Medical University of Vienna

Physical exercise is an effective treatment for depression, yet little is known about the temporal dynamics of symptom improvement during exercise interventions. In this randomized controlled trial, 64 adults with moderate to severe depressive symptoms were allocated to a 10-week supervised Nordic walking (NW) program (n=48) or a non-active control condition (n=16). The NW group completed two weekly training sessions at moderate intensity (65-75% HRmax). Depressive symptoms were assessed at baseline, mid-intervention (Week 5), and post-intervention (Week 10) using the Beck Depression Inventory-II. Primary analyses examined Group × Time effects on symptom severity. Secondary analyses explored (via a Group × Depression intensity × Time ANOVA) whether baseline depression intensity moderated treatment response. A significant Group × Time interaction indicated greater reductions in depressive symptoms in the NW group compared with controls. Symptom improvement was most pronounced during the first half of intervention (Hedges's g=-0.98), with smaller changes thereafter (Hedges's g=-0.40 from mid- to post-intervention). In addition, a significant Group × Depression intensity × Time interaction suggests that participants with severe baseline depression experienced larger and more rapid improvement than those with moderate symptoms in the first five weeks. Supervised Nordic walking was found to be associated with substantial reductions in depressive symptoms within five weeks, particularly among individuals with severe depression. Implications of our findings and study's limitations are discussed.

Functional movement disorder (FMD), characterized by abnormal movements and motor weakness, represents a common manifestation within the spectrum of functional neurological disorders (FND). Integrative therapy, comprising specialised physiotherapy, psychotherapy, and patient education, has demonstrated efficacy in improving motor function and quality of life. To assess symptom severity and treatment response, both patient-reported outcome measures (PROMs) and clinician-rated outcome measures (CROMs) can be employed. In a preliminary analysis of an ongoing transdisciplinary treatment study, we examined the association between the 'Simplified FMD Rating Scale' (S-FMDRS, CROM) and the 'FMD Questionnaire' (FMDQ, PROM) during integrative therapy and explored their suitability for monitoring treatment-related changes over time. Twenty-six patients contributed 60 paired longitudinal assessments. Linear mixed-effects modelling demonstrated significant associations between clinician-rated motor severity (S-FMDRS) and patient-reported total FMDQ scores as well as all functional domains. In the subgroup with complete pre-post data (n=15), both S-FMDRS and FMDQ scores improved significantly during treatment (S-FMDRS: p=.003, r=0.76; FMDQ: p=.012, r=0.65). Concordance in MCID-based responder classification was partial, with 53% agreement between instruments. Clinician- and patient-reported measures in FMD are significantly associated but not interchangeable at the individual level, supporting their complementary use in treatment evaluation.

The discovery of a resident urinary microbiome has challenged the long-standing view of the bladder as sterile. Overactive bladder, a common and burdensome condition, has been linked to urinary dysbiosis, yet the origins of bladder colonization and its relationship to adjacent microbiomes remain unclear. To compare the urinary microbiome profiles of women with overactive bladder to those of healthy controls, to assess intraindividual relationships between the urinary and other urogenital or mucosal microbiomes-including the vaginal, urethral, buccal sites, and stool-and to identify potential colonization pathways by analyzing microbial overlap within and between individuals. In a cross-sectional study, we profiled the microbiomes of 50 women with overactive bladder and 49 healthy controls across urine, urethra, vagina, oral cavity, and stool. DNA was extracted using standardized protocols and the V3 to V4 region of the 16S rRNA gene was sequenced on the Illumina MiSeq platform. Reads were processed with Divisive Amplicon Denoising Algorithm 2 and taxonomically classified using the SILVA ribosomal RNA database. Diversity metrics (alpha and beta diversity), differential abundance testing (DESeq2), and cross-site microbial overlap analyses were performed in R using established packages (phyloseq, vegan, mia, and microViz). Subgroup analyses accounted for menopausal status. Overactive bladder cases exhibited higher alpha diversity in urethral and vaginal samples and significantly different beta diversity across all sites compared with controls (P<.004). The urethra of overactive bladder cases contained reduced Lactobacillus but was enriched with Bacteroides, Bifidobacterium, Gardnerella, Hydrotalea, Streptococcus, and other genera. Six taxa (Alistipes, Bacteroides, Bifidobacterium, Bradyrhizobium, Hydrotalea, and Neisseria) consistently met thresholds for abundance and prevalence in urethra and were also elevated in overactive bladder urine, vagina, and oral cavity, but not stool. Intraindividual analyses showed greater urethra-urine and urethra-vagina divergence in overactive bladder than in controls, indicating disruption of the normal microbial continuum. Subgroup analyses confirmed between-group differences irrespective of menopausal status. Notably, dysbiosis in overactive bladder over-rode the premenopausal/postmenopausal contrasts observed in controls. Women with overactive bladder seem to have a distinct multisite dysbiosis, most pronounced in the urogenital tract, characterized by the loss of Lactobacillus and enrichment of selected taxa across urethra, urine, vagina, and oral cavity. The observed microbial overlap across urogenital sites, compared with stool, is consistent with predominant urogenital microbial relatedness in this cross-sectional cohort. These findings provide insight into microbiome alterations in overactive bladder and highlight the need for longitudinal studies to clarify mechanisms and evaluate potential microbiome-targeted strategies. Given the cross-sectional design, these findings describe associations and cannot establish causality or the directionality of microbial transmission between compartments.

