The Antiatherogenic Properties of HDL in Psychiatric Patients With and Without Antipsychotic Therapy

Background:

Among individuals with schizophrenia, there is an increased prevalence of obesity, dyslipidemia ,diabetes mellitus and related conditions such as cardiovascular disease. People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. Number of epidemiological studies of patients with schizophrenia have documented a higher incidence of cardiovascular disease than in the general population, and patients with schizophrenia may be at an elevated risk for cardiovascular disease even in the absence of antipsychotic treatment.

Affinity for the H1 receptor is most closely linked to increased weight gain, although affinity for D2, 5-HT1A, 5-HT2C and a2-receptors may also be involved. Drug affinity for the H1, M3 and 5-HT2C receptors is correlated with an increased risk of diabetes.

High-density lipoprotein cholesterol (HDL-C) concentration in the blood is independently and inversely associated with an increased risk of cardiovascular disease(CVD). However many patients with 'normal' or even 'elevated' plasma HDL experience clinical events. HDL may not always be atheroprotective and in some conditions, it paradoxically enhances the process of atherosclerosis. In addition to its role in reverse cholesterol transport, HDL shows many other protective properties towards atherosclerosis. HDL inhibits the chemotaxis of monocytes , prevents endothelial dysfunction and apoptosis, prohibit slow-density lipoprotein (LDL ) oxidation, and stimulates the proliferation of endothelial cells and smooth muscle cells. These anti-inflammatory, antioxidative, antiaggregatory, anti-coagulant, and pro-fibrinolytic activities are exerted by different components of HDL

Aim of the study:

To investigate the functional properties of HDL in psychiatric patients before and during antipsychotic therapy.

Patients and methods:

The blood will be drawn at baseline before the initiation of antipsychotic drugs and 2 months under the antipsychotic treatment.

Study procedures:

Full lipid profile including triglycerides, LDL-C, Total cholesterol, HDL-cholesterol, apo AI, apoAII and apoB100.

Serum Paraoxanase Activity

LDL oxidation and resistance to oxidation (measured by conjugated diens formation during incubation in the presence of copper).

HDL composition: total and unesterified cholesterol, triglycerides and phospholipids, TBARS content before and after exposure to AAPH as a major indicator of oxidative stress, PON activity using phenylacetate as a substrate, apoA1and PAF.

Serum parameters e.g. Diacyl glycerol acyltransferase activity, free ApoA1 and LCAT activity.

3 [H]-Cholesterol efflux will be measured by incubating J744 macrophages with serum. Radioactivity will measured by β counter in the cell lysate and the medium.

Statistical methods:

One-way AVOVA and Student's t-test for paired samples will be used for comparison of multiple groups and paired samples, respectively. p<0.05 will be considered significant.