BACKGROUND

The 4-item Patient Health Questionnaire-4 (PHQ-4) is an ultra-brief self-report questionnaire that consists of a 2-item depression scale (PHQ-2) and a 2-item anxiety scale (GAD-2). Given that PHQ-4, PHQ-2, and GAD-2 have not been validated in the general population, this study aimed to investigate their reliability and validity in a large general population sample and to generate normative data.

METHODS

A nationally representative face-to-face household survey was conducted in Germany in 2006. The survey questionnaire consisted of the PHQ-4, other self-report instruments, and demographic characteristics.

RESULTS

Of the 5030 participants (response rate=72.9%), 53.6% were female and mean (SD) age was 48.4 (18.0) years. The sociodemographic characteristics of the study sample closely match those of the total populations in Germany as well as those in the United States. Confirmatory factor analyses showed very good fit indices for a two-factor solution (RMSEA .027; 90% CI .023-.032). All models tested were structurally invariant between different age and gender groups. Construct validity of the PHQ-4, PHQ-2, and GAD-2 was supported by intercorrelations with other self-report scales and with demographic risk factors for depression and anxiety. PHQ-2 and GAD-2 scores of 3 corresponded to percentile ranks of 93.4% and 95.2%, respectively, whereas PHQ-2 and GAD-2 scores of 5 corresponded to percentile ranks of 99.0% and 99.2%, respectively.

CONCLUSIONS

A criterion standard diagnostic interview for depression and anxiety was not included.

CONCLUSIONS

Results from this study support the reliability and validity of the PHQ-4, PHQ-2, and GAD-2 as ultra-brief measures of depression and anxiety in the general population. The normative data provided in this study can be used to compare a subject's scale score with those determined from a general population reference group.

Given the relevance of child maltreatment for the development and treatment of many mental disorders, the objective of our study was the psychometric evaluation of the German version of the Childhood Trauma Questionnaire (CTQ). In a sample of psychiatric patients (N=1 524) the established factor structure (i.e. sexual, physical and emotional abuse as well as physical and emotional neglect) was replicated by means of confirmatory factor analysis. The internal consistency of all scales (apart from physical neglect) was high (Cronbachs α ≥ 0.89). Correlations between the CTQ and self-report measures for posttraumatic stress, dissociation and general psychopathology were low to moderate. The psychometric properties of the German version of the CTQ were similar to the American original; it proved to be a reliable and valid screen for the retrospective assessment of child maltreatment.

In addition to neuroendocrine changes PTSD pathophysiology may also involve dysfunction of the innate immune inflammatory system. PTSD patients have been found to exhibit increased concentrations of circulating inflammatory markers such as C-reactive protein and interleukin-6, suggesting dysfunction of the innate immune inflammatory system. However, few studies have investigated molecular signaling pathways known to critically regulate inflammation. Additionally, the relationship between inflammatory function and immune cell glucocorticoid sensitivity has not been extensively explored in PTSD. Nuclear factor-κB (NF-κB) pathway activity was examined in peripheral blood mononuclear cells obtained from 12 women with childhood abuse-related PTSD and 24 healthy controls (ages 19-48) using DNA-binding ELISA. Glucocorticoid sensitivity of monocytes in whole blood was measured as the concentration of dexamethasone needed to suppress in vitro lipopolysaccharide-induced tumor necrosis factor-alpha production by 50% (DEX IC(50)). Women with PTSD displayed increased NF-κB pathway activity compared to controls (t [34]=2.45, p=0.02) that was positively correlated with PTSD severity (determined by PTSD symptom severity scale) (r(s)=0.39, p=0.02). Increased NF-κB pathway activity was associated with increased whole blood monocyte DEX IC(50) (i.e. decreased sensitivity of monocytes to glucocorticoids) across all participants (r=0.66, p<0.001). These findings suggest that enhanced inflammatory system activity in participants with childhood abuse-related PTSD is observable at the level of NF-κB, and that in general decreased immune cell glucocorticoid sensitivity may contribute to increased NF-κB pathway activity. Enhanced inflammation may contribute to co-morbid somatic disease risk in persons with childhood abuse-related PTSD.

