C-reactive protein, pre- and postdexamethasone cortisol levels in post-traumatic stress disorder.

BACKGROUND: Dysregulations of the hypothalamic-pituitary-adrenal axis may impact inflammatory processes in post-traumatic stress disorder (PTSD), possibly resulting in a low-grade inflammation as reflected by elevated levels of C-reactive protein (CRP). METHODS: Serum CRP levels and salivary cortisol before and after the dexamethasone suppression test (DST) were assessed in 50 inpatients with main diagnoses PTSD, major depressive disorder or borderline personality disorder. RESULTS: A strong trend for lower CRP levels was found in PTSD positive individuals compared with patients without PTSD. CONCLUSIONS: Our study does not support the hypothesis of elevated serum CRP levels in PTSD compared with other psychiatric patients. However, a dysbalanced immune system with suppressed CRP might contribute to the elevated somatic comorbidity in PTSD.

The impact of self-reported childhood trauma on emotion regulation in borderline personality disorder and major depression.

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.

Cortisol effects on autobiographic memory retrieval in PTSD: an analysis of word valence and time until retrieval.

In healthy participants, cortisol administration has been found to impair autobiographic memory retrieval. We recently reported that administration of 10 mg of hydrocortisone had enhancing effects on autobiographical memory retrieval, i.e. more specific memory retrieval, in patients with posttraumatic stress disorder (PTSD), while in healthy controls the impairing effects were replicated. We here report a re-analysis of these data with respect to cue-word valence and retrieval time. In a placebo-controlled cross-over study, 43 patients with PTSD and 43 age- and sex-matched healthy controls received either placebo or hydrocortisone orally before the autobiographical memory test was performed. We found that the effects of cortisol on memory retrieval depended on cue-word valence and group (significant interaction effects of drug by group and drug by valence by group). The enhancing effect of cortisol on memory retrieval in PTSD seemed to be relatively independent of cue-word valence, while in the control group the impairing effects of cortisol were only seen in response to neutral cue-words. The second result of the study was that in patients as well as in controls, cortisol administration led to faster memory retrieval compared to placebo. This was seen in response to positive and (to lesser extend) to neutral cue-words, but not in response to negative cue-words. Our findings illustrate that the opposing effects of cortisol on autobiographical memory retrieval in PTSD patients and controls are further modulated by the emotionality of the cue-words.

Effects of noradrenergic stimulation on memory in patients with major depressive disorder.

Major depressive disorder (MDD) has been associated with alterations in the noradrenergic system and impaired memory function. In turn, enhanced memory function has been associated with noradrenergic stimulation. In this study, we examined whether noradrenergic stimulation would differentially improve memory function in patients with MDD and healthy controls. In a placebo-controlled crossover study, 20 patients with MDD and 18 age- and sex-matched healthy controls received either placebo or 5 mg of yohimbine, an alpha-2-adrenoceptor antagonist that causes increased noradrenergic activity, orally before memory testing. A word list paradigm was used to test memory consolidation. Furthermore, the autobiographical memory test assessing memory retrieval and a working memory test were administered. Salivary alpha-amylase and blood pressure were measured. Yohimbine improved memory consolidation (word list learning) across groups (main effect of yohimbine: p = 0.05). This effect was more prominent in depressed patients compared with controls (post hoc t-test: MDD p = 0.01, controls p = 0.77). Memory retrieval (autobiographical memory specificity) and working memory were not affected by yohimbine. Across groups, yohimbine administration resulted in an increase in blood pressure and alpha-amylase. In sum, these results further support the hypothesis that noradrenergic stimulation enhances memory consolidation. The mechanism by which yohimbine leads to stronger memory consolidation in depressed patients compared with healthy controls remains to be elucidated.

Memory bias for emotional and illness-related words in patients with depression, anxiety and somatization disorders: an investigation with the directed forgetting task.

