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Psychosomatic Medicine 67:407-412 (2005)
© 2005 American Psychosomatic Society

ORIGINAL ARTICLES

Visceral Fat Deposition and Insulin Sensitivity in Depressed Women With and Without Comorbid Borderline Personality Disorder

Kai G. Kahl, MD, Maxim Bester, MD, Wiebke Greggersen, MD, Sebastian Rudolf, MD, Leif Dibbelt, MD, Beate M. Stoeckelhuber, MD, Hans-Björn Gehl, MD, Valerija Sipos, MD, Fritz Hohagen, MD and Ulrich Schweiger, MD

From the Department of Psychiatry and Psychotherapy (K.G.K., M.B., W.G., S.R., V.S., F.H., U.S.), Institute of Radiology (B.M.S.), Institute of Clinical Chemistry (L.D.), University of Luebeck, Germany.

Address correspondence and reprint requests to Kai G. Kahl, MD, Klinik für Psychiatrie und Psychotherapie, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. E-mail: kahl.k{at}psychiatry.uni-luebeck.de


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 CONCLUSIONS
 NOTES
 REFERENCES
 
Objective: Major depressive disorder (MDD) is associated with increased intra-abdominal fat, an important antecedent of noninsulin-dependent diabetes mellitus (NIDDM) and cardiovascular disorders. Furthermore, MDD is commonly accompanied by endocrine and immune dysregulation that has also been discussed in connection with the pathogenesis of NIDDM and ischemic heart disease. In borderline personality disorder (BPD), a dysregulation of the hypothalamic–pituitary–adrenal system has also been described. Therefore, our study aimed at examining visceral fat, insulin resistance, and alterations of cortisol and cytokines in young depressed women with and without comorbid BPD.

Methods: Visceral fat was measured in 18 premenopausal women with MDD and in 18 women comorbid with MDD and BPD by means of magnetic resonance tomography at the level of the first lumbar vertebral body. Twelve BPD patients without MDD and 20 healthy women served as the comparison groups. Concentrations of fasting cortisol, tumor necrosis factor-{alpha}, and interleukin-6 were measured, and indicators of insulin resistance and ß-cell sensitivity were calculated according to the homeostasis assessment model.

Results: We found increased visceral fat in women comorbid with MDD and BPD, and to a lesser extent, in women with MDD but without BPD. Insulin sensitivity was reduced in comorbid patients. Serum interleukin-6 (IL-6) and tumor necrosis factor-{alpha} concentrations were significantly increased in both groups of depressed patients. Reduced insulin sensitivity correlated with the amount of visceral fat and with serum concentrations of IL-6.

Conclusion: Young depressed women with and without comorbid BPD display increased visceral fat and may constitute a risk group for the development of NIDDM and the metabolic syndrome. Our data support the hypothesis that the immune and endocrine alterations associated with MDD and BPD may contribute to the pathophysiologic processes associated with NIDDM.

Key Words: major depressive disorder • borderline personality disorder • hypothalamic–pituitary–adrenal system • interleukin-6 • tumor necrosis factor-{alpha}

Abbreviations: BMI = body mass index; BPD = borderline personality disorder; ES = effect size; HOMA = homeostasis model assessment (-IR: insulin resistance; –S: ß-cell sensitivity); IL-6 = interleukin-6; MDD = major depressive disorder; NIDDM = noninsulin-dependent diabetes mellitus; TNF-{alpha} = tumor necrosis factor-{alpha}; VF/L = visceral fat at the level of the first lumbar vertebral body (VF/L1-: 10 mm below L1; VF/L1+ = 10 mm above L1).


