Nutrition and Exercise for Wellness and Recovery: A Randomized Controlled Trial of a Community-Based Health Intervention.

OBJECTIVE: The purpose of this study was to examine the efficacy of the Nutrition and Exercise for Wellness and Recovery (NEW-R) intervention for improving competency and behaviors related to diet, physical activity, and weight management. METHODS: Participants with psychiatric disabilities were recruited from four community mental health agencies and a hospital-based psychiatric outpatient clinic and randomly assigned to the NEW-R intervention (N=55) or control condition (N=58). Outcome measures included the Perceived Competence Scale, Health-Promoting Lifestyle Profile (HPLP), and weight change; random-effects regression models were used. A follow-up analysis examined the interactions of group, time, and site. RESULTS: Fifty of the 55 intervention participants and 57 of the 58 control participants completed the study. The two groups did not differ significantly on any measured baseline characteristic. The intervention group had statistically significant improvements, compared with the control group, in perceived competence for exercise and healthy eating, total HPLP score, and scores on two HPLP subscales (nutrition and spiritual growth). No significant difference between groups was found for weight loss. A study condition × time × site effect was observed: at the three sites where mean weight loss occurred, NEW-R participants lost significantly more weight than did control participants. CONCLUSIONS: NEW-R offers promise as an intervention that can initiate the change to healthy lifestyle behaviors and boost perceived competence in a healthy lifestyle. It may also be effective for weight loss when administered in supportive settings.

Treatment with the antipsychotic risperidone is associated with increased M1-like JAK-STAT1 signature gene expression in PBMCs from participants with psychosis and THP-1 monocytes and macrophages.

Clinical studies demonstrate alterations to immune measures in psychosis that can vary with illness stage and severity. For example, recent data show that changes to the JAK-STAT1 transcriptional signature, characteristic of an "M1" proinflammatory monocyte and macrophages phenotype, are related to illness duration. While antipsychotics have demonstrated immunomodulatory properties, their effects on this important immune signaling pathway are unknown. The primary aims of this study were to determine the effects of risperidone, a commonly prescribed antipsychotic drug, on the JAK-STAT1 transcriptional signature. Selected measures of JAK-STAT1 signature gene expression in peripheral blood mononuclear cells (PBMCs) from a clinical sample with psychosis were compared to examine differences induced by risperidone treatment. Additionally, the direct effects of risperidone on the JAK-STAT1 signature were investigated using a THP-1 human monocyte and macrophage cell model. Comparisons within the clinical sample demonstrated that the JAK-STAT1 signature was elevated in PBMCs from participants treated with risperidone who had a longer illness duration compared to untreated participants and those who were risperidone treated but had a shorter illness duration. Results of the in-vitro experiments showed a consistent potentiating effect of risperidone on expression of JAK-STAT1 signature genes in activated monocytes and monocyte-derived macrophages. Collectively these data indicate that risperidone may skew myeloid cells to a more proinflammatory phenotype, potentially contributing to increases in expression of JAK-STAT1 signature genes in participants with a longer illness duration.

Long non-coding and endogenous retroviral RNA levels are associated with proinflammatory cytokine mRNA expression in peripheral blood cells: Implications for schizophrenia.

Recent research indicates that the expression of long non-coding and endogenous retroviral RNAs is coordinated with the activity of immune molecules often dysregulated in schizophrenia. We measured the expression of TMEVPG1, NRON, HERV-W env and HERV-W gag in blood cells from participants with schizophrenia and controls. We report that a) expression levels of these non-coding RNAs are correlated with proinflammatory cytokine mRNA expression in all participants, b) HERV-W transcripts are negatively correlated with atypical antipsychotic use in participants with schizophrenia, and c) that these RNAs are transcribed in response to proinflammatory stimuli in a THP-1 monocyte cell line.

The value of interleukin 6 as a peripheral diagnostic marker in schizophrenia.

BACKGROUND: Associations between a pro-inflammatory state and schizophrenia have been one of the more enduring findings of psychiatry, with various lines of evidence suggesting a compelling role for IL-6 in the underlying pathogenesis of schizophrenia. METHODS: In this study, we examined IL-6 mRNA levels by real-time RT-PCR from fresh extracted peripheral blood mononuclear cells (PBMC) in normal controls and participants with schizophrenia. RESULTS: We found that peripheral PBMC IL-6 mRNA levels, in the absence of any other information, reliably discriminated between a diagnosis of schizophrenia and normal controls. Furthermore, in participants with schizophrenia, we also found elevated levels of IL-6 mRNA with earlier ages of illness onset and worse positive symptom presentation, as measured by the Positive and Negative Syndrome Scale. CONCLUSIONS: These findings provide important and continued support for a pathophysiological role of inflammation in patients with schizophrenia. Future utilization of peripheral IL-6 mRNA levels could be clinically useful during an initial diagnosis and help tailor individualized treatment plans for patients with schizophrenia.

Evidence of a sex-dependent restrictive epigenome in schizophrenia.

