Attentional bias in individuals with depression and adverse childhood experiences: influence of the noradrenergic system?

Rationale: Major depressive disorder (MDD) is a severe mental disorder with affective, cognitive, and somatic symptoms. Mood congruent cognitive biases, including a negative attentional bias, are important for development, maintenance, and recurrence of depressive symptoms. MDD is associated with maladaptive changes in the biological stress systems such as dysregulations of central noradrenergic alpha2-receptors in the locus coeruleus-noradrenergic system, which can affect cognitive processes including attention. Patients with adverse childhood experiences (ACE), representing severe stress experiences in early life, might be particularly affected. Objectives: With an experimental design, we aimed to gain further knowledge about the role of noradrenergic activity for attentional bias in MDD patients with and without ACE. Methods: We tested the effect of increased noradrenergic activity induced by the alpha2-receptor blocker yohimbine on attentional bias in a placebo-controlled repeated measures design. Four groups were included as follows: MDD patients with and without ACE, and healthy participants with and without ACE (total N = 128, all without antidepressant medication). Results: A significant effect of MDD on attentional bias scores of sad face pictures (p = .037) indicated a facilitated attentional processing of sad face pictures in MDD patients (compared to non-MDD individuals). However, we found no such effect of ACE. For attentional bias of happy face pictures, we found no significant effects of MDD and ACE. Even though a higher increase of blood pressure and salivary alpha-amylase following yohimbine compared to placebo indicated successful noradrenergic stimulation, we found no significant effects of yohimbine on attentional bias of happy or sad face pictures. Conclusions: Our results are consistent with the hypothesis of a negative attentional bias in MDD patients. However, as we found no effect of ACE or yohimbine, further research is needed to understand the mechanisms by which ACE increases the risk of MDD and to understand the biological basis of the MDD-related negative attentional bias

Inflammatory measures in depressed patients with and without a history of adverse childhood experiences

Background: Major depressive disorder (MDD) is a complex psychiatric condition with different subtypes and etiologies. Exposure to adverse childhood experiences (ACE) is an important risk factor for the development of MDD later in life. Evidence suggests that pro-inflammatory processes may convey this risk as both MDD and ACE have been related to increased levels of inflammation. In the present study, we aimed to disentangle the effects of MDD and ACE on inflammation levels. Methods: Markers of inflammation (plasma interleukin(IL)-6 and high sensitive C-reactive protein (hsCRP) concentrations, white blood cell (WBC) count and a composite inflammation score (CIS) combining all three) were assessed in 23 MDD patients with ACE, 23 MDD patients without ACE, 21 healthy participants with ACE, and 21 healthy participants without ACE (mean age: 35 +/- 11 (SD) years). None of the patients and participants was taking psychotropic medication. ACE was assessed with the Early Trauma Inventory (ETI) and was defined as moderate to severe exposure to sexual or physical abuse. Results: Group differences in the different inflammatory measures were observed. MDD patients with ACE showed significantly higher IL-6 concentrations (p = 0.018), higher WBC counts (p = 0.003) and increased general inflammation levels as indicated by the CIS (p = 0.003) compared to healthy controls. In contrast, MDD patients without ACE displayed similar inflammation levels to the control group (p = 0.93). Conclusion: We observed elevated inflammation in MDD patients with a history of ACE, which could indicate a subtype of "inflammatory depression". Accordingly, MDD patients with ACE might potentially benefit from anti-inflammatory therapies

Psychosocial stress increases testosterone in patients with borderline personality disorder, post-traumatic stress disorder and healthy participants

Background: The gonadal hormone testosterone not only regulates sexual behavior but is also involved in social behavior and cognition in both sexes. Changes in testosterone secretion in response to stress have been reported. In addition, stress associated mental disorders such as borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) are characterized by alterations in basal testosterone metabolism. However, testosterone changes to stress have not been investigated in mental disorders such as BPD and PTSD so far. Methods: In the study described, we investigated testosterone reactivity to an acute psychosocial stressor, the Trier Social Stress Test (TSST). Our sample consisted of young adult women with BPD (n = 28), PTSD (n = 22) or both disorders (n = 22), and healthy control (n = 51). Based on previous studies on basal testosterone secretion in these disorders, we expected the stress-associated testosterone reactivity to be higher in the BPD group and lower in the PTSD group, when compared to the healthy control group. Results: The study could demonstrate an increase in testosterone after acute stress exposure across all groups and independent of BPD or PTSD status. Different possible explanations for the absence of a group effect are discussed. Conclusions: From the results of this study, we conclude that stress-related changes in testosterone release are not affected by BPD or PTSD status in a female patient population. This study expands the knowledge about changes in gonadal hormones and stress reactivity in these disorders

Inflammatory Measures in Depressed Patients With and Without a History of Adverse Childhood Experiences

