Alexandra Philipsen

Psychiatric syndromes can be caused by underlying autoimmune encephalitis (AE). This represents a diagnostic challenge at the interface of psychiatry and neurology. While AE mostly manifests with a combined, complex neuropsychiatric syndrome, some patients with AE may (initially) present with predominant or isolated psychiatric symptoms. These cases can be difficult to classify, and diagnostic approaches vary considerably across clinical settings. This paper from the GErman NEtwork for Research on AuToimmune Encephalitis (GENERATE) provides interdisciplinary expert recommendations from psychiatry and neurology for the diagnostic evaluation of patients with suspected AE as the cause of psychiatric syndromes for psychiatric care settings. It integrates current scientific evidence with practical, empirical considerations from routine clinical care in different healthcare settings. The proposed diagnostic approach to detect psychiatric manifestations of AE emphasizes a rational, stepwise evaluation incorporating clinical assessment, magnetic resonance imaging, electroencephalography, blood testing, cerebrospinal fluid (CSF) analysis, and neuronal/glial antibody testing in serum and CSF. In diagnostically ambiguous individuals, [¹⁸F]fluorodeoxyglucose positron-emission-tomography and advanced antibody testing (e.g., live-cell-based assays) or neuroimaging techniques (e.g., volumetric analysis) may provide additional supportive information. Typical findings and limitations of diagnostic modalities are discussed to facilitate appropriate interpretation and to avoid under-recognition or overdiagnosis. Importantly, these recommendations do not aim to define new disease entities or diagnostic criteria, but rather to support a harmonized and pragmatic diagnostic approach to patients presenting with psychiatric syndromes suspected to be caused by underlying AE. Finally, key unresolved issues in this evolving field of immunopsychiatry are outlined, and promising research strategies are described.

Background: Dissociative symptoms arise in reaction to significant stress and are common in post-traumatic stress disorder (PTSD). Methods: We longitudinally investigated the course of dissociative symptoms in psychiatric patients over the first year of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic situation (04/2020–05/2021). The group was separated into patients with relevant symptoms of PTSD at study start (Group 1: PTSDG) and those without (Group 2: noPTSDG), and we also employed a control group (Group 3: CG). Dissociative symptoms were tracked using the “Fragebogen zu Dissoziativen Symptomen” (FDS), an adapted and extended German version of the “Dissociative Experience Scale” (DES). Datasets of 93 participants were analyzed over up to three time periods. In addition, the regional incidence of positive SARS-CoV-2 tests (7di) and the intensity of non-pharmacological interventions (NPI) were included in multilevel linear models. Results: Patients reported stronger dissociative symptoms in the PTSDG than in the noPTSDG, while the CG showed the lowest symptom intensity. Importantly, regarding the course of symptoms over time, while public counts of positive SARS-CoV-2 tests had no influence, dissociative symptom severity was significantly impacted by the intensity of non-pharmacological interventions, particularly in the PTSDG and regarding depersonalization and derealization. Conclusion: Patients with relevant symptoms of PTSD at study start suffered from intense dissociative symptoms over the first year of the SARS-CoV-2 pandemic situation, driven by non-pharmacological interventions. In a milder way, other psychiatric patients were also affected. The results underline the responsivity of these patient groups regarding social and political stress.

In recent years, digital health interventions have proven effective for treating depression. However, it remains unclear which therapeutic components drive these effects, and the effectiveness of digital stress reduction interventions is under-researched. The present RCT investigated the effectiveness of a four-week self-guided digital stress regulation intervention in individuals with depression. After confirming the diagnosis of major depression, we randomly assigned N = 62 adults to either a control group receiving treatment as usual or to a digital intervention group receiving an additional digital stress regulation intervention. Self-reported depressive symptoms were our primary outcome. Secondary outcomes included anxiety, perceived stress, quality of life, usability and participant satisfaction. Descriptively, depressive symptoms improved in both groups with larger decreases in the digital intervention group at post-treatment (T0: M = 13.48, SD = 4.90; T1: M = 13.00, SD = 4.80) compared to the control group (T0: M = 14.26, SD = 3.69; T1: M = 14.11, SD = 4.80). However, compared to treatment as usual alone, the stress regulation intervention neither led to a significant reduction in depressive symptoms (F(2, 97.47) = 0.77, p = .464) nor to a significant improvement in any of the secondary outcomes. On average, participants rated the intervention’s usability as good and expressed medium to high user satisfaction. Our findings suggest that digital stress regulation interventions may be a feasible option for individuals with depression. Nevertheless, contrary to previous studies, our results do not provide evidence of superiority over treatment as usual alone.

