[Clinical management of treatment-resistant depression]. / Klinisches Management der therapieresistenten Depression.

Treatment-resistant depression (TRD) is a complex disorder. Although no standardized definition has been established to date, there are promising and well-established treatment options for the condition. Looking at the current pharmacological and neuromodulatory strategies, there is an urgent need for fast-acting and well-tolerated treatment options. The search for new mechanisms of action goes beyond the monoamine hypothesis. For example, esketamine is already an established treatment method that is fast-acting and well tolerated, while psychedelics or esmethadone are currently still undergoing clinical trials. Compounds that can be used off-label, such as dextromethorphan or anti-inflammatory strategies are also presented. Pharmacological approaches that focus on the modulation of the glutamatergic system or belong to the class of psychedelics, appear to be of particular importance for current research and development. These particularly include substances that rapidly exert clinical effects and have a favorable side-effect profile.

Altered reward network responses to social touch in major depression.

BACKGROUND: Social touch is an integral part of social relationships and has been associated with reward. Major depressive disorder (MDD) is characterized by severe impairments in reward processing, but the neural effects of social touch in MDD are still elusive. In this study, we aimed to determine whether the neural processing of social touch is altered in MDD and to assess the impact of antidepressant therapy. METHODS: Before and after antidepressant treatment, 53 MDD patients and 41 healthy controls underwent functional magnetic resonance imaging (fMRI) while receiving social touch. We compared neural responses to social touch in the reward network, behavioral ratings of touch comfort and general aversion to interpersonal touch in patients to controls. Additionally, we examined the effect of treatment response on those measures. RESULTS: Clinical symptoms decreased after treatment and 43.4% of patients were classified as responders. Patients reported higher aversion to interpersonal touch and lower comfort ratings during the fMRI paradigm than controls. Patients showed reduced responses to social touch in the nucleus accumbens, caudate nucleus and putamen than controls, both before and after treatment. Contrary to our hypotheses, these effects were independent of touch velocity. Non-responders exhibited blunted response in the caudate nucleus and the insula compared to responders, again irrespective of time. CONCLUSIONS: These findings suggest altered striatal processing of social touch in MDD. Persistent dysfunctional processing of social touch despite clinical improvements may constitute a latent risk factor for social withdrawal and isolation.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Prevalence of COVID-19 and Psychotropic Drug Treatment in Psychiatric In-patients in Germany in 2020: Results from a Nationwide Pilot Survey.

INTRODUCTION: In patients with a pre-existing mental disorder, an increased risk for a first manifestation of a psychiatric disorder in COVID-19 patients, a more severe course of COVID-19 and an increased mortality have been described. Conversely, observations of lower COVID-19 incidences in psychiatric in-patients suggested protective effects of psychiatric treatment and/or psychotropic drugs against COVID-19. METHODS: A retrospective multi-center study was conducted in 24 German psychiatric university hospitals. Between April and December 2020 (the first and partly second wave of COVID-19), the effects of COVID-19 were assessed on psychiatric in-patient care, the incidence and course of a SARS-CoV-2 infection, and treatment with psychotropic drugs. RESULTS: Patients (n=36,322) were admitted to the hospitals. Mandatory SARS-CoV-2 tests before/during admission were reported by 23 hospitals (95.8%), while 18 (75%) conducted regular testing during the hospital stay. Two hundred thirty-two (0.6%) patients were tested SARS-CoV-2-positive. Thirty-seven (16%) patients were receiving medical treatment for COVID-19 at the psychiatric hospital, ten (4.3%) were transferred to an intermediate/intensive care unit, and three (1.3%) died. The most common prescription for SARS-CoV-2-positive patients was for second-generation antipsychotics (n=79, 28.2%) and antidepressants (SSRIs (n=38, 13.5%), mirtazapine (n=36, 12.9%) and SNRIs (n=29, 10.4%)). DISCUSSION: Contrary to previous studies, our results showed a low number of infections and mortality in SARS-CoV-2-positive psychiatric patients. Several preventive measures seem effective to protect this vulnerable group. Our observations are compatible with the hypothesis of a protective effect of psychotropic drugs against COVID-19 as the overall mortality and need for specific medical treatment was low.

Effects of NMDA-receptor blockade by ketamine on mentalizing and its neural correlates in humans: a randomized control trial.

