence and 29 healthy controls (19 males and 10 females) age 18-45 years old were recruited for clinical assessment and imaging scan. FreeSurfer was used to segment the hippocampus bilaterally, and hippocampal volumes were extracted for group and gender comparisons. Cognitive function was measured using the CogState Battery Chinese language version (CSB-C). Analysis of covariance (ANCOVA) controlling for education showed a significant group by gender interaction for the right hippocampal relative volume adjusted for total brain size (p = 0.020); there was a significant difference between male controls and female controls (p < 0.001), but such a difference did not exist between male patients and female patients (p = 0.203). No significant correlations were found between hippocampal volume and cognitive measures. There seems to be a gender difference in how MA affects hippocampal volume in abstinent MA users. Hippocampus might be an important treatment target for cognitive improvement and functional recovery in this patient population, especially in females.

Racial disparity in mental disorder diagnosis and treatment between non-hispanic White and Asian American patients in a general hospital

PURPOSE The present study sought to examine the diagnosis and treatment of mental disorders comparing Asian American (AA) and non-Hispanic Whites (WNH) drawn from a population accessing a large general hospital for any reason. Socio-demographic predictors of diagnosis and treatment were also explored. METHODS Data were obtained from de-identified medical records in the Partner Health Care Systems Research Patient Data Registry. RESULTS The final sample included 345,070 self-identified WNH and 16,418 self-identified AAs between January 1, 2009 and December 31, 2009. WNH patients were more likely than AA patients to carry a diagnosis of a mental disorder (18.1% vs. 8.6%, p < 0.0001) and were more likely to receive psychotropic medication treatment (15.0% vs 8.5%, p < 0.0001). Logistic regression analyses of the AA cohort identified several risk factors (i.e. language, religion, gender, age) predicting the diagnosis of a mental disorder or use of psychotropic medication. CONCLUSIONS Our findings on the racial disparity in mental disorder diagnosis and treatment between AA and WNH patients suggest that mental disorders are under-recognized and mental health services are under-utilized in the AA community. There remains a need for health care providers to improve screening services and to gain a better understanding of the cultural barriers that hinder mental health care among AA patients.

Relationship between serum uric acid level and cardiometabolic risks in nondiabetic patients with schizophrenia.

This study examined the relationship between serum levels of uric acid and insulin resistance and metabolic syndrome in nondiabetic patients with schizophrenia. Outpatients diagnosed with schizophrenia or schizoaffective disorder participated in a multicenter, cross-sectional study. Fasting blood samples were obtained to determine serum levels of metabolic measures. A total of 135 patients were recruited for the study. A significant positive relationship was found between serum levels of uric acid and the homeostasis model of assessing insulin resistance (log transformed, r=0.394, P<0.001), and a significant negative relationship was found between serum levels of uric acid and low-density lipoprotein particle size (log transformed, r=−0.306, P=0.001) after controlling for potential confounding variables. Hierarchical multiple regression suggested that serum uric acid level is a significant predictor of insulin resistance (P=0.001) and of low-density lipoprotein particle size (P<0.015). Further, logistic regression showed that serum uric acid levels strongly predicted the condition of metabolic syndrome (odds ratio 0.630, 95% confidence interval 0.463–0.856, P=0.003). This study suggested that uric acid may be a clinically useful biomarker to indicate cardiometabolic risks in nondiabetic patients with schizophrenia.

Phenotypic characteristics in metabolically healthy but obese patients with schizophrenia

The purpose of this study was to characterize phenotypic characteristics of metabolically healthy but obese individuals with schizophrenia. Participants were non-diabetic outpatients 19 to 75 years old diagnosed with schizophrenia or schizoaffective disorder. Obese patients (body mass index (BMI)>30 kg/m(2)) were included in the present analysis. Patients were further defined as metabolically healthy but obese or obese individuals with metabolic abnormalities based on a cut-off value of 2.5 using the homeostasis model assessment of insulin resistance (HOMA-IR). Fasting blood samples were collected to determine levels of various metabolic parameters. Lipoprotein subclass concentrations and sizes were analyzed using nuclear magnetic resonance (NMR) spectroscopy. Fourteen metabolically healthy but obese patients and 62 obese patients with metabolic abnormalities were identified from 206 patients with schizophrenia. After controlling for age, there were no significant differences between the two groups on anthropometric measures. However, the metabolically healthy but obese group had significantly lower levels of large VLDL particle, significantly higher levels of intermediate VLDL particle, and significantly smaller mean particle size in VLDL compared with the obese group with metabolic abnormalities (metabolically obese). A metabolically healthy but obese phenotype characterized by high levels of intermediate VLDL particle and low levels of large VLDL particle exists in obese, non-diabetic patients with schizophrenia.