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Background/Objectives : Identity disruption is a key feature of borderline personality disorder (BPD), characterized by disturbances in self-image. This study aimed to use the Dimensions of Identity Development Scale (DIDS) in a population aged 16-25, to assess differences in identity status and correlations with BPD features as well as whether a correlation exists between the BPD features, the scores obtained on the DIDS and the scores of the different dimensions of this disorder. Methods: We analyzed data from 132 individuals: 44 with BPD using the Diagnostic Interview for Borderline-Revised (DIB-R). Statistical analyses included quantile regression to determine the differences in the DIDS after adjusting for confounding factors identified during group comparisons and Spearman correlation between the DIDS, the BPD features and the DIB-R. Results: Results indicated significantly lower DIDS scores in the BPD group, particularly in commitment making, exploration breadth (EB), identity with commitment (IM) and ruminative exploration (RE). After adjusting, only EB differs significantly between the two groups. All dimensions of the DIDS except for the exploration in depth (ED) are correlated with BPD features. Significant correlations could be demonstrated between cognitive dimension and ED, between the total DIDS and the number of suicide attempt (SA) and between the IM and the number of SA. Conclusions: Our clinical sample showed distinct identity formation compared to controls, with a lower EB associated with BPD. RE correlated with BPD, suggesting that the individuals engage in repetitive exploratory processes. SA was negatively associated with overall identity development and commitment, indicating impulsive behaviors in BPD intersect with identity struggles.

Functions of the cerebellar cortex, from motor learning to emotion and cognition, depend on the appropriate molecular composition at diverse synapse types. Glutamate receptor distributions have been partially mapped using immunogold electron microscopy. However, information is lacking on the distribution of many other components, such as Shank2, a postsynaptic scaffolding protein whose cerebellar dysfunction is associated with autism spectrum disorders. Here, we used an adapted Magnified Analysis of the Proteome, an expansion microscopy approach, to map multiple glutamate receptors, scaffolding and signaling proteins at single synapse resolution in the cerebellar cortex. Multiple distinct synapse-selective distribution patterns were observed. For example, AMPA receptors were most concentrated at synapses on molecular layer interneurons and at climbing fiber synapses, Shank1 was most concentrated at parallel fiber synapses on Purkinje cells, and Shank2 at both climbing fiber and parallel fiber synapses on Purkinje cells but little on molecular layer interneurons. Our results are consistent with gene expression data but also reveal input-selective targeting within Purkinje cells. In specialized glomerular structures of the granule cell layer, AMPA receptors as well as most other synaptic components preferentially targeted to synapses. However, NMDA receptors and the synaptic GTPase activating protein SynGAP preferentially targeted to extrasynaptic sites. Thus, glomeruli may be considered integrative signaling units through which mossy fibers differentially activate synaptic AMPA and extrasynaptic NMDA receptor complexes. Furthermore, we observed NMDA receptors and SynGAP at adherens junctions, suggesting a role in structural plasticity of glomeruli. Altogether, these data contribute to mapping the cerebellar 'synaptome'., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Robinson, Delhaye and Craig.)

Objective: Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk., Methods: In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay., Results: A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups., Conclusion: We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo., Trial Registration Number: ClinicalTrials.gov number, NCT01855841)., Competing Interests: Declaration of competing interest All the authors declare that they have no conflict of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Growing evidence suggests a remarkable diversity and complexity in the molecular composition of synapses, forming the basis for the brain to execute complex behaviors. Hence, there is considerable interest in visualizing the spatial distribution of such molecular diversity at individual synapses within intact brain circuits. Yet this task presents significant technical challenges. Expansion microscopy approaches have revolutionized our view of molecular anatomy. However, their use to study synapse-related questions outside of the labs developing them has been limited. Here we independently adapted a version of Magnified Analysis of the Proteome (MAP) and present a step-by-step protocol for visualizing over 40 synaptic proteins in brain circuits. Surprisingly, our findings show that the advantage of MAP over conventional immunolabeling was primarily due to improved antigen recognition and secondarily physical expansion. Furthermore, we demonstrated the versatile use of MAP in brains perfused with paraformaldehyde or fresh-fixed with formalin and in formalin-fixed paraffin-embedded tissue. These tests expand the potential applications of MAP to combinations with slice electrophysiology or clinical pathology specimens. Using male and female mice expressing YFP-ChR2 exclusively in interneurons, we revealed a distinct composition of AMPA and NMDA receptors and Shank family members at synapses on hippocampal interneurons versus on pyramidal neurons. Quantitative single synapse analyses yielded comprehensive cell type distributions of synaptic proteins and their relationships. These findings exemplify the value of the versatile adapted MAP procedure presented here as an accessible tool for the broad neuroscience community to unravel the complexity of the "synaptome" across brain circuits and disease states., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Introduction: Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers., Methods: Children and adolescents ( n  = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response., Results: For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only., Discussion: Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies., Competing Interests: YA was employed by myBrain Technologies; AB and LM were employed by Mensia Technologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. DP-O reports personal fees and nonfinancial support from Medice and Shire, nonfinancial support from HAC Pharma and Boehringer Ingelsheim, outside the submitted work. HB has received lecture fees from Takeda, BIAL, laboratorios Rubio, and laboratorios Rovi. He is PI of a research of the SINCRONIA project, funded by the Start-up Bitsphi, www.bitsphi.com, and co-Founder of Haglaia Solutions. EA reports personal fees and nonfinancial support from HAC Pharma, nonfinancial support from Shire, outside the submitted work. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Novartis and Shire. He received conference support or speaker’s fees from Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire and Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien and Oxford University Press. AB reports personal fees from Mensia Technologies outside the submitted work. LM has a patent EP3181043A1 pending, a patent EP3335630A1 pending and a patent EP3217869A1 pending and was employee and shareholder of Mensia Technologies SA, a company offering class IIa certified medical device for ADHD in children and teenagers. KM has received speaker’s fees by Takeda and Medice. The present work is unrelated to these relationships. OR reports personal fees and nonfinancial support from HAC Pharma, from Shire and from Novalac outside the submitted work. SW has received in the last 5 years royalties from Thieme, Hogrefe, Kohlhammer, Springer, Beltz. In 2023 she received speakers honorary from Takeda. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kaiser, Aggensteiner, Blasco Fontecilla, Ros, Acquaviva, Attal, Banaschewski, Baumeister, Bousquet, Bussalb, Delhaye, Delorme, Drechsler, Goujon, Häge, Mayaud, Mechler, Menache, Revol, Tagwerker, Walitza, Werling, Bioulac, Purper-Ouakil and Brandeis.)