OBJECTIVE

Emotional dysregulation is a key feature of borderline personality disorder (BPD) with altered inhibitory functions having suggested as being crucial. The anterior cingulate cortex and further prefrontal brain regions are crucial for response inhibition. The regulation of emotions is ensured via inhibitory control over the amygdala. The present study aimed to investigate neural correlates of response inhibition in BPD by using an emotional Stroop paradigm extending the task to word stimuli which were related to stressful life events.

METHODS

Twenty BPD patients and 20 healthy controls underwent functional magnetic resonance imaging (fMRI) while performing the individual emotional Stroop task. A block design was used with the following word type conditions: neutral words, general negative words, and individual negative words. The individual negative words were recruited from a prior interview conducted with each participant.

RESULTS

While BPD patients had overall slower reaction times in the Stroop task compared to healthy controls, there was no increased slowing with emotional interference. Controls exhibited significant fMRI blood oxygenation level-dependent signal increases in the anterior cingulate cortex as well as in frontal cortex contrasting generally negative vs. neutral and individual negative vs. neutral conditions, respectively. BPD patients did not show equivalent signal changes.

CONCLUSIONS

These results provide further evidence for a dysfunctional network of brain areas in BPD, including the ACC and frontal brain regions. These areas are crucial for the regulation of stress and emotions, the core problems of BPD patients.

OBJECTIVE

Chronic pelvic pain (CPP) and fibromyalgia syndrome (FMS) have been associated with hypothalamic-pituitary-adrenal (HPA) axis alterations, i.e., mild hypocortisolism and enhanced feedback sensitivity. We tested the hypothesis of reduced cortisol release in response to a psychosocial stressor and pharmacological stimulation. Furthermore, glucocorticoid (GC) sensitivity was evaluated.

METHODS

Plasma total and salivary-free cortisol concentrations were measured in response to a standardized social laboratory stressor, the Trier Social Stress Test, and to adrenocorticotropin (ACTH)(1-24) stimulation. In the Trier Social Stress Test, we additionally measured ACTH. GC sensitivity was measured by dexamethasone inhibition of lipopolysaccharide-induced interleukin-6 and tumor necrosis factor-alpha production in whole blood.

RESULTS

There were no HPA axis alterations in women with CPP (N = 18) in these tests. Patients with FMS (N = 17) showed lower total cortisol release in response to the social stressor and exogenous ACTH, but normal free cortisol and ACTH levels compared with controls (N = 24). GC sensitivity was similar in all groups.

CONCLUSIONS

Our results suggest normal HPA responses to stress and ACTH stimulation in patients with CPP but reduced adrenal reactivity in patients with FMS, namely in total cortisol release. Free cortisol on the other hand was unaltered, possibly reflecting an adaptation to reduced circulating total cortisol.

Stress hormones, i.e. cortisol in human and cortisone in rodents, influence a wide range of cognitive functions, including hippocampus-based declarative memory performance. Cortisol enhances memory consolidation, but impairs memory retrieval. In this context glucocorticoid receptor sensitivity and hippocampal integrity play an important role. This review integrates findings on the relationships between the hypothalamus-pituitary-adrenal (HPA) axis, one of the main coordinators of the stress response, hippocampus, and memory. Findings obtained in healthy participants will be compared with selected mental disorders, including major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). These disorders are characterized by alterations of the HPA axis and hippocampal dysfunctions. Interestingly, the acute effects of stress hormones on memory in psychiatric patients are different from those found in healthy humans. While cortisol administration has failed to affect memory retrieval in patients with MDD, patients with PTSD and BPD have been found to show enhanced rather than impaired memory retrieval after hydrocortisone. This indicates an altered sensitivity to stress hormones in these mental disorders.

BACKGROUND

Patients with borderline personality disorder (BPD) frequently report unresolved life events but it is still poorly understood, how these experiences are represented in the brain. Using functional magnetic resonance imaging (fMRI), the present study aimed at investigating the neural correlates of the recall of unresolved life events in patients with BPD and healthy controls.

