Evaluation of a new body-focused group therapy versus a guided self-help group program for adults with psychogenic non-epileptic seizures (PNES): a pilot randomized controlled feasibility study.

OBJECTIVE: Psychogenic non-epileptic seizures (PNES), a common phenomenon in neurological settings, are regarded as a paroxysmal type of functional neurological disorder (FND). In a substantial proportion, PNES are disabling with poor long-term outcomes and high economic costs. Despite the clinical and financial consequences of PNES, there is still a lack of controlled clinical trials on the treatment of this challenging disorder. The study aims to evaluate the feasibility and collect first evidence of the efficacy of a group based-intervention in PNES-patients. METHODS: A pilot randomized controlled feasibility study with a parallel-group design was performed in adult outpatients with PNES to evaluate a new body-focused group therapy (CORDIS) versus guided self-help groups. Self-assessment of dissociation (Dissociation Experience Scale-DES-20) and seizure severity (Liverpool Seizure Severity Scale-LSSS) were assessed two weeks before and two weeks after the treatment intervention and also six months after treatment as primary outcome parameters. RESULTS: A total of 53 patients were recruited from a specialized outpatient clinic, and out of those, 29 patients completed either the body-focused group therapy program (n = 15) or a guided self-help group (SHG) therapy (n = 14). When analyzing the ITT sample (n = 22 CORDIS group, n = 20 SHG), both groups showed an effect on seizure severity and level of dissociation. In the per protocol sample (n = 13 CORDIS group, n = 12 SHG), CORDIS was superior to the self-help group for reducing seizure severity 6 months after the treatment. SIGNIFICANCE: CORDIS is a newly developed body-focused group therapy program for adults with PNES. Further studies should include a multicentric design with a higher number of participants.

Executive Functions and Attention in Patients With Psychogenic Nonepileptic Seizures Compared With Healthy Controls: A Cross-Sectional Study.

OBJECTIVE: Psychogenic nonepileptic seizures (PNESs) are considered functional neurological symptoms and are highly prevalent in specialized epilepsy clinics. The underlying mechanisms of PNES are not fully understood. Recent findings point toward possible alterations in attention and executive functions. This study aimed to extend the current knowledge of attention and executive function in patients with PNES and to assess possible relationships between seizures and dissociation, childhood trauma, and cognitive function. METHODS: We recruited 40 patients with PNES and 40 sex-, age-, and education-matched healthy controls (HCs) in this study. Participants completed self-report questionnaires to assess early life stress (Childhood Trauma Questionnaire [CTQ]), dissociation (the German version of the Dissociative Experience Scale, or Fragebogen zu dissoziativen Symptomen), and depression (Patient Health Questionnaire-9). Executive functions and attention were assessed with the Trail Making Test (TMT), Digit Span, and Attention Network Task. RESULTS: Compared with HCs, patients with PNES reported significantly higher levels of childhood trauma, depression, and dissociation. Patients with PNES also had reduced performance indices for Digit Span Forward (d = 0.62), Digit Span Backward (d = 0.62), and TMT (d = 0.67) but not Attention Network Task. CTQ scores positively correlated with TMT and Digit Span Backward performance in patients with PNES. Adjusting for CTQ scores attenuated the observed group difference in TMT performance. Depression and dissociation did not explain the observed findings. CONCLUSIONS: These results contribute to the evidence of impaired executive functions in patients with PNES. Furthermore, childhood trauma scores, but not (trait) dissociation or depression scores, seem to drive group differences (HC versus patients with PNES).

Immunological substrates of depressive symptoms in patients with severe obesity: An exploratory study.

In this pilot study, we explored the immune phenotype of patients with severe obesity and comorbid depressive symptoms compared to non-depressed patients with obesity and normal-weight controls. Immune cell subsets were analysed by flow cytometry and depressive symptoms assessed using the Patient Health Questionnaire (PHQ-9). Cell frequencies were correlated with depressive symptom scores and waist-to-hip ratio (WHR). Patients with obesity and comorbid depression showed significantly lower numbers of circulating cytotoxic natural killer cells, dendritic cells and CD8+ effector memory T cells, compared to normal-weight controls. Regulatory T cells and CD4+ central memory T cells were increased compared to non-depressed patients with obesity and compared to normal-weight controls, respectively. Frequencies of cytotoxic natural killer cells and CD4+ central memory T cells significantly correlated with PHQ-9 scores, but not with WHR. Reduced numbers of dendritic cells were observed in both patient groups with obesity and correlated with PHQ-9 scores and WHR. These findings provide evidence for an altered immune composition in comorbid obesity and depression, supporting a pathobiological overlap between the two disorders.

