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Psychosomatic Medicine 66:548-552 (2004)
© 2004 American Psychosomatic Society


ORIGINAL ARTICLES

Total Serum Cholesterol and Suicidality in Anorexia Nervosa

Angela Favaro, MD, PhD, MSc, Lorenza Caregaro, MD, Lorenza Di Pascoli, MD, Francesca Brambilla, MD and Paolo Santonastaso, MD

From the Department of Neuroscience (A.F., P.S.) and Clinical and Experimental Medicine (L.C., L.D.P.), University of Padua, Padua, Italy; and the Department of Neuroscience (F.B.), Sacco Hospital, Milan, Italy.

Address correspondence and reprint requests to Paolo Santonastaso, Psychiatric Clinic, Department of Neurology and Psychiatry, Via Giustiniani 3, 35128 Padova, Italy. E-mail: paolo.santonastaso{at}unipd.it


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: No published study has evaluated the relationship between serum cholesterol and suicidality in anorexia nervosa (AN).

AIMS: To assess psychiatric and nutritional correlates of serum cholesterol in a sample of AN patients.

METHODS: Serum cholesterol and nutritional status were evaluated in a sample of 74 AN patients, before starting any type of refeeding. All subjects underwent a structured clinical interview and completed the Hopkins Symptom Checklist.

RESULTS: Subjects who reported previous suicide attempts, impulsive self-injurious behavior, or current suicidal ideation showed significantly lower cholesterol levels than subjects without suicidality. Cholesterol levels were negatively correlated with the severity of depressive symptoms in all the patients with the exception of those with recurrent binge eating. A multivariate analysis showed that the relationships between cholesterol levels and suicidal behavior and ideation do not seem to be affected by the nutritional and metabolic factors considered in the study.

CONCLUSIONS: Notwithstanding the influence of important metabolic factors affecting cholesterolemia in AN, our research tends to confirm previous studies that have found an association between low cholesterol levels and suicidality.

Key Words: anorexia nervosa, • serum cholesterol, • self-injurious behavior, • suicidality, • depression.

Abbreviations: AN = anorexia nervosa;; ANR = restricting-type AN;; ANBP = binge eating/purging-type AN;; BMI = body mass index;; DSM-IV = Diagnostic and Statistical Manual for Mental Disorders, 4th edition;; SCL = Hopkins Symptom Checklist;; T3 = free triiodotyronine;; T4 = free tyroxine.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The ongoing debate about the possible link between cholesterol and mental health began when the findings from the early clinical trials of cholesterol-lowering treatments raised concerns about the risk of increased deaths from suicides and violence (1). It has been proposed that low levels of blood cholesterol may decrease the activity of serotonin receptors and serotonin transporter by decreasing the lipid microviscosity of the membrane of the neural cell (2). Various studies have provided evidence that suicidality parameters are significantly correlated with lower cholesterol levels (3–5). Other studies have found a significant relationship between low serum cholesterol and depressive traits in healthy men and women (6,7). However, no studies to date have examined the association of cholesterol levels with psychiatric symptoms in anorexia nervosa (AN). In depressed patients, the hypothesis that recent weight loss could account for low cholesterol levels among suicidal patients has not been confirmed by studies that controlled for this potential confounding factor (3,5).

The aim of the present study was to assess the relationship between cholesterol and suicidality in AN.


    METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Seventy-four patients with AN participated in the study. All patients were referred to our Eating Disorders Unit and were assessed before starting any type of refeeding. Forty-eight patients were diagnosed as having restricting AN, and 26, binge eating/purging type AN. In the latter subgroup, only 10 patients reported recurrent binge eating, while the other 16 were included in this group because of the presence of recurrent self-induced vomiting and/or purging behavior.

