BackgroundMajor depressive disorder (MDD) is a chronic disease with a large global impact. There are currently no clinically useful predictors of treatment outcome, and the development of biomarkers to inform clinical treatment decisions is highly desirable.MethodsIn this exploratory study we performed fixel-based analysis of diffusion MRI data from the International Study to Predict Optimized Treatment in Depression with the aim of identifying novel biomarkers at baseline that may relate to diagnosis and outcome to treatment with antidepressant medications. Analyses used MR data from individuals with MDD (n = 221) and healthy controls (n = 67).ResultsWe show focal, gender-specific differences in the anterior limb of the internal capsule (males) and bilaterally in the genu of the corpus callosum (females) associated with diagnosis. Lower fibre cross-section in the tapetum, the conduit between the right and left hippocampi, were also associated with a decreased probability of remission. Analysis of conventional fractional anisotropy showed scattered abnormalities in the corona radiata, cerebral peduncles and mid-brain which were much lower in total volume compared to fixel-based analysis.ConclusionsFixel-based analysis appeared to identify different underlying abnormalities than conventional tensor-based metrics, with almost no overlap between significant regions. We show that MDD is associated with gender specific abnormalities in the genu of the corpus callosum (females) and in the anterior limb of the internal capsule (males), as well as gender-independent differences in the tapetum that predict remission. Diffusion MRI may play a key role in future guidance of clinical decision-making for MDD.

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Detection of ADA to therapeutic large molecule tumour necrosis factor (TNF) inhibitors has established utility in the management of chronic inflammatory diseases. 1 ADA are of two types: neutralising (nADA) and binding (bADA). 2 HMSA differentiates between dimer and multimer drug-ADA complexes. We describe a 52-year-old male with psoriatic arthritis who was switched to infliximab infusions every 8 weeks with good therapeutic response. However, by the third to fourth maintenance infusion he reported 'wear-off' at around 4-6 weeks post-infusion and this pattern persisted. Trough drug concentrations were found to be low/undetectable between infusions. Dimeric, not multimeric, ADA were detected on each occasion. No neutralising ADA were detected by competitive ELISA. 3 A pharmacokinetic study demonstrated accelerated infliximab clearance. Because of limited therapeutic options therapy with infliximab was continued (now >2 years). The pattern of wear-off has persisted as has the pattern of drug-ADA complexes. This case demonstrates the value of discriminating between nADA and bADA by HMSA, allowing a more nuanced approach to individual patient treatment. Studies have shown that multimers are invariably associated with nADA with loss of clinical response. Dimers are mostly bADA and rarely associated with neutralisation. 3 Such information may help guide clinicians in their treatment choices. References 1. Mitrev N, Casteele NV, Seow CH, et al. Review article: consensus statements on therapeutic drug monitoring of antitumor necrosis factor therapy in inflammatory bowel diseases.