Hypothalamic-pituitary-adrenal axis response in borderline personality disorder without post-traumatic features

Hypothalamic–pituitary–adrenal (HPA) axis sensitivitywas investigated in 32 non-medicated patients with borderlinepersonality disorder without comorbid post-traumatic syndromesand in 18 normal individuals using a modified dexamethasonesuppression test (0.25 mg). Enhanced cortisol suppression wasfound in the patients v. controls (P<0.05) and the percentageof participant's with non-suppression was smaller in the patient(34%) than in the control group (89%) (P<0.01). Baselinecortisol levels in the patients were also lower than in thecontrols (P<0.05). The 0.25 mg dexamethasone suppressiontest reveals increased feedback inhibition of the HPA in borderlinepersonality disorder.

INTRODUCTION

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INTRODUCTION

Hypothalamic–pituitary–adrenal (HPA) axis responsein borderline personality disorder is controversial. Severalstudies published two decades ago reported high rates of non-suppressionwith the 1 mg dexamethasone test in patients with borderlinepersonality features, suggesting an association of the conditionwith affective disorders (Sternbach et al, 1983). However,recent studies suggest some similarities with HPA axis disturbancesfound in post-traumatic stress disorder (PTSD). Studies of peoplewith PTSD have reported lower cortisol levels than in a normal comparison group, increased lymphocyte glucocorticoid receptordensity and enhanced cortisol suppression with a 0.5 mg dexamethasonetest (Rinne et al, 2002; Yehuda et al, 2004). On the otherhand, several studies with the 0.5 mg dexamethasone test have reported enhanced cortisol suppression in patients with borderlinepersonality disorder and comorbid post-traumatic symptoms (Grossman et al, 2003, Lange et al, 2005), but not in patients with this personalitydisorder but without PTSD. However, cortisol suppression wasvery high in the normal control group in these studies, rangingfrom 70% to 85%, which might have reduced the discriminatory power of the 0.5 mg test. A preliminary study with a lowerdose (0.25 mg) of dexamethasone (Carrasco et al, 2003) reportedenhanced cortisol suppression in borderline personality disorderwith no comorbid PTSD compared with other personality disordersand demonstrated high specificity for detection of cortisol suppression. However, the conclusions were limited by the absenceof a comparison group of normal individuals.

METHOD

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METHOD

Patients were selected at the emergency room for repetitiveself-aggressive behaviour (at least two episodes in the preceding6 months) and evaluated by a senior psychiatrist with the StructuredClinical Interview for DSM–IV Axis I Disorders (SCID–I;First et al, 1995) and Axis II Personality Disorders (SCID–II;First et al,,1997), as well as with the Childhood Trauma Questionnaire (Bernstein et al, 2003) and the Zanarini Rating Scale forBorderline Personality Disorder (ZAN–BPD; Zanarini et al, 2003).

Fifty-one patients with a diagnosis of borderline personalitydisorder were selected. Those with comorbid PTSD (n=4) wereexcluded, as were those with current major depression (n=9)or substance dependence (n=4) and a lifetime history of bipolardisorder (n=1) or schizophreniform disorder (n=1). Finally,32 patients with no major metabolic or hormonal disease enteredthe study and were admitted to the hospitalisation unit fora wash-out period to eliminate medication and other drugs.The control group included 18 healthy individuals recruitedfrom a healthcare prevention programme and matched with thepatients for age and gender.

Biological tests followed a wash-out period of at least 1 weekfor anxiolytic medication and 3 weeks for other medicationsand illicit drugs (5 weeks for fluoxetine). Participants wereadmitted to the psychoendocrinology research unit at 07.30h on day 1. An intravenous catheter was inserted at 08.00 h,allowing subsequent blood sampling exempt from the stress-inducing effects of needle-sticks. After 30 min, a blood sample wastaken for measurement of plasma cortisol. At 23.00 h on day1 the participants were administered an oral capsule containing0.25 mg dexamethasone, and on day 2 at 08.00 h blood sampleswere taken again for cortisol measurement. Participants weretested under strictly controlled conditions, including minimalactivity, 8 h fasting and sleep from 23.00 h the previous night.

Between-group comparisons employed analysis of covariance (ANCOVA)for differences in percentage cortisol suppression and chi-squaredtests for differences in the rate of non-suppressor participants.Within the patient group relationships between variables wereexplored using Pearson's correlation coefficients. All statisticalanalyses were two-tailed with a 0.05 level of significance.