Schizophrenia is associated with various deficits in social cognition that remain relatively unaltered by antipsychotic treatment. While faulty glutamate signaling has been associated with general cognitive deficits as well as negative symptoms of schizophrenia, no direct link between manipulation of glutamate signaling and deficits in mentalizing has been demonstrated thus far. Here, we experimentally investigated whether ketamine, an uncompetitive N-methyl-D-aspartate receptor antagonist known to induce psychotomimetic effects, influences mentalizing and its neural correlates. In a randomized, placebo-controlled between-subjects experiment, we intravenously administered ketamine or placebo to healthy participants performing a video-based social cognition task during functional magnetic resonance imaging. Psychotomimetic effects of ketamine were assessed using the Positive and Negative Syndrome Scale. Compared to placebo, ketamine led to significantly more psychotic symptoms and reduced mentalizing performance (more "no mentalizing" errors). Ketamine also influenced blood oxygen level dependent (BOLD) response during mentalizing compared to placebo. Specifically, ketamine increased BOLD in right posterior superior temporal sulcus (pSTS) and increased connectivity between pSTS and anterior precuneus. These increases may reflect a dysfunctional shift of attention induced by ketamine that leads to mentalizing deficits. Our findings show that a psychotomimetic dose of ketamine impairs mentalizing and influences its neural correlates, a result compatible with the notion that deficient glutamate signaling may contribute to deficits in mentalizing in schizophrenia. The results also support efforts to seek novel psychopharmacological treatments for psychosis and schizophrenia targeting glutamatergic transmission.

Acceleration of inferred neural responses to oddball targets in an individual with bilateral amygdala lesion compared to healthy controls.

Detecting unusual auditory stimuli is crucial for discovering potential threat. Locus coeruleus (LC), which coordinates attention, and amygdala, which is implicated in resource prioritization, both respond to deviant sounds. Evidence concerning their interaction, however, is sparse. Seeking to elucidate if human amygdala affects estimated LC activity during this process, we recorded pupillary responses during an auditory oddball and an illuminance change task, in a female with bilateral amygdala lesions (BG) and in n = 23 matched controls. Neural input in response to oddballs was estimated via pupil dilation, a reported proxy of LC activity, harnessing a linear-time invariant system and individual pupillary dilation response function (IRF) inferred from illuminance responses. While oddball recognition remained intact, estimated LC input for BG was compacted to an impulse rather than the prolonged waveform seen in healthy controls. This impulse had the earliest response mean and highest kurtosis in the sample. As a secondary finding, BG showed enhanced early pupillary constriction to darkness. These findings suggest that LC-amygdala communication is required to sustain LC activity in response to anomalous sounds. Our results provide further evidence for amygdala involvement in processing deviant sound targets, although it is not required for their behavioral recognition.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Reduced vmPFC-insula functional connectivity in generalized anxiety disorder: a Bayesian confirmation study.

Differences in the correlated activity of networked brain regions have been reported in individuals with generalized anxiety disorder (GAD) but an overreliance on null-hypothesis significance testing (NHST) limits the identification of disorder-relevant relationships. In this preregistered study, we applied both a Bayesian statistical framework and NHST to the analysis of resting-state fMRI scans from females with GAD and matched healthy comparison females. Eleven a-priori hypotheses about functional connectivity (FC) were evaluated using Bayesian (multilevel model) and frequentist (t-test) inference. Reduced FC between the ventromedial prefrontal cortex (vmPFC) and the posterior-mid insula (PMI) was confirmed by both statistical approaches and was associated with anxiety sensitivity. FC between the vmPFC-anterior insula, the amygdala-PMI, and the amygdala-dorsolateral prefrontal cortex (dlPFC) region pairs did not survive multiple comparison correction using the frequentist approach. However, the Bayesian model provided evidence for these region pairs having decreased FC in the GAD group. Leveraging Bayesian modeling, we demonstrate decreased FC of the vmPFC, insula, amygdala, and dlPFC in females with GAD. Exploiting the Bayesian framework revealed FC abnormalities between region pairs excluded by the frequentist analysis and other previously undescribed regions in GAD, demonstrating the value of applying this approach to resting-state FC data in clinical investigations.

