major depressive disorder ( mdd ) is the most common mood disorder with a significant effect on the progression of medical conditions.1 factors accompanying depression , such as patients ' failure to look after their health , inability to adapt to their environment , social dissociation , chronic stresses of life , cigarette smoking , reduced physical activity , inappropriate nutrition and poor compliance with medical advice , make depression one of the risk factors of noncommunicable diseases.2   in addition to the effect of depression on lifestyle , the direct effect of depression on metabolic factors has been shown in many studies.3 recently , a relationship has been observed between depression and serum levels of lipoproteins and apolipoproteins ( apo ) , which are known risk factors of obesity and cardiovascular diseases.4 one theory of this relationship suggests a disturbance in function of the serotonergic system .
in addition , metabolic changes in patients with mdd are due to genetic changes in the coding of serum lipoproteins.5 other theories describe changes in interleukin 2 , number of total tcells , melatonin and other cytokines in depressed patients.6 - 8   despite these studies , controversy exists about the relationship between depression and the lipid profile . studies have shown different results for the level of apo a 
one of the highdensity lipoprotein cholesterol ( hdlc ) subgroups , and of apo b  the major protein of lowdensity lipoprotein cholesterol ( ldlc ) , in patients with mdd.4,9,10   sevincok and sarandol showed that the serum level of apo a in depressed patients was lower than that in control group.4,9 another study showed no significant difference in the serum levels of apolipoproteins between depressed patients and the control group.11   the lack of evidence and controversial results of previous studies led us design this study to compare the serum levels of apolipoproteins in depressed patients and normal individuals .
a population of 153 patients with mdd ( 63 women , 90 men , aged 2147 years ) in 2007 were included in this case  control study .
all the patients were diagnosed with mdd according to the structured clinical interview ( scidi ) for diagnostic and statistical manual of mental disorders , fourth edition ( dsmiv ) .
relatives of hospitalized patients and hospital university staff comprised the control group ( 78 women , 69 men , aged 1847 years ) .
patients with an axis i or ii disorder in addition to their depression , patients with mdd with psychotic features , bipolar disorder , cyclothymia , dysthymia , anxiety disorder and patients at significant risk of suicide were excluded from the study via the structured clinical interview for dsmiv . exclusion criteria for both case and control
groups included the presence of organic diseases such as hypertension , diabetes , cardiovascular , adrenal , hepatic and thyroid diseases documented by physical examination and laboratory tests ; history of antilipid and blocker consumption ; and menopause in women .
laboratory tests , including complete blood count , serum electrolyte assay , liver function tests , thyroid function tests , urine analyses and electrocardiography , were performed for all participants to screen for major health problems .
in addition , after explanation of the study , informed consent was obtained from all participants .
the study protocol was approved by the ethical committee of the isfahan university of medical sciences .
all participants completed a selfadministered questionnaire to determine demographic characteristics such as age , gender , socioeconomic status ( occupation , marital status and educational level ) , smoking status , drug history , family history of depression , physical activity and diet .
subjects were considered to be  current smokers  if they reported smoking at least one cigarette a day during the past year .
anthropometric characteristics ( height and weight ) were measured with the subjects wearing thin clothes .
body mass index ( bmi ) was calculated by dividing a participant 's weight by their height squared ( kg / m ) .
regular physical activity was defined as exercise of at least 15 minutes ' duration at least twice each week.13   participants provided details of their dietary habits by completing a food frequency questionnaire ( ffq).14 this instrument was designed according to the whoffq , with some changes .
the validity of this questionnaire was confirmed before its use by the medical education development center affiliated to isfahan university of medical sciences.15 the ffq was used to access the consumption of different food groups such as meat , oils , cereals , vegetables and fruits .
eligible participants also completed a 17item hamilton rating scale for depression ( hamd ) , which is the most commonly used observerrated depressive symptom rating scale .