OBJECTIVE: Memory bias to emotion- and illness-related information plays a prominent role in many mental disorders, particularly major depressive disorder, anxiety disorders and somatoform disorder. The current study aimed to investigate memory bias in different mental disorders by using neutral, emotionally valenced and illness-related word stimuli in a directed forgetting task. METHODS: Seventy-eight inpatients from a university-based psychosomatic hospital participated in the study. The item method of the directed forgetting task was used, in which participants are instructed to either forget or remember each item immediately after it has been presented. Memory performance was tested with a free recall test. Overall, 36 words were presented - 6 from each of 6 categories: neutral, negative, positive, illness related ('somatoform'), depression related, and anxiety related. Three words of each category were to be remembered and 3 were to be forgotten. RESULTS: Independently of the patients' diagnoses, we found that most patients had relative difficulties remembering anxiety- and depression-related words, compared to neutral words, when they were instructed to remember them. By contrast, in the 'instructed forgetting' condition, patients showed deficits in the ability to forget illness-related stimuli relative to neutral material. These effects were unspecific with regard to diagnosis. CONCLUSIONS: The results in the 'instructed remembering' condition might be interpreted in the context of cognitive avoidance instead of a memory bias. In the 'instructed forgetting' condition, it appeared that illness-related words were more difficult to suppress compared to the other word types, which could explain the observed memory bias.

Normal mind-reading capacity but higher response confidence in borderline personality disorder patients.

AIM: 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.

[The reliable, valid and economic assessment of early traumatization: first psychometric characteristics of the German version of the Adverse Childhood Experiences Questionnaire (ACE)]. / Reliable, valide und ökonomische Erfassung früher Traumatisierung: Erste psychometrische Charakterisierung der deutschen Version des Adverse Childhood Experiences Questionnaire (ACE).

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.

Mood-congruent memory in depression - the influence of personal relevance and emotional context.

The investigation of veridical mood-congruent memory (MCM) in major depressive disorder (MDD) has been subject of many studies, whereas mood-congruent false memory has received comparatively little attention. The present study examined the influence of valence, personal relevance and the valence of the context of the learning material on true and false MCM in 20 inpatients with MDD and 20 healthy controls. Sixty positive, negative, neutral or personally relevant nouns were either combined with a positive, negative or neutral adjective. Word pairs were presented to participants in a learning trial. In a recognition task, participants had to identify the previously studied word pairs. A MCM effect could not be found for hits. However, in exploratory analyses, word pairs containing personally relevant nouns were more rated towards old by the patient relative to the control group. Furthermore, depressed patients tended to rate items more towards old than controls when the words were presented in a negative new context. Results are in line with previous findings in depression research emphasizing the role of mood-congruent false memories for mood disorders.

Noradrenergic blockade and memory in patients with major depression and healthy participants.

OBJECTIVE: Patients with major depressive disorder (MDD) often suffer from impaired declarative, episodic and working memory. Further, MDD is associated with alterations in the noradrenergic system. There is evidence that presynaptic α2 receptors that inhibit release of noradrenaline are upregulated in MDD. Results from our recent study demonstrated that increasing noradrenergic activity by blocking the α2 receptor with yohimbine leads to stronger memory consolidation in MDD patients. In the current study, we further examined the role of noradrenaline on memory in MDD by administering clonidine that activates presynaptic α2 receptors and thereby globally suppresses the noradrenergic output. METHODS: In a placebo-controlled, within-subject crossover design, 20 patients with MDD and 20 healthy controls received either 0.15 mg of clonidine or placebo orally before memory testing. A word list paradigm (memory consolidation), an autobiographical memory test (retrieval) and a working memory test were applied. Salivary alpha-amylase and blood pressure were measured. RESULTS: Across groups, clonidine decreased blood pressure and alpha-amylase. Clonidine impaired memory consolidation (word list learning) in depressed patients and controls. Memory retrieval and working memory were not affected by clonidine. CONCLUSIONS: Reducing noradrenergic activity had a specific effect on memory consolidation in patients with MDD and healthy controls. The underlying mechanisms need further scrutiny.

