Increased testosterone levels and cortisol awakening responses in patients with borderline personality disorder: Gender and trait aggressiveness matter
Introduction
Borderline personality disorder (BPD) is a severe mental disorder characterized by antagonism, negative affectivity, disinhibition, and impairments in interpersonal functioning, including enhanced anger-related impulsive aggression (American Psychiatric Association, 2013). Interpersonal problems such as impulsive aggression may be related to endocrine alterations. In healthy volunteers and highly aggressive populations, there is some evidence for associations between the hypothalamus–pituitary–gonadal (HPG) and hypothalamus–pituitary–adrenal (HPA) stress axis functioning and aggression (for reviews, see Van Honk et al., 2010, Carre and Mehta, 2011, Haller, 2013, Haller, 2014). Although results are inconsistent (Archer et al., 2005), increased basal testosterone levels have been reported in more aggressive individuals, and (weak) positive correlations between testosterone and aggression were found – particularly in those with low basal cortisol secretion (Popma et al., 2007, Carre and Mehta, 2011). As for cortisol secretion, positive associations with aggression have been found with both decreased and increased levels in healthy volunteers and aggressive individuals (e.g., Gerra et al., 2007, van Goozen et al., 2007, Böhnke et al., 2010a, Böhnke et al., 2010b) suggesting a general association between HPA axis dysregulations and aggressiveness (Haller, 2013, Haller, 2014).
In BPD, only few studies have investigated endocrine alterations and their association with the patients’ interpersonal impairments. This is surprising as structural and functional alterations in brain regions that are crucially involved in the processing of social threats, the regulation of the fight/flight response, and the endocrine system have been reported in BPD. Besides reduced hippocampal and amygdalar gray matter volumes, which are the most consistent structural alteration in BPD (for meta-analysis, see Nunes et al., 2009), abnormalities in gray matter volume of the anterior cingulate cortex (e.g., Hazlett et al., 2005, Minzenberg et al., 2008), the hypothalamus (Kuhlmann et al., 2013), and pituitary (Garner et al., 2007) have been observed. In addition, exaggerated and prolonged amygdala responses (e.g., Herpertz et al., 2001, Hazlett et al., 2012) seem to be a neural correlate for BPD patients’ hypersensitivity to social threats (Bertsch et al., 2013a). Patients with BPD also report more frequent and intense daily hassles (Jovev and Jackson, 2006) and elevated levels of stress-associated inner tension (Kuo and Linehan, 2009), which often precede self-injury and impulsive aggression (Kleindienst et al., 2008). As about 80% of patients diagnosed with BPD report traumatic childhood experiences, early stress and related HPA axis alterations have been discussed to play a prominent role in the etiology of BPD (Herman et al., 1989, Ogata et al., 1990). Although results of the few previous studies on HPA axis functioning are heterogeneous and may be influenced by comorbid disorders, in particular current major depression and posttraumatic stress disorder (PTSD; for review, see Zimmerman and Choi-Kain, 2009, Wingenfeld et al., 2010), there is evidence for elevated cortisol secretion and thus a basal HPA hyperactivity in BPD (Lieb et al., 2004, Wingenfeld et al., 2007, Carvalho Fernando et al., 2012). Regarding HPG activity, so far only one study investigating the occurrence of polycystic ovary (PCO) syndrome in a small group of partly medicated female patients with BPD and healthy women has shown increased plasma testosterone levels that could not be explained by PCO status or weight (Roepke et al., 2010).
Taken together, elevated basal cortisol and testosterone secretion have been reported in BPD who are characterized by more frequent and intense reactions to potential social threats and stressors and elevated stress-related inner tension which often triggers dysfunctional behaviors, such as anger-related impulsive aggression. However, little is known about effects of gender and comorbid disorders – current major depression and PTSD, in particular – as well as trait anger and aggressiveness with respect to HPG and HPA axes functioning in BPD.
The current study therefore aimed to investigate alterations in HPG and HPA axes functioning in female and male patients with BPD compared to healthy women and men controlling for comorbid conditions of current major depression and PTSD and their relationship with self-reported anger and aggressiveness. Therefore, we recruited a relatively large clinical sample of medication-free female and male patients with a current DSM-IV diagnosis of BPD and healthy women and men who provided two saliva samples to assess mean saliva testosterone levels as well as eight saliva samples at four fixed time points after awakening on two consecutive weekdays to assess the cortisol awakening response, a reliable measure for the HPA axis functioning (Schmidt-Reinwald et al., 1999, Hellhammer et al., 2007). In addition, anger and aggressiveness – as well as depressiveness, borderline symptom severity, and history of childhood traumatization – were measured with self-report questionnaires. Based on previous results, we hypothesized increased saliva testosterone levels and cortisol awakening responses in patients with BPD compared to healthy volunteers. We also expected increased testosterone levels in male compared to female patients and healthy volunteers and explored group by gender interactions as well as associations between endocrine data and self-reported anger and aggressiveness in BPD.