[Assessment of Direct (COVID-19-Related) and Collateral, Psychosocial Pandemic Consequences for Vulnerable Groups by the Example of Serious Mental Illness]. / Erfassung direkter (COVID-19-bezogener) und kollateraler, psychosozialer Folgen für vulnerable Gruppen am Beispiel schwerer psychischer Erkrankungen.

The indirect pandemic consequences could by far exceed the direct effects of SARS-CoV-2 in terms of costs, morbidity, and mortality. This essay includes a proposed method (matrix) to visualize virus-related and psychosocial risks for different populations side by side in a systematic and concise manner. COVID-19-related and psychosocial vulnerability, stressors, direct and indirect consequences are derived on a theoretical and empirical basis. An exemplary quantification of the matrix for the vulnerable group of people with severe mental illness revealed a very high risk for severe COVID-19 consequences, as well as a pronounced risk for psychosocial collateral effects. The proposed approach could be further discussed for a risk-graded pandemic management, crisis recovery, and future preparedness to adequately address psychosocial collateral effects and better identify and protect vulnerable groups in this regard.

Feasibility of six-month outpatient cognitive remediation in schizophrenia: Experience from the randomized controlled integrated social cognition and social skills therapy study.

Patients with schizophrenia often have cognitive impairments that contribute to diminished psychosocial functioning. Cognitive remediation therapy (CRT) has proven efficacy and is recommended by evidence-based treatment guidelines. Important moderators of efficacy include integration of CRT into a psychiatric rehabilitation concept and patient attendance at a sufficient number of therapy sessions. These conditions can probably best be met in an outpatient setting; however, outpatient treatment is prone to higher rates of treatment discontinuation and outpatient settings are not as well protected as inpatient ones and less closely supervised.The present study investigated the feasibility of outpatient CRT in schizophrenia over a six-month period. Adherence to scheduled sessions and safety parameters were assessed in 177 patients with schizophrenia randomly assigned to one of two matched CRT programs.Results showed that 58.8 % of participants completed the CRT (>80 % of scheduled sessions) and 72.9 % completed at least half the sessions. Predictor analysis revealed a high verbal intelligence quotient as favorable for good adherence, but this factor had only low general predictive power. During the six-month treatment phase, serious adverse events occurred in 15.8 % (28/177) of the patients, which is a comparable rate to that reported in the literature.Our findings support the feasibility of six-month outpatient CRT in schizophrenia in terms of adherence to scheduled sessions and safety. Trial registration number: NCT02678858, DRKS00010033.

Glucagon-like peptide-1 receptor-agonists treatment for cardio-metabolic parameters in schizophrenia patients: a systematic review and meta-analysis.

Aims: We performed this meta-analysis to evaluate the efficacy and safety of glucagon-like peptide-1 receptor-agonists (GLP-1RA) treatment on cardio-metabolic parameters among antipsychotic-treated patients with schizophrenia. Methods: We searched the Web of Science, Cochrane Central Register of Controlled Trials, PubMed, PsycINFO, and Scopus for relevant Randomized Clinical trials (RCTs) from inception until 1 August 2022. Documents were screened for qualified articles, and all concerned outcomes were pooled as risk ratios (RR) or mean difference (MD) in the meta-analysis models using Review Manager (RevMan version 5.4). Results: Pooling data from 7 RCTs (398 patients) showed that GLP-1 RA was superior to placebo with regard to body weight [MD = - 4.68, 95% CI (-4.90,-4.46), P < 0.00001], waist circumference [MD = - 3.66, 95% CI (-3.89,-3.44), P < 0.00001], body mass index (BMI) [MD = - 1.09, 95% CI (-1.25,-0.93), P < 0.00001], systolic blood pressure (SBP) [MD = - 3.07, 95% CI (-3.61,-2.53), P < 0.00001], and diastolic blood pressure (DBP) [MD = - 2.02, 95% CI (-2.42,-1.62), P < 0.00001]. The total effect did not favor either of the two groups with respect to insulin and respiratory adverse events {[MD = - 0.06, 95% CI (-0.36, 0.24), p = 0.70], [RR = 0.66, 95% CI (0.31, 1.40), p = 0.28]; respectively}. Conclusion: Our analysis revealed that GLP-1 RA treatment is safe and effective on cardio-metabolic parameters over control in antipsychotic-treated patients with schizophrenia. Nevertheless, the present evidence is not sufficient to confirm the safety and efficacy of GLP-1RA treatment on insulin and respiratory adverse events. Therefore, further studies are recommended. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022333040.