the original scale has 21 items but , as hamilton has suggested , only the initial 17 items were scored in this study because the last 4 items rarely occur and deal only with aspects of illness .
items with quantifiable severity were ranked on a scale of 04 and those measuring symptoms that are difficult to assess reliably were ranked on a scale of 02 .
the range of the 17item scale was 050 , with 14 considered to be the cutoff point of this scale ; higher scores indicated more severe depression . according to hamd
, patients were classified into 3 groups of mild mdd ( score 1518 ) , moderate mdd ( score 1922 ) and severe mdd ( score 23).16,17   a blood sample was taken after 1214 hours ' fasting through the antecubital vein .
all the blood sampling procedures were performed in the central laboratory of the isfahan cardiovascular research centre .
serum triglyceride ( tg ) , total cholesterol ( tc ) , hdlc , ldlc and apo a and b were measured for each patient .
tc and tg levels were measured within 24  h by an enzymatic method using an elan 2000 autoanalyze .
ldlc was calculated by the friedewald formula,18 but in cases with tg400  mg / dl , it was measured directly .
apo a and b were measured by immunoturbidimetry using pars azmoon kits accredited by bioactiva diagnostica ( germany ) .
continuous variables were expressed as mean  sd and a ttest was used to compare the means between the two groups .
qualitative variables were expressed as frequency and a  test used to compare frequencies between the two groups .
a pearson correlation test was used to evaluate the correlation of depression with apo a and apo b. to study the association of depression and apo a and b ( apo a and b , separately ) , multiple linear regression models were used .
apo a and b were entered as dependent variables , and the group ( case vs. control ) , smoking status ( smokers vs. nonsmokers ) , bmi , tc , ldlc and hdlc were entered as independent variables .
the enter approach was selected for regression model , and for each apo a and b a unique model was created .
data were analyzed by spss version 15.0 ( spss inc , chicago , illinois , usa ) .
patients with an axis i or ii disorder in addition to their depression , patients with mdd with psychotic features , bipolar disorder , cyclothymia , dysthymia , anxiety disorder and patients at significant risk of suicide were excluded from the study via the structured clinical interview for dsmiv . exclusion criteria for both case and control
groups included the presence of organic diseases such as hypertension , diabetes , cardiovascular , adrenal , hepatic and thyroid diseases documented by physical examination and laboratory tests ; history of antilipid and blocker consumption ; and menopause in women .
laboratory tests , including complete blood count , serum electrolyte assay , liver function tests , thyroid function tests , urine analyses and electrocardiography , were performed for all participants to screen for major health problems .
in addition , after explanation of the study , informed consent was obtained from all participants .
the study protocol was approved by the ethical committee of the isfahan university of medical sciences .
all participants completed a selfadministered questionnaire to determine demographic characteristics such as age , gender , socioeconomic status ( occupation , marital status and educational level ) , smoking status , drug history , family history of depression , physical activity and diet .
subjects were considered to be  current smokers  if they reported smoking at least one cigarette a day during the past year .
anthropometric characteristics ( height and weight ) were measured with the subjects wearing thin clothes . body mass index ( bmi )
was calculated by dividing a participant 's weight by their height squared ( kg / m ) .
regular physical activity was defined as exercise of at least 15 minutes ' duration at least twice each week.13   participants provided details of their dietary habits by completing a food frequency questionnaire ( ffq).14 this instrument was designed according to the whoffq , with some changes .
the validity of this questionnaire was confirmed before its use by the medical education development center affiliated to isfahan university of medical sciences.15 the ffq was used to access the consumption of different food groups such as meat , oils , cereals , vegetables and fruits .
eligible participants also completed a 17item hamilton rating scale for depression ( hamd ) , which is the most commonly used observerrated depressive symptom rating scale .
the original scale has 21 items but , as hamilton has suggested , only the initial 17 items were scored in this study because the last 4 items rarely occur and deal only with aspects of illness .