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 CONCLUSIONS
 NOTES
 REFERENCES
 
Impaired glucose tolerance and relative insulin resistance have repeatedly been observed in patients with major depressive disorder (MDD) (1,2). Furthermore, recent epidemiological studies have revealed that patients with MDD are at an increased risk of developing noninsulin-dependent diabetes mellitus (NIDDM, diabetes mellitus type II) and cardiovascular diseases, particularly myocardial infarction and heart failure (3–6). An increased volume of visceral fat has been discussed as an antecedent of the metabolic syndrome and the subsequent development of NIDDM and cardiovascular diseases (7). To date, two studies concerning visceral fat deposits in depressed women have yielded partly conflicting results. Thakore and coworkers found increased intra-abdominal fat in premenopausal women when compared with a healthy comparison group (8), whereas Weber-Hamann and coworkers found no global difference of visceral fat in depressed postmenopausal women compared with a comparison group, but a positive correlation of visceral fat with cortisol concentrations (9). Increased cortisol concentrations have been associated with alterations of the regional fat distribution and with an increase of visceral fat volume [reviewed in (10)]. Both major depression and borderline personality disorder (BPD) have been associated with a dysregulation of the hypothalamus–pituitary–adrenal system with increased cortisol secretion and lowered feedback sensitivity after stimulation with dexamethasone (11–14).

Approximately 70% of major depressive episodes in young women occur in the context of personality disorders (15). In women admitted to hospitals because of depressive disorders, the leading associated personality disorders are avoidant personality disorder and BPD (up to 30% comorbidity) (16). Epidemiological research of recent years gave evidence to the hypothesis that metabolic diseases may have their roots before birth or during early childhood (17). Findings from preclinical laboratory animal studies have provided evidence that maternal deprivation and adverse rearing conditions in nonhuman primates are capable of inducing long-lived changes in endocrine and metabolic systems (18,19). Several studies have consistently shown that the majority of BPD patients had experienced adverse events early in life such as childhood abuse and neglect as well as parental loss. This type of chronic stress may lead to long-lasting alterations of endocrine and immune systems and body composition.

In the light of these results, our study aimed at examining whether young depressed patients with and without BPD may display increased visceral fat, and whether patients comorbid with MDD and BPD differ from the above-mentioned patient groups. We determined indicators of insulin resistance and ß-cell sensitivity according to the homeostasis model assessment (HOMA-IR and HOMA-S) (20) to explore whether possible alterations in the volume of visceral fat may be associated with alterations of glucose metabolism. Furthermore, we measured the pro-inflammatory cytokines tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6), which have been reported to be increased in MDD (21,22) and have also been implicated in the development of insulin resistance and NIDDM (23,24).


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 CONCLUSIONS
 NOTES
 REFERENCES
 
The study was approved by the local ethics committee, and all subjects gave their informed written consent. Eighteen depressed patients without borderline personality disorder (MDD), 18 patients comorbid with depression and borderline personality disorder (MDD/BPD), and 12 patients with borderline personality disorder but without depression (BPD) were included. Diagnosis was made according to DSM-IV criteria and was confirmed by means of a standardized interview (SCID I/II; German version). Exclusion criteria were schizophrenia, oligophrenia, pregnancy, body mass index (BMI) ≤18.5 kg/m2 or ≥30 kg/m2, and an age of 17 years or younger. Twenty healthy women recruited by announcement at university bulletin boards served as a further comparison group (CG). A standardized psychiatric interview gave no evidence of either an individual or family history of major psychiatric disorders in any subject in this group. None of the study subjects suffered from an acute infectious or lifetime autoinflammatory disease or received nonpsychotropic medication. Eleven of 18 patients with MDD/BPD, 14/18 depressed patients without BPD, and 5/12 patients with BPD received treatment with selective serotonin reuptake-inhibitors, but no other psychotropic medication.

Visceral fat was quantified by means of magnetic resonance tomography (25,26). After a scout view, visceral fat areas in all study subjects were examined at the level of the first lumbar vertebral body (VF/L1). Additional scans were performed 10 mm above (VF/L1+) and below (VF/L1-) L1 to gain more detailed information about the distribution of fat. Mean scores for each level and mean sum scores (for the three levels) were analyzed for each group. The areas (mm2) of fat were calculated on the basis of the total number of pixels of fat density (–70/–150 signal intensity units) within the anatomic compartments delineated with a graph pen. The raters were blind to the diagnostic status of the subjects.

Fasting serum samples were collected between 07:00 and 08:00 and stored at –80°C until analysis. Concentrations of fasting cortisol and fasting insulin were determined with established immunoassays (DPC, Los Angeles, CA and Nichols Institute Diagnostics, Bad Vilbel, Germany).