A multinational cross-sectional study on the awareness and concerns of healthcare providers toward monkeypox and the promotion of the monkeypox vaccination.

Background: The aim of this study was to explore potential healthcare workers' (HCWs) concerns about the monkeypox virus in order to create practical solutions to manage this disease. Methods: Online cross-sectional research was conducted in 11 Arabic countries (Egypt, Saudi Arabia, Yemen, Syria, Libya, Algeria, Tunisia, Iraq, Palestine, Jordan, and Sudan) from 2 August 2022 to 28 December 2022. Results: Approximately 82% of respondents felt the need to acquire further information. The acceptability of the vaccine against monkeypox has been indicated by more than half of the participants (54.5%). Furthermore, we state that 45% of the participants are knowledgeable about the monkeypox virus, and 53.1% of the participants have never been affected with COVID-19 before are more worried about COVID-19 than about monkeypox. Participants diagnosed with COVID-19 were 0.63 times less likely to worry about monkeypox than those who were not diagnosed with COVID-19. A greater willingness to get the monkeypox vaccination was seen among the age group 21-30 years (42.4%) compared to the other age groups. Conclusion: Most healthcare professionals have a moderate knowledge of the monkeypox virus. Furthermore, they demonstrated a low willingness to get the vaccination against the monkeypox virus.

Affectionate touch and diurnal oxytocin levels: An ecological momentary assessment study.

Background: Affectionate touch, which is vital for mental and physical health, was restricted during the Covid-19 pandemic. This study investigated the association between momentary affectionate touch and subjective well-being, as well as salivary oxytocin and cortisol in everyday life during the pandemic. Methods: In the first step, we measured anxiety and depression symptoms, loneliness and attitudes toward social touch in a large cross-sectional online survey (N = 1050). From this sample, N = 247 participants completed ecological momentary assessments over 2 days with six daily assessments by answering smartphone-based questions on affectionate touch and momentary mental state, and providing concomitant saliva samples for cortisol and oxytocin assessment. Results: Multilevel models showed that on a within-person level, affectionate touch was associated with decreased self-reported anxiety, general burden, stress, and increased oxytocin levels. On a between-person level, affectionate touch was associated with decreased cortisol levels and higher happiness. Moreover, individuals with a positive attitude toward social touch experiencing loneliness reported more mental health problems. Conclusions: Our results suggest that affectionate touch is linked to higher endogenous oxytocin in times of pandemic and lockdown and might buffer stress on a subjective and hormonal level. These findings might have implications for preventing mental burden during social contact restrictions. Funding: The study was funded by the German Research Foundation, the German Psychological Society, and German Academic Exchange Service.

Correction: Digital Phenotyping for Differential Diagnosis of Major Depressive Episode: Narrative Review.

[This corrects the article DOI: 10.2196/37225.].

Monkeypox Post-COVID-19: Knowledge, Worrying, and Vaccine Adoption in the Arabic General Population.