Social anxiety disorder (SAD) frequently co-occurs with major depressive disorder (MDD). We examined the prevalence and clinical correlates of SAD across three heterogeneous MDD cohorts. Secondary analyses were conducted in adult (CO-MED: n=482; GSRD: n=1398) and late-life (IRL-GREY: n=438) patients. SAD was assessed dimensionally (PDSQ) and categorically (MINI; SCID-1). Cohort-specific instruments were used to assess depressive severity (QIDS; MADRS), suicidality (CHRT; MADRS; SIS) and hypomanic symptoms (ASRM; YMRS). In late-life depression, neurocognitive tests were administered. Multivariate models were adjusted for depression and anxiety levels. SAD prevalence varied markedly by samples and diagnostic definitions (CO-MED: 46.7% with PDSQ≥6; 17.0% with PDSQ>12; GSRD: 3.0%; IRL-GREY: 8.7%). Across cohorts, SAD was associated with earlier MDD onset (CO-MED: p<0.001 d=-0.36; GSRD: p=0.014 d=-0.39; IRL-GREY: p=0.002 d=-0.54) and greater anxiety comorbidity (CO-MED: GAD: p<0.001 d=1.24; panic: p<0.001 d=1.29; GSRD: GAD: p<0.001; panic: p<0.001; IRL-GREY: agoraphobia: p<0.001). After controlling for depression and anxiety levels, SAD was linked to higher suicide risk in both adult cohorts (CO-MED: OR 1.04 (1.01-1.08); GSRD: OR 1.29 (1.04-1.64)) and to lower 6-week remission in CO-MED cohort (OR 0.51 (0.29-0.91)). In MDD, SAD has consistent associations with earlier illness onset and anxiety burden, modest associations with suicidality and antidepressant outcomes, and reduced impact in late life.

Homozygosity for the SERPINA1 Pi*Z deficiency allele is the culprit of alpha-1 antitrypsin deficiency-related liver disease, while harbouring a single Z-allele (e.g., the common Pi*MZ genotype) is the strongest genetic risk factor for advanced chronic liver disease (ACLD) and its progression. However, the impact of the Pi*MZ genotype on hepatocellular carcinoma (HCC) development in patients who have already progressed to ACLD has yet to be established. Thus, we investigated the impact of the Pi*MZ genotype on the development of HCC among longitudinally followed ACLD patients. Patients undergoing hepatic venous pressure gradient (HVPG) measurement and genotyping at the Vienna Hepatic Haemodynamic Lab were included, excluding those with HCC. Competing risk analyses with HCC as the outcome of interest and death/liver transplantation as competing events were performed. We included 815 patients (mean age: 54 ± 11 years; viral hepatitis: 53%, alcohol-related liver disease: 37% and metabolic dysfunction-associated steatotic liver disease: 10%). Overall, 30 patients (4%) harboured the Pi*MZ genotype. During a median follow-up of 47.3 months, 68 patients developed an HCC (8/30 with Pi*MZ). The Pi*MZ genotype was associated with increased risks of HCC development in univariable as well as in multivariable analyses, accounting for other important factors (i.e., age, sex, removal of the primary aetiological factor, aspartate-aminotransferase, albumin and HVPG) identified in our study (adjusted subdistribution hazard ratio [aSHR]: 3.31 [95% confidence interval (CI): 1.26-8.65]; p = 0.015). The impact of the Pi*MZ genotype was confirmed adjusting for the aMAP score (aSHR: 2.94 [95% CI: 1.45-5.97]; p = 0.003). The SERPINA1 Pi*MZ genotype is associated with an increased risk of HCC development in patients with ACLD, independently of other HCC risk factors.