Effects of stress-related neuromodulators on amygdala and hippocampus resting state functional connectivity.

BACKGROUND: The human stress response is characterized by increases in neuromodulators, including norepinephrine (NE) and cortisol. Both neuromodulators can enter the brain and affect neurofunctional responses. Two brain areas associated with stress are the amygdala and the hippocampus. The precise influence of NE and cortisol on the amygdala and hippocampal resting state functional connectivity (RSFC) is poorly understood. AIMS: To investigate the influence of NE and cortisol on the amygdala and hippocampal RSFC. METHODS: We recruited 165 participants who received 10 mg yohimbine and/or 10 mg hydrocortisone in a randomized, placebo-controlled design. With seed-based analyses, we compared RSFC of the hippocampus and amygdala separately between the three groups that received medication versus placebo. RESULTS: We found no differences between yohimbine and placebo condition or between hydrocortisone and placebo condition regarding amygdala or hippocampal FC. Compared with placebo, the yohimbine/hydrocortisone condition showed increased amygdala and hippocampal RSFC with the cerebellum. Also, they had increased hippocampal RSFC with the amygdala and cerebral white matter. DISCUSSION: The group with elevated NE and cortisol showed significantly increased RSFC between the amygdala, hippocampus, and cerebellum compared to placebo. These three brain areas are involved in associative learning and emotional memory, suggesting a critical role for this network in the human stress response. Our results show that NE and cortisol together may influence the strength of this association. Compared to placebo, we found no differences in the groups receiving only one medication, suggesting that increasing one neuromodulator alone may not induce differences in neurofunctional responses. The study procedure has been registered at clinicaltrials.gov (ID: NCT04359147).

The effects of yohimbine and hydrocortisone on selective attention to fearful faces: An fMRI study.

INTRODUCTION: Selective attention to salient emotional information can enable an advantage in the face of danger. The present study aims to investigate the influence of the stress neuromodulators, norepinephrine and cortisol, on selective attention processes to fearful faces and its neuronal activation. METHODS AND MATERIALS: We used a randomized, double-blind, placebo-controlled design. 167 healthy men between 18 and 35 years (mean [SD] age: 25.23 [4.24] years) participated in the study. Participants received either: (A) yohimbine (n= 41), (B) hydrocortisone (n = 41), (C) yohimbine and hydrocortisone (n = 42) or (D) placebo only (n= 43) and participated in a dot-probe task with fearful and neutral faces in an fMRI scanner. RESULTS: We found an attentional bias toward fearful faces across all groups and related neuronal activation in the left cuneus. We did not find any differences between experimental treatment groups in selective attention and its neuronal activation. DISCUSSION: Our results provide evidence that fearful faces lead to an attentional bias with related neuronal activation in the left cuneus. We did not replicate formerly reported activation in the amygdala, intraparietal sulcus, dorsal anterior cingulate cortex, and thalamus. Suitability of the dot-probe task for fMRI studies and insignificant treatment effects are discussed.

No changes in triple network engagement following (combined) noradrenergic and glucocorticoid stimulation in healthy men.

Successful recovery from stress is integral for adaptive responding to the environment. At a cellular level, this involves (slow genomic) actions of cortisol, which alter or reverse rapid effects of noradrenaline and cortisol associated with acute stress. At the network scale, stress recovery is less well understood but assumed to involve changes within salience-, executive control-, and default mode networks. To date, few studies have investigated this phase and directly tested these assumptions. Here, we present results from a double-blind, placebo-controlled, between-group paradigm (N = 165 healthy males) administering 10 mg oral yohimbine and/or 10 mg oral hydrocortisone two hours prior to resting state scanning. We found no changes in within-network connectivity of the three networks, both after single and combined drug administration. We further report the results of Bayesian parameter inference to provide evidence for the null hypothesis. Our results contrast with previous findings, which may be attributable to systematic differences between paradigms, highlighting the need to isolate paradigm-specific effects from those related to stress.

Childhood trauma and cortical thickness in healthy women, women with post-traumatic stress disorder, and women with borderline personality disorder.