The mean age of the sample was 23.6 (SD = 7.4; range 14–57) and the mean body mass index (BMI) 14.8 (SD = 1.9; range 9.6–17.4). Other characteristics of the sample are reported in Table 1. All patients were female and amenorrheic. All patients were starving themselves at the time of assessment. Criteria of exclusion from the study were: presence of any systemic illness, history of any Axis I or II psychiatric disorder before the onset of AN, comorbidity with alcohol or drug abuse, and taking any medication known to affect lipid metabolism (including oral contraceptives). Diagnosis of eating disorder and Axis I and II psychiatric disorders were evaluated by means of a structured interview: the SCID for DSM-IV. Diagnostic and psychopathological assessments were made by investigators (psychiatrists and psychologists) who were formally trained in the use of the SCID-IP and SCID-II. All patients gave informed consent to the use of data in an anonymous form. In addition to the diagnostic structured interview, patients underwent a second semistructured interview and completed the Hopkins Symptom Checklist (8), which is a self-reported questionnaire that measures psychiatric symptoms. The global score and the depression, anxiety, and hostility subscales of the Symptom Checklist were calculated. A modified depression subscale score was also computed, omitting the suicidality items. The presence of suicidal attempts, impulsive self-injurious behavior, and suicidal ideation were assessed by means of the semistructured interview. In addition, suicidal ideation was also measured by the relevant two items from the Symptom Checklist. The history of suicide attempts was verified by previous psychiatric records (wherever they were available) and/or by parents’ reports. Self-injurious behavior is usually defined as a behavior involving the deliberate infliction of direct physical harm to one’s own body, without any intent to die as a consequence of the behavior. Examples of impulsive self-injurious behavior are skin cutting or burning. They can be distinguished from compulsive self-injurious behavior because they are usually episodic, egosyntonic, and involve little resistance (9).


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TABLE 1. Characteristics of the Sample
 
A blood sample was taken between 8:30 AM and 9:30 AM after overnight fasting. The total serum cholesterol level (in mmol/L) was determined by the enzymatic method (10). Thyroid hormones were determined using commercial kits.

Anthropometric and biochemical parameters were assessed on the same day. Anthropometric assessment included the measurements of body weight, height, and skinfold anthropometry. Skinfold measurements and the calculation of percentage body fat and muscular mass were carried out in a manner that was consistent with previous studies (11,12). Energy, nutrient, and cholesterol intake was calculated from three consecutive 24-hour dietary recalls, by means of a computer-assisted interview. A program utilizing food pictures was used to estimate portion sizes, and for calculations of energy intake (Winfood 1.5, Medimatica srl, Martinsicuro, Italy). The energy, nutrient, and cholesterol intake of patients with binge eating/purging-type AN was not calculated.

Statistical Analyses
Statistical analyses were carried out with the SPSS program, release 10.0. Comparisons between groups were made using Mann-Whitney U tests. Given the exploratory nature of the study, no correction for multiple testing was carried out. The correlation between serum cholesterol and the variables of interest were calculated using Pearson’s correlation coefficient. To better understand the relationship between cholesterol and psychiatric symptoms, taking into consideration the role of nutritional and clinical factors, we performed a series of regression analyses. Multiple linear regression analysis was used to test whether cholesterol levels were an independent predictor of suicidal ideation (measured by the two items of the SCL scale) and depression. Logistic regression analysis was used with the same aims when the dependent variable was dichotomous.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Table 1 shows the characteristics of the sample as a whole, and for the two separate diagnostic subgroups. The mean cholesterol level in the whole sample was 4.4 ± 1.2 mmol/L (range 1.8–8.1 mmol/L). Seven subjects (9.5%) had hypercholesterolemia (> 6.19 mmol/L), which comprised 6% of the restricting and 15% of the binge eating/purging-type anorexics.