Cardiovascular disease remains the leading global cause of morbidity and mortality. Although advances in prevention, diagnostics, and disease-modifying therapies have prolonged survival, many individuals now live longer with high symptom burden, functional decline, and complex decisional needs. Palliative care (PC) for adults with advanced cardiovascular disease can improve quality of life, support caregivers, and align treatments with patient values and goals. Core elements include symptom management, effective communication, shared decision-making, advance care planning, and integration of psychosocial and spiritual support across the disease trajectory and different care settings. Current evidence demonstrates that early PC intervention can improve symptom control, enhance quality of life, reduce psychological distress, and decrease high-intensity yet low-value care near the end of life. Nevertheless, outside of heart failure populations, gaps in widespread PC implementation across populations supported with cardiac devices as well as across diverse cultural and health systems remain. This state-of-the-art review (i) synthesizes conceptual foundations, referral triggers, and delivery models for PC in cardiovascular medicine; (ii) reviews disease-specific considerations across heart failure, valvular disease, pulmonary hypertension, arrhythmias, and congenital heart disease; (iii) outlines ethical and legal issues including advance directives and device deactivation; (iv) provides practical guidance for symptom management and communication frameworks; and (v) proposes a pragmatic algorithm to support clinical integration of PC into cardiovascular medicine.

Introduction: This study evaluated the effectiveness of a stepped-care approach – a staged model that escalates from lower- to higher-intensity treatments according to clinical response – for the treatment of adolescents and adults with ADHD, taking into account symptom severity and prior treatment response. Methods: In a multicenter study, adolescents and adults with ADHD (16–45 years) participated in a two-step treatment program including randomized controlled trials (RCTs). In step 1, patients were (block-)randomized to 3 months of psychoeducation (PE), telephone-assisted self-help (TASH), or waiting control (WC). In step 2 based on step 1 response (full, partial, none), patients either received counseling or were randomized to counseling with/without neurofeedback (NF) or pharmacological treatment (with/without NF) for 6 months. The primary outcome was change in clinician-rated ADHD symptoms, analyzed using linear (mixed-)effects models for repeated measures to account for correlations within participants over time. Results: Between January 2015, and September 2020, N = 299 (mean age = 28 years, 55.2% male) patients were randomized in step 1. The primary outcome showed no significant between-group differences (PE vs. TASH: d = −0.12, 95% CI: −3.18, 1.19, p = 0.64; PE vs. control: d = −0.26, 95% CI: −4.25, 0.05, p = 0.13; TASH vs. control: d = −0.14, 95% CI: −3.24, 1.04, p = 0.57). However, significant within-group effects emerged (PE: d = −0.60; TASH: d = −0.48; WC: d = −0.34; p < 0.001). Step 2 also showed no between-group differences but significant within-group effects (MPH: d = −0.59; MPH+NF: d = −0.76; counseling: d = −0.57/−1.35, p = 0.01/p < 0.001). Mixed models revealed symptom reduction in all step 1 responders and step 1 non-responders in step 2. Conclusions: The lack of step 1 RCT differences questions the specific effects of PE/TASH. Similar patterns emerged in step 2, but intensified treatment for step 1 non-responders improved outcomes in MPH groups. Step 1 response influenced later treatment success. Some stepped-care combinations did not further reduce symptoms, but no rebound effects occurred. The main limitations of this study are the two-step design complexity, limited information on certain (additional) psychosocial components, and the need to make assumptions about missing data. Nevertheless, findings support the feasibility and partial effectiveness of a stepped-care approach.