RESULTS

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RESULTS

Distribution of age (patients, mean 30.6 years, s.d=6.4; controls,mean 29.7 years, s.d.=5.5) and gender (patients, 59% female;controls, 61%) showed no significant difference between groups.Across all groups, cortisol suppression was 55% (s.d.=31.4)in women and 50% (s.d.=35.0) in men, with no significant difference(t=0.52, d.f.=41, P=0.6).

Cortisol non-suppression was defined as a post-test cortisollevel >5 µg/dl. In the borderline personality disordergroup, 10 out of 29 patients (34%) were non-suppressors, v.14 of 16 control participants (88%) ( ${chi}$ ²=11.6, d.f.=1, P<0.01).Analysis of covariance revealed that the patient group hadsignificantly lower cortisol levels pre-test (F=4.0, d.f.=1,P<0.05) and post-test (F=19.8, d.f.=1, P<0.01) comparedwith controls, as well as a significantly greater percentagecortisol suppression suppression (F=11.09, d.f.=1, P>0.01) (Table 1). The difference in cortisol levels was not significantlyaltered by reanalysis with age, anxiety or depression scoresas covariates.

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Table 1 Cortisol suppression in the 0.25 mg dexamethasone test

Percentage cortisol suppression significantly correlated withseverity of disorder on the Zanarini scale (r=0.42, P<0.05)but not with scores on the Childhood Trauma Questionnaire (r=0.068, P=0.73), which were higher in the patient group (mean 30.1,s.d.=8.1, range 16–54) than the controls (mean 23.2,s.d.=9.7, range 15–48; t=3.0, d.f.=66, P<0.01).

DISCUSSION

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DISCUSSION

Significantly low baseline cortisol levels and enhanced cortisol suppression with 0.25 mg dexamethasone in borderline personalitydisorder without comorbid PTSD seem to be contrary to findingsin previous studies (Rinne et al, 2002; Grossman et al, 2003; Lange et al, 2005) reporting enhanced cortisol suppressionin borderline personality disorder to be associated specificallywith PTSD symptoms. The relationship of enhanced cortisol suppressionand borderline personality disorder in our study is furthersupported by significant correlation with severity of disorder (ZAN–BPD) and the lack of significant correlation withchildhood trauma scores.

Interestingly, the rate of comorbid PTSD in our patient sample(10%) was lower than that reported in previous studies (Grossman et al, 2003; Lange et al, 2005), which found rates of PTSD comorbidityof 25–50%. This suggests that the patients in our samplemight have been clinically different from those in other studies,who were recruited by advertisements or from veterans' hospitalsor facilities for abused women. This might have increased homogeneity,thereby favouring detection of biological abnormalities in borderlinepersonality disorder, which is composed of different clinicaland biological domains.

Also, methodological differences might explain the discrepancyof our results with other studies reporting high salivary baselinecortisol levels and increased rates of non-suppression in borderlinepersonality disorder (Lieb et al, 2004). In addition, methodologicaldifferences in cortisol measurement might also lead to differentresults. We used a laboratory method with strictly controlled conditions of environmental stress, including 30–60 minof relaxed delay before sample extraction. Ambulatory conditionsfor cortisol salivary sampling in the previously mentionedstudy might not be free of external stress influences, whichcould account for increased cortisol levels.

The very low dose (0.25 mg) of dexamethasone might be responsiblefor the strong group effect which was not found in previousstudies using 0.5 mg doses. As predicted, 0.25 mg dexamethasoneproduced milder cortisol suppression in the control group thanthe 0.5 mg dose as reported in previous studies (31% v. 60–80%) (Rinne et al, 2002; Grossman et al, 2003; Lange et al, 2005). Furthermore, 65% of the patients in our study were categorisedas complete suppressors (cortisol level <5 µg/dl)compared with only 12% of controls, suggesting that the 0.25mg dexamethasone test could be useful for discriminating abnormalHPA axis functioning in personality disorders.

In conclusion, our results show low plasma cortisol levels andenhanced cortisol suppression in a 0.25 mg dexamethasone suppressiontest in individuals with borderline personality disorder withno PTSD compared with healthy controls. Increased HPA feedbackinhibition probably reflects increased lymphocyte glucocorticoidreceptor density, which might be secondary to previous intenseand persistent stress in both disorders (Yehuda et al, 2004). However, these results apply to a specific subgroup of patientsselected by the presence of repetitive self-aggressive behavioursin the previous 6 months, and should not be generalised toall people with borderline personality disorder.

REFERENCES

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