Insecure and Unresolved/Disorganized Attachment in Patients With Psychogenic Nonepileptic Seizures.

BACKGROUND: Psychogenic nonepileptic seizures (PNES) are still poorly understood and difficult to treat. Attachment theory could add new aspects to the understanding of the multifactorial genesis and maintenance of PNES and the therapeutic needs of this patient group. OBJECTIVE: The aim of the present study is to systematically assess attachment in adult patients with PNES with a focus on the role of unresolved/disorganized attachment. METHODS: A cross-sectional design was chosen to compare patients with confirmed PNES (n = 44) and healthy controls (n = 44) matched for gender, age, and education. Attachment was assessed using the Adult Attachment Projective Picture System. Psychometric questionnaires included the Childhood Trauma Questionnaire; Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) axis II disorders, Patient Questionnaire; the Somatoform Dissociation Questionnaire; and the Patient Health Questionnaire. RESULTS: We found significantly less secure (P = 0.006) and more unresolved/disorganized (P = 0.041) attachment classifications in the PNES group. Among patients with PNES, 7% were classified secure and 43% were classified unresolved/disorganized. Patients with an unresolved attachment representation were significantly more likely to be screened positive for personality pathology in the Structured Clinical Interview for DSM-IV axis II disorders, Patient Questionnaire (P = 0.03) and to report more emotional abuse in the Childhood Trauma Questionnaire (P = 0.007) than patients with other attachment classifications. CONCLUSIONS: Our findings suggest that unresolved/disorganized attachment might be the predominant attachment style in patients with PNES and might be associated with more severe personality pathology. This could be of therapeutic relevance. The present study is the first to assess adult attachment in patients with PNES using a semi-structured interview in comparison to matched healthy controls.

[Pilot Data from the Evaluation of an Integrative Body Psychotherapy Program for Patients with Psychogenic Non-Epileptic Seizures]. / Pilotäre Zwischenergebnisse zur Evaluation eines störungsspezifischen, körperpsychotherapeutisch orientierten Gruppenbehandlungsprogramms für Menschen mit psychogenen Anfällen.

Psychogenic non-epileptic seizures (PNES) occur in the context of various diseases. Therefore, PNES patients represent a heterogeneous group with different causative disorders. The etiology is still poorly understood. Previous concepts assume an increased rate of trauma disorders in PNES, which has been proven several times by previous studies 1 2. The clinical picture is threatening, which means that those affected often receive intensive care measures without benefiting from them 3. PNES patients accumulate especially in epilepsy centers, since a diagnostic differentiation from epileptic seizures is possible at those specialized centers. Often, the transition from making the diagnosis in epilepsy centers to follow-up treatment in psychosomatic/psychiatric settings is difficult. A reason could be that patients and practitioners are often involved in somatic disease concepts, which might be caused by the threatening clinical picture of PNES 28. Due to this difficulties, a special outpatient clinic was set up at the Charité Berlin for people with dissociative seizures, which settles in the transition from neurology to psychosomatics and works as a cooperation project 27. Out of the ambulance, a group treatment program (CORDIS) was developed, which aims at a better care of PNES patients at the interface between neurology and psychosomatic medicine. This modularized 10-week treatment program will be presented in this article and is the subject of a currently ongoing randomized, controlled evaluation study. The pilot data from the ongoing RCT study presented here showed significant effects in the effectiveness of the program, in particular the primary and secondary outcome measures.

Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity. METHODS AND ANALYSIS: This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients' self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226-EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences. TRIAL REGISTRATION NUMBERS: NCT04301271, DRKS00021119, EudraCT 2018-002947-27.

Ictal level of awareness in psychogenic nonepileptic seizures correlates with the experience of traumatic events in childhood: A cross sectional study.