The homeostasis model assessment of insulin resistance and ß-cell function was calculated as proposed by Matthews and coworkers (20). This mathematical model of the glucose–insulin interaction allows an estimation of insulin resistance (HOMA-IR) and pancreatic ß-cell sensitivity (HOMA-S) from individual fasting plasma insulin and glucose concentrations. Assuming that normal-weight subjects aged <35 years have a 100% ß-cell function, and an insulin resistance of 1, the values for a patient are assessed from the insulin and glucose concentrations by the formulae: insulin resistance = insulin/(22.5e –ln glucose), and ß-cell function (%) = 20X insulin/(glucose –3.5). The estimates of the HOMA models were shown to correlate with other measures of insulin resistance and ß-cell function (euglycemic and hyperglycemic clamp technique, oral and intravenous glucose tolerance test) in healthy subjects and in diabetic patients (20,27,28).

Concentrations of TNF-{alpha} and IL-6 were assayed using high sensitivity ELISA kits according to the manufacturer’s instructions (HS Quantikinine; R&D Systems, Wiesbaden, Germany). Data were analyzed using SPSS (version 10.0). Study groups were compared using analysis of variance. Further analysis was performed with multivariate analysis of covariance (MANCOVA) and ANCOVA. Pearson’s product-moment correlation coefficients were calculated. A p value below 0.05 was considered significant. All values are given as mean ± SD.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
CONCLUSIONS
 NOTES
 REFERENCES
 
There were no significant differences among the study groups with regard to height, weight, and BMI (Table 1). Patients with MDD in the absence of BPD tended to be older than the other groups (F = 5.6; df = 3; p = .002). Therefore, further statistical analysis was performed with the covariate age.


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  		TABLE 1. Basal Data, Pro-inflammatory Cytokines and Endocrine Measures in Patients and Healthy Subjects (Mean ± SD)

 

MANCOVA with the dependent variables VF/L1, VF/L1+, and VF/L1– and the covariate age revealed significant differences between the groups (Wilks-Lambda, F = 2.4; df = 9; p = .014) after standardization for age (mean 28.9 years). Post hoc analysis confirmed increased visceral fat in depressed women with (MDD/BPD; p = .023) and without BPD (MDD; p = .048) at VF/L1- when compared with the healthy comparison group (CG) and in MDD/BPD when compared with BPD (p = .044). At VF/L1, visceral fat was increased in MDD/BPD patients when compared with the CG (p = .004). Post hoc pairwise analysis revealed a larger amount of the sum of visceral fat areas in MDD/BPD (p = .02) and a trend toward increased visceral fat areas in MDD when compared with CG (p = .077) (Figure 1).



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  		Figure 1. Visceral fat in patients and in healthy women at the level of the first lumbar vertebral body (VF/L1; B), 10 mm below (VF/L1–; A) and above (VF/L1+; C), and mean sum scores for the 3 levels (D). *Represents a p value < .05

 

MANCOVA with the dependent variables HOMA-IR and HOMA-S and the covariate age revealed significant differences between the groups (Wilks-Lambda, F = 2.3; df = 6; p = .036). Post hoc analysis confirmed increased relative insulin-resistance in MDD/BPD when compared with CG (HOMA-IR; p = .001) and a trend toward increased HOMA-IR when compared with BPD (p = .076). A relative decrease in ß-cell function expressed as HOMA-S was observed in MDD/BPD when compared with the healthy comparison group (p = .028) (Table 1).

Furthermore, ANCOVA with the covariate age revealed significant differences between the groups concerning fasting insulin (F = 4.1; df = 3; p = .01), TNF-{alpha} (F = 15.6; df = 3; p < .001), and a trend toward a significant group difference concerning IL-6 (F = 2.4; df = 3; p = .079) (Table 1). Post hoc analysis revealed increased fasting insulin (p = .002) and TNF-{alpha} serum concentrations (p = .004) in MDD/BPD versus CG, and increased TNF-{alpha} serum concentrations in MDD/BPD when compared with BPD (p = .009). TNF-{alpha} serum concentrations were increased in MDD patients when compared with all other groups (Table 1). IL-6 serum concentrations were increased in MDD and MDD/BPD when compared with CG (p = .042 and p = .015; Table 1). Blood glucose concentrations were increased in MDD/BPD versus CG (p = .048). We found a trend toward increased blood glucose concentrations (p = .081) and a trend toward increased serum cortisol in MDD when compared with CG (p = .058).