Restricting AN subjects differed significantly from those with binge eating/purging-type AN in terms of their age (z = 3.50; p < .001), duration of illness (z = 3.60; p < .001), SCL global score (z = 3.00; p < .005), SCL depression subscale (z = 2.98; p < .005), modified SCL depression subscale (z = 3.13; p < .005), SCL anxiety subscale (z = 2.65; p < .01), and SCL suicidal ideation (z = 2.65; p < .01). There were, however, no significant differences for body mass index, body composition, and the biological variables (including cholesterol levels). When compared with restricting anorexics, binge eating/purging-type AN subjects reported higher rates of suicide attempts (odds ratio = 3.6; 95% CI, 0.8–16.4; not significant), impulsive self-injurious behavior (odds ratio = 4.3; 95% CI, 1.4–13.1; p < .01) and suicidal ideation (odds ratio = 3.4; 95% CI, 1.3–9.4; p < .03).

Subjects with at least one experience of suicidal behavior (including suicide attempts, impulsive self-injurious behavior, and/or suicidal ideation) had significantly lower cholesterol levels in comparison with subjects without: 4.1 ± 1.1 vs. 4.8 ± 1.3; z = 2.42; p < .02. This was the case for the whole sample, and also for the two diagnostic subgroups even when each suicidal behavior was considered separately (Table 2).


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TABLE 2. Cholesterol Levels in Subjects Who Reported Suicide Attempts, Impulsive Self-injurious Behavior or Current Suicidal Ideation Compared to Those of Subjects Without Suicidality
 
Table 3 shows the correlation between total cholesterol levels and nutritional status in restricting and binge eating/purging-type anorexics. In the restricting group, there was not a significant correlation between nutritional status and cholesterol. We observed, however, that cholesterol levels in restricting anorexics appeared to increase with the decrease of body mass index, although they were low in the two patients with the lowest body weight (BMI of 9.6 and 10.2). When we excluded those two patients, there was a negative correlation between total cholesterol and BMI (r = –0.31; p < .04) and also between total cholesterol and free T3 (r = –0.38; p < .03).


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TABLE 3. Correlations Between Total Cholesterol Levels and Clinical Variables
 
To assess the effects of pathological eating behavior on cholesterol levels, patients with binge eating/purging-type AN were divided into patients who presented with binge eating (binging/purging anorexics) and those with only purging behavior (that is, without binge eating; purging anorexics). There was no difference in the cholesterol level between these two groups (4.9 ± 1.7 vs. 4.4 ± 1.2), but hypercholesterolemia was present in 30% of the binging anorexics and 6% of those who showed only the purging behavior. In patients with recurrent binge eating, total cholesterol was highly correlated with age and duration of illness, but the correlation between duration of illness and cholesterol became nonsignificant when we controlled for the effect of age. Moreover, in this subgroup, low total cholesterol was associated with a higher frequency of vomiting and high free T4.

Table 3 also shows the correlation’s of total cholesterol levels and SCL scores. With the exception of the binging subgroup, total serum cholesterol was significantly correlated with depression and suicidal ideation in all anorexic patients.

To better understand the relationship between cholesterol and psychiatric symptoms, taking into consideration the role of nutritional and clinical factors, we performed a series of multiple linear regression analyses, in which suicidal ideation and/or depression were the dependent variables. In the first model, we considered SCL suicidal ideation as the dependent variable and cholesterol levels, diagnostic subgroup, presence of binge eating, age, BMI, and percentage of fat mass, as independent variables. The resulting model explained 31% of the variance (F (6, 60) = 5.82; p < .001). Cholesterol levels and diagnostic subgroup were significant predictors, even when the other variables were taken into account (cholesterol levels: ß = –0.38; t = 3.53; p = .001; diagnostic subgroup: ß = 0.40; t = 2.87; p = .006). When we entered into the analysis, the modified SCL depression as a further independent variable, the amount of explained variance increased to 53% (F (7, 58) = 11.50; p < .001). In that regression, the variables with an independent significant effect on suicidal ideation were the modified SCL depression subscale (ß = 0.51; t = 5.18; p = .001), age (ß = –0.30; t = 2.89; p = .005), cholesterol levels (ß = –0.22; t = 2.45; p < .02), and diagnostic subgroup (ß = 0.30; t = 2.62; p < .02).