There is a great amount of research regarding the particular ictal manifestations of psychogenic nonepileptic seizures (PNES) with a focus on the differences to epileptic seizures (Vogrig et al., 2019 [4]; Tyson et al., 2018 [5]; De Paola et al., 2016 [6]). Most of the research aims to define guidelines for diagnosing PNES in differentiation from epilepsy, because this differentiation is clinically relevant for clinical neurological settings. In contrast, very few studies aimed to gain insight about particular ictal manifestations of the different semiological appearances of PNES regarding distinctive psychological processes or prognostic outcomes (Brown, 2016 [7]; Pick et al., 2017 [8]; Brown, 2006 [9]; Cohen, 2013). One study revealed that a higher level of mental dissociation and cognitive impairment was associated with a higher level of traumatization in patients with PNES (Pick et al., 2017 [8]). We analyzed the seizure semiology with a focus on the level of awareness in 60 patients with PNES. Patients were divided into two groups: one with an impaired awareness during their seizures and the other one with preserved awareness during their seizures. We assessed the amount of adverse traumatic experience in childhood with the "Childhood Trauma Questionnaire (CTQ)". We found that patients with PNES with impaired awareness showed more childhood traumatic experiences in the CTQ, especially on the subscales of sexual and emotional abuse as well as physical neglect. Furthermore, patients with PNES with impaired awareness during seizures were significantly younger, more often female, showed a lower degree on education, and a higher amount of self-harm behavior compared with patients with PNES with preserved awareness during seizures. Our study presents clinical evidence for the potential significance of the level of awareness during PNES for the etiology of PNES. Our results point toward the existence of clinical subgroups of patients with PNES with distinctive etiological mechanisms and indicate that seizure semiology might help to differentiate those potential subgroups.

Childhood trauma and diagnosis of major depression: Association with memory and executive function.

Cognitive function is often impaired in patients with major depressive disorder (MDD). Childhood trauma is a risk factor for developing MDD and is also associated with cognitive impairments in later life. We aimed to investigate the effects of childhood trauma on cognitive function in MDD. 68 medication-free MDD patients and 75 healthy controls (HC) participated. We tested cognitive function with the Autobiographical Memory Test, Auditory Verbal Learning Test (AVLT), Trail Making Test A and B, Rey-Osterrieth/Taylor Complex Figure Test, and Digit Span Backward. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ). Patients and HC did not differ with respect to age, sex, education. Mean CTQ sum scores differed significantly for depressed and HC with mean 47.8 (19.2) and 31.0 (6.8), respectively. Depressed patients and HC (without taking childhood trauma into account) differed only in AVLT performance. When childhood trauma was considered, this group difference disappeared. Subsequent regression analyses revealed that higher CTQ scores but not a diagnosis of MDD were associated with less specific autobiographical memories. Associations of CTQ with other cognitive domains failed significance after correction for multiple testing. Our results suggest that cognitive function is influenced by childhood trauma in MDD. However, the effects are small.

Mineralocorticoid receptor function in depressed patients and healthy individuals.

BACKGROUND: Many studies have shown disturbed glucocorticoid receptor (GR) in depressed patients. In contrast, only few studies targeted mineralocorticoid receptor (MR) function with inconclusive results. We examined the effects of the MR antagonist spironolactone on cortisol secretion in depressed patients and healthy individuals. METHODS: Forty-eight unmedicated depressed patients (mean age 41.6years) and 45 age- and sex-matched healthy participants (40.7years) received the MR antagonist spironolactone (300mg) or placebo with three days apart in a randomized, double-blind, within-subject cross-over design. We measured salivary cortisol before ingestion of study medication (baseline) as well as +60min, +90min, +120min, +150min and 180min after baseline. RESULTS: Repeated-measures ANOVA for area under the curve (AUCg) cortisol revealed a treatment effect with higher cortisol after spironolactone and a treatment by group interaction. Post-hoc analyses revealed higher cortisol in depressed patients compared to healthy participants in the placebo condition. In the spironolactone condition, the cortisol levels were not significantly different. CONCLUSIONS: Potentially, impaired MR or GR signaling could be responsible for higher cortisol levels in depressed patients in the placebo condition. However, after MR blockade that increased cortisol secretion across groups leading to higher GR occupation, we found no differences between depressed patients and healthy controls. Thus, our results argue for depression-associated alterations in MR signaling rather than disturbed GR-mediated feedback inhibition.