Section snippets
Participants
Participants were 55 patients with a current DSM-IV diagnosis of BPD (including self-injury and/or aggression; BPD; N = 35 women; Mage = 27.4, SD = 7.2, range: 18–44 years) and 47 age-, gender-, and intelligence-matched healthy volunteers (CON; N = 26 women, Mage = 28.0, SD = 6.5, range: 19–49 years) who had never received a psychiatric diagnosis or undergone any psychological or psychiatric treatment. The study was part of the German Clinical Research Unit: Mechanisms of Disturbed Emotion Processing in
Comorbidities
The comorbidity of current major depression was 23% (lifetime: 86%) in female BPD patients and 25% (lifetime: 75%) in male BPD patients and current PTSD was diagnosed in 31% (lifetime: 37%) of female and 35% (lifetime: 35%) of male BPD patients. Female and male patients did not differ significantly in the frequency of comorbid major depression or PTSD (p > .157; see Table 1 for details and statistical parameters). Further comorbid disorders comprised: anxiety disorders (female BPD: 49% current,
Discussion
The major findings of the present study are increased basal testosterone levels in a relatively large clinical sample of medication-free female and male patients with BPD as well as elevated cortisol awakening responses in female patients with BPD compared to healthy volunteers. Furthermore, cortisol awakening responses were positively correlated with trait anger and aggressiveness in female patients with BPD, while data did not indicate an association between anger/aggressiveness and
Summary and conclusions
Taken together, the results of the present study indicate increased basal saliva testosterone levels in a relatively large clinical sample of medication-free female and male patients with BPD as well as elevated cortisol awakening responses in female patients with BPD compared to a well-matched group of healthy women and men. In addition, cortisol awakening responses were positively related to trait anger and aggressiveness in female patients with BPD, but no associations were found with basal
Role of funding sources
The study was funded by the German Research Foundation (DFG; He 2660/12-1; He 2660/7-2).
Conflict of interest
The authors declare no conflict of interest.
Acknowledgement
The study was part of the clinical research unit 256 (www.kfo256.de; Schmahl et al., 2014), funded by the German Research Foundation (DFG; He 2660/12-1; He 2660/7-2).
References (73)
- et al.
Estrogen and apoptosis in the developing sexually dimorphic preoptic area in female rats
Neurosci. Res.
(1996) - et al.
Testosterone and aggression: a reanalysis of Book, Starzyk, and Quinsey's (2001) study
Aggress. Violent Behav.
(2005) - et al.
Reduced plasma oxytocin levels in female patients with borderline personality disorder
Horm. Behav.
(2013) - et al.
Exogenous cortisol enhances aggressive behavior in females, but not in males
Psychoneuroendocrinology
(2010) - et al.
Aggressive behavior and change in salivary testosterone concentrations predict willingness to engage in a competitive task
Horm. Behav.
(2008) - et al.
Associations of childhood trauma with hypothalamic–pituitary–adrenal function in borderline personality disorder and major depression
Psychoneuroendocrinology
(2012) - et al.
CSF testosterone: relationship to aggression, impulsivity, and venutresomeness in adult males with personality disorder
J. Psychiatr. Res.
(2007) - et al.
Pituitary volume in teenagers with first-presentation borderline personality disorder
Psychiatry Res.
(2007) - et al.
Experimentally induced aggressiveness in heroin-dependent patients treated with buprenophine: comparison of patients receiving metahdone and healthy subjects
Psychiatry Res.
(2007) The neurobiology of abnormal manifestations of aggression – a review of hypothalamic mechanisms in cats, rodents, and humans
Brain Res. Bull.
(2013)
Reduced anterior and posterior cingulate gray matter in borderline personality disorder
Biol. Psychiatry
Potentiated amygdala response to repeated emotional pictures in borderline personality disorder
Biol. Psychiatry
Several daily measurements are necessary to reliably assess the cortisol rise after awakening: state- and trait components
Psychoneuroendocrinology
Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study
Biol. Psychiatry
Roles of steroid hormones and their receptors in structural organization in the nervous system
Neurosci. Res.
Increased diurnal salivary cortisol in women with borderline personality disorder
J. Psychiatr. Res.
Estrogen formation in the mammalian brain: possible role of aromatase in sexual differentiation of the hippocampus and neocortex
Steroids
Testosterone and cortisol jointly regulate dominance: evidence for a dual-hormone hypothesis
Horm. Behav.
Frontolimbic structural changes in borderline personality disorder
J. Psychiatr. Res.
Relations among posttraumatic stress disorder, comorbid depression, and HPA function: a systematic review and meta-analysis
Clin. Psychol. Rev.
Cortisol moderates the relationship between testosterone and aggression in delinquent male adolescents
Biol. Psychiatry
Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change
Psychoneuroendocrinology
Incidence of polycystic ovaries and androgen serum levels in women with borderline personality disorder
J. Psychiatr. Res.
Initial evidence for sex-specific effects of early emotional abuse on affective processing in bipolar disorder
Eur. Psychiatry
Adolescent adrenocortical activity and adiposity: differences by sex and exposure to early maternal depression
Psychoneuroendocrinology
The cortisol response to awakening in relation to different challenge tests and a 12-hour cortisol rhythm
Life Sci.
Neuronal correlates of cognitive reappraisal in borderline patients with affective instability
Biol. Psychiatry
Diurnal salivary cortisol in relation to perceived stress at home and at work in healthy men and women
Biol. Psychol.
Borderline personality disorder: hypothalamus pituitary adrenal axis and findings from neuroimaging studies
Psychoneuroendocrinology
Diagnostic and Statistical Manual of Mental Disorders
Beck-Depressions-Inventar: BDI, 2., überarb. Aufl.
Childhood Traume Questionnaire. A Retrospective Self-report: Maunal
Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder
Am. J. Psych.
The relationship between basal and acute HPA axis activity and aggressive behavior in adults
J. Neural Transm.
The short version of the Borderline Symptom List (BSL-23): development and initial data on psychometric properties
Psychopathology
The aggression questionnaire
J. Pers. Soc. Psychol.
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