Access to evidence-based psychosocial interventions for adults with attention-deficit/hyperactivity disorder (ADHD) remains limited, despite strong patient demand for nonpharmacological options such as cognitive behavioral therapy (CBT). Digital interventions may offer a scalable, low-threshold solution to meet this need and complement existing care. This pragmatic randomized controlled trial evaluated the effectiveness of attexis , a fully self-guided digital intervention based on CBT and mindfulness principles, as an adjunct to treatment as usual (TAU). A total of 337 adults with confirmed ADHD were randomized to either attexis + TAU or TAU alone. The primary outcome was ADHD symptom severity (Adult ADHD Self-Report Scale total score) at 3 months post-randomization (T1). Secondary outcomes included functional impairment, depressive symptoms, self-esteem, and health-related quality of life. Follow-up was conducted at 6 months (T2). Intent-to-treat analyses showed significantly lower ADHD symptom severity in the intervention group at T1 (baseline-adjusted mean difference = −5.0 points; d = 0.85, p < .001). Significant improvements were also observed across all secondary outcomes, and effects remained stable at T2. Responder analyses confirmed the clinical relevance of the findings. Subgroup analyses demonstrated consistent effects across sex, medication use, psychotherapy status, and treatment changes. No adverse events related to attexis were reported. attexis was effective in reducing ADHD symptoms and improving a broad range of functional and psychosocial outcomes. As a safe, low-threshold, fully self-guided intervention, it may serve as a valuable adjunct to routine care and help address existing gaps in access to psychosocial treatment for adults with ADHD.

Background: Over the past 2 decades, virtual reality–based neuropsychological tasks have gained traction as tools for objectively assessing symptoms of attention-deficit/hyperactivity disorder (ADHD), offering enhanced ecological validity by simulating naturalistic environments. To complement realistic settings with an ecologically valid task, we recently developed the virtual email sorting task (VEST), which immerses participants into an office environment where they sort emails while being exposed to distractors. Objective: This study examined for the first time the VEST’s sensitivity to medication effects and its specificity in differentiating ADHD from other psychiatric disorders that share overlapping cognitive symptoms, such as major depressive disorder (MDD). Methods: A total of 23 unmedicated individuals with ADHD, 23 medicated individuals with ADHD, and 16 unmedicated individuals with MDD completed the VEST. During alternating distractor phases (DP) and nondistractor phases (NDP), we recorded the participants’ task performance; head, torso, and leg actigraphy; eye movements; and brain activity using functional near-infrared spectroscopy (fNIRS), and subjective symptom ratings. Correlational analyses of main objective and subjective task-related parameters were computed. Data were analyzed using mixed-design ANOVAs. Results: Processing time variability increased over time in participants with MDD and unmedicated ADHD as indicated by a group × block interaction (P=.04; η2p=0.10), while a group × phase interaction (P=.009; η2p=0.15) revealed that medicated participants with ADHD showed an increase during DP compared to NDP. Moreover, both ADHD groups exhibited increased head movements during DP compared to NDP (trend group × phase interaction: P=.09; η2p=0.08), an effect not observed in the MDD group, and higher rotation during DP in unmedicated individuals with ADHD (P<.001; η2p=0.23). Also, scores in 3 out of 4 subjective symptom intensity ratings of inattention, impulsivity, and emotional dysregulation were higher in at least 1 of the ADHD groups compared to the MDD group. No significant group differences were found in actigraphy measures of the arm and torso, fNIRS brain activity, or eye-tracking data. Regarding correlational analyses, inattention was correlated to off-task gaze (r=0.28; P=.03), hyperactivity with mean processing time (r=0.33; P=.01) and head movement (r=0.35; P=.006), and impulsivity with error rate (r=0.35; P=.006), and various significant correlations between objective parameters were found. Conclusions: Our findings highlight the potential of the VEST to differentiate between ADHD and MDD, as well as to detect medication-related effects within ADHD. The results underscore the value of multimodal and ecological assessment approaches with distractors in the evaluation of attentional and behavioral symptoms. The VEST may offer a standardized way to investigate complex behavior in mental disorders in research settings and, potentially, in clinical practice. However, further studies with greater statistical power are needed to confirm these findings. Trial Registration: German Clinical Trials Register DRKS00031259; https://www.drks.de/search/de/trial/DRKS00031259/details