Association between major depression and cardiovascular risk: the role of antidepressant medication.

RATIONALE AND OBJECTIVES: Major depressive disorder (MDD) is associated with an increased risk for cardiovascular disease (CVD). Apart from biological and life style factors, the use of antidepressants and their potentially adverse effects might contribute to the increased CVD risk. Therefore, we compared cardiovascular risk profiles between relatively young depressed patients without CVD with and without antidepressant medication and healthy participants. METHODS: We investigated 44 depressed patients (with antidepressants N = 20 (13 women), mean age 43.2 years; without antidepressants N = 24 (15 women), mean age 40.0) and 41 healthy participants (matched for sex, age, education). As markers of CVD risk, blood pressure, body mass index (BMI), and plasma levels of fasting glucose, cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and high sensitivity C-reactive protein (h-CRP) were measured. RESULTS: We found significant differences between groups for BMI (p < .01), systolic (p = .02) and diastolic blood pressure (p < .01), and glucose (p < .001). Post hoc analyses indicated differences between both patient groups compared to the healthy control group, but not between patients groups. Further controlling for BMI diminished the effect of diagnosis on blood pressure; however, this was not the case for glucose level. There were no between-group differences in cholesterol, LDL, HDL, and h-CRP. CONCLUSIONS: We found a clearly increased CVD risk in this group of rather young depressed patients. Importantly, there was no significant difference in CVD risk between patients with vs. without antidepressants. This suggests that major depression per se and not antidepressant medication is associated with increased CVD risk.

Effects of mineralocorticoid receptor blockade on empathy in patients with major depressive disorder.

BACKGROUND: The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex and is involved in social cognition. We recently found that pharmacological stimulation of the MR enhances emotional empathy but does not affect cognitive empathy. In the current study, we examined whether blockade of the MR impairs empathy in patients with major depressive disorder (MDD) and healthy individuals. METHODS: In a placebo-controlled study, we randomized 28 patients with MDD without psychotropic medication and 43 healthy individuals to either placebo or 300 mg spironolactone, a MR antagonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy. RESULTS: In the MET, we found no significant main effect of treatment or main effect of group for cognitive empathy but a highly significant treatment by group interaction (p < 0.01). Patients had higher cognitive empathy scores compared to controls in the placebo condition but not after spironolactone. Furthermore, in the spironolactone condition reduced cognitive empathy was seen in MDD patients but not in controls. Emotional empathy was not affected by MR blockade. In the MASC, no effect of spironolactone could be revealed. CONCLUSION: Depressed patients appear to exhibit greater cognitive empathy compared to healthy individuals. Blockade of MR reduced cognitive empathy in MDD patients to the level of healthy individuals. Future studies should further clarify the impact of MR functioning on different domains of social cognition in psychiatric patients.

Does fludrocortisone influence autobiographical memory retrieval? A study in patients with major depression, patients with borderline personality disorder and healthy controls.

There is evidence that stimulation of mineralocorticoid receptors (MR) enhances memory in healthy subjects and in patients with major depression (MDD). In contrast, in patients with borderline personality disorder (BPD), this effect seems to be task dependent. The aim of this study was to investigate the effect of MR stimulation on autobiographical memory retrieval in healthy individuals, patients with MDD, and patients with BPD. We conducted a placebo-controlled study in an intra-individual cross-over design. Twenty-four patients with MDD, 37 patients with BPD, and 67 healthy participants completed an autobiographical memory test after receiving 0.4 mg fludrocortisone, a mineralocorticoid receptor preferring agonist, or placebo in a randomized order. Healthy subjects, patients with MDD, and patients with BPD did not differ in their autobiographical memory retrieval. Furthermore, the administration of fludrocortisone had no effect on autobiographical memory. In conclusion, the stimulation of MR does not influence autobiographical memory retrieval in healthy subjects, patients with MDD, and patients with BPD. Our results do not support a role of MR in autobiographical memory.

Cognitive function in older adults with major depression: Effects of mineralocorticoid receptor stimulation.

