Jaspreet S. Brar

Serum interleukin-6 concentration in schizophrenia: Elevation associated with duration of illness

Using an enzyme immunoassay (ELISA), we measured serum interleukin-6 (IL-6) concentration in 128 schizophrenic patients (24 of whom were never medicated) and in 110 normal control subjects. Mean serum IL-6 concentration was significantly higher in the schizophrenic patients as compared with the control subjects (p = 0.009). Comparisons within the patient group revealed that serum IL-6 was significantly correlated with duration of illness (r = 0.32, p = 0.0004). After covariation for duration of illness, there was no relationship between IL-6 levels and the production of autoantibodies, clinical state, or medication status. Thus, elevated serum IL-6 levels in schizophrenia develop during the course of illness and may be related to treatment or to disease progression.

Autoimmunity in Schizophrenia: A Review of Recent Findings

The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed.

Body mass index and quality of life in community-dwelling patients with schizophrenia

OBJECTIVE To examine the associations between sociodemographic variables, body weight and quality of life in schizophrenic outpatients. METHODS Assessments included an interview to obtain sociodemographic data, administration of a Quality of Life questionnaire (the MOS SF-36) and measurement of height and weight. Body mass index was calculated (kg/m(2)). SF-36 subscores were examined for statistical differences based on BMI categories: healthy weight (BMI<or=24.9), overweight (BMI 25-29.9) and obese (BMI>or=30). Correlations with sociodemographic variables were also examined. RESULTS Body weight was inversely correlated (level p<or=0.005) to the SF-36 items: physical functioning (PF, -0.452), role limitations due to physical functioning (-0.279), role limitations due to emotional functioning (-0.256), vitality (-0.200), general health (GH, -0.367) and physical component score (PCS, -0.400). Mental component score (MCS) was not significantly correlated to body weight. When comparing quality of life across BMI categories, obese subjects had worse physical functioning (p<or=0.0005) and general health (p<or=0.005), reported more role limitations due to emotional functioning (p<or=0.05) and a lower physical component score (p<or=0.005). Mental component score was not significantly influenced by BMI. CONCLUSIONS Quality of life in schizophrenic patients is related to body weight. The burden of obesity is primarily experienced as a physical problem.

Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open-label, nonrandomized chart review.

BACKGROUND Subsets of psychiatric patients gain excess body weight while receiving mood-stabilizing agents such as lithium carbonate or valproate sodium. Patients who gain excess weight may discontinue therapy, with severe consequences. Among the newer anticonvulsant agents, topiramate is a candidate agent for bipolar disorder and is associated with weight loss when used as adjunctive treatment. OBJECTIVE This open-label, nonrandomized, chart-review study assessed changes in body weight and body mass index (BMI) in patients receiving topiramate, lithium, or valproate. METHODS Data were extracted from the medical charts of patients admitted in 1999 and 2000 to a state psychiatric hospital with either schizophrenia, schizoaffective disorder, bipolar disorder, or other psychiatric diagnoses who were prescribed valproate, lithium, or topiramate and were reviewed for changes in body weight and BMI. The use of concomitant psychotropic medicines was recorded (eg, antipsychotic agents, antidepressant agents, other mood stabilizers such as gabapentin or carbamazepine). Continuous variables were analyzed using a factorial analysis of variance and the Student t test. Contingency statistics were used to analyze categorical variables. RESULTS A total of 214 patients were included in the chart review (123 men, 91 women; mean age, 39.4 years). Significantly more women than men received topiramate (P = 0.004). Patients receiving either lithium or valproate gained a mean (SD) of 6.3 (9.0) kg and 6.4 (9.0) kg, respectively, whereas patients receiving topiramate lost a mean 1.2 (6.3) kg (F = 11.54, df = 2,198; P < 0.001). Lithium- or valproate-treated patients experienced an increase in BMI (mean, 2.1 [3.0] for both groups), whereas topiramate-treated patients experienced a reduction in BMI (mean, -0.5 [2.4]); this result was statistically significant (F = 11.40, df = 2,198; P < 0.001). Finally, lithium- or valproate-treated patients gained >8% of their baseline body weight (8.2% [11.5%] for lithium-treated patients and 8.5% [11.9%] for valproate-treated patients), whereas topiramate-treated patients lost 0.7% (7.2%) of their body weight (F = 9.93, df= 2,198; P < 0.001). CONCLUSIONS Controlled studies for the efficacy of topiramate therapy in various psychiatric conditions are awaited. These data indicate that patients receiving topiramate experience body weight loss and a reduction in BMI. This advantage of topiramate may promote long-term adherence to treatment among psychiatric patients and possibly decrease the medical risks associated with obesity.