Effects of acute cortisol administration on response inhibition in patients with major depression and healthy controls.

Glucocorticoids (GCs) have repeatedly been shown to impair hippocampus-mediated, declarative memory retrieval and prefrontal cortex-based working memory in healthy subjects. However, recent experimental studies indicated that patients with major depressive disorder (MDD) lack these impairing effects. These missing effects have been suggested to result from dysfunctional brain GC receptors. The purpose of the present study was to investigate whether response inhibition, an executive function relying on the integrity of the prefrontal cortex, would be impaired after cortisol administration in patients with MDD. In a placebo-controlled, double blind crossover study, 50 inpatients with MDD and 54 healthy control participants conducted an emotional go/no-go task consisting of human face stimuli (fearful, happy, and neutral) after receiving a dose of 10 mg hydrocortisone and after placebo. GC administration had an enhancing effect on inhibitory performance in healthy control participants, indicated by faster responses, while no GC effect was revealed for the patients group. Moreover, patients showed an overall worse performance than healthy participants. In conclusion, this study further supports the hypothesis of impaired central glucocorticoid receptor function in MDD patients. Regarding the importance of inhibitory functioning for daily living, further studies are needed to examine the impact of glucocorticoids on response inhibition.

Acute glucocorticoid effects on response inhibition in borderline personality disorder.

INTRODUCTION: Growing evidence suggests inhibition dysfunctions in borderline personality disorder (BPD). Moreover, abnormalities in hypothalamic-pituitary-adrenal (HPA) axis functioning have also been found in BPD patients. In healthy individuals, response inhibition has been sensitive to acute stress, and previous research indicates that effects mediated by the HPA axis become particularly apparent when emotional stimuli are processed. This study aimed to explore the influence of acute hydrocortisone administration on response inhibition of emotional stimuli in BPD patients compared to healthy control participants. METHODS: After a single administration of 10mg hydrocortisone or placebo, 32 female BPD patients and 32 healthy female participants performed an adapted emotional go/no-go paradigm to assess response inhibition for emotional face stimuli in a cross-over study. RESULTS: Acute cortisol elevations decreased the reaction times to target stimuli in both BPD patients and healthy controls. Patients and controls did not differ in task performance; however, BPD patients with comorbid posttraumatic stress disorder (PTSD) displayed longer reaction times than patients without PTSD. In contrast, the occurrence of comorbid eating disorder had no significant impact on go/no-go performance. No significant interaction effect between the treatment condition and the emotional valence of the face stimuli was found. CONCLUSIONS: Acute hydrocortisone administration enhances response inhibition of face stimuli in BPD patients and healthy controls, regardless of their emotional valence. Our results agree with the suggestion that moderate cortisol enhancement increases the inhibition of task-irrelevant distracters.

Associations of childhood trauma with hypothalamic-pituitary-adrenal function in borderline personality disorder and major depression.

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). METHOD: 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.

Cortisol has enhancing, rather than impairing effects on memory retrieval in PTSD.

BACKGROUND: In the present study, we aimed to compare the effect of exogenous cortisol on memory retrieval in posttraumatic stress disorder (PTSD) with the effects in healthy controls. In healthy participants, administration of cortisol impairs declarative memory retrieval. Only a few studies have investigated these effects in PTSD yielding mixed results. METHODS: In a placebo-controlled crossover study, 44 patients with PTSD and 65 healthy controls received either placebo or 10mg of hydrocortisone orally before memory testing. In addition to declarative memory retrieval (word list learning), we also tested autobiographical memory retrieval specificity. RESULTS: In both tasks opposing effects of cortisol on memory were observed when comparing patients with controls. In controls, cortisol had impairing effects on memory retrieval, while in PTSD patients cortisol had enhancing effects on memory retrieval in both memory domains. CONCLUSIONS: The present results suggest beneficial effects of acute cortisol elevations on hippocampal mediated memory processes in PTSD. Possible neurobiological mechanisms underlying these findings are discussed.