BACKGROUND: Structural brain changes have been associated with childhood trauma (CT) and several trauma-associated mental disorders. It is not known whether specific brain alterations are rather associated with CT as such or with disorders that are common sequelae of CT. In this study, we characterized cortical thickness in three distinct groups with CT: healthy women (HC/CT), women with posttraumatic stress disorder (PTSD/CT) and women with borderline personality disorder (BPD/CT). These three CT-exposed groups were compared with healthy controls not exposed to CT (HC). METHODS: We recruited 129 women (n = 70 HC, n = 25 HC/CT, n = 14 PTSD/CT, and n = 20 BPD/CT) and acquired T1-weighted anatomical images. FreeSurfer was used for conducting whole-brain cortical thickness between-group comparisons, applying separate generalized linear models to compare cortical thickness of each CT-exposed group with HC. RESULTS: The HC/CT group had lower cortical thickness in occipital lobe areas (right lingual gyrus, left lateral occipital lobe) than the HC group. The BPD/CT group showed a broader pattern of reduced cortical thickness compared to the HC group, including the bilateral superior frontal gyrus, and bilateral isthmus, the right posterior, and left caudal anterior of the cingulate cortex as well as the right lingual gyrus of the occipital lobe. We found no differences between PTSD/CT and HC. CONCLUSIONS: Cortical thickness reduction in the right lingual gyrus of the occipital lobe seem to be related to CT but is also present in BPD patients even after adjusting for severity of CT. Possibly, reduced cortical thickness in the lingual gyrus presents a CT-related vulnerability factor for CT-related adult psychopathologies such as BPD. Reduced cortical thickness in the frontal and cingulate cortex may represent unique neuroanatomical markers of BPD possibly related to difficulties in emotion regulation.

Association between baseline dissociation levels and stress-induced state dissociation in patients with posttraumatic-stress disorder, borderline personality disorder, and major depressive disorder.

INTRODUCTION: Dissociative symptoms are highly prevalent in patients with trauma-related disorders such as borderline personality disorder (BPD) and posttraumatic-stress disorder (PTSD), and also occur in patients with depressive disorders. Acute dissociative states are theorized to be stress-related, and some individuals experience recurring patterns of dissociation. The relationship between the intensity of dissociative episodes (trait-like dissociation) and acute dissociative states, however, is incompletely understood. In the present study, we investigated how levels of baseline (trait-like) dissociation relate to changes in dissociative states during a laboratory stress induction. METHODS: Our female sample comprised 65 patients with BPD and/or PTSD, 84 patients with major depressive disorder (MDD) and 44 non-clinical controls (NCC). Baseline dissociation was assessed at the start of the study using the Dissociation Tension Scale past week version (DSS-7). All participants underwent the Trier Social Stress Test (TSST) and a placebo version (P-TSST). Before and after the TSST or P-TSST, state dissociation was assessed using the Dissociation Tension Scale acute (DSS-4). We used structural equation models to estimate changes in state dissociation items (somatoform dissociation, derealization, depersonalization, analgesia), and to test whether these changes relate to levels of baseline dissociation. RESULTS: We found significant increases in all state dissociation items in response to the TSST in patients with BPD and/or PTSD and patients with MDD, but not in NCCs. Increases in somatoform dissociation and derealization during the TSST were significantly related to higher levels of baseline dissociation in patients with BPD and/or PTSD, but not in patients with MDD or NCCs. Results indicate no significant changes in state dissociation during the P-TSST. CONCLUSION: Our results replicate earlier findings that patients with BPD and/or PTSD report higher levels of stress-related state dissociation than NCC and extend them to patients with MDD. In addition, our findings indicate that baseline levels of dissociation relate to stress-induced changes in state dissociation among patients with BPD and PTSD, but not patients with MDD. In clinical applications, measures of baseline dissociation could be used to facilitate the prediction and treatment of stress-related dissociative states in patients with BPD and/or PTSD.

Association between childhood trauma and brain anatomy in women with post-traumatic stress disorder, women with borderline personality disorder, and healthy women.