Memory and executive function are often impaired in older adults with major depression. Mineralocorticoid receptors (MR) are abundantly expressed in the hippocampus and in the prefrontal cortex, brain areas critical for memory and executive function. In both aging and depression, MR expression in the brain is reduced. Therefore, diminished MR function could contribute to impaired cognition in older adults with depression and might be a promising target for pharmacological intervention. Twenty-three older adults with major depression (mean age 61.6 yrs ± 8.1, n = 13 women) without medication and 24 age-, sex- and education-matched healthy participants received the MR-agonist fludrocortisone (0.4 mg) or placebo in a randomized, double-blind, within-subject cross-over design. We measured psychomotor speed, executive function, verbal learning and memory, and visuospatial memory. Compared to controls, depressed patients performed worse in psychomotor speed (group effect p = 0.01), executive function (group effect p < 0.01), verbal learning (group effect p = 0.02), and verbal memory (group effect p < 0.01) but not in visuospatial memory. There were no significant treatment effects. However, we found a group × treatment interaction in verbal learning (p = 0.04) and visuospatial memory (p = 0.02) indicating that depressed patients performed worse after fludrocortisone whereas controls performed better after fludrocortisone. Our data suggest that -in contrast to younger depressed patients-older adults with depression do not benefit from MR stimulation but deteriorate in cognitive function.

Visual Attention and Saccadic Oculomotor Control in Parkinson's Disease.

BACKGROUND: In patients with Parkinson's disease (PD) we aimed at differentiating the relation between selective visual attention, deficits of programming and dynamics of saccadic eye movements while searching for a target and hand-reaction time as well as hand-movement time. Visual attention is crucial for concentrating selectively on one aspect of the visual field while ignoring other aspects. Eye movements are anatomically and functionally related to mechanisms of visual attention. Saccadic dysfunction might confound selective visual attention in PD. METHODS: We studied visual selective attention in 22 medicated PD patients (clinical ON status, mild to moderate disease severity) and 22 age matched controls. We looked for possible interferences through oculomotor deficits. Two tasks were compared: free viewing of photographs and time optimal visual search of a hidden target. Visual search times (VST), task related dynamics of saccades, and hand-reaction and hand-movement times were analyzed. RESULTS: In the free viewing task mild to moderately affected PD patients did not differ statistically from healthy subjects with respect to saccade dynamics. However, patients differed significantly from healthy subjects in the time optimal visual search task with 25% lower rates of successful searches. Hand movement reaction time did not differ in both groups, whereas hand movement execution time was significantly prolonged in PD patients. CONCLUSION: Saccadic oculomotor control and hand movement reaction times were intact, whereas in our less severely affected treated PD patients, visual selective attention was not. The highly reduced successful search rate might be related to disturbed programming and delayed execution of saccades during time optimal visual search due to decreased execution of serial-order sequential generation of saccades.

Effects of mineralocorticoid receptor stimulation via fludrocortisone on memory in women with borderline personality disorder.

In a previous study, we found that in contrast to healthy controls, hydrocortisone administration had enhancing effects on memory in patients with borderline personality disorder (BPD). Because hydrocortisone acts on glucocorticoid receptors (GR) and mineralocorticoid receptors (MR), it is unclear which receptor mediated these effects. The aim of the current study was to test whether more selective MR stimulation with fludrocortisone improves memory in BPD. In a placebo-controlled, randomized, within-subject, cross-over study, 39 medication-free women with BPD and 39 healthy women received placebo or 0.4mg fludrocortisone prior to cognitive testing. We measured verbal memory, visuospatial memory, and working memory. We found a significant group by fludrocortisone interaction on verbal memory and visuospatial memory. In both tests patients with BPD, but not healthy women, had impaired memory performance after fludrocortisone compared to placebo. In contrast, working memory was improved after fludrocortisone compared to placebo in both groups. Contrary to our hypothesis, we found impairing effects of MR stimulation on hippocampus-mediated verbal memory and visuospatial memory in BPD but not in healthy controls. In contrast, working memory, which depends more on the prefrontal cortex, was improved after MR stimulation across groups. Future studies should systematically disentangle beneficial and adverse effects of MR stimulation in health and disease.

Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions.