Partial correlations with the covariate age revealed significant correlations between HOMA-IR and VF/L1 (p = .002), VF/L1+ (p = .002), HOMA-S (p < .001), the mean sum score of all visceral fat areas measured (p = .009), and serum concentrations of IL-6 (p = .033) (Table 2). Fasting insulin also correlated with VF/L1 (p = .008), VF/L1+ (p = .005), HOMA-S (p < .001), HOMA-IR (p < .001), the mean sum score off all visceral fat areas measured (p = .016), and IL-6 (p = .041). HOMA-IR, fasting insulin, fasting glucose, IL-6, and HOMA-S did not correlate with BMI. BMI and serum IL-6 concentrations correlated with the amount of visceral fat at VF/L1– (p = .009), VF/L1 (p = .002), VF/L1+ (p = .002), and the mean sum score of the three fat areas (p = .006). Furthermore, we found correlations between all visceral fat areas measured (p < .001), between fasting glucose and HOMA-S, and between TNF-{alpha} and serum cortisol concentrations. No other correlations were found between any of the parameters determined (Table 2).


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  		TABLE 2. Partial Correlation Coefficients (r) With Age as Covariate Between Visceral Fat, Indices of Insulin Resistance, and Pro-inflammatory Cytokines

 

Power analysis for the sum score of all visceral fat areas showed a power of 0.85 for the contrast MDD/BPD versus CG, a power of 0.72 for the contrast MDD versus CG, and a power of 0.30 for the contrast BPD versus CG.

Logistic regression analysis revealed no influence of SSRI treatment on the results (data not shown).


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 CONCLUSIONS
NOTES
 REFERENCES
 
One major finding of the present study is that we found a larger mass of visceral fat in young depressed women with comorbid BPD, and to a lesser extent, in women with MDD without comorbid BPD when compared with a healthy CG. The sample of depressed patients examined here was relatively young (mean age 28.9 ± 6.7 years) when compared with other studies concerning an association of MDD and visceral fat (mean age 36.6 ± 4.4 years and 65.1 ± 9.2 years, respectively), and BMI was in a comparable range (mean 24.8 ± 3.3 kg/m2 versus 24.4 ± 1.7 kg/m2 and 24.5 ± 2.3 kg/m2 in both other studies) (8,9). Furthermore, in contrast to other studies concerning visceral fat in depressed patients, our patient sample was stratified for axis II diagnosis. This makes the study sample more homogeneous. The effect size (ES) of the difference between MDD/BPD patients and controls in our study (ES = 1.14) is similar to the effect size found by Weber-Hamann and coworkers between hypercortisolemic and eucortisolemic depressed patients (ES = 1.09) but lower than the effect size described by Thakore and coworkers between depressed patients and controls (ES = 3.7). All effect sizes are in the high range, and together the data support the hypothesis of an increased volume of visceral fat associated with MDD. Because of the exploratory nature of the study, we were not able to perform an ex ante power analysis. With the observed data, the power was satisfactory to reject a false null hypothesis for the contrast between MDD/BPD and MDD versus the healthy comparison group respectively, but not for the contrast between BPD and the healthy comparison group. At the present time, positive findings are limited to women with major depression. However, our data may suggest an intermediate status of patients with BPD only, pointing to a potential continuum between psychiatric normalcy and severe depression. The data may also be interpreted as suggesting that the onset of metabolic and body composition alterations is in early adulthood or even before. Women with MDD/BPD tended to have higher visceral fat areas than depressed women without BPD and were more sharply separated from the healthy CG. It may be hypothesized that this finding is related to a history of chronic stress related to a higher frequency of adverse conditions of upbringing in patients with MDD/BPD. However, this assumption is limited by the lack of reliable data about exposure to adverse conditions during childhood in our patients and the general retrospective character of information about childhood conditions.