METHODS

Twenty female BPD patients and 21 healthy control subjects underwent fMRI. During measurement subjects recalled unresolved and resolved negative life events. Individual cue words were used to stimulate autobiographical memory. After scanning, subjects rated their emotional states during the recall of both types of memories.

RESULTS

When contrasting unresolved and resolved life events, patients showed significant bilateral activation of frontotemporal areas including the insula, amygdala, and the anterior cingulate cortex, the left posterior cingulate cortex, right occipital cortex, the bilateral cerebellum and the midbrain. In healthy subjects, no differential brain activation was related to these conditions. The 2 x 2 factorial analysis (DeltaBPD - Deltacontrols) revealed similar results with bilateral activation of the frontal cortex including parts of the insula and of the orbitofrontal cortex, temporal activation including the amygdala, activation of the right occipital cortex, and parts of the cerebellum. Patients but not controls reported higher levels of anxiety and helplessness during the unresolved versus resolved memory condition.

CONCLUSIONS

The activation of both, the amygdala and prefrontal areas, might reflect an increased effortful but insufficient attempt to control intensive emotions during the recall of unresolved life events in patients with BPD.

Dysfunctions in hypothalamic-pituitary-adrenal (HPA) axis have been reported for several mental disorders that are also often characterized by memory disturbances. It is now well established that glucocorticoids influence cognitive processes by enhancing memory consolidation and impairing memory retrieval. There is further evidence for an association between HPA axis related disturbances and memory function in mental disorders. The present selective review provides a brief overview of HPA axis dysfunction and its impact on memory function in major depressive disorder, posttraumatic stress disorder, and borderline personality disorder. Furthermore, the relevance of these findings for therapeutic intervention is discussed.

Early life stress is said to play a critical role in the development of borderline personality disorder (BPD) and major depressive disorder (MDD), but the underlying mediating factors remain uncertain. This study aimed to investigate self-reported childhood trauma, emotion regulation difficulties, and their associations in a sample of BPD (n = 49) and MDD (n = 48) patients and healthy control participants (n = 63). Multiple regressions were used to evaluate the impact of the quality and severity of self-reported childhood trauma on self-reported emotion regulation. The results supported an association between self-reported maltreatment experiences, especially emotional abuse and neglect, and emotion regulation difficulties. Additional analyses showed that emotion regulation difficulties influence the association between self-reported emotional abuse and acute symptomatology in the BPD subgroup. Emotion regulation difficulties may be 1 pathway through which early life stress, particularly emotional abuse, increases the risk for developing BPD symptomatology.

Childhood maltreatment has diverse, lifelong impact on morbidity and mortality. The Childhood Trauma Questionnaire (CTQ) is one of the most commonly used scales to assess and quantify these experiences and their impact. Curiously, despite very widespread use of the CTQ, scores on its Minimization-Denial (MD) subscale-originally designed to assess a positive response bias-are rarely reported. Hence, little is known about this measure. If response biases are either common or consequential, current practices of ignoring the MD scale deserve revision. Therewith, we designed a study to investigate 3 aspects of minimization, as defined by the CTQ's MD scale: 1) its prevalence; 2) its latent structure; and finally 3) whether minimization moderates the CTQ's discriminative validity in terms of distinguishing between psychiatric patients and community volunteers. Archival, item-level CTQ data from 24 multinational samples were combined for a total of 19,652 participants. Analyses indicated: 1) minimization is common; 2) minimization functions as a continuous construct; and 3) high MD scores attenuate the ability of the CTQ to distinguish between psychiatric patients and community volunteers. Overall, results suggest that a minimizing response bias-as detected by the MD subscale-has a small but significant moderating effect on the CTQ's discriminative validity. Results also may suggest that some prior analyses of maltreatment rates or the effects of early maltreatment that have used the CTQ may have underestimated its incidence and impact. We caution researchers and clinicians about the widespread practice of using the CTQ without the MD or collecting MD data but failing to assess and control for its effects on outcomes or dependent variables.