Zusammenfassung: Einleitung: Mittels Virtueller Realität (VR) kann eine realitätsnahe und komplexe Szenerie erschaffen werden, die dabei zeitgleich vollständig kontrollierbar ist. Daher ermöglicht VR, Symptome und Krankheitsmechanismen psychischer Störungen wie der Aufmerksamkeitsdefizit-Hyperaktivitätsstörung (ADHS) unter realistischen und trotzdem standardisierten Bedingungen zu untersuchen. Methoden: In der vorliegenden Übersichtsarbeit wird die bisherige Forschungsaktivität zur Verwendung von VR zur Untersuchung der ADHS anhand ausgewählter Anwendungsbereiche aufgezeigt. Zu jedem vorgestellten Bereich wird eine Kurzzusammenfassung der Studienlage sowie des erreichten Reifegrads gegeben. Ergebnisse und Diskussion: Die meisten Studien wurden bisher zu virtuellen Lehrraum-Szenarien sowie Straßenverkehrsszenarien durchgeführt. Die Lehrraum-Szenarien liefern gute Belege dafür, dass mit VR neuropsychologische Testumgebungen entwickelt werden können, die eine Unterscheidung von Personen mit und ohne ADHS sowie von medikamentösen und nicht medikamentösen Zuständen ermöglichen. Die vorgestellten Straßenverkehrsszenarien wiederum liefern erste Hinweise, dass sie zur Untersuchung der Fahrleistung und des Straßenüberquerungsverhaltens von Personen mit ADHS gut geeignet erscheinen. Trotz der vielversprechenden Ergebnisse müssen weitere Validierungsstudien durchgeführt und Zulassungsprozesse durchlaufen werden, bevor die VR-basierten Tests auch in der regulären Patientenversorgung genutzt werden können.

Background: Mobile apps that implement disorder-specific psychotherapy for panic disorder (PD) with and without agoraphobia can be used in real-life situations that trigger symptoms and, therefore, are a promising novel therapeutic tool. Objective: This randomized controlled trial aimed to expand the currently limited evidence base for the efficacy of mobile interventions for PD with and without agoraphobia by evaluating a mobile app focusing on interoceptive and in-vivo exposure therapy. Methods: After establishing the diagnosis of PD with and without agoraphobia using a secure video communication platform, we randomized 111 adults to 3 equally sized groups: disorder-specific exposure therapy app, mindfulness meditation app unrelated to the disorder (active control condition), and waiting list (passive control condition). Participants used the apps in a self-guided manner. Additional psychotherapy was not allowed during the study. Self-reported PD with and without agoraphobia symptom severity was our primary outcome parameter and measured by the Panic and Agoraphobia Scale and symptom subset scales. Secondary outcome parameters included depressive symptoms and quality of life. We conducted assessments at baseline, after the intervention (allocation+5 wk), and at follow-up (allocation+13 wk). Results: We observed significantly lower overall PD with and without agoraphobia symptom severity in the exposure app group compared to waiting list post-treatment ( P =.04, Cohen d =0.55) and at follow-up ( P =.04, Cohen d =0.60). At follow-up, the exposure app group demonstrated significantly stronger improvements than the waiting list group in depressive symptoms ( P =.007, Cohen d =0.75) and psychological quality of life ( P =.01, Cohen d =0.63). We observed no significant differences between the exposure and the meditation apps in overall PD with and without agoraphobia symptom severity (post-treatment: P >.99, follow-up: P =.84). In the exposure app group, 35% (n=11) of participants showed reliable improvement in overall PD with and without agoraphobia symptom severity at post-treatment (meditation app: n=2, 6%; waiting list: n=2, 7%; P =.002 ) . The dropout rate after 5 weeks was 14% (5/37) in the exposure app group (meditation app: 3/37, 8%; waiting list: 6/37, 16%; P =.68). No adverse outcomes were reported in the exposure app group. Conclusions: Our findings suggest that app-guided exposure therapy can be a useful further treatment option in addition to established psychological and pharmacological strategies. However, superiority compared to the disorder-unspecific meditation app remains unclear.