Like others [reviewed in (13)], we found a tendency toward higher serum cortisol in patients with MDD. Hypercortisolism may contribute to insulin resistance, glucose intolerance, and hypertension, and produces central obesity (e.g., in Cushing’s syndrome) (10). Hypercortisolemia-associated resistance to insulin is thought to be an important regulator of visceral fat accumulation (29). Cortisol and insulin stimulate lipid uptake by activating lipoprotein lipase, an effect that is facilitated by high concentrations of the cortisol-activating enzyme 11-ß-hydroxysteroiddehydrogenase type I and glucocorticoid receptors in intra-abdominal fat (29,30). However, in contrast to Hamann and coworkers, we did not find a correlation between serum cortisol and volume of visceral fat. This discrepancy may be explained by different methods in cortisol measurements in both studies. Determination of cortisol concentrations by serum cortisol profiles more precisely represents alterations of the hypothalamus–pituitary–adrenal system than single fasting cortisol measurements. Furthermore, patients in our study were premenopausal, whereas Weber-Hamann et al. examined postmenopausal women (9), who tend to have higher cortisol concentrations. However, a firm relationship between cortisol concentrations and alterations of body composition and metabolic alterations in depression is not well established.

An alternative interpretation is that the only slightly elevated cortisol concentrations point to a role of insufficient cortisol signaling in the presence of inflammatory cytokines (31). As a result of insufficient glucocorticoid signaling, the release of pro-inflammatory elements from glucocorticoid-mediated inhibitory control (such as TNF-{alpha} and IL-6) may contribute to altered glucose metabolism. IL-6 production from fat cells, a major source of circulating IL-6, is negatively regulated by glucocorticoids. Impaired glucocorticoid signaling may thus lead to increased concentrations of IL-6 and subsequently to impaired insulin resistance (32). Interestingly, antidepressants have been discussed to increase glucocorticoid receptor and mineralocorticoid receptor function and expression (33). Thus, antidepressants may improve glucose metabolism by enhancing glucocorticoid signaling.

Our findings extend the existing literature in that even young depressed women with and without comorbid BPD may be at increased risk for the development of NIDDM and other disorders associated with the metabolic syndrome. Depressed patients had no overt NIDDM, and their concentrations of fasting insulin and blood glucose were each in the upper range of the reference population. HOMA results have been shown to correlate with other measures of ß-cell function and insulin resistance, such as hyperglycemic clamp technique and intravenous glucose tolerance test (20). The findings are consistent with the observations by others who found an impaired oral glucose tolerance test and resistance to insulin during depression (1,2,34). We also found a correlation of relative insulin resistance (HOMA-IR) and serum insulin concentrations with the amount of visceral fat. Visceral fat accumulation has already been described as an independent risk factor for cardiovascular diseases, hypertension, and NIDDM. Furthermore, visceral fat has been associated with a significant increase in overall morbidity and mortality (35,36). In contrast, BMI did not correlate with fasting insulin concentrations or with relative insulin resistance (expressed as HOMA-IR).

Another important finding is that of increased serum concentrations of the proinflammatory cytokines TNF-{alpha} and IL-6 in women with MDD/BPD and MDD. Both cytokines have been discussed as part of an "inflammatory response syndrome" accompanying MDD (23). Furthermore, we found a correlation of IL-6 serum concentrations with HOMA-IR. In the context of the development of NIDDM, TNF-{alpha} and IL-6 have been discussed to contribute to insulin resistance (37). TNF-{alpha} has been shown to be a potent inhibitor of the tyrosine kinase activity of the insulin receptor and mediate the development of insulin resistance in NIDDM and obesity (38,39). TNF-{alpha} and IL-6 have been shown to stimulate the release of the diabetogenic hormones growth hormone and adrenocorticotropic hormone from the anterior pituitary gland, increase the production of corticotropin-releasing hormone, and modulate the activity of the hypothalamus–pituitary–adrenal system (40,41). Furthermore, the inhibitory effect of TNF-{alpha} and IL-6 on pancreatic ß-cell function has been recognized in the context of a possible role in the etiology of islet cell destruction (42). Taken together with these findings, our data suggest that the observed increase of pro-inflammatory cytokines may contribute at least in part to insulin resistance in depressed patients with and without comorbid BPD, and increase their risk of developing NIDDM.

