Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia

Abstract

OBJECTIVE:To investigate visceral fat distribution in patients with schizophrenia. DESIGN: Cross sectional study using CT scanning in patients with drug-naive and drug-free schizophrenia. SUBJECTS: Fifteen (13 men and two women) subjects with schizophrenia (mean age 33.7 y; mean body mass index (BMI) ¼ 26.7 kg=m 2 ), and 15 age-and sex-matched controls (mean age 30.5 y; mean BMI ¼ 22.8 kg= 2 ). MEASUREMENTS: Various fatness and fat distribution parameters (by CT scanning and anthropometry) and 16:00 h plasma cortisol. RESULTS: In comparison to controls, patients with schizophrenia had central obesity and had significantly higher levels of plasma cortisol. Furthermore, previous neuroleptic exposure did not appear to influence these findings as both drug-naive and drug-free patients had equally high levels of visceral fat deposition. CONCLUSION: Central obesity is a well recognized risk factor in developing certain general medical conditions. This study shows that patients with schizophrenia have increased intra-abdominal fat which may provide one explanation for why they die prematurely. International Journal of Obesity (2002 Keywords: schizophrenia; cortisol; imaging IntroductionReduced life expectancy is a well recognized feature of psychiatric illness. 1 -3 With respect to schizophrenia, the precise reasons underlying this excessive mortality are as yet unknown. 4,5 However, it is clear that suicide cannot fully account for these findings. 6,7 A meta-analysis of the relevant literature by Harris and Barraclough found that 'unnatural' causes of death such as suicide and accidents were far more likely to occur than expected in patients with schizophrena. 8 However, the standardized mortality ratios for 'natural causes', such as cardiovascular illness, was also significantly increased, a finding which was supported by Allbeck 9 and Ruschena et al. 3 A number of reasons may explain the excessive death rate due to 'natural causes' observed in schizophrenia; these include psychosocial deprivation, an unhealthy lifestyle and psychotropic medication. 10 -12 Yet, the general medical illnesses which tend to occur in those suffering from schizophrenia form a cluster which is termed the metabolic syndrome. 13 Hypertension, type 2 diabetes mellitus and dyslipidaemias are the primary constituents of this syndrome and are associated with increased intra-abdominal fat deposition. 14,15 Abdominal fat distribution consists of two discrete depots, subcutaneous and visceral (intra-abdominal) and numerous variables can account for the pattern of body fat deposition observed in the general population. 16,17 Of note is the fact that cortisol has a marked effect on regional fat distribution, in that patients with Cushing's syndrome who have marked hypercortisolaemia, have increased visceral fat distribution as measured by computerized axial tomography (CT) scanning. 18,19 Indeed, reduction of plasma cortisol in this subgroup of patients leads to a decrease in intra-abdominal fat stores 20 and also a normalization of certain features...

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

“…The basic mechanisms behind these metabolic irregularities have not been fully elucidated, but it appears that antipsychotic medications could play an important role (Newcomer, 2005). Moreover, high rates of obesity and type II diabetes mellitus, observed in drug-naive/free patients (Mukherjee et al, 1996;Allison et al, 1999a;Thakore et al, 2002;Ryan et al, 2003Ryan et al, , 2004 before Kohen, 2004) and after the advent of antipsychotics and in nonschizophrenic blood relatives (Dynes, 1969;Mukherjee et al, 1989;Cheta et al, 1990;Martins et al, 2001;Lamberti et al, 2004), were potentially attributed to genetic factors (Stone et al, 2004), illness neurobiology (Thakore, 2005) and to unhealthy lifestyle (Brown et al, 1999). The interpretability of the preneuroleptic era data (reviewed in Kohen, 2004) is, however, limited by flaws in epidemiological methodology including lack of evaluation of and adjustments for adiposity, lifestyle, and anthropometric measures together with inconsistent diagnostic criteria for schizophrenia and glucose/insulin abnormalities Newcomer, 2005).…”

“…Seeking to tackle serious methodological limitations of the early research, Thakore et al (2002) applied a wellvalidated technique of computed tomography (Mayo-Smith et al, 1989) to directly measure abdominal adiposity in a sample of drug-naive/free schizophrenic patients and ageand sex-matched healthy controls. They found that schizophrenic patients had higher body mass index (BMI) and over three times more abdominal fat , accumulation of which poses even greater cardiovascular/ diabetes risks than overall obesity .…”

Antipsychotic drugs and diabetes—an application of the Austin Bradford Hill criteria

“…Studies of Irish first-episode psychosis patients have shown that they are more insulin-resistant and have higher fasting blood glucose concentrations than carefully matched controls [55]. Patients also have more intraabdominal fat and hypercortisolaemia, suggesting that schizophrenia in itself is associated with an increased risk of diabetes [56]. These findings have not been replicated in Chinese and Spanish populations, but methodological and subject differences may explain this discrepancy [57,58].…”

Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects

“…However, the results of these analyses may have been biased because some patients with very low or very high BMI, as well as those with significant medical illness, were excluded. Efforts to study this phenomenon in patients who are drug naïve or early in treatment compared to age-and sex-matched controls have been limited and yielded mixed results: some but not all (Ryan et al, 2004;Zhang et al, 2004a) studies found higher BMI in patients, and some (Ryan et al, 2004;Thakore et al, 2002) but not all (Zhang et al, 2004a) studies found higher intra-abdominal fat (IAF) in patients.…”