BACKGROUND: The outbreak of monkeypox was declared a global public health emergency by the World Health Organization on 23 July 2022. There have been 60,000 cases reported worldwide, most of which are in places where monkeypox has never been seen due to the travel of people who have the virus. This research aims to evaluate the general Arabic population in regard to the monkeypox disease, fears, and vaccine adoption after the WHO proclaimed a monkeypox epidemic and to compare these attitudes to those of the COVID-19 pandemic. METHODS: This cross-sectional study was performed in some Arabic countries (Syria, Egypt, Qatar, Yemen, Jordan, Sudan, Algeria, and Iraq) between 18 August and 7 September 2022. The inclusion criteria were the general public residing in Arabic nations and being older than 18. This questionnaire has 32 questions separated into three sections: sociodemographic variables, prior COVID-19 exposure, and COVID-19 vaccination history. The second portion assesses the knowledge and anxieties about monkeypox, while the third section includes the generalized anxiety disorder (GAD7) scale. Logistic regression analyses were performed to compute the adjusted odds ratios (aOR) and their confidence intervals (95%CI) using STATA (version 17.0). RESULTS: A total of 3665 respondents from 17 Arabic countries were involved in this study. Almost two-thirds (n = 2427, 66.2%) of the participants expressed more worry about COVID-19 than monkeypox diseases. Regarding the major cause for concern about monkeypox, 39.5% of participants attributed their anxiety to the fear that they or a member of their family may contract the illness, while 38.4% were concerned about monkeypox becoming another worldwide pandemic. According to the GAD 7 score, 71.7% of the respondents showed very low anxiety toward monkeypox and 43.8% of the participants scored poor levels of knowledge about monkeypox disease. Participants with previous COVID-19 infection showed a 1.206 times greater acceptance to receive the monkeypox vaccine than those with no previous infection. A 3.097 times higher concern for monkeypox than COVID-19 was shown by the participants who perceived monkeypox as dangerous and virulent than those who did not. Participants who have a chronic disease (aOR: 1.32; 95%CI: 1.09-1.60); participants worried about monkeypox (aOR: 1.21; 95%CI: 1.04-1.40), and perceived monkeypox as a dangerous and virulent disease (aOR: 2.25; 95%CI: 1.92-2.65); and excellent knowledge level (aOR: 2.28; 95%CI: 1.79-2.90) have emerged as significant predictors. CONCLUSIONS: Our study reported that three-fourths of the participants were more concerned about COVID-19 than monkeypox disease. In addition, most of the participants have inadequate levels of knowledge regarding monkeypox disease. Hence, immediate action should be taken to address this problem. Consequently, learning about monkeypox and spreading information about its prevention is crucial.

Effects of exogenous oxytocin and estradiol on resting-state functional connectivity in women and men.

Possible interactions of the neuropeptide oxytocin and the sex hormone estradiol may contribute to previously observed sex-specific effects of oxytocin on resting-state functional connectivity (rsFC) of the amygdala and hippocampus. Therefore, we used a placebo-controlled, randomized, parallel-group functional magnetic resonance imaging study design and measured amygdala and hippocampus rsFC in healthy men (n = 116) and free-cycling women (n = 111), who received estradiol gel (2 mg) or placebo before the intranasal administration of oxytocin (24 IU) or placebo. Our results reveal significant interaction effects of sex and treatments on rsFC of the amygdala and hippocampus in a seed-to-voxel analysis. In men, both oxytocin and estradiol significantly decreased rsFC between the left amygdala and the right and left lingual gyrus, the right calcarine fissure, and the right superior parietal gyrus compared to placebo, while the combined treatment produced a significant increase in rsFC. In women, the single treatments significantly increased the rsFC between the right hippocampus and the left anterior cingulate gyrus, whereas the combined treatment had the opposite effect. Collectively, our study indicates that exogenous oxytocin and estradiol have different region-specific effects on rsFC in women and men and that the combined treatment may produce antagonistic effects.

Digital Phenotyping for Differential Diagnosis of Major Depressive Episode: Narrative Review.

BACKGROUND: Major depressive episode (MDE) is a common clinical syndrome. It can be found in different pathologies such as major depressive disorder (MDD), bipolar disorder (BD), posttraumatic stress disorder (PTSD), or even occur in the context of psychological trauma. However, only 1 syndrome is described in international classifications (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5]/International Classification of Diseases 11th Revision [ICD-11]), which do not take into account the underlying pathology at the origin of the MDE. Clinical interviews are currently the best source of information to obtain the etiological diagnosis of MDE. Nevertheless, it does not allow an early diagnosis and there are no objective measures of extracted clinical information. To remedy this, the use of digital tools and their correlation with clinical symptomatology could be useful. OBJECTIVE: We aimed to review the current application of digital tools for MDE diagnosis while highlighting shortcomings for further research. In addition, our work was focused on digital devices easy to use during clinical interview and mental health issues where depression is common. METHODS: We conducted a narrative review of the use of digital tools during clinical interviews for MDE by searching papers published in PubMed/MEDLINE, Web of Science, and Google Scholar databases since February 2010. The search was conducted from June to September 2021. Potentially relevant papers were then compared against a checklist for relevance and reviewed independently for inclusion, with focus on 4 allocated topics of (1) automated voice analysis, behavior analysis by (2) video and physiological measures, (3) heart rate variability (HRV), and (4) electrodermal activity (EDA). For this purpose, we were interested in 4 frequently found clinical conditions in which MDE can occur: (1) MDD, (2) BD, (3) PTSD, and (4) psychological trauma. RESULTS: A total of 74 relevant papers on the subject were qualitatively analyzed and the information was synthesized. Thus, a digital phenotype of MDE seems to emerge consisting of modifications in speech features (namely, temporal, prosodic, spectral, source, and formants) and in speech content, modifications in nonverbal behavior (head, hand, body and eyes movement, facial expressivity, and gaze), and a decrease in physiological measurements (HRV and EDA). We not only found similarities but also differences when MDE occurs in MDD, BD, PTSD, or psychological trauma. However, comparative studies were rare in BD or PTSD conditions, which does not allow us to identify clear and distinct digital phenotypes. CONCLUSIONS: Our search identified markers from several modalities that hold promise for helping with a more objective diagnosis of MDE. To validate their potential, further longitudinal and prospective studies are needed.

