A cross-sectional evaluation of adiponectin plasma levels in patients with schizophrenia and schizoaffective disorder

Abstract

Abstract:Background: In recent years, several studies showed increased rates of hyperglycaemia, diabetes, dyslipidemia, metabolic syndrome as well as cardiovascular disease in schizophrenic patients. The underlying mechanism, however, is poorly understood. Adiponectin is a recently identified adipocyte-derived protein, with low adiponectin levels being associated with metabolic abnormalities such as obesity, insulin resistance and type 2 diabetes. Methods: Fasting adiponectin levels were assessed in a cross-sectional sample of 386 patients with schizophrenia or schizoaffective disorder. All patients were on monotherapy of second-generation antipsychotics (SGA) and underwent an extensive metabolic screening including an oral glucose tolerance test (OGTT). Results: Adiponectin plasma levels were inversely correlated with BMI, and differed significantly between patients with normal weight, overweight or obesity (p<0.05). Patients who met criteria for the metabolic syndrome, according to adapted National Cholesterol Educational Program -Adult Treatment Panel criteria (NCEP-ATP III) (29.3%), had significantly lower adiponectin levels than patients not meeting metabolic syndrome criteria (p<0.0001). Patients without glucose abnormalities (78%) had significantly higher adiponectin levels than patients with diabetes (5.7%) (p<0.05). After controlling for components of metabolic syndrome and sex, antipsychotic medication independently influenced adiponectin levels (p< 0.0001), with the lowest mean levels in patients on clozapine and olanzapine. Conclusions: Adiponectin levels in schizophrenic patients mirror what is observed in the general population, with the lowest levels in the most metabolically comprised subjects. However, antipsychotic medication may also influence adiponectin regulation independently, a finding that should be confirmed in longitudinal studies.

Antipsychotics-induced metabolic alterations: Focus on adipose tissue and molecular mechanisms

“…Adiponectin induces direct inhibition of proinflammatory pathways, including those regulated by toll-like receptors (TLRs) (Neumeier et al, 2006), via inhibition of NF-κB in several cell types (Lira et al, 2012). Hipoadiponectinemia has been found in schizophrenic patients (Hanssens et al, 2008) and antipsychotic therapy also contributes to this condition (Birkenaes et al, 2009;Oriot et al, 2008;Wampers et al, 2012), suggesting that antipsychotic medication may influence adiponectin homeostasis.…”

Body and liver fat content and adipokines in schizophrenia: a magnetic resonance imaging and spectroscopy study

“…Previous studies have reported that dysregulation of adipokines, i.e., adipocyte-derived peptides, is also linked with antipsychotic-induced metabolic abnormalities (Lu et al 2015;Sugai et al 2012). Leptin and adiponectin are key adipokines of interest owing to their critical roles in obesity and body fat distribution (Aye et al 2015;Baptista and Beaulieu 2002;Bredella et al 2011;Hanssens et al 2008).…”

“…Previous studies have shown that obesity is significantly associated with the disruption of leptin signaling (Yang and Barouch 2007;Myers et al 2008). There have been reports on the associations between plasma adipokines and metabolic parameters including body mass index (BMI) in patients with antipsychotics (Baptista and Beaulieu 2002;Hanssens et al 2008;Henderson et al 2015;Jin et al 2008). It has been postulated that adiponectin levels might relate to mechanisms of weight gain and other metabolic dysregulations induced by antipsychotics (Bartoli et al 2015).…”

“…Although adipokines and their links to certain metabolic parameters have been investigated in patients with schizophrenia on antipsychotic treatment (Hanssens et al 2008;Kishida et al 2011;Starrenburg and Bogers 2009), to date, there are few reports on how body fat deposit on a specific tissue is associated with key adipokines in those patients, which may provide crucial information about antipsychotic-induced changes in lipid metabolism. Only one MRI study has been conducted, where the effects of the initial antipsychotic treatment on abdominal fat deposition were investigated in patients with schizophrenia (Zhang et al 2004).…”

Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine

“…[12][13][14] Other studies found no statistically significant impacts of antipsychotics on glucose levels, glycohemoglobin, insulin levels or insulin resistance. 15 The incretin gastrointestinal hormones affect insulin secretion by pancreatic b cells. Glucose-dependent insulinotropic polypeptide (GIP) is one of two incretin hormones that stimulate an insulin response after an oral glucose challenge.…”