Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=

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The Prevalence of Hepatitis E in a Patient Cohort Presenting With Addictive Injection Behavior

International audienceIntroduction: Hepatitis E is the most common cause of acute viral hepatitis worldwide. Seroprevalence is approximately 15% in developed countries, and 22% in France. hepatitis E virus (HEV) can be transmitted via transfusions and therefore possibly intravenous (IV) drug use. Hepatitis E serology is routinely tested in patients who seek medical advice for addictive injection behavior at the addiction treatment, support and prevention unit of Toulouse University Hospital. We assume that hepatitis E is more prevalent in patients presenting with addictive injection behavior than in the general French population.Methods: Hepatitis E serological assays [immunoglobulin M (IgM) and IgG] were carried out for all patients presenting with addictive injection behavior during an initial evaluation. The controls were taken from a cohort of 3,353 blood donors living in southern France and who donated blood during the first 2 weeks of October 2011.Results: We included 52 patients presenting with addictive injection behavior and 103 healthy controls matched for age, sex, and area of residence. We found no difference between patients and controls for the prevalence of hepatitis E: patients vs. healthy controls: positive IgGs: 42.31%, 95% confidence interval (CI) (28.73–56.80%) vs. 43.43%, 95% CI (33.50–53.77%) (p = 0.89) and positive IgMs: 3.85%, 95% CI (0.47–13.22%) vs. 4.85%, 95% CI (0.16–10.97%) (p = 0.57).Conclusion: There was no difference in HEV seroprevalence between IV drug users and the general population, suggesting that the IV route of HEV infection is not significant in this population

Developing and Testing a Local Expert-Based Reading Process for Use to Examine Discrepancies Between Guidelines and Current Clinical Practices

International audienceThe use of relevant guidelines is critical in psychiatric clinical practice to ensure the homogeneity of the global care provided. Consequently, it is important to identify whether they are utilized successfully and, if not, why. This would enable pragmatic solutions to be agreed to improve the organization of care and the removal of any barriers to the guidelines' implementation. The first step in this process, before any exploration of the limitations of the guidelines themselves, involves a determination of whether they are actually applied in clinical practice. We therefore evaluated discrepancies between the guidelines relating to patients with borderline personality disorder and current practices in the psychiatric Emergency Department at Toulouse University Hospital. This was achieved using a reading process involving a panel of eight local experts who analyzed relevant medical files extracted from a database. They were guided by, and instructed to answer, six standardized questions in relation to each file to determine the method's feasibility. A total of 333 files were analyzed to determine whether, in the local experts' judgment, the care provided reflected current guidance. This reading process revealed substantial agreement (0.85%; Fleiss Kappa −0.69), which is a promising outcome and suggests that such methods could be used in future protocols. Moreover, the process is practical and reliable and requires very few materials

Significant Decrease in Hippocampus and Amygdala Mean Diffusivity in Treatment-Resistant Depression Patients Who Respond to Electroconvulsive Therapy

International audienceIntroduction: The hippocampus plays a key role in depressive disorder, and the amygdala is involved in depressive disorder through the key role that it plays in emotional regulation. Electroconvulsive therapy (ECT) may alter the microstructure of these two regions. Since mean diffusivity (MD), is known to be an indirect marker of microstructural integrity and can be derived from diffusion tensor imaging (DTI) scans, we aim to test the hypothesis that treatment-resistant depression (TRD) patients undergoing bilateral (BL) ECT exhibit a decrease of MD in their hippocampus and amygdala. Methods: Patients, between 50 and 70 years of age, diagnosed with TRD were recruited from the University Hospital of Toulouse and assessed clinically (Hamilton Depression Rating Scale, HAM-D) and by DTI scans at three time points: baseline, V2 (during treatment), and V3 within 1 week of completing ECT. Results: We included 15 patients, who were all responders. The left and right hippocampi and the left amygdala showed a significant decrease in MD at V3, compared to baseline [respectively: β = -2.78, t = -1.97, p = 0.04; β = -2.56, t = -2, p = 0.04; β = -2.5, t = -2.3, p = 0.04, false discovery rate (FDR) corrected]. MD did not decrease in the right amygdala. Only the left amygdala was significantly associated with a reduction in HAM-D (ρ = 0.55, p = 0.049, FDR corrected). Conclusion: MD is an indirect microstructural integrity marker, which decreases in the hippocampus and the left amygdala, during BL ECT in TRD populations. This could be interpreted as a normalization of microstructural integrity in these structures

Grey Matter changes in treatment-resistant depression during electroconvulsive therapy

International audienceIntroduction: 20-30% of depressed patients experience Treatment Resistant Depression (TRD). Electroconvulsive Therapy (ECT) remains the treatment of choice for TRD. However, the exact mechanism of ECT remains unclear. We aim to assess