Background: Childhood trauma (CT) is associated with altered brain anatomy. These neuroanatomical changes might be more pronounced in individuals with a psychiatric disorder. Post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD) are more prevalent in individuals with a history of CT. Objective: In this study, we examined limbic and total brain volumes in healthy women with and without a history of CT and in females with PTSD or BPD and a history of CT to see whether neuroanatomical changes are a function of psychopathology or CT. Method: In total, 128 women (N = 70 healthy controls without CT, N = 25 healthy controls with CT, N = 14 individuals with PTSD, and N = 19 individuals with BPD) were recruited. A T1-weighted anatomical MRI was acquired from all participants for Freesurfer-based assessment of total brain, hippocampus, and amygdala volumes. Severity of CT was assessed with a clinical interview and the Childhood Trauma Questionnaire. Group differences in hippocampal and amygdala volumes (adjusted for total brain volume) and total brain volume (adjusted for height) were characterized by analysis of covariance. Results: Volume of the total brain, hippocampus, and amygdala did not differ between the four groups (p > .05). CT severity correlated negatively with total brain volume across groups (r = -0.20; p = .029). Conclusions: CT was associated with reduced brain volume but PTSD or BPD was not. The association between CT and reduced brain volume as a global measure of brain integrity suggests a common origin for vulnerability to psychiatric disorders later in life.

Antecedentes: El trauma infantil (TI) se asocia con alteraciones en la anatomía cerebral. Estos cambios neuroanatómicos pueden ser más pronunciados en individuos con trastornos psiquiátricos. El trastorno de estrés postraumático (TEPT) y el trastorno de personalidad limítrofe (TPL) son más prevalentes en individuos con historia de TI.Objetivo: En este estudio, examinamos los volúmenes límbico y cerebral total en mujeres sanas con y sin historia de TI y mujeres con TEPT o TPL e historia de TI para ver si los cambios neuroanatómicos son una función de la psicopatología o del TI.Método: En total, 128 mujeres (N= 70 controles sanas sin TI, N= 25 controles sanas con TI, N= 14 individuos con TEPT y N= 19 individuos con TPL) fueron reclutadas. Se obtuvo una RNM anatómica ponderada en T1 de todas las participantes para la evaluación basada en Freesurfer de los volúmenes totales del cerebro, hipocampo y amígdala. La severidad del TI fue evaluada con una entrevista clínica y con el Cuestionario de Trauma Infantil. Las diferencias grupales en los volúmenes del hipocampo y amígdala (ajustadas por el volumen cerebral total) y el volumen cerebral total (ajustadas por altura) se caracterizaron mediante análisis de covarianza.Resultados: El volumen total del cerebro, hipocampo y amígdala no difirieron entre los cuatro grupos (p > .05). La severidad del TI se correlacionó negativamente con el volumen cerebral total en todos los grupos (r = −0.20; p =.29).Conclusiones: El TI estuvo asociado a un volumen cerebral reducido, pero el TEPT o TPL no se asociaron. La asociación entre TI y volumen cerebral disminuido como una medida global de la integridad cerebral sugiere un origen común de vulnerabilidad a los trastornos psiquiátricos más adelante en la vida.

Effects of glucocorticoid and noradrenergic activity on implicit and explicit facial emotion recognition in healthy young men.

The ability to recognize emotions from facial expressions is crucial for social interaction. Only few studies have examined the effect of stress hormones on facial emotion recognition, although stressful events affect social interactions on a daily basis. Those studies that examined facial emotion recognition mostly used explicit prompts to trigger consciously controlled processing. However, facial emotions are processed mainly implicitly in real life. Therefore, we investigated separate and combined effects of noradrenergic and glucocorticoid stimulation on implicit and explicit facial emotion recognition. One hundred and four healthy men (mean age = 24.1 years ±SD 3.5) underwent the Face Puzzle task to test implicit and explicit facial emotion recognition after receiving either 10 mg hydrocortisone or 10 mg yohimbine (an alpha 2-adrenergic receptor antagonist that increases noradrenergic activity) or 10 mg hydrocortisone/10 mg yohimbine combined or placebo. Salivary cortisol and salivary alpha amylase (sAA) were measured during the experiment. Compared to the placebo condition hydrocortisone significantly increased salivary cortisol and yohimbine significantly increased sAA. Participants were better and faster in explicit than in implicit facial emotion recognition. However, there was no effect of separate and combined noradrenergic and glucocorticoid stimulation on implicit and explicit facial emotion recognition performance compared to placebo. Our results do not support an essential role of the glucocorticoid and noradrenergic system in FER in young healthy men.

Comparison of Four fMRI Paradigms Probing Emotion Processing.

