Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

The incidence of facial palsy has been rising worldwide, with recent evidence emerging of links to COVID-19 infection. To date, guidance on cost-effective treatments is limited to medication (prednisolone). In terms of physical therapy, neuromuscular retraining (NMR) to restore balanced facial function has been most widely evaluated, but not in terms of cost effectiveness. The added value of telerehabilitation is unknown.

A multistage technology assessment was conducted, which included the following:

• • a national survey of current therapy pathways in the UK and patients’ and clinicians’ views on the benefits and challenges of telerehabilitation;

• • a systematic review of clinical effectiveness trials evaluating facial NMR therapy;

• • calculation of long-term morbidity costs (national economic burden) based on incidence, patient recovery profiles, health-related quality of life, and national facial palsy treatment costs (valuation of clinical improvements in monetary terms was provided by a national Delphi panel); and

• • evaluation of the cost effectiveness of telerehabilitation (remote monitoring wearables) added to current face-to-face NMR delivery.

Nationally, approximately five percent of patients with facial palsy (17% of unresolved cases) are referred for facial NMR. The long-term economic burden associated with unresolved cases is estimated to range from GBP351 (EUR417) to GBP584 (EUR692) million, indicating substantial savings if long-term recovery can be improved. Medical treatment costs are GBP86.34 (EUR102) million per annual cohort, and physical and psychological therapy costs are GBP643,292 (EUR762,561). Economic modeling showed that telerehabilitation was cost effective, producing a health gain and a cost-saving of GBP468 (EUR555) per patient. If scaled to the national level for all patients who do not recover fully, an annual saving of GBP3.075 (EUR3.65) million is possible.

Economic modeling indicates that NMR could improve patient outcomes and reduce costs. The national survey demonstrated that access to NMR therapy services is limited, so introduction of telerehabilitation could improve access for currently underserved populations. Future clinical trials need to incorporate economic evaluations to help inform decision-making.

Understanding post-stroke spasticity (PSS) treatment in everyday clinical practice may guide improvements in patient care.

This was a retrospective cohort study that used population-level administrative data. Adults (aged ≥18 years) who initiated PSS treatment (defined by the first PSS clinic visit, focal botulinum toxin injection, or anti-spasticity medication dispensation [baclofen, dantrolene and tizanidine] with none of these treatments occurring during the 2 years before the stroke) were identified between 2012 and 2019 in Alberta, Canada. Spasticity treatment use, time to treatment start and type of prescribing/treating physician were measured. Descriptive statistics were performed.

Within the cohort (n = 1,079), the most common PSS treatment was oral baclofen (initial treatment: 60.9%; received on/after the initial treatment date up to March 31, 2020: 69.0%), largely prescribed by primary care physicians (77.6%) and started a median of 348 (IQR 741) days after the stroke. Focal botulinum toxin (23.3%; 37.7%) was largely prescribed by physiatrists (72.2%) and started 311 (IQR 446) days after the stroke; spasticity clinic visits (18.6%; 23.8%) were also common.

We found evidence of gaps in provision of spasticity management in persons with PSS including overuse of systemic oral baclofen (that has common adverse side effects and lacks evidence of effectiveness in PSS) and potential underuse of focal botulinum toxin injections. Further investigation and strategies should be pursued to improve alignment of PSS treatment with guideline recommendations that in turn will support better outcomes for those with PSS.

We aimed to (1) report updated estimates of direct healthcare costs for people living with MS (pwMS), (2) contrast costs to a control population and (3) explore differences between disability levels among pwMS.

Administrative data were used to identify adult pwMS (MS cohort) and without (control cohort) in Alberta, Canada; disability level (based on the Expanded Disability Status Scale) among pwMS was estimated. One- and two-part generalized linear models with gamma distribution were used to estimate the incremental direct healthcare cost (2021 $CDN) of MS during a 1-year observation period.

Adjusting for confounders, the total healthcare cost ratio was higher in the MS cohort (n = 13,089) versus control (n = 150,080) (5.24 [95% CI: 5.08, 5.41]) with a predicted incremental cost of $15,016 (95% CI: $14,497, $15,535) per person-year. Among the MS cohort, total predicted direct healthcare costs were higher with greater disability, $14,430 (95% CI: $13,980, $14,880) to $58,697 ($51,514, $65,879) per person-year in mild and severe disability, respectively. The primary health resource cost component shifted from disease-modifying therapies in mild disability to supportive care in moderate and severe disability.

Adult pwMS had greater direct healthcare costs than those without. Extrapolating to the population level (where 14,485 adult pwMS were identified in the study), it is estimated that $218 million per year in healthcare costs may be attributable to MS in Alberta. The significantly larger economic impact associated with greater disability underscores the importance of preventing or delaying disease progression and functional impairment in MS.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations.

This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples.

We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18–0.34, p = 8.5 × 10−6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI −0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06–0.08), female sex (beta = 0.160, 95% CI 0.15–0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03–0.07), while neither the depression PGS (beta = 0.004, 95% CI −0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI −0.01 to 0.03) were strongly associated with MDD.

Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.