When compared to women, men have a higher incidence of schizophrenia, with increases in negative and cognitive symptoms, and an overall poorer disease course. Schizophrenia is conceptualized as a disorder of aberrant gene transcription and regulation. Thus, epigenetics, the study of environmentally induced changes in gene regulation, could advance our understanding of the molecular underpinnings of schizophrenia. Peripheral histone methyltransferase (HMT) mRNA levels have been previously shown to be significantly increased in patients with schizophrenia and correlate with symptomology. In this independent study, peripheral lymphocytes were extracted and clinical symptoms were measured on 74 participants, (40 patients with schizophrenia (19 women, 21 men) and 34 healthy individuals (19 women, 15 men)). HMT (G9α, SETDB1 and GLP) mRNA levels and their resulting histone modification H3K9me2 were measured with RT-PCR and ELISA respectively. Plasma estradiol levels were also measured via ELISA and correlated with HMT mRNA. Clinical symptoms were measured utilizing the Positive and Negative Syndrome Scale (PANSS) and the Heinrichs Carpenter Quality of Life Scale (QLS). The results indicate that men with schizophrenia expressed the highest levels of G9α, SETDB1 mRNA and H3K9me2 protein levels. Additionally, higher levels of symptom presentation and an overall poorer quality of life were correlated with higher HMT mRNA and H3K9me2 protein levels in a sex-dependent pattern. These data support the hypothesis of a sex-dependent restrictive epigenome contributing towards the etiology of schizophrenia. The histone methyltransferases measured here could be potential future therapeutic targets for small molecule pharmacology.

Metabolic and inflammatory genes in schizophrenia.

Energy metabolism and immunity are characterized as abnormal in schizophrenia. Because these two systems are highly coordinated, we measured expression of prototypic obesogenic and immunogenic genes in freshly harvested PBMC from controls and participants with schizophrenia. We report significant increases in PPARγ, SREBP1, IL-6 and TNFα, and decreases in PPARα and C/EPBα and mRNA levels from patients with schizophrenia, with additional BMI interactions, characterizing dysregulation of genes relating to metabolic-inflammation in schizophrenia.

Treatment settings and metabolic monitoring for people experiencing first-episode psychosis.

Monitoring for metabolic sequelae of antipsychotic medications is inconsistent in clinical settings. In this study, frequency of such monitoring in 40 individuals experiencing a first episode of psychosis was analyzed according to the setting in which they received treatment (i.e., inpatient unit, outpatient clinic, or metabolic screening clinic). The traditional outpatient clinic was the least likely of the three settings to monitor blood glucose, blood pressure, weight, and waist circumference. In any setting, blood lipids were measured in only 2 of the 40 patients. Reasons for these findings and recommendations for reducing barriers to screening are presented.

Assessment of a point-of-care metabolic risk screening program in outpatients receiving antipsychotic agents.

STUDY OBJECTIVE: To assess the usefulness of a metabolic risk screening program, including point-of-care glucose testing, to quantify baseline metabolic risk in outpatients receiving antipsychotics. DESIGN: Retrospective, cross-sectional, cohort study. SETTING: University-affiliated department of psychiatry clinic. PATIENTS: A total of 92 adult outpatients (49 women, 43 men; mean +/- SD age 38.96 +/- 12 yrs) who were receiving antipsychotics and had undergone screening for metabolic syndrome at the clinic during 2004-2007. MEASUREMENTS AND MAIN RESULTS: Patient data were recorded on a metabolic screening checklist by a pharmacist or nurse. The checklist captured demographics, vital signs (height, weight, body mass index [BMI], blood pressure, waist and hip circumference, point-of-care random glucose level), personal and family knowledge of current illnesses (diabetes mellitus, hypertension, hyperlipidemia), modifiable risk factors (smoking, alcohol, level of activity), current drug therapy, and recommendations to the psychiatrist. The patient population who underwent screening included 49 African-Americans (53%), 21 Caucasians (23%), 16 Hispanics (17%), and 6 Asians (7%). Diagnoses were documented for 88 patients: schizophrenia or schizoaffective disorder in 53 patients (60%), and bipolar disorder and major depressive disorder was equally divided in the remaining 35 patients (40%). Of 89 patients (three patients had missing data on waist circumference), 63 (71%) met criteria for level 1 metabolic risk (abdominal obesity); of these 63 patients, 38 (60%) met criteria for level 2 risk (abdominal obesity plus hypertension). Patients with a random glucose level greater than 140 mg/dl had a higher likelihood for being at level 2 risk than level 1 risk (chi(2)=5.99, df=1, p=0.014). Women had a significantly higher likelihood for level 1 metabolic risk compared with men (chi(2)=5.99, df=1, p=0.019). African-Americans had a significantly higher likelihood of level 1 risk (p=0.026) and BMI greater than 30 kg/m(2) (p=0.003) compared with Caucasians. Patients with a BMI greater than 30 kg/m(2) had a significantly higher likelihood of diabetes (p=0.006), hypertension (p=0.03), and hyperlipidemia (p=0.05). Overall, 5 (5%) of the 92 patients met criteria for prediabetes risk. CONCLUSION: Point-of-care metabolic risk screening, done with a systematic interprofessional team approach, can provide clinicians with a practical method for identifying metabolic risk in patients prescribed antipsychotics.