Previous fMRI research has applied a variety of tasks to examine brain activity underlying emotion processing. While task characteristics are known to have a substantial influence on the elicited activations, direct comparisons of tasks that could guide study planning are scarce. We aimed to provide a comparison of four common emotion processing tasks based on the same analysis pipeline to suggest tasks best suited for the study of certain target brain regions. We studied an n-back task using emotional words (EMOBACK) as well as passive viewing tasks of emotional faces (FACES) and emotional scenes (OASIS and IAPS). We compared the activation patterns elicited by these tasks in four regions of interest (the amygdala, anterior insula, dorsolateral prefrontal cortex (dlPFC) and pregenual anterior cingulate cortex (pgACC)) in three samples of healthy adults (N = 45). The EMOBACK task elicited activation in the right dlPFC and bilateral anterior insula and deactivation in the pgACC while the FACES task recruited the bilateral amygdala. The IAPS and OASIS tasks showed similar activation patterns recruiting the bilateral amygdala and anterior insula. We conclude that these tasks can be used to study different regions involved in emotion processing and that the information provided is valuable for future research and the development of fMRI biomarkers.

Effects of hydrocortisone and yohimbine on selective attention to emotional cues.

INTRODUCTION: Facial expressions contain important affective information, and selective attention to facial expression provides an advantage in the face of loss, stress and danger. In addition, the sympathetic nervous system and hypothalamus-pituitary-adrenal axis mediate the organism's response to loss and danger. Here, we aimed at investigating the influence of sympathetic nervous system and hypothalamus-pituitary-adrenal axis activation on selective attention to affective facial stimuli. METHODS AND MATERIALS: One hundred-and-four healthy men between 18-35 years old (mean (standard deviation) age: 24.1 (3.5) years) participated in the study. We used a randomised, double-blind, placebo-controlled design. Participants received either: (a) yohimbine, (b) hydrocortisone, (c) yohimbine and hydrocortisone or (d) placebo only and participated in a dot-probe task with sad, happy and neutral faces. We collected salivary samples to measure cortisol and alpha amylase activity in addition to measurements of blood pressure and heart rate. Salivary cortisol served as correlate of hypothalamus-pituitary-adrenal axis activation and salivary alpha amylase activity, blood pressure and heart rate as correlates of sympathetic nervous system activation. Measurements were carried out before and after drug administration. RESULTS: We did not find a main effect or interaction effect of hydrocortisone or yohimbine administration on selective attention to happy faces. However, we found an interaction of yohimbine and hydrocortisone on selective attention to sad faces. Post-hoc t-test revealed an attentional bias away from sad stimuli and towards neutral faces in the hydrocortisone-only group. DISCUSSION: Only hydrocortisone administration led to an attentional bias away from sad faces. Future studies should investigate these effects in major depression disorder, as this disorder is characterised by glucocorticoid resistance and increased processing of sad stimuli.

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.

Facial emotion recognition in borderline patients is unaffected by acute psychosocial stress.

Borderline Personality Disorder (BPD) is characterized by difficulties in social cognition and social interactions, which exacerbate under stress. A previous study found better facial emotion recognition (FER) in patients with personality disorders and healthy controls (HC) after stress. We recently reported that emotional empathy scores, i.e. the emotional response to another person's emotional state, were significantly lower in BPD patients than in HC after psychosocial stress. Cognitive empathy scores remained unaltered. The present study aims to further investigate the effect of psychosocial stress induced by the Trier Social Stress Test (TSST) on FER as part of social cognition in patients with BPD. We randomized 43 women with BPD and 46 female HC to either the TSST or a placebo condition. Afterwards, participants were asked in an emotion recognition test to identify emotions in faces showing anger or sadness at low and high intensity. Both groups recognized emotions better at high intensity compared with low intensity. There was no effect of stress on FER performance and we found no difference between groups. This is in line with prior research on social cognition in BPD patients demonstrating that the ability to understand another person's perspective might be unaffected by acute stress.