Immune Abnormalities in Schizophrenia: Evidence for the Autoimmune Hypothesis

&NA; The autoimmune basis for schizophrenia has been investigated for the last 60 years. Although numerous immune abnormalities have been reported, the current literature is viewed with much skepticism because most of the studies have failed to control for extraneous factors that may have influenced the findings. Principally, antipsychotic medication, duration of illness, and current clinical state (acutely psychotic or remitted) may considerably alter immune response, as may other factors such as nutritional status, substance abuse, and concurrent medical illness. We review recent studies that employed current diagnostic criteria and modern immunologic techniques. (These studies were located by use of a Medline search on the terms schizophrenia and psychosis, cross‐referenced with immune abnormalities, lymphokines, antibodies, lymphocytes, HLA, and medication, and by perusing the reference lists in the articles found through this search.) Immune abnormalities that have been replicated in studies of schizophrenic patients include increased prevalence of antinuclear antibodies, decreased production of interleukin‐2, and increased serum concentrations of inferleukin‐2 receptor and interleukin‐6. Given the current importance of autoimmunity as an etiologic mechanism in several branches of medicine, further studies are needed, especially those having a longitudinal design and including drug‐naive patients.

Altered interleukin-2 production in schizophrenia: Association between clinical state and autoantibody production

Mitogen-stimulated interleukin-2 (IL-2) production was measured in 122 patients who met Research Diagnostic Criteria for schizophrenia and 98 normal control subjects. The presence of autoantibodies against seven common antigens was also determined. There was no relationship between the presence of circulating autoantibodies and IL-2 production in control subjects. In patients, however, autoantibody-positive, acutely ill patients had significantly lower IL-2 production as compared with other patients and control subjects. Never-medicated patients showed the same trends for decreased IL-2 production in association with autoantibodies. These data suggest that decreased IL-2 production is associated with acute illness in schizophrenic patients who produce autoantibodies, a trait known to be associated with increased vulnerability to autoimmune disease.

Increased caffeine and nicotine consumption in community-dwelling patients with schizophrenia

INTRODUCTION It is known that people with schizophrenia make poor dietary choices and smoke at alarmingly high rates. There is also anecdotal evidence that they may ingest large amounts of caffeine. However, while smoking habits in this population have been examined, no recent study has quantified caffeine consumption taking into account various dietary caffeine sources unrelated to coffee including convenience foods such as candy bars, chocolate or soft drinks, and compared results to US population data. METHODS We employed 24-h diet recalls to assess dietary habits in a sample of outpatients suffering from schizophrenia or schizoaffective disorder. Caloric intake and caffeine consumption were quantified and the relationship to various sociodemographic variables including body mass index (BMI) and dietary quality was examined. RESULTS 146 patients were recruited. Mean BMI in the sample was 32.7+/-7.9. Patients ingested 3,057+/-1,132 cal on average. Patients smoked at higher rates (59.6% vs. 23.4%, p< or =0.001), higher numbers of cigarettes/day (24+/-14.4 vs. 13.5+/-11.3, t=8.549, p<0.001) and ingested more caffeine (471.6+/-584.6 mg vs. 254.2+/-384.9 mg, t=6.664, p<0.001) than US population comparisons. Caffeine consumption was correlated to the number of cigarettes smoked daily (r=0.299, p< or =0.001), but not to BMI (r=0.134, p=0.107) or dietary parameters such as caloric intake (r=0.105, p=0.207). CONCLUSION Community-dwelling schizophrenia patients consume significantly more caffeine and nicotine than US population comparisons. Clinicians should be aware that while a significant proportion of patients are overweight and have poor dietary quality - which merits lifestyle counseling on its own - there is a lack of correlation between those factors and smoking and caffeine intake. Thus, lifestyle modification counseling in all patients should address smoking and caffeine intake concurrently.