items with quantifiable severity were ranked on a scale of 04 and those measuring symptoms that are difficult to assess reliably were ranked on a scale of 02 .
the range of the 17item scale was 050 , with 14 considered to be the cutoff point of this scale ; higher scores indicated more severe depression . according to hamd
, patients were classified into 3 groups of mild mdd ( score 1518 ) , moderate mdd ( score 1922 ) and severe mdd ( score 23).16,17   a blood sample was taken after 1214 hours ' fasting through the antecubital vein .
all the blood sampling procedures were performed in the central laboratory of the isfahan cardiovascular research centre .
serum triglyceride ( tg ) , total cholesterol ( tc ) , hdlc , ldlc and apo a and b were measured for each patient .
tc and tg levels were measured within 24  h by an enzymatic method using an elan 2000 autoanalyze .
ldlc was calculated by the friedewald formula,18 but in cases with tg400  mg / dl , it was measured directly . apo a and b were measured by immunoturbidimetry using pars azmoon kits accredited by bioactiva diagnostica ( germany ) .
continuous variables were expressed as mean  sd and a ttest was used to compare the means between the two groups .
qualitative variables were expressed as frequency and a  test used to compare frequencies between the two groups .
a pearson correlation test was used to evaluate the correlation of depression with apo a and apo b. to study the association of depression and apo a and b ( apo a and b , separately ) , multiple linear regression models were used . apo a and b were entered as dependent variables , and the group ( case vs. control ) , smoking status ( smokers vs. nonsmokers ) , bmi , tc , ldlc and hdlc were entered as independent variables .
the enter approach was selected for regression model , and for each apo a and b a unique model was created .
data were analyzed by spss version 15.0 ( spss inc , chicago , illinois , usa ) .
the baseline variables sex , age , marital state and occupation were similar in case and control groups .
the mean age of participants was 31.2110.41 years in the group with mdd vs. 32.008.21 years in the control group .
depressed patients were significantly more likely to have a family history of depression and a past history of smoking ( p<0.05 ) .
fiftyfour patients were mildly depressed ( 35.3% ) , 69 were moderately depressed ( 45.1% ) and 30 were severely depressed ( 19.6% ) .
there were no statistically significant differences between the two groups in bmi and physical activity .
consumption of different groups of foods , which was assessed by the ffq , showed no significant statistical difference between the two groups .
concentrations of all serum lipids and apo a and b differed significantly between the two groups .
tc , ldlc and apo b were higher , while hdlc and apo a were lower , in the case group than in controls ( table 1 ) .
linear regression analysis showed that serum apo a levels were negatively ( p<0.01 ) and serum apo b levels were positively ( p<0.05 ) predicted by depression .
serum tc levels predicted negatively ( p<0.05 ) and hdlc levels predicted positively ( p<0.01 ) the serum apo a levels .
smoking status and bmi did not significantly predict the apo a and b levels ( table 2 ) .
the correlation between depression severity according to hamd and serum levels of the apolipoproteins indicated an inverse relationship between depression severity and serum apo a levels ( r  =  0.453 , p<0.01 ) and a direct relationship between depression severity and serum apo b levels ( r  =  0.521 , p<0.05 ) .
our findings showed a significant correlation between serum levels of apolipoproteins and depression so that the serum level of hdlc and apo a were lower , while ldlc and apo b ( atherogenic lipoproteins ) were higher , in patients with mdd than those in the control group .
in addition , severity of depression correlated with an increment in serum apo b level and a decrement in serum apo a level .
sarandol et al . investigated the oxidation of apo bcontaining lipoproteins and the serum paraoxonase and arylesterase activities in mdd .
their case group included patients with mdd who had not received antidepressant drugs for at least 3 weeks .
higher tc , hdlc , ldlc and apo b , and lower apo a , levels were found in the case group .