In young women with MDD and comorbid BPD and to a slightly lower extent in women with MDD only, we found increased visceral fat and relative insulin resistance, which are accompanied by an upregulation of pro-inflammatory cytokines. The early onset of these alterations of body composition and metabolism suggest a high impact on lifetime general health. We conclude that depressed patients are at an increased risk of developing NIDDM and other disorders associated with the metabolic syndrome.


   NOTES
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 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 CONCLUSIONS
 NOTES
REFERENCES
 

This study was supported by a grant of the University of Luebeck (MUL 2301).

DOI:10.1097/01.psy.0000160458.95955.f4


   REFERENCES
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 INTRODUCTION
 METHODS
 RESULTS
 CONCLUSIONS
 NOTES
 REFERENCES
 

  1. Mueller PS, Heninger GR, McDonald RK. Intravenous glucose tolerance test in depression. Arch Gen Psychatry 1969;21:470–7.
  2. Winokur A, Maislin G, Phillips JL, Amsterdam JD. Insulin resistance after oral glucose tolerance testing in patients with major depression. Am J Psychiatry 1988;145:325–30.[Abstract/Free Full Text]
  3. Glassmann AH, Shapiro PA. Depression and the course of coronary artery disease. Am J Psychiatry 1998;155:4–11.[Abstract/Free Full Text]
  4. Musselmann DL, Betan E, Larsen H, Phillips LS. Relationship of depression to diabetes type 1 and 2: epidemiology, biology and treatment. Biol Psychiatry 2003;54:317–29.[CrossRef][Medline]
  5. Rudisch B, Nemeroff CB. Epidemiology of comorbid coronary artery disease and depression. Biol Psychiatry 2003;54:227–40.[CrossRef][Medline]
  6. Williams SA, Kasl SV, Heiat A, Abramson JL, Krumholz HM, Vaccarino V. Depression and risk of heart failure among the elderly: a prospective community-based study. Psychosom Med 2002;64:6–12.[Abstract/Free Full Text]
  7. Björntorp P. The association between obesity, adipose tissue distribution and disease. Acta Med Scand 1987;723:121–34.
  8. Thakore JH, Richards PJ, Reznek RH, Martin A, Dinan TG. Increased intra-abdominal fat deposition in patients with major depressive illness as measured by computer tomography. Biol Psychiatry 1997;41:1140–2.[CrossRef][Medline]
  9. Weber-Hamann B, Hentschel F, Kniest A, Deuschle M, Colla M, Lederbogen F, Heuser I. Hypercortisolemic depression is associated with increased intra-abdominal fat. Psychosom Med 2002;64:274–7.[Abstract/Free Full Text]
  10. Wajchenberg LB. Subcutaneous and visceral adipose tissue. Their relation to the metabolic syndrome. Endocr Rev 2000;21:697–738.[Abstract/Free Full Text]
  11. Carroll BJ, Greden JF, Feinberg M, Lohr N, James NM, Steiner M, Haskett RF, Albala AA, DeVigne JP, Tarika J. Neuroendocrine evaluation of depression in borderline patients. Psychiatr Clin North Am 1981;4:89–99.[Medline]
  12. De la Fuente JM, Mendlewicz J. TRH stimulation and dexamethasone suppression in borderline personality disorder. Biol Psychiatry 1996;40:412–8.[CrossRef][Medline]
  13. Heuser I. The hypothalamic-pituitary-adrenal axis in depression. Pharmacopsychiatry 1998;31:10–13.[Medline]
  14. Lahmeyer HW, Reynolds CF, Kupfer DJ, King R. Biologic markers in borderline personality disorder: a review. J Clin Psychiatry 1989;50:217–25.[Medline]
  15. Corruble E, Ginestet D, Guelfi JD. Comorbidity of personality disorders and unipolar major depression: a review. J Affect Disord 1996;37:157–70.[CrossRef][Medline]
  16. Rossi A, Marinangeli MG, Butti G, Scinto A, Di Cicco L, Kalyvoka A, Petruzzi C. Personality disorders in bipolar and depressive disorders. J Affect Disord 2001;65:3–8.[CrossRef][Medline]
  17. Godfrey KM, Barker DJP. Fetal nutrition and adult disease. Am J Clin Nutr 2000;1344S–52S
  18. Plotsky PM, Meaney MJ. Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology 1993;137:1212–8.
