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OBJECTIVES: Therapeutic response in depression is a major challenge since more than one third of patients are not in remission after two attempts of antidepressant treatment and will present a treatment-resistant depression. In order to better adapt therapeutic strategies for treatment-resistant patients, predictive indicators and markers of therapeutic response still need to be identified. In parallel, patients with depression exhibit disturbances in cognitive functioning. This study aims to describe and compare cognitive performances collected at inclusion of patients presenting treatment-resistant depression who will be responders at 6 months to those of non-responders, and to evaluate the predictive value of cognitive indicators on clinical therapeutic response at 6 months after a therapeutic modification. METHODS: Observational study. Patients were evaluated at the clinical (HDRS and BDI-II) and cognitive levels using standardized tools assessing memory, executive functions, attention, and social cognition, prior to a change in antidepressant treatment. Six months after inclusion, they were reassessed and classified into two groups based on the presence or absence of therapeutic response, defined by a 50% improvement on HDRS and BDI-II. The cognitive scores collected at inclusion were then compared. Additionally, univariate logistic regression models were used. RESULTS: Thirty patients were included in this study. Only 13 could be evaluated at 6 months. Among these patients, four had responded to the new treatment while nine were non-responders. Both groups of patients presented deviant cognitive performances compared to norms on tests evaluating executive functions and attention. Statistical analyses did not reveal any difference between the cognitive performances of responders and non-responders at 6 months. Regression analyses showed no association between cognitive scores and therapeutic response at 6 months. CONCLUSION: Executive functioning plays a significant role in treatment-resistant depression. In order to improve the understanding and identification of subtypes of depression, cognitive indicators should be systematically integrated into future research.
RESUMO
RNA binding proteins assemble on mRNAs to control every single step of their life cycle, from nuclear splicing to cytoplasmic localization, stabilization or translation. Consistent with an essential role of RNA binding proteins in neuronal maturation and function, mutations in this class of proteins, in particular in members of the hnRNP family, have been associated with neurological diseases. To date, however, the physiological function of hnRNPs during in vivo neuronal development has remained poorly explored. Here, we have investigated the role of Drosophila Hrp48, a fly homologue of mammalian hnRNP A2/B1, during central nervous system development. Using a combination of mutant conditions, we showed that hrp48 is required for the formation, growth and guidance of axonal branches in Mushroom Body neurons. Furthermore, our results revealed that hrp48 inactivation induces an overextension of Mushroom Body dorsal axonal branches, with a significantly higher penetrance in females than in males. Finally, as demonstrated by immunolocalization studies, Hrp48 is confined to Mushroom Body neuron cell bodies, where it accumulates in the cytoplasm from larval stages to adulthood. Altogether, our data provide evidence for a crucial in vivo role of the hnRNP Hrp48 in multiple aspects of axon guidance and branching during nervous system development. They also indicate cryptic sex differences in the development of sexually non-dimorphic neuronal structures.