Findings on the association between hypothalamic-pituitary-adrenal (HPA) axis activity and metabolic risk are equivocal. Different methods of measuring HPA activity might indicate adverse vs. beneficial effects of HPA activity on metabolic risk thus contributing to heterogenous findings. In this study, we aimed to determine whether (1) the salivary cortisol awakening response (CAR) as a marker of awakening-induced activation of the HPA axis and (2) hair cortisol as a marker of long-term cortisol secretion are associated with criteria of the metabolic syndrome. Therefore, we recruited 41 healthy individuals (26 women, mean age: 41.2 years) and 44 patients with major depression (28 women, 41.4 years) and assessed CAR and hair cortisol values as well as all criteria of the metabolic syndrome (abdominal obesity, blood pressure, plasma glucose, triglycerides and high-density cholesterol levels) according to the International Diabetes Federation. CAR and hair cortisol values were divided into tertiles. Across groups, participants with hair cortisol or hair cortisone in the highest tertile showed significantly more criteria of the metabolic syndrome compared to participants in the medium or low tertile (F2,64=3.37, p=.04). These results were corroborated by significant positive correlations between mean hair cortisol values with waist circumference (r=.29, p=.03), triglycerides (r=.34, p=.01) and systolic blood pressure (r=.29, p=.04) and between mean hair cortisone and triglycerides (r=.46, p<.01). In contrast, mean CAR values correlated negatively with diastolic (r=-.29, p=.03) and systolic blood pressure (r=-.32, p=.02). Our results indicate that higher hair cortisol and hair cortisone levels but lower CAR values are associated with an unfavorable metabolic and cardiovascular risk profile.

Stimulation of the mineralocorticoid receptor improves memory in young and elderly healthy individuals.

Glucocorticoids play an important role in cognitive function and act on glucocorticoid receptors and mineralocorticoid receptors (MRs) in the brain. Previously, the blockade of the MR has been shown to impair visuospatial and working memory in healthy young men. Here, we investigated the effects of the MR agonist fludrocortisone on memory in young and elderly healthy individuals. Thirty-one young (mean age 25.4 ± 4.6 years) and 22 elderly (mean age 63.2 ± 8.2 years) healthy participants received the MR agonist fludrocortisone (0.4 mg) or placebo at least 3 days apart in a randomized, double-blind within-subject cross-over design. We measured verbal memory (auditory verbal learning test), nonverbal memory (Rey/Taylor complex figure test), and working memory (digit-span task). As expected, young participants performed significantly better than elderly individuals in visuospatial memory (effect of group: F = 42.7, p < 0.01), verbal memory (F = 33.1, p < 0.01), and working memory (digit-span backward: F = 4.5, p = 0.04). For visuospatial memory (F = 5.0, p = 0.03) and short-term and working memory (digit-span forward: F = 4.2, p = 0.05), we found a significant treatment effect indicating better memory performance after fludrocortisone compared with placebo across groups. In concert with the previous studies, our data suggest a role of the MR in memory function. A cognitive enhancing effect by MR stimulation warrants future studies.

Mineralocorticoid receptor stimulation improves cognitive function and decreases cortisol secretion in depressed patients and healthy individuals.

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.

Enhanced emotional empathy after mineralocorticoid receptor stimulation in women with borderline personality disorder and healthy women.

The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex. MR have an important role in appraisal processes and in modulating stress-associated emotional reactions but it is not known whether the MR affects empathy. Borderline personality disorder (BPD) is characterized by disturbed emotion regulation and alterations in empathy. In the current study, we examined whether stimulation of the MR enhances empathy in patients with BPD and healthy individuals. In a placebo-controlled study, we randomized 38 women with BPD and without psychotropic medication, and 35 healthy women to either placebo or 0.4 mg fludrocortisone, an MR agonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy. Eighteen BPD patients and 18 healthy women received placebo, whereas 20 BPD patients and 17 healthy women received fludrocortisone. In the MET, fludrocortisone enhanced emotional empathy across groups, whereas cognitive empathy was not affected. In the MASC, no effect of fludrocortisone could be revealed. In both tests, BPD patients and healthy women did not differ significantly in cognitive and emotional empathy and in their response to fludrocortisone. Stimulation of MR enhanced emotional empathy in healthy women and in BPD patients. Whether fludrocortisone might have a therapeutic role in psychotherapeutic processes, remains to be elucidated.