© Borgis - New Medicine 1/2014, s. 19-23
*Dominika Berent1, Agata Orzechowska2, Marian Macander3
Hyperlipidemy in patients with major depressive disorder is associated with less severe depressive symptoms
1Babiński Memorial Hospital in Łódź, Poland
2Department of Adult Psychiatry, Medical University of Łódź, Poland
3Military Institute of Aviation Medicine, Warsaw, Poland
Introduction. There is a high comorbidity of depression and cardiovascular disease which implicates course and prognosis of both disorders. Accidentally discovered correlation between low cholesterol and suicidal behavior in non-depressed population triggered robust interesting on this issue in depression. Major depressive disorder (MDD) patients display disturbed lipoprotein pattern. It was hypothesized that cholesterol depletion counteract 5-HT(7) receptor-mediated intracellular signaling in the central nervous system which can result in depressive symptoms onset.
Aim. We aimed to assess the possible correlation between blood lipids (total cholesterol (TCh), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG)) and basic depression characteristics: current age, age at onset, disease duration, number of hospitalization, number of suicide attempts and HDRS(17) rating.
Material and methods. Thirty eight MDD patients admitted to the psychiatry ward were included into the study and evaluated for serum lipids levels, body mass index (BMI) and depression severity on Hamilton Rating Scale for Depression-17 (HRSD(17)). Patients with currently disturbed lipid serum levels (TCh > 200mg/dL or HDL < 35mg/dL or HDL < 23% or LDL > 150 mg/dL or TG > 190 mg/dL) or who had been already treated with statins were considered hyperlipidemic.
Results. There were no differences in basic depression characteristics, BMI and lipids serum concentrations when compared males and females. We found no significant correlation between BMI and basic depression characteristics. Blood lipids also showed no significant correlation, except for LDL. LDL concentrations were significantly higher in patients with longer disease duration (R = 0.41, p = 0.010). Patients with mixed hyperlipidemia scored significantly lover on HDRS(17) (Z = -2.05, p = 0.040).
Conclusions. We can carefully conclude that not only cholesterol, but also its fractions and triglycerides may impact on depression severity. Currently depressed patients, especially with less severe depressive symptoms, should be a particular subject of cardiovascular preventive strategies.
There is a high comorbidity of depression and cardiovascular disease which implicates course and prognosis of both disorders (1). First, depression can seriously influence final clinical outcome in the light of being an independent risk factor for mortality in patients with coronary heart disease (CHD) (2). Second, depressed patients suffering from general somatic disorders are more likely than non-depressed patients to commit suicide, be non-concordant with treatment regimens, have greater somatic symptoms and disability, have a poorer quality of life and a higher rate of non-suicide-related deaths (3). There are few mechanisms explaining aetiological relationship between depression and cardiovascular disease, including: hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and cortisol elevation; decreased heart rate variability; elevated plasma levels of pro-inflammatory cytokines leading to atherosclerosis; platelet activation and hypercoagulability (4). Elevated pro-inflammatory cytokines and dyslipidemia act together while building atherosclerotic plate. Hypercholesterolemia, one of traditional cardiovascular risk factors (serum cholesterol levels over 200 mg/dL) (5), has been described as correlated with lower suicide risk in non-depressed population. In 1990 Muldoon et al. (6) found that reduction of cholesterol concentrations in patients with cancer resulted in significant increase in deaths not related to illness (deaths from accidents, suicide, violence). Disturbed lipid pattern and its significance in depression was described in depression with contradictory results. Some researches confirmed correlation between blood lipids and depression severity or suicide attempts, other did not (7).
Lipids, including cholesterol, are significant components of cell membrane and membrane receptors. It was hypothesized that cholesterol depletion counteract serotonin – receptor binding in the central nervous system which may impact on depression symptoms onset. Sjögren et al. (8) examined the effects of cholesterol depletion on serotonin (5-HT) binding and signaling via 5-hydroxytryptamine (7) (5-HT) (7) receptors in stably transfected HeLa cells. The study demonstrated that cholesterol depletion decreases binding of both agonist and antagonist radioligands to 5-HT(7) receptors and counteract 5-HT(7) receptor-mediated intracellular signaling. Singh et al. (9) shown that the ligand binding activity of the hippocampal serotonin(1A) receptor is reduced upon cholesterol depletion and could be restored upon replenishment with cholesterol.
Analysis of sensitivity of the serotonin(1A) receptor to thermal deactivation, pH, and proteolytic digestion in control, cholesterol-depleted and cholesterol-enriched membranes comprehensively demonstrate that membrane cholesterol stabilizes the serotonin(1A) receptor (10).