  19. Vickers MH, Reddy S, Ikenasio BA, Breier BH. Dysregulation of the adipoinsular axis—a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming. J Endocrinol 2001;170:323–32.[Abstract]
  20. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.[CrossRef][Medline]
  21. Maes M. Major depression and activation of the inflammatory response syndrome. Adv Exp Med Biol 1999;461:25–46.[Medline]
  22. Dantzer R, Wollman E, Vitkovic L, Yirmiya R. Cytokines and depression: fortuitous or causative association? Mol Psychiatry 1999;4:328–32.[CrossRef][Medline]
  23. Nilsson J, Jovinge S, Niemann A, Reneland R, Lithell H. Relation between plasma tumor necrosis factor-alpha and insulin sensitivity in elderly men with non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1998;18:1199–1202.[Abstract/Free Full Text]
  24. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997;40:1286–92.[CrossRef][Medline]
  25. Seidell JC, Bakker CJ, van der Kooy K. Imaging techniques for measuring adipose tissue distribution—a comparison between computed tomography and 1.5-T magnetic resonance. Am J Clin Nutr 1990;51:953–7.[Abstract/Free Full Text]
  26. van der Kooy K, Seidell J. Techniques for the measurement of visceral fat: a practical guide. Int J Obes Relat Metab Disord 1993;17:187–96.[Medline]
  27. Conwell LS, Trost SG, Brown WJ, Batch JA. Indexes of insulin resistance and secretion in obese children and adolescents: a validation study. Diabetes Care 2004;27:314–9.[Abstract/Free Full Text]
  28. Hermans MP, Levy JS, Morris RJ, Turner RC. Comparison of tests of ß-cell function across a range of glucose tolerance from normal to diabetes. Diabetes 1999;48:1779–86.[Abstract]
  29. Rebuffé-Scrive M, Walsh UA, McEwen B, Rodin J. Effect of chronic stress and exogenous glucocorticoids on regional fat distribution and metabolism. Physiol Behav 1992;52:583–90.[CrossRef][Medline]
  30. Rebuffé-Scrive M, Bronnegard M, Nilsson A, Eldh J, Gustafsson J, Björntorp P. Steroid hormone receptors in human adipose tissue. J Clin Endocrinol Metab 1990;71:1215–9.[Abstract]
  31. Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry 2003;160:1554–65.[Abstract/Free Full Text]
  32. Vicennati V, Vottero A, Friedman C, Papanicolaou DA. Hormone regulation of interleukin-6 production in human adipocytes. Int J Obesity 2002;26:905–11.[CrossRef][Medline]
  33. Pariante CM, Thomas SA, Lovestone S, Makoff A, Kerwin RW. Do antidepressants regulate how cortisol affects the brain? Psychoneuroendocrinology 2003;29:423–47.
  34. Weber B, Schweiger U, Deuschle M, Heuser I. Major depression and impaired glucose tolerance. Exp Clin Endocrinol Diabetes 2000;108:187–90.[CrossRef][Medline]
  35. Björntorp P. Metabolic implications of fat distribution. Diabetes Care 1991;14:1132–43.[Abstract]
  36. Després J-P. Health consequences of visceral obesity. Ann Med 2001;33:534–41.[Medline]
  37. Fernández-Real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003;24:278–301.[Abstract/Free Full Text]
  38. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM. Tumor necrosis factor-alpha inhibits signalling from the insulin receptor. Proc Natl Acad Sci U S A 1994(a);91:4854–8.
  39. Hotamisligil GS, Spiegelman BM. Tumor necrosis factor-alpha: a key component of the obesity-diabetes link. Diabetes 1994(b);43:1271–8.
  40. Akira S, Taga T, Kishimoto T. Interleukin-6 in biology and medicine. Adv Immunol 1993;54:1–78.[Medline]
  41. Jaattela M. Biological activities and mechanisms of action of tumor necrosis factor-alpha/cachectin. Lab Invest 1991;64:724–42.[Medline]
  42. Bendtzen K, Buschard K, Diamant M, Horn T, Svenson M. Possible role of IL-1, tumor necrosis factor-alpha and IL-6 in insulin-dependent diabetes mellitus and autoimmune thyroid disease. Lymphokine Res 1989;8:335–41.[Medline]



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