Blunted salivary cortisol response to psychosocial stress in women with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by alterations in the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS). There is evidence for a blunted HPA axis reactivity to psychosocial stress. Less is known about how the SNS reacts to psychosocial stress. Here, we compared the HPA axis and SNS responses to psychosocial stress and a non-stressful condition in patients with PTSD and in healthy individuals. Twenty-one women with PTSD and 32 healthy women participated in the Trier social stress test (TSST) and placebo TSST (P-TSST). We measured salivary cortisol, alpha amylase activity and blood pressure before and after the tests. Subjective perceived stress response was also assessed. We found a blunted cortisol response to the TSST in patients with PTSD compared with healthy participants 10 min (t (51) = -2.58, p = .01) and 25 min (t (51) = -2.16, p = .04) after TSST. We found no evidence for an increased SNS reactivity after psychosocial stress in patients with PTSD (all p > .05). Patients with PTSD, but not healthy participants, reported more dissociative symptoms (t (20) = -2.31, p = .03) and being more tired (t (20) = 2.90, p = .01) directly after TSST compared with the placebo condition. Our results suggest a blunted HPA stress reactivity and an increased subjective perceived stress response in female patients with PTSD. Longitudinal studies could test if these altered stress responses constitute a predisposition to or a cause of PTSD. Future studies should investigate whether these results are transferable to men.

Effects of hydrocortisone and yohimbine on decision-making under risk.

INTRODUCTION: Many studies have investigated the influence of stress on decision-making. However, results are equivocal and the exact role of increased noradrenaline and cortisol after stress remains unclear. Using pharmacological manipulation, we investigated the influence of noradrenergic and glucocorticoid activity on risky decision-making in a gambling task that included mixed-gamble trials (gains and losses are possible) and gain-only trials. METHODS AND MATERIALS: One hundred-and-four healthy young men participated in our randomized, double-blind, placebo-controlled, between-group study. Participants were randomly assigned to one of four groups: (A) yohimbine, (B) hydrocortisone, (C) yohimbine and hydrocortisone, or (D) placebo. Frequency of risky choices, i.e., monetary risk taking, was the dependent variable. We also investigated the influence of hydrocortisone and yohimbine on loss aversion, which is the tendency to overweigh losses compared with gains. RESULTS: Participants chose the risky option less often after receiving hydrocortisone compared with no hydrocortisone. This effect was strongest in the gain-only trials. Yohimbine had no effect. Loss aversion was not affected by hydrocortisone or yohimbine. DISCUSSION: Decreased reward processing may explain the reduction of risk taking by hydrocortisone in gain-only trials. The effects of stress hormones on different decision-related constructs and processes hence require further investigation.

Effects of hydrocortisone on autobiographical memory retrieval in patients with posttraumatic stress disorder and borderline personality disorder: the role of childhood trauma.

In a previous study, we found that patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD) showed better autobiographical memory (AM) retrieval after hydrocortisone administration than after placebo administration. Here we investigate the neural correlates of AM retrieval after hydrocortisone administration in patients with PTSD or BPD. We recruited 78 female participants for this placebo-controlled crossover study: 40 healthy controls, 20 patients with PTSD, and 18 patients with BPD (all without medication). All participants received an oral placebo or 10 mg hydrocortisone in a randomized order before performing an AM task. Neural activity was monitored during the task by functional magnetic resonance imaging. Neural activation did not differ between the three groups during AM retrieval, neither in the placebo condition nor after hydrocortisone intake. Multiple regression analysis revealed that Childhood Trauma Questionnaire scores correlated positively with hydrocortisone effects on activation in the anterior medial prefrontal cortex (amPFC), ventrolateral prefrontal cortex (vlPFC), posterior cingulate cortex (PCC), angular gyrus, and cerebellum. These results suggest that hydrocortisone-induced neural activation pattern during AM retrieval is related to childhood trauma. Previously described effects in the hippocampus, which were absent in the current study, might be related to PTSD caused by trauma in adulthood. The effects of hydrocortisone on brain activation and how these effects are influenced by childhood trauma, trauma in adulthood, and PTSD symptoms should be determined in future studies.

Effects of glucocorticoid and noradrenergic activity on spatial learning and spatial memory in healthy young adults.