Using modified SCL depression as the dependent variable, the model explained 16% of the variance (F (6, 59) = 3.09; p < .02) and cholesterol level was the only variable that was found to be a significant predictor (ß = –0.25; t = 2.14; p < .04).

We analyzed the predictors of a history of suicide attempts and the presence of impulsive self-injurious behavior within a logistic regression analysis, using the same independent variables as for the multiple linear regression analysis. For the history of suicide attempts, there were no significant predictors. In contrast, impulsive self-injurious behavior was significantly predicted by cholesterol levels (Wald = 4.47; df = 1; p < .04) and diagnostic subgroup (Wald = 4.21; df = 1; p < .05). Entering the modified SCL depression subscale into this final analysis did not change the amount of variance explained (22%), nor did it remove the significance of the effect of cholesterol levels and diagnostic subgroup.


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The aim of the present study was to explore the relationship between cholesterol levels and suicidality in a sample of patients with AN. However, in eating disorders, in general, and in AN in particular, these types of studies are complicated by the fact that metabolic and nutritional factors must be taken in consideration. Indeed, while the available literature about cholesterol levels in AN pays attention to nutritional and metabolic factors, no studies have attempted to assess the relationship between lipid levels and psychiatric symptoms. We therefore begin our discussion section with the findings about nutritional factors.

Cholesterol Levels and Nutritional Status
Whereas most AN patients have normal levels of serum cholesterol (13,14), a certain percentage show hypercholesterolemia (15–18). The rate of hypercholesterolemia varies from 16% to 50% across different samples, but several methodological pitfalls (such as the use of different diagnostic criteria and often the small number of subjects) limit the generalizability of the findings from these studies. Metabolic regulation of total cholesterol in AN is a very complex issue. Low lipid intake, chronic hypoglycemia and hypoinsulinemia due to the low energy intake, hypoestrogenemia, and hypothyroidism are some of the factors that have been proposed as putative causes of altered lipid metabolism in AN (14,16,18–20). In addition, when hypercholesterolemia is present, it seems to normalize after refeeding (17,20).

The findings from our study confirm previous research (14,18,20) in which high levels of cholesterol have been found in some AN patients. In restricting subjects, cholesterol levels appear to increase with the decrease in BMI. As in the study of Feillet et al. (20), the relationship between cholesterol and BMI became evident only when patients with very severe emaciation were excluded (an alteration of the liver function, due to extreme starvation, might be the reason why serum cholesterol was low in the two patients with the lowest BMI). Hypothyroidism could account for the increase in cholesterol observed in starving anorexics (20), since we found a negative correlation between thyroid hormones and cholesterol level in both restricting- and binge eating/purging-type patients.

Different factors, such as the duration of the illness and the frequency of vomiting, seemed to affect cholesterol levels in binging AN patients. Binge eating anorexics have very disordered eating patterns, which include binge eating, vomiting, and fasting. The total lipid intake during binge eating can be very high (21), and it is well known that the frequency of eating and intake levels can influence endogenous cholesterol synthesis and metabolism (22). In addition, according to some authors (21), the binge eating/purging type of AN is the subgroup of eating disordered patients with the highest risk of hypercholesterolemia. Our study appears to confirm this possibility, although that conclusion needs to be drawn cautiously because this subgroup was very small in our sample.