PET brain mapping study of auditory verbal supraspan memory versus visual fixation in schizophrenia

Changes in regional cerebral blood flow (rCBF), associated with performance of an auditory verbal supraspan memory task, were studied in eight remitted DSM-III-R schizophrenic patients and eight pair-wise matched normal controls. Four positron emission tomography (PET) scans, using the [15O]-H2O technique, were acquired: two while subjects fixated a cross hair and two while performing a verbal free-recall supraspan memory task. Task performance showed typical patterns of recency and primacy effects in both groups; however, patients performed more poorly than controls on the primary (working) memory aspect of the task. Regions showing rCBF changes overlapped in both groups and were similar to those seen in previous studies of normals; however, patients had smaller increases in rCBF than controls in frontal and superior temporal cortical regions bilaterally. Our results suggest that remitted patients with schizophrenia demonstrate impairments of capacity-limited information processing, which may be related to metabolic dysfunction within a distributed network of brain structures, including the prefrontal and temporal cortical regions; however, dysfunction limited to the frontal cortex cannot be ruled out by the results of this experiment.

Weight gain over 4 months in schizophrenia patients: a comparison of olanzapine and risperidone

Weight gain frequently accompanies treatment with antipsychotics. In order to determine whether newer antipsychotic agents differ from each other with respect to weight gain, we compared two cohorts of patients with DSM-IV schizophrenia who had newly started treatment with either risperidone or olanzapine. After obtaining informed consent, data regarding body weight and height were culled from existing medical records of 100 patients (50 patients in each treatment group). Baseline body weight, close to the time of starting the new medication, and body mass index [BMI = weight (kg)/height (m) squared] were compared to the body weight and BMI following 4 months of treatment. There was no significant change in mean body weight or BMI in the group treated with risperidone (baseline weight = 83.1 kg +/- 20.5, follow-up = 82.8 kg +/- 19.9; matched pair t = 0.66, P = n.s.; baseline BMI = 29.6 +/- 9.4, follow-up = 29.5 +/- 9.1; matched pair t = 0.79, P = n.s.). However, in the group treated with olanzapine, there was a significant increase in both mean body weight and BMI (baseline weight = 84.9 kg +/- 25.0, follow-up = 87.1 kg +/- 25.1; matched pair t = 4.62, P < 0.001; baseline BMI = 29.5 +/- 7.4, follow-up = 30.3 +/- 7.5; matched pair t = 4.43, P < 0.001). In this naturalistic study, treatment with olanzapine was associated with a mean weight gain of about 2 kg from baseline, in patients with schizophrenia, while treatment with risperidone was associated with no mean weight change.

Self-reported body weight perception and dieting practices in community-dwelling patients with schizophrenia

INTRODUCTION Many patients with schizophrenia are exposed to serious health risks associated with their excess body weight. Evidence exists that even a moderate amount of weight loss may have significant health benefits. Thus, weight control in schizophrenia patients has become an important treatment goal. Although studies in the general population show that satisfaction with body weight is an important predictor for engagement in various weight loss measures, the perspective of schizophrenia patients has not been assessed. METHOD Information on self-reported weight perception, desire to lose weight as well as weight loss attempts was obtained according to methods employed in the National Health and Nutrition Examination Survey, Cycle III (NHANES III). Body weight and height were measured and body mass index (BMI) was calculated. RESULTS Perception of body weight and desire to lose weight were correlated to BMI. Both obese female and male subjects (BMI30) were aware of their weight status. However, whereas overweight females (BMI>25< or =29.9) accurately perceived themselves so, males in this category had difficulties perceiving themselves overweight, and consequently neither wanted to lose weight, nor tried to lose weight. As means of weight loss, caloric restriction (diet) was most frequently employed (by more than 80% of study subjects); yet only a third of study subjects (34.4%) engaged in the recommended combination of diet and exercise to lose weight. Questionable weight loss practices were also frequently employed, especially among women. CONCLUSIONS Obese patients (BMI> or =30) were generally aware of their excess body weight and wanted to lose weight. Only non-obese, yet overweight males (BMI>25< or =29.9) did not perceive themselves as overweight and consequently did not try to lose weight. Weight loss practices did not always follow established recommendations. Especially women were likely to approach weight loss with questionably appropriate and unsafe methods.