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Frankia cluster-2 strains are diazotrophs that engage in root nodule symbiosis with actinorhizal plants of the Cucurbitales and the Rosales. Previous studies have shown that an assimilated nitrogen source, presumably arginine, is exported to the host in nodules of Datisca glomerata (Cucurbitales), while a different metabolite is exported in the nodules of Ceanothus thyrsiflorus (Rosales). To investigate if an assimilated nitrogen form is commonly exported to the host by cluster-2 strains, and which metabolite would be exported in Ceanothus, we analysed gene expression levels, metabolite profiles, and enzyme activities in nodules. We conclude that the export of assimilated nitrogen in symbiosis seems to be a common feature for Frankia cluster-2 strains, but which source is host-dependent. The export of assimilated ammonium to the host suggests that 2-oxoglutarate is drawn from the TCA cycle at a high rate. This specialised metabolism obviates the need for the reductive branch of the TCA cycle. We found several genes encoding enzymes of the central carbon and nitrogen metabolism were lacking in Frankia cluster-2 genomes: the glyoxylate shunt and succinate semialdehyde dehydrogenase. This led to a linearization of the TCA cycle, and we hypothesize this could explain the low saprotrophic potential of Frankia cluster-2., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Objective: Over time, most patients with schizophrenia wish to reduce or discontinue their antipsychotic medication treatment. In Denmark, a specialized government-funded outpatient clinic was established to offer guided antipsychotic dose reduction. This study aimed to provide data on motivations for and previous experiences with antipsychotic tapering among patients attending the clinic., Methods: Patients completed an open-ended survey on their motivations for discontinuing or tapering antipsychotic medication and recorded their expectations about these outcomes. They also provided information on previous experiences with discontinuing medication and their level of symptoms, functioning, and side effects., Results: The survey was completed by 76 (86%) of 88 patients. The main motivations for discontinuing antipsychotics were adverse effects (71%) and uncertainty about the necessity of taking antipsychotics (29%). Other factors included concerns about long-term effects, disagreeing with the diagnosis, experiencing an insufficient effect, and feeling stigmatized by taking medication. Previous experience with discontinuation of antipsychotics was reported by 42 patients, of whom 23 reported relapse as the outcome. Most patients believed they could succeed in dose reduction (N=73 of 75, 97%) or discontinuation (N=62 of 75, 83%)., Conclusions: Motivational factors reported for professionally guided antipsychotic dose reduction align with previous studies examining patients choosing to discontinue these medications. Despite reports of relapse during prior discontinuation attempts, most patients still reported motivation for and belief in successful dose reduction or discontinuation. An understanding of patients' motivations and beliefs is paramount to an optimal treatment alliance. Offering guided dose reduction may reduce sudden and unsupported discontinuation of antipsychotics., Competing Interests: Dr. Nøstdal has received honoraria from Lundbeck. Dr. Hilker has received honoraria from Lundbeck, Otsuka, and Janssen. Dr. J. Nielsen has received honoraria from Lundbeck and Bristol Myers Squibb. Dr. M. Ø. Nielsen reports no financial relationships with commercial interests.

Background: While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse., Methods: Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction., Results: After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects ( p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak., Conclusions: We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.