BACKGROUND: Acute stress leads to a rapid release of noradrenaline and glucocorticoids, which in turn influence cognitive functions such as spatial learning and memory. However, few studies have investigated noradrenergic and glucocorticoid effects on spatial learning and memory in humans. Therefore, we examined the separate and combined effects of noradrenergic and glucocorticoid stimulation on spatial learning and memory. METHODS: One hundred and four healthy men (mean age = 24.1 years ±SD 3.5) underwent the virtual Morris Water Maze (vMWM) task to test spatial learning and spatial memory retrieval after receiving either 10 mg hydrocortisone or 10 mg yohimbine (an alpha 2-adrenergic receptor antagonist that increases noradrenergic activity), 10 mg hydrocortisone and 10 mg yohimbine combined, or placebo. The vMWM task took place 90 min after yohimbine was administered and 75 min after hydrocortisone was administered. Placebo was given at the same times. Salivary cortisol and alpha amylase levels were measured to check pharmacological stimulation. RESULTS: Hydrocortisone and yohimbine increased salivary cortisol and alpha amylase levels. Participants' task performance improved over time, suggesting successful spatial learning. However, separate and combined noradrenergic and glucocorticoid stimulation had no effect on spatial learning and spatial memory retrieval compared with placebo. CONCLUSIONS: In healthy young men, hydrocortisone and/or yohimbine did not alter spatial learning or spatial memory retrieval. Importantly, pharmacological stimulation took place prior to learning. Further studies should examine the effects of glucocorticoid and noradrenergic stimulation during encoding, consolidation, and retrieval.

Resting-state functional connectivity after hydrocortisone administration in patients with post-traumatic stress disorder and borderline personality disorder.

In a previous study, we found that - in contrast to healthy individuals - patients with borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD) showed better memory retrieval performance after hydrocortisone administration compared to placebo. As these results suggest an altered function of corticosteroid receptors in the brain in PTSD and BPD, we examined the effect of hydrocortisone on brain activation in both disorders. We recruited 40 female healthy controls, 20 female unmedicated patients with PTSD and 18 female unmedicated patients with BPD. We conducted a placebo-controlled cross-over study, in which all participants underwent two resting state MRI measurements after they received either a placebo or 10 mg hydrocortisone orally and in randomized order. There was a time interval of one week between the measurements. We analysed resting state functional connectivity (RSFC) with the hippocampus and the amygdala as seed regions. Compared to healthy controls, both patient groups showed reduced hippocampus RSFC to dorsomedial prefrontal cortex (dmPFC). Positive hippocampus dmPFC RSFC correlated negatively with childhood trauma (r = -0.47) and with severity of clinical symptoms, measured with the Borderline Symptom List (r = -0.44) and the Posttraumatic Stress Diagnostic Scale (r = -0.45). We found neither differences in amygdala RSFC nor an effect of hydrocortisone administration. Childhood trauma might lead to decreased positive hippocampus dmPFC RSFC. This might explain symptoms of PTSD and BPD that are characterized by dysfunctional fear regulation.

Psychophysiological stress response and memory in borderline personality disorder.

Background: Previously, we found that patients with borderline personality disorder (BPD) but not healthy controls (HC) showed improved memory retrieval after hydrocortisone administration. Objective: In this study, we examined whether increases in endogenous cortisol after psychosocial stress are associated with memory function in patients with BPD and in healthy individuals. Methods: We recruited 49 female patients with BPD and 49 female HC. All participants were exposed to a psychosocial stressor, the Trier Social Stress Test (TSST) and a control condition (Placebo (P-)TSST) in randomized order. Salivary cortisol, alpha amylase (sAA) and blood pressure were measured in response to stress. Subsequently, we examined free recall of a previously learned word list, autobiographical memory, and working memory. Results: We found a stress*time*group interaction effect for the cortisol response and for sAA to stress, which is mainly triggered by a slightly different increase in cortisol between groups from pre to post TSST. Furthermore, BPD patients showed a less pronounced increase in diastolic blood pressure compared to HC after stress. There was no effect of stress on memory performance in any tests, either in healthy controls or in patients with BPD. Conclusion: Our results suggest a slightly blunted response of the HPA axis and the sympathetic nervous system to stress in BPD compared to healthy women. In contrast to hydrocortisone administration, psychosocial stress did not improve memory retrieval in BPD patients. This might be explained by lower cortisol concentrations and parallel increases in norepinephrine and negative affect after stress.