Cholesterol Levels and Suicidality
As in previous research with other patients groups (4,5), we found significantly lower cholesterol levels among subjects with suicidal symptoms or behavior. This association does not appear to be affected by nutritional factors, as was shown by the series of multivariate analyses we performed. Furthermore, although low cholesterol levels seem to be associated with depressive symptoms, the effects of cholesterol levels and depression on suicidal ideation appear to be independent from each other. In addition to the common measures of suicidality studied in previous literature, such as the presence of suicide attempts and suicidal ideation, we included among the suicidality parameters the presence of impulsive self-injurious behavior. This type of behavior is rather common in patients with eating disorders (9) and appears to be specifically linked to the eating psychopathology (23,24). The finding of a significant relationship between this behavior and low cholesterol levels is interesting because impulsive self-injurious behavior has no suicidal intent. Thus, the link between suicidality and cholesterol levels appears to be related both to an increase in depressive symptoms and to an increase in impulsivity and behavioral activation. That proposal is confirmed by the logistic regression analysis we performed to identify significant predictors of impulsive self-injurious behavior. Low cholesterol levels and belonging to the binge eating/purging-type diagnostic subgroup significantly increased the risk of reporting impulsive self-injurious behavior, whereas depressive symptoms did not seem to play a role. In contrast, depressive symptoms were associated with an increased risk of reporting suicidal ideation.

Our findings seem to indicate that cholesterol levels are significantly predictive of suicidal ideation, impulsive self-injurious behavior, and depressive symptoms. This effect appears to be independent of nutritional status, age, and diagnostic subgroup, which we examined as possible confounding variables. However, from a theoretical point of view, these findings are not easy to be explained. Engelberg (2) has hypothesized that low levels of blood cholesterol may decrease the activity of serotonin receptors and serotonin transporter by increasing the fluidity of the membrane of the neural cell. In a study performed in a group of anorexic patients, Lejoyeux et al. (25) have found a decreased fluidity of the hydrophobic part of the erythrocyte membrane that was associated with higher cholesterol levels but tended to recover after refeeding. Since serotonin function is involved in the regulation of satiety/hunger, mood, and impulsivity, Engelberg’s hypothesis (2) has important clinical implications. Hypercholesterolemia in severe AN might have a protective role against depression and self-aggressive impulsivity but might also have the effect of increasing satiety. This possibility requires further investigation because it would be possible that cholesterol might play a role in the maintenance of AN.

We did not find a relationship between cholesterol levels and depressive symptoms, in the binging subgroup. It is possible that the very disordered eating that patients with binge eating reported did not allow us to detect that relationship. However, with the exception of this subgroup, our findings provide further support for the observations in previous literature that there is a presence of a significant association between lower cholesterol levels and suicidality in various psychiatric samples (3–5). It is important to acknowledge, however, that other confounding variables, not considered by our study, could explain this relationship in our sample and in previous studies. Hibbeln and Salem (26) pointed out, for example, that the relationship between serum cholesterol and depression is affected by dietary long-chain polyunsaturated fatty acids, which have a specific and crucial role in the regulation of the function of cardiovascular, nervous, and immunity systems. Dietary polyunsaturated fats, as well as monounsaturated fats, have a direct influence on membrane fluidity (27). In AN, polyunsaturated fatty acids seems to be depleted (28), but the relationship between fatty acids, cholesterol, and psychiatric symptoms in AN has not yet been subjected to empirical scrutiny.

Our findings should be regarded with caution because of the limitations of the study. Some of the variables considered in the study are self-reported and the sample size is small, particularly when diagnostic subgroups are analyzed. The study should be replicated on a different and larger sample, since the power of some of the findings is modest. Furthermore, the study has an exploratory design, which often implies the use of multiple testing and limits the power of the study.

In conclusion, although our findings need to be considered cautiously, they nevertheless highlight the need to gain a better understanding of the relationship between dietary lipids and psychopathology. In AN, many factors appear to influence the cholesterol levels, namely, degree of emaciation, age, and hypothyroidism. Despite the presence of important metabolic factors affecting cholesterolemia, our study revealed a significant relationship between low cholesterol levels on the one hand and severity of depressive symptoms, impulsive self-injurious behavior, and suicidal ideation, on the other. This association does not seem to be affected by nutritional factors, age, and diagnostic status. It therefore confirms the findings concerning the association between low cholesterol concentration and suicidal symptoms from previous studies with patients suffering from depression.

Received for publication April 23, 2003.


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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