Memory and executive function are often impaired in patients with major depression, while cortisol secretion is increased. Mineralocorticoid receptors (MR) are abundantly expressed in the hippocampus and in the prefrontal cortex, brain areas critical for memory, executive function, and cortisol inhibition. Here, we investigated whether MR stimulation with fludrocortisone (1) improves memory and executive function and (2) decreases cortisol secretion in depressed patients and healthy individuals. Twenty-four depressed patients without medication and 24 age-, sex-, and education-matched healthy participants received fludrocortisone (0.4 mg) or placebo in a randomized, double-blind, within-subject cross-over design. We measured verbal memory, visuospatial memory, executive function, psychomotor speed, and salivary cortisol secretion during cognitive testing between 1400 and 1700 hours. For verbal memory and executive function, we found better performance after fludrocortisone compared with placebo across groups. No treatment effect on other cognitive domains emerged. Depressed patients performed worse than healthy individuals in psychomotor speed and executive function. No group effect or group × treatment interaction emerged on other cognitive domains. Fludrocortisone decreased cortisol secretion across groups and there was a significant correlation between cortisol inhibition and verbal memory performance. Our data suggest a crucial role of MR in verbal memory and executive function and demonstrate the possibility to improve cognition in depressed patients and healthy individuals through MR stimulation.

Early life stress (ELS) is associated with altered stress responsivity, structural and functional brain changes and an increased risk for the development of psychopathological conditions in later life. Due to its behavioral and physiological effects, the neuropeptide oxytocin (OXT) is a useful tool to investigate stress responsivity, even though the neurobiological underpinnings of its effects are still unknown. Here we investigate the effects of OXT on cortisol stress response and neural activity during psychosocial stress. Using functional magnetic resonance imaging in healthy subjects with and without a history of ELS, we found attenuated hormonal reactivity and significantly reduced limbic deactivation after OXT administration in subjects without a history of ELS. Subjects who experienced ELS showed both blunted stress reactivity and limbic deactivation during stress. Furthermore, in these subjects OXT had opposite effects with increased hormonal reactivity and increased limbic deactivation. Our results might implicate that reduced limbic deactivation and hypothalamic-pituitary-adrenal axis responsivity during psychosocial stress are markers for biological resilience after ELS. Effects of OXT in subjects with a history of maltreatment could therefore be considered detrimental and suggest careful consideration of OXT administration in such individuals.

OBJECTIVE

There is a lack of a psychometrically sound screening questionnaire that assesses important dimensions of traumatic experiences during childhood and adolescence in a time-efficient way. Based on the German version of the "Childhood Trauma Questionnaire" (CTQ, 28 items) we developed a five-item self-report childhood trauma screener (CTS) that covers sexual, emotional and physical abuse and emotional and physical neglect.

METHODS

The data set of the SHIP-LEGEND study (n = 1668) was used to extract five items of the CTQ that optimally covered the five dimensions and showed a high correlation with the total score. In two validation samples (clinical sample [n = 211] and subjects from the BiDirect study [n = 288]) the psychometric properties of the CTS were evaluated.

RESULTS

The correlations between the five CTS Items and the corresponding dimensions from the CTQ were r = 0.55 to 0.87 (p < 0.0001) within the clinical sample. Furthermore, we found high correlations (r = 0.88; p < 0.0001) with the total CTQ score. The internal consistency was 0.757 (Cronbachs α).

CONCLUSIONS

The CTS is a reliable, valid and economic screener for the retrospective assessment of adverse childhood experiences especially in large epidemiological studies.

BACKGROUND

Alterations of the hypothalamus-pituitary-adrenal (HPA) axis are hallmarks in major depressive disorder (MDD) and there is some evidence about similar patterns in borderline personality disorder (BPD). This study examines HPA axis abnormalities with respect to clinical characteristics in both BPD (n=24) and MDD patients (n=33) as well as in healthy control participants (n=41).

METHODS

A 0.5mg dexamethasone suppression test was administered to evaluate basal cortisol release and HPA feedback sensitivity via salivary cortisol. Traumatic experiences in childhood as well as severity of borderline and depressive symptom severity and dissociation were obtained by self-report questionnaires.