We enrolled to our study major depressive disorder (MDD) patients and aimed to assess the possible correlation between blood lipids (total cholesterol (TCh), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG)) and current age, age at onset, disease duration, number of hospitalization, number of suicide attempts and HDRS(17) rating.
Material and Methods
We enrolled 38 MDD patients (20 males, 18 females), aged 51.29 ± 11.55 (mean ± SD), admitted to a psychiatric ward between 2008 and 2010 for a treatment of depression. Patients fulfilled diagnostic criteria for MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (11). Written informed consent was obtained from all the participants of the study. The study protocol had been approved by the Local Bioethics Committee No. RNN/126/13/KB.
The patients were recruited for this study during the first week of hospitalization, just before or at the very beginning of SSRI treatment (first 2-3 days of treatment).
Basic depression characteristics of the study group (current age, age at depression onset, disease duration, number of hospitalization, number of suicide attempts, depression severity assessed with Hamilton Rating Scale for Depression-17 (HDRS(17)) are listed in table 1. Patients scored on HDRS(17) between 8 and 30 points (slight to very severe depression). Eleven patients (28.95%) confirmed family history of depression.
Table 1. Basic characteristics of the MDD patients (N = 38).
| ||M ± SD||Samples (n (%))||Significance (M versus F)|
|M|| ||20 (52.63)|| |
|F|| ||18 (47.37)|| |
|Current age||51.29 ± 11.55|| ||Z = 0.89; p = 0.373|
|Age at onset||42.92 ± 12.16|| ||Z = 0.10; p = 0.919|
|Disease duration||8.55 ± 8.52|| ||Z = 0.91; p = 0.365|
|Total number of hospitalization||2.61 ± 1.99|| ||Z = 0.09; p = 0.93|
|Number of suicide attempts||0.55 ± 1.03|| ||Z = -0.63; p = 0.530|
|Presence of family history of depression|| ||11 (28.95)|| |
|HDRS(17)||18.95 ± 5.90 points|
Range 8-30 points
| ||Z = -0.91; p = 0.365|
|Hyperlipidemia|| ||22 (57.89)|| |
|BMI [kg/m2]||27.30 ± 5.46|
| ||Z = -0.47; p = 0.640|
|TCh [mg/dl]||207.29 ± 45.46|| ||Z = -0.94; p = 0.350|
|HDL [mg/dl]||51.45 ± 16.11|| ||Z = 0.34; p = 0.737|
|HDL [%]||25.42 ± 8.29|| ||Z = 0.01; p = 0.988|
|LDL [mg/dl]||126.13 ± 37.43|| ||Z = -0.48; p = 0.630|
|TG [mg/dl]||150.79 ± 80.67|| ||Z = -1.40; p = 0.161|
MDD – major depressive disorder; M – male patients; F – female patients; HDRS(17) – 17-itemic Hamilton Rating Scale for Depression; BMI – body mass index; TCh – total cholesterol; LDL – low density lipoprotein; HDL – high density lipoprotein; TG – triglycerides; M – arithmetic mean; ± SD – standard deviation; Z – Mann-Whitney U-test; p – level of statistical significance.
The mean BMI, serum lipids concentrations (TCh, HDL, LDL, TG) are listed in table 1. Twenty two patients were hyperlipidemic (57.89%). Nine of them were treated with 20 mg simvastatin/day for at least 3 months. Even though blood lipids were currently disturbed. The major limitation of this study is lack of the control group.
Depression severity rating
Depression severity was measured on admission with HRSD(17). The highest score in HRSD(17) is 52 points. Patients scoring between 0 and 7 points have no depression; 8-12 points – slight depression; 13-17 points – moderate depression; 18-29 points – severe depression; 30-52 points – very severe depression (12, 13).
Lipid serum levels assessment
Lipid serum levels (TCh, LDL, HDL, TG) were measured during the first week of hospitalization. Peripheral blood samples were drawn in the morning, between 7.00-9.00 AM after an all night fast. They were centrifugated and lipids were measured with enzymatic colorimetric method on the instrument Cobas Integra 400 plus of the Roche Diagnostics company. A reference values for the local laboratory were for TCh: 140-200 mg/dL; HDL ≥ 35 mg/dL; HDL ≥ 23%; LDL ≤ 150 mg/dL; TG: 60-190 mg/dL. Patients with currently disturbed lipid serum levels (TCh > 200 mg/dL or HDL < 35 mg/dL or HDL < 23% or LDL > 150 mg/dL or TG > 190 mg/dL) or who had been already treated with statins were considered hyperlipidemic.
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