Psychotic-like cognitive biases in borderline personality disorder.

Whereas a large body of research has linked borderline personality disorder (BPD) with affective rather than psychotic disorders, BPD patients frequently display psychotic and psychosis-prone symptoms, respectively. The present study investigated whether cognitive biases implicated in the pathogenesis of psychotic symptoms, especially delusions, are also evident in BPD. A total of 20 patients diagnosed with BPD and 20 healthy controls were administered tasks measuring neuropsychological deficits (psychomotor speed, executive functioning) and cognitive biases (e.g., one-sided reasoning, jumping to conclusions, problems with intentionalizing). Whereas BPD patients performed similar to controls on standard neuropsychological tests, they showed markedly increased scores on four out of five subscales of the Cognitive Biases Questionnaire for Psychosis (CBQp) and displayed a one-sided attributional style on the revised Internal, Personal and Situational Attributions Questionnaire (IPSAQ-R) with a marked tendency to attribute events to themselves. The study awaits replication with larger samples, but we tentatively suggest that the investigation of psychosis-related cognitive biases may prove useful for the understanding and treatment of BPD.

Hydrocortisone impairs working memory in healthy humans, but not in patients with major depressive disorder.

OBJECTIVE: Several studies have shown that stress or the administration of glucocorticoids can impair hippocampus-based declarative memory retrieval and prefrontal dependent working memory performance in healthy subjects. Major Depressive Disorder (MDD) is often characterized by memory impairment and increased cortisol secretion. Studies indicate that the impairing effects of glucocorticoids on declarative memory performance are missing in patients with MDD. The purpose of our study was to investigate whether the finding of missing effects of acute cortisol administration on memory performance in MDD is also seen when examining prefrontal-based working memory. METHODS: In a placebo-controlled study, 57 patients with MDD and 56 sex- and age-matched healthy control subjects received either placebo or 10 mg of hydrocortisone orally before memory testing. To test the verbal modality of working memory, the Word Suppression Test was applied with one negative and one neutral test part. RESULTS: After hydrocortisone intake, healthy subjects showed a significantly poorer working memory performance compared to placebo treatment when negative interference words were administered. In contrast, memory performance of MDD patients was not affected by hydrocortisone treatment. CONCLUSIONS: The missing effects of glucocorticoid administration on working memory in MDD might be interpreted in the context of reduced central glucocorticoid receptor function.

Effects of acute hydrocortisone administration on declarative memory in patients with major depressive disorder: a placebo-controlled, double-blind crossover study.

OBJECTIVE: Major depressive disorder (MDD) has been associated with hypercortisolism, reduced glucocorticoid feedback sensitivity, and impaired memory function. In healthy subjects, administration of hydrocortisone impairs declarative memory. The aim of this study was to examine the effects of acute hydrocortisone administration on memory retrieval in MDD patients and healthy controls. We further tested whether the enhancing or impairing effects of hydrocortisone would prevail when it was given after encoding and when delayed retrieval was tested at a time point when glucocorticoid levels were still elevated. METHOD: In a placebo-controlled, double-blind crossover study, 44 patients with DSM-IV MDD and 51 healthy control participants received either placebo or 10 mg of hydrocortisone orally before memory testing. A word list paradigm and the Logical Memory Test from the Wechsler Memory Scale were applied. The study was conducted from April 2008 until April 2010 at sites in Bielefeld and Hamburg, Germany. RESULTS: In both memory tests, patients with MDD performed worse than controls. Healthy controls showed impaired memory performance after hydrocortisone administration compared to placebo. In contrast, hydrocortisone had no effects on memory in MDD patients. Furthermore, in healthy controls we found that administration of hydrocortisone immediately after learning did not lead to an enhanced free recall during increased cortisol levels. CONCLUSIONS: It appears that the impairing effects of hydrocortisone on memory performance are missing in patients with MDD. This might be interpreted in the context of reduced central glucocorticoid receptor functioning.