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Section 22
Serum Cholesterol Level

Question 22 | Test | Table of Contents

Panic disorder seems to be associated with elevated serum cholesterol levels, but the clinical significance of these findings is still not evident. Since prospective epidemiologic studies leave no doubt about the importance of cholesterol in the development of cardiovascular diseases, elevated cholesterol levels in panic disorder could contribute to the increase in cardiovascular morbidity and mortality found in these patients. Recently, Peter and others reported clinically relevant cholesterol elevations in patients with panic disorder and phobia. First, patients also had elevated low-density lipoprotein (LDL) values and elevated cholesterol-high-density lipoprotein (HDL) ratios. Both variables were not assessed in earlier external studies. Variables are considered more specifically correlated with risk of coronary disease. Second, following the guidelines of the Expert Panel of the American National Cholesterol Education Program, patients showed a borderline high or high cholesterol range almost 3 times as frequently as control subjects and a borderline high or high LDL range 2.5 times as frequently as control subjects.

Several reports suggest that cholesterol elevation is not so much a specific pattern of panic disorders (most reports up to now) but may be associated generally with anxiety disorders. In fact, 2 studies found a cholesterol elevation in patients with general anxiety disorder (GAD). Another study showed increased lipoproteins in a mixed population of patients with panic disorder and phobia. This raises the question whether the same holds true for obsessive-compulsive disorder (OCD), which, according to DSM-IV, is classified as anxiety disorder. So far, there are 2 studies on cholesterol in OCD patients, with controversial results. Freedman and others found normal cholesterol levels, and Peter and others reported increased cholesterol values in OCD patients, compared with control subjects.

Method
Anxiety disorder patients either received treatment at our outpatient behaviour therapy unit or were admitted for inpatient treatment. They met ICD-10 criteria for anxiety disorders: panic disorder (n = 23), social phobia (n = 14), agoraphobia with panic disorder (n = 12), specific phobia (n = 5), agoraphobia without panic disorder (n = 2), adjustment disorder with predominant anxiety symptoms (n = 2), generalized anxiety disorder (n = 1), and posttraumatic stress disorder with predominant anxiety symptoms (n = 1).

OCD patients were treated as inpatients either in the University Hospital of Hamburg or at Freiburg. All subjects were participants in a multicentre study comparing the outcome of multimodal behaviour therapy (MBT) and fluvoxamine vs placebo. They all had to meet DSM-III-R criteria for an OCD. Diagnoses were made after a structured clinical interview for DSM-III-R (SCID). Patients with a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or more were included in the study.

Control subjects were recruited mainly from the staff of a large company (n = 35) or from the authors' social surrounding (n = 25). Control subjects had to be free of current or past psychiatric illnesses. They volunteered without any payment. To avoid selection bias, control subjects were unaware of their cholesterol levels and did not come from the same families. Anxiety disorder and OCD patients and control subjects were matched according to sex (30 men and 30 women) and age. Mean age in the entire population was 35.2 years (SD 10.3, range 18 to 61 years). Body mass index (BMI) was controlled in all anxiety patients, in control subjects, and in all except 1 OCD patient (Table 1).

Procedure
We drew all blood samples of anxiety disorder patients, OCD patients, and control subjects after a night of fasting. We measured cholesterol by means of enzymatic procedures (cholesterol oxidase/ phenylperoxidaseamino-phenozonphenol [CHOD-PAP], Boehringer Mannheim), adapted to the Hitachi Analyzer 747. HDL and LDL cholesterol were measured in anxiety patients and control subjects only. OCD patients participated in a study design wherein only cholesterol levels were assessed. HDL was measured by the same enzymatic procedure and by spectrometric analysis. We calculated LDL cholesterol according to the method of Friedewald and colleagues.

Results
Cholesterol levels in patients with anxiety disorder or OCD were significantly higher than were levels in normal control subjects. Cholesterol levels did not differ between anxiety disorder and OCD patients (Table 1).  We performed a more detailed comparison of serum lipoproteins between anxiety patients and control subjects. Compared with normal control subjects, there was a highly significant increase in LDL, and HDL was significantly decreased (Table 1).

The Expert Panel of the US National Education Program guidelines classify total cholesterol levels below 200 mg/dl and LDL values below 130 mg/dl as "desirable" values. Total cholesterol levels above 199 mg/dl and LDL values above 129 mg/dl, however, are classified as borderline high or high cholesterol (≥ 240 mg/dl) and borderline high LDL or high LDL (≥ 160 mg/dl), respectively. Of the anxiety disorder patients, 41/60 (68%) had borderline high or high cholesterol, as did 39/60 (65%) OCD patients. Of the control subjects, 18/60 (30%) had these levels. In addition, 14 anxiety disorder patients (23%) and 18 OCD patients (30%), compared with 8 control subjects (13%), exceeded the upper threshold of 240 mg/dl (χ² = 23.7, df 4, P = 0.0001). Of 60 anxiety disorder patients, 34 (56%) and of 60 control subjects 15 (25%) had high or borderline high LDL levels. Similarly, 15 anxiety disorder patients (25%) and only 6 control subjects (10%) exceeded the upper threshold of 160 mg/dl (χ² = 13.1, df 2, P = 0.001).

Conclusions
Some evidence exists that serum cholesterol levels in panic disorder patients are increased, compared with normal control subjects (1–3). Our data support the assumption that cholesterol elevation may be associated generally with anxiety disorders and not with panic disorder only, which up to now most reports suggest. First, our patients with anxiety disorder had elevated cholesterol levels regardless of the occurrence of panic attacks; in a previous study, patients without panic disorder had even higher cholesterol and LDL levels than had panic disorder patients. Second, cholesterol levels in OCD patients were also increased, compared with normal control subjects. OCD is an anxiety-related disorder, one that the DSM-IV also classifies as anxiety disorder.