RESULTS

Compared to the healthy control group, BPD and MDD patients exhibited both enhanced cortisol concentrations before and after the administration of 0.5mg dexamethasone. Higher cortisol levels were positively correlated to a history of childhood trauma, current dissociative symptoms and severity of borderline and depressive symptoms. Regression analyses revealed that some aspects of early trauma were associated with cortisol release before and after dexamethasone, whereas psychopathology did not contribute to the regression model.

CONCLUSIONS

HPA dysfunctions appear to be related rather to childhood trauma than to psychopathology in adulthood. Exposure to childhood trauma may contribute to long-lasting alterations in HPA activity and might enhance the risk for the development of later mental disorder.

Borderline personality disorder (BPD) is a complex and serious mental disorder that is commonly seen psychiatric practice. Although stress, especially early life stress, seems to be associated with the development of the disorder, there has been far less research on the function of the hypothalamic-pituitary-adrenal (HPA) axis in BPD, compared to other psychiatric disorders, such as major depressive disorder and post-traumatic stress disorder. Stress has been suggested to exert damaging effects on the brain, particularly the hippocampus; therefore, neuroimaging studies yield important insight into the neurobiology of BPD. This article reviews research on the HPA axis and neuroimaging studies in BPD and aims to integrate these findings.

OBJECTIVE

To investigate the association between childhood trauma and multiple sclerosis (MS) by comparing histories of child abuse and neglect between patients with MS and adults from the general population in a cross-sectional case-control study. Previous research has demonstrated a connection between MS and a variety of emotional stressors, but childhood trauma, which is known to have long-lasting negative consequences for physical health decades into adulthood, has not been studied.

METHODS

The self-reported Childhood Trauma Questionnaire for the assessment of emotional, physical, and sexual abuse and emotional and physical neglect was administered to 234 patients with definite MS and 885 adults from the general population.

RESULTS

After adjusting for sociodemographic factors and current depression, patients with MS scored significantly higher in all Childhood Trauma Questionnaire subscales apart from physical abuse and neglect than adults from the general population. Adjusted odds ratios for these types of childhood trauma were higher in the MS group than in controls, ranging from 2.0 for emotional neglect (95% confidence interval = 1.3-3.2) to 3.4 for emotional abuse (95% confidence interval = 2.0-5.7). Although childhood trauma was not associated with the degree of current MS-related disability, patients with MS with histories of physical and/or sexual abuse had significantly higher relapse rates than patients without early-life stress.

CONCLUSIONS

Our findings suggest an association between childhood trauma and MS in this cross-sectional study. Larger prospective longitudinal studies are needed to clarify the relationship between early-life stress and the risk for MS in genetically susceptible individuals.

OBJECTIVE

Borderline personality disorder (BPD) is characterized by a pattern of instability in interpersonal relationships. Therefore, the investigation of social cognition is of compelling interest for the understanding of BPD. One important aspect of social cognition is theory of mind (ToM), which describes the ability to understand others' mental states, such as beliefs, desires and intentions. The aim of the present study was to further investigate ToM in BPD patients.

METHODS

The Reading the Mind in the Eyes Test was assessed in 31 BPD patients and 27 healthy controls. In addition, the test was complemented by a response confidence rating.

RESULTS

BPD patients and healthy controls did not differ in their mind-reading ability with respect to accuracy, but patients were significantly more often highly confident in their decisions than controls.

CONCLUSIONS

Overconfidence might contribute to the severe difficulties in interpersonal relationships often observed in BPD patients.