Background: Major depressive disorder (MDD) is a complex psychiatric condition with different subtypes and etiologies. Exposure to adverse childhood experiences (ACE) is an important risk factor for the development of MDD later in life. Evidence suggests that pro-inflammatory processes may convey this risk as both MDD and ACE have been related to increased levels of inflammation. In the present study, we aimed to disentangle the effects of MDD and ACE on inflammation levels.Methods: Markers of inflammation (plasma interleukin(IL)-6 and high sensitive C-reactive protein (hsCRP) concentrations, white blood cell (WBC) count and a composite inflammation score (CIS) combining all three) were assessed in 23 MDD patients with ACE, 23 MDD patients without ACE, 21 healthy participants with ACE, and 21 healthy participants without ACE (mean age: 35 ± 11 (SD) years). None of the patients and participants was taking psychotropic medication. ACE was assessed with the Early Trauma Inventory (ETI) and was defined as moderate to severe exposure to sexual or physical abuse.Results: Group differences in the different inflammatory measures were observed. MDD patients with ACE showed significantly higher IL-6 concentrations (p = 0.018), higher WBC counts (p = 0.003) and increased general inflammation levels as indicated by the CIS (p = 0.003) compared to healthy controls. In contrast, MDD patients without ACE displayed similar inflammation levels to the control group (p = 0.93).Conclusion: We observed elevated inflammation in MDD patients with a history of ACE, which could indicate a subtype of “inflammatory depression”. Accordingly, MDD patients with ACE might potentially benefit from anti-inflammatory therapies

Noradrenergic activation induced by yohimbine decreases interoceptive accuracy in healthy individuals with childhood adversity

Acute stress affects interoception, but it remains unclear if this is due to activation of the sympatho-adreno-medullary (SAM) or hypothalamicpituitary-adrenocortical axis. This study aimed to investigate the effect of SAM axis activation on interoceptive accuracy (IAcc). Central alpha2-adrenergic receptors represent a negative feedback mechanism of the SAM axis. Major depressive disorder and adverse childhood experiences (ACE) are associated with alterations in the biological stress systems, including central alpha2-adrenergic receptors. Here, healthy individuals with and without ACE as well as depressive patients with and without ACE (n=114; all without antidepressant medication) were tested after yohimbine (alpha2-adrenergic antagonist) and placebo. We assessed IAcc and sensibility in a heartbeat counting task. Increases in systolic and diastolic blood pressure after yohimbine confirmed successful SAM axis activation. IAcc decreased after yohimbine only in the healthy group with ACE, but remained unchanged in all other groups (‘group’ × ‘drug’ interaction). This effect may be due to selective up-regulation of alpha2-adrenergic receptors after childhood trauma, which reduces capacity for attention focus on heartbeats. The sympathetic neural pathway including alpha2-adrenergic circuitries may be essential for mediating interoceptive signal transmission. Suppressed processing of physical sensations in stressful situations may represent an adaptive response in healthy individuals who experienced ACE

Non-instrumental information-seeking is resistant to acute stress

Previous research has shown that people intrinsically value non-instrumental information, which cannot be used to change the outcome of events, but only provides an early resolution of uncertainty. This is true even for information about rather inconsequential events, such as the outcomes of small lotteries. Here we investigated whether participants’ willingness to pay for non-instrumental information about the outcome of simple coin-flip lotteries with guaranteed winnings was modulated by acute stress. Stress was induced using the Socially Evaluated Cold Pressor Test (SECPT), and information-seeking choices were compared to a warm water control group. Our results neither support the hypothesis that stress decreases information-seeking by directing cognitive resources away from the relevance of the lotteries, nor the opposite hypothesis that stress increases information-seeking by driving anxiety levels up. Instead, we found that despite successful stress induction, as evidenced by increased saliva cortisol levels in the SECPT group, information valuation was remarkably stable. This finding is in line with recent findings that experimentally increased state anxiety did not modulate non-instrumental information seeking. Together, these results suggest that the aversiveness of “not knowing” is a stable cognitive state and not easily modulated by situational context, such as acute stress

Telomere length in individuals with and without major depression and adverse childhood experiences

Major depressive disorder (MDD) and adverse childhood experiences (ACE) are associated with poor physical and mental health in adulthood. One underlying mechanism might be accelerated cellular aging. For example, both conditions, MDD and ACE, have been related to a biological marker of cellular aging, accelerated shortening of telomere length (TL). Since MDD and ACE are confounded in many studies, we aimed with the current study to further disentangle the effects of MDD and ACE on TL using a full-factorial design including four carefully diagnosed groups of healthy participants and MDD patients with and without ACE (total N = 90, all without use of antidepressants). As dependent variable, TL was assessed in leukocytes. We found no group differences based on MDD and ACE exposure in TL. While TL was negatively associated with age and male sex, TL was not associated with any measure of severity of MDD, ACE or current stress. One possible explanation for our null result may be the comparatively good physical health status of our sample. Future research is needed to elucidate the relation of TL, MDD and ACE, taking potential effect modification by medication intake and physical health status into account

Effects of stress on human mating preferences: stressed individuals prefer dissimilar mates

Although humans usually prefer mates that resemble themselves, mating preferences can vary with context. Stress has been shown to alter mating preferences in animals, but the effects of stress on human mating preferences are unknown. Here, we investigated whether stress alters men's preference for self-resembling mates. Participants first underwent a cold-pressor test (stress induction) or a control procedure. Then, participants viewed either neutral pictures or pictures of erotic female nudes whose facial characteristics were computer-modified to resemble either the participant or another participant, or were not modified, while startle eyeblink responses were elicited by noise probes. Erotic pictures were rated as being pleasant, and reduced startle magnitude compared with neutral pictures. In the control group, startle magnitude was smaller during foreground presentation of photographs of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to self-resembling mates. In the stress group, startle magnitude was larger during foreground presentation of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to dissimilar mates. Our findings show that stress affects human mating preferences: unstressed individuals showed the expected preference for similar mates, but stressed individuals seem to prefer dissimilar mates

Measures of the startle response: eye blink (EMG)-, skin conductance and heart rate responses.

<p>Measures of the startle response: eye blink (EMG)-, skin conductance and heart rate responses.</p