So far, only 1 report has provided information about the clinical importance of cholesterol levels in these patients, suggesting a clinically relevant elevation in the lipometabolism. Because panic disorder was found to be associated with increased cardiovascular mortality, this issue needs further investigation. So far, there are no reports about cardiovascular morbidity in patients with phobias, GAD, and OCD. The data from our present study support the assumption that cholesterol alteration in anxiety disorder patients may be of clinical relevance. First, following the guidelines of the Expert Panel of the American National Cholesterol Education Program, the proportion of our anxiety disorder patients with borderline high or high cholesterol levels was 2.3 times higher than in normal control subjects. Second, anxiety patients also show elevated LDL and decreased HDL values. We consider both variables to correlate more specifically with risk of coronary disease. Third, anxiety patients showed high LDL levels that were 2.5 times as frequent as in control subjects. Further, the proportion of OCD patients with high cholesterol levels was 2.3 times higher than in normal control subjects.

The quality of our cholesterol data is in some aspects higher than in previous studies. To date, this is the first study that compares cholesterol levels of anxiety disorder patients, OCD patients, and normal control subjects where subjects of all 3 groups were sex- and age-matched. Likewise, the participants' BMI was adjusted among the 3 groups. Thus, the main intervening variables influencing cholesterol levels were controlled. To obtain specific information about the clinical importance of these findings, further studies in OCD should perform a more detailed analysis of the lipoproteins.
If cholesterol levels in anxiety disorders are frequently elevated, the question arises about whether these alterations represent a trait or a state factor. Up to now, only 2 studies provided data on the treatment effect on cholesterol levels in these patients. Coryell and others could not find any influence of diazepine medication in panic disorder patients on cholesterol levels. Peter and others found significantly reduced cholesterol levels in OCD patients after MBT with fluvoxamine or placebo. We need further treatment studies to settle the question about whether cholesterol levels in anxiety disorder and OCD patients benefit to a clinically meaningful extent from successful treatment of these disorders.

Table 1 Comparison: patients with anxiety disorder, patients with OCD, and normal control subjects (n = 60)
Legend for Chart: A - Anxiety disorder: Mean   B - Anxiety disorder: (SD)   C - OGD: Mean   D - OGD: (SD)  E - Controls: Mean
F - Controls: (SD)  G - ANOVA[a]: F   H - ANOVA[a]: df    I - ANOVA[a]: P

                            A                B                C

                            D                E                F

                            G                H                I

Age                  35.4            (9.6)             34.8

                       (10.8)             35.5           (10.6)

                        0.086                2             0.92

BMI                 23.7            (4.0)             24.5

                        (4.4)             23.3            (4.4)

                        1.167                2             0.31

Cholesterol     211.6           (34.3)            219.2

                       (45.1)            189.8           (38.7)

                        8.917                2           0.0002

LDL               136.3           (15.1)          —

                          —            109.2           (34.0)

                       21.272              1           0.0000

HDL               52.4           (15.5)          —

                        —             60.0           (15.1)

                       5.898               1            0.017
  

Personal Reflection Exercise #8
The preceding section contained information about serum cholesterol level and anxiety.  Write three case study examples regarding how you might use the content of this section in your practice.

Update
Efficacy of Mobile-Based Cognitive
Behavioral Therapy on Lowering Low-density
Lipoprotein Cholesterol Levels in Patients With
Atherosclerotic Cardiovascular Disease:
Multicenter, Prospective Randomized Controlled Trial

- Li, D., Xu, T., Xie, D., Wang, M., Sun, S., Wang, M., Zhang, S., Yang, X., Zhang, Z., Wang, S., Kuang, M., Tang, J., Liu, H., Hong, X., Fu, G., & Zhang, W. (2023). Efficacy of Mobile-Based Cognitive Behavioral Therapy on Lowering Low-density Lipoprotein Cholesterol Levels in Patients With Atherosclerotic Cardiovascular Disease: Multicenter, Prospective Randomized Controlled Trial. Journal of medical Internet research, 25, e44939.

Peer-Reviewed Journal Article References:
Jardin, C., Mayorga, N. A., Bakhshaie, J., Garey, L., Viana, A. G., Sharp, C., Cardoso, J. B., & Zvolensky, M. J. (2018). Clarifying the relation of acculturative stress and anxiety/depressive symptoms: The role of anxiety sensitivity among Hispanic college students. Cultural Diversity and Ethnic Minority Psychology, 24(2), 221–230.

Mesirow, M. S. C., Roberts, S., Cecil, C. A. M., Maughan, B., Jacka, F. N., Relton, C., & Barker, E. D. (2019). Serum cholesterol, MTHFR methylation, and symptoms of depression in children. Developmental Psychology, 55(12), 2575–2586.

Thorvaldsson, V., Skoog, I., & Johansson, B. (2020). Cholesterol and cognitive aging: Between-person and within-person associations in a population-based representative sample not on lipid-lowering medication. Psychology and Aging, 35(4), 508–516.

Wendell, C. R., Zonderman, A. B., Katzel, L. I., Rosenberger, W. F., Plamadeala, V. V., Hosey, M. M., & Waldstein, S. R. (2016). Nonlinear associations between plasma cholesterol levels and neuropsychological function. Neuropsychology, 30(8), 980–987.

QUESTION 22
What did Peter’s study show concerning serum cholesterol levels in anxiety disorder patients, OCD patients, and control subjects? To select and enter your answer go to Test.

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