Results on hypothalamicpituitary-adrenal (HPA) axis function in fibromyalgia are heterogeneous and studies that integrate psychological and biological mechanisms in the search for pathways to fibromyalgia are rare. The goal of the study was to evaluate cortisol release and HPA axis feedback regulation in fibromyalgia and its association with psychopathology and pain. Beneath assessment of pain thresholds and self-report of pain, salivary free cortisol release over the day before and after intake of 0.5 mg of dexamethasone was measured in 21 female patients with fibromyalgia and 26 control women. Depression was assessed by questionnaires and clinical interview. We found reduced feedback sensitivity and slightly enhanced cortisol release in patients with fibromyalgia compared with healthy control subjects. Post hoc analyses showed that these effects are exclusively found in those patients, who also had major depressive disorder. Patients with fibromyalgia had lower pain pressure threshold, whereas heat pain thresholds were comparable with control subjects. Pain pressure and heat pain thresholds were not associated with cortisol release. On the other hand measurements of affective pain experience and depression were positively correlated with salivary cortisol over the day. Our results support the hypotheses that HPA axis related alterations are associated with affective disturbances, for example, depression, in patients with fibromyalgia.

CONCLUSIONS

The presented data suggest depression to be an important factor in HPA axis-related dysfunction in fibromyalgia. This might be one explanation for equivocal findings in the literature.

OBJECTIVE

Fibromyalgia syndrome (FMS) has been associated with decreased cortisol secretion. Patients with posttraumatic stress disorder (PTSD) exhibit similar hypocortisolism in the context of increased negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis. Because trauma and PTSD have been associated with fibromyalgia, we evaluated whether patients with fibromyalgia demonstrate increased HPA feedback sensitivity.

METHODS

Baseline blood samples were obtained at 0800 h, and 0.5 mg of dexamethasone was administered to 15 female patients with FMS and 20 normal controls at 2300 h. Adrenocorticotropin (ACTH), cortisol, and dexamethasone levels were measured at 0800 h after dexamethasone intake.

RESULTS

There were no group differences in mean ACTH or cortisol levels or in ACTH/cortisol ratio at baseline. After dexamethasone intake, patients with FMS exhibited more pronounced suppression of cortisol but not of ACTH, as well as increased ACTH/cortisol ratios compared with controls. Percent cortisol suppression was associated with pain and fatigue, while ACTH/cortisol ratio and dexamethasone availability were associated with stress and anxiety measures.

CONCLUSIONS

Our results suggest increased sensitivity to glucocorticoid feedback, manifested at the adrenal level, in FMS.

Free cortisol was investigated in BPD patients and healthy controls. A positive association was found between cortisol and depression scores, while the number of PTSD symptoms was negatively correlated with cortisol release. These findings suggest that alterations in cortisol release in BPD are strongly associated with the severity of psychopathology.

There are only few questionnaires for the retrospective assessment of traumatic experiences during childhood and adolescence. The "Childhood Trauma Questionnaire" (CTQ) is one of the most widely used scales. The CTQ includes 28 items covering several domains of early abuse and neglect on a 5-point Likert scale. The "Adverse Childhood Experiences Questionnaire" (ACE) consists of only 10 items. In this study we investigated 102 psychosomatic inpatients as well as 99 students and 100 adults from the general population. The internal consistency of the ACE was satisfying. Furthermore, we found high correlations with the CTQ, while the associations between depression, anxiety and bodily symptoms and ACE scores were low to moderate. In sum, the ACE is a reliable, valid and economic screen for the retrospective assessment of adverse childhood experiences.

Current research indicates altered inhibitory functioning in borderline personality disorder (BPD). The emotional stroop task is a widely used method for investigating inhibition of interference. In the present study we used an individualized version of the emotional stroop task to investigate inhibitory functioning in BPD with respect not only to valence but also to personal relevance of the stimuli. Thirty-one BPD patients and 49 healthy controls performed the individual emotional stroop task that consisted of (1) words related to personal negative life events that were currently relevant (2) words related to personal negative life events that were not currently relevant, (3) negative words that were not personally relevant, and (4) neutral words. BPD patients showed greater interference only for words related to personal negative life events with current relevance. A comparison between BPD patients with and without posttraumatic stress disorder (PTSD) revealed reduced inhibitory functioning only in BPD patients with PTSD. Inhibition of interference in BPD patients seems not to be altered in general but is exclusively disturbed in those with comorbid PTSD when highly relevant personal factors are the focus of attention.