Antecedentes: Previamente, encontramos que los pacientes con trastorno de personalidad límite (TPL), contrariamente a los controles sanos (CS), mostraron una mejor recuperación de memoria después de la administración de hidrocortisona.Objetivo: En este estudio, examinamos si los aumentos en el cortisol endógeno, después del estrés psicosocial están asociados con el funcionamiento de la memoria en pacientes con TPL y en individuos sanos.Métodos: Se reclutaron 49 pacientes de sexo femenino con TPL y 49 mujeres CS. Todas las participantes fueron expuestas a un estresante psicosocial, la Prueba de estrés social de Trier (TSST) y una condición de control (Placebo (P-) TSST) en orden aleatorio. El cortisol salival, la alfa amilasa (sAA) y la presión arterial se midieron en respuesta al estrés. Posteriormente, examinamos la recuperación libre de una lista de palabras previamente aprendida, la memoria autobiográfica y memoria de trabajo.Resultados: Encontramos un efecto de interacción grupal estrés*tiempo* para la respuesta de cortisol y para sAA al estrés, gatillada principalmente por un aumento ligeramente diferente en el cortisol entre los grupos desde el pre al post TSST. Además, las pacientes con TPL mostraron un aumento menos pronunciado en la presión arterial diastólica en comparación con las CS después del estrés. No hubo efecto del estrés en el rendimiento de la memoria en ninguna prueba, ni en controles sanos ni en pacientes con TLP.Conclusión: Nuestros resultados sugieren una respuesta ligeramente atenuada del eje Hipotálamo-Hipófisis-Adrenal y del sistema nervioso simpático al estrés en TPL en comparación con mujeres sanas. En contraste con la administración de hidrocortisona, el estrés psicosocial no mejoró la recuperación de la memoria en pacientes con TPL. Esto podría explicarse por menores concentraciones de cortisol y aumentos paralelos de norepinefrina y afecto negativo después del estrés.

Neural correlates of glucocorticoids effects on autobiographical memory retrieval in healthy women.

It is well known that elevated cortisol after stress or after exogenous administration impairs episodic memory retrieval including autobiographical memory (AM) retrieval. This impairment might be mediated by deactivation of a neural network associated with memory retrieval including the prefrontal cortex (PFC) and limbic structures. However, the neural underpinnings of these cortisol effects on AM retrieval have not been investigated yet. In this study, thirty-three healthy women received either placebo or 10 mg hydrocortisone in a double blind cross-over design before completing an AM test during fMRI. In this test, participants are asked to recall specific events from their own past in response to a cue word. In a first step, we analyzed the neural underpinnings of AM retrieval in the placebo condition. We found an activation pattern consistent with core regions involved in autobiographical memory recall, including the ventromedial PFC, anterior medial (am)PFC, inferior frontal gyrus, the posterior cingulate cortex, the tempoparietal junction, the middle temporal gyrus and the hippocampus. Further, we analyzed brain activation during AM retrieval after hydrocortisone compared to placebo. Region of interest (ROI) analyses revealed a hydrocortisone-induced deactivation during AM retrieval in the right amPFC. Results of the ROI analyses were non-significant in the left and right hippocampus, the left and right vmPFC and the left amPFC In sum, during AM retrieval hydrocortisone had the most pronounced effects on the amPFC. This might be explained by the strong involvement of this brain region in self-referential behavior, which is essential for recalling autobiographic information.

Aberrant working memory processing in major depression: evidence from multivoxel pattern classification.

Major depressive disorder (MDD) is often accompanied by severe impairments in working memory (WM). Neuroimaging studies investigating the mechanisms underlying these impairments have produced conflicting results. It remains unclear whether MDD patients show hyper- or hypoactivity in WM-related brain regions and how potential aberrations in WM processing may contribute to the characteristic dysregulation of cognition-emotion interactions implicated in the maintenance of the disorder. In order to shed light on these questions and to overcome limitations of previous studies, we applied a multivoxel pattern classification approach to investigate brain activity in large samples of MDD patients (N = 57) and matched healthy controls (N = 61) during a WM task that incorporated positive, negative, and neutral stimuli. Results showed that patients can be distinguished from healthy controls with good classification accuracy based on functional activation patterns. ROI analyses based on the classification weight maps showed that during WM, patients had higher activity in the left DLPFC and the dorsal ACC. Furthermore, regions of the default-mode network (DMN) were less deactivated in patients. As no performance differences were observed, we conclude that patients required more effort, indexed by more activity in WM-related regions, to successfully perform the task. This increased effort might be related to difficulties in suppressing task-irrelevant information reflected by reduced deactivation of regions within the DMN. Effects were most pronounced for negative and neutral stimuli, thus pointing toward important implications of aberrations in WM processes in cognition-emotion interactions in MDD.