Effort-cost decision-making in psychotic and mood disorders.

Avolition and anhedonia are core symptoms across psychosis and mood disorders. One important mechanism thought to relate to these symptoms is effort-cost decision-making (ECDM), the valuation and estimation of work required to obtain a given reward. While recent work suggests impairments in ECDM in both mood disorders and psychosis relative to controls, limited work has taken a transdiagnostic approach to examine how these deficits relate to different symptom profiles across disorders. The present study investigated ECDM across schizophrenia/schizoaffective disorder (N = 33), bipolar disorder (N = 47), unipolar depression (N = 61), and healthy controls (N = 58) to examine willingness to expend physical effort. Moreover, we examined the relationship between ECDM and motivation and pleasure symptoms across participants. We found that people with schizophrenia and bipolar disorder showed a reduced willingness to expend physical effort at high reward values relative to controls, while as a group, those with depression showed no differences relative to controls. However, individual differences in self-reported motivation and pleasure predicted reduced ECDM, particularly at high reward values, suggesting that both severity of symptoms and diagnostic categories are important for understanding altered ECDM in psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I/IIa Clinical Trial, Cohorts 1-5.

PURPOSE: To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4. DESIGN: Nonrandomized multicenter phase I/IIa clinical trial. METHODS: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment. MAIN OUTCOME MEASURES: The primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography. RESULTS: The subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment. CONCLUSIONS: Subretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.