the patients were treated with a standard dosage of antidepressant drugs for 6 weeks , which did not alter the serum levels of lipid profiles.4 however , there is some evidence that antidepressant agents may affect serum lipid profile levels.9 thus , we excluded patients who had taken antidepressant drugs during the past 6 months .
our results , except those for hdlc , were in line with those of sarandol et al .
association between serum hdlc and ldlc levels as predictors of coronary heart disease ( chd ) and mdd is one of the fields which has been investigated.19 few studies have shown an inverse association between them.2 a metaanalysis on the association of cholesterol and depression showed that tc and depression were inversely related.21 on the other hand , some studies , such as that of chen et al . , demonstrated lower hdlc and higher ldlc and tc levels in patients with mdd.22 similarly , nakao and yano showed significant direct association between hypercholesterolemia and patients with mdd in japanese men.23 since apo a is known to be a major fraction of hdlc and apo b is known to be a major fraction of ldlc , our results were in accordance with the results of these studies .
depression is associated with chd  that is , depressed patients are more prone to develop chd.24,25 because of this association , the relationship between depression and other risk factors of chd such as serum apolipoprotein levels is an important subject that should examined more closely .
one hypothesis suggests that genetic factors associated with depression may contribute to a change in serum lipid levels.26 a second theory proposes that cholesterol may be an important factor in reducing the possibility of correction of metabolic defects . as a result of these defects , segmental cerebral hypoxia , which may associated with depression ,
could occur.27 altered lipid profile levels through changes in serotonergic systems might also lead to mdd.28   this study has some limitations .
owing to the crosssectional design of the study , the cause and effect relationship and mechanisms of the association between depression and lipid profile could not be determined .
also , some of our data were based on selfreported questionnaires , which are less reliable sources of information than direct measurement . also , as previously mentioned , although our case and control groups had no differences in socioeconomic status , some of the control group comprised university hospital staff .
the results of the study demonstrated lower serum levels of apo a and hdlc and higher serum levels of apo b and ldlc in depressed patients than in the control group .
thus in depressed patients , biochemical problems should be considered and evaluated together with psychological interventions . given the relationship between apolipoproteins and depression , checking the lipid profile as predicting factors of chd to prevent the appearance of extra cardiovascular risk factors seems necessary .
 objective : to investigate the relation between major depressive disorder and metabolic risk factors of coronary heart disease.introduction:little evidence is available indicating a relationship between major depressive disorder and metabolic risk factors of coronary heart disease such as lipoprotein and apolipoprotein.methods:this case  control study included 153 patients with major depressive disorder who fulfilled the criteria of the diagnostic and statistical manual of mental disorders , fourth edition ( dsmiv ) , and 147 healthy individuals . 
 all participants completed a demographic questionnaire and hamilton rating scale for depression . 
 anthropometric characteristics were recorded . 
 blood samples were taken and total cholesterol , high and lowdensity lipoproteins and apolipoproteins a and b were measured . to analyze the data , ttest , 2 test , pearson correlation test and linear regression were applied.results:depression was a negative predictor of apolipoprotein a (   =  0.328 , p<0.01 ) and positive predictor of apolipoprotein b (   =  0.290 , p<0.05 ) . 
 apolipoprotein a was inversely predicted by total cholesterol (   =  0.269 , p<0.05 ) and positively predicted by highdensity lipoprotein (   =  0.401 , p<0.01 ) . 
 also , lowdensity lipoprotein was a predictor of apolipoprotein b (   =  0.340 , p<0.01 ) . 
 the severity of depression was correlated with the increment in serum apolipoprotein b levels and the decrement in serum apolipoprotein a level.conclusion:in view of the relationship between apolipoproteins a and b and depression , it would seem that screening of these metabolic risk factors besides psychological interventions is necessary in depressed patients . 
INTRODUCTION
METHODS
Exclusion Criteria
Measurements
Statistical Analysis
RESULTS
DISCUSSION
CONCLUSION