Exogenous estradiol and oxytocin modulate sex differences in hippocampal reactivity during the encoding of episodic memories.

Considerable evidence supports sex differences in episodic memory. The hormones estradiol and oxytocin both affect episodic memory and may contribute to these sex differences, but possible underlying hormonal interactions have not been tested in a sample involving both sexes. To this end, we conducted a randomized, placebo-controlled, parallel-group functional magnetic resonance imaging (fMRI) study including healthy free-cycling women (n = 111) and men (n = 115). The fMRI session was conducted under four experimental conditions: 1. transdermal estradiol (2 mg) and intranasal oxytocin (24 IU), 2. transdermal placebo and intranasal oxytocin, 3. transdermal estradiol and intranasal placebo, 4. transdermal placebo and intranasal placebo. Participants were scanned during the encoding of positive, neutral, and negative scenes. Recognition memory was tested three days following the scanning sessions without additional treatments. Under placebo, women showed a significantly better recognition memory and increased hippocampal responses to subsequently remembered items independent of the emotional valence compared to men. The separate treatments with either hormone significantly diminished this mnemonic sex difference and reversed the hippocampal activation pattern. However, the combined treatments produced no significant effect. Collectively, the results suggest that both hormones play a crucial role in modulating sex differences in episodic memory. Furthermore, possible antagonistic interactions between estradiol and oxytocin could explain previously observed opposing hormonal effects in women and men.

Decision Conflicts in Clinical Care during COVID-19: A Multi-Perspective Inquiry.

Background: The early COVID-19-pandemic was characterized by changes in decision making, decision-relevant value systems and the related perception of decisional uncertainties and conflicts resulting in decisional burden and stress. The vulnerability of clinical care professionals to these decisional dilemmas has not been characterized yet. Methods: A cross-sectional questionnaire study (540 patients, 322 physicians and 369 nurses in 11 institutions throughout Germany) was carried out. The inclusion criterion was active involvement in clinical treatment or decision making in oncology or psychiatry during the first year of COVID-19. The questionnaires covered five decision dimensions (conflicts and uncertainty, resources, risk perception, perception of consequences for clinical processes, and the perception of consequences for patients). Data analysis was performed using ANOVA, Pearson rank correlations, and the Chi²-test, and for inferential analysis, nominal logistic regression and tree classification were conducted. Results: Professionals reported changes in clinical management (27.5%) and a higher workload (29.2%), resulting in decisional uncertainty (19.2%) and decisional conflicts (22.7%), with significant differences between professional groups (p < 0.005), including anxiety, depression, loneliness and stress in professional subgroups (p < 0.001). Nominal regression analysis targeting "Decisional Uncertainty" provided a highly significant prediction model (LQ p < 0.001) containing eight variables, and the analysis for "Decisional Conflicts" included six items. The classification rates were 64.4% and 92.7%, respectively. Tree analysis confirmed three levels of determinants. Conclusions: Decisional uncertainty and conflicts during the COVID-19 pandemic were independent of the actual pandemic load. Vulnerable professional groups for the perception of a high number of decisional dilemmas were characterized by individual perception and the psychological framework. Coping and management strategies should target vulnerability, enable the handling of the individual perception of decisional dilemmas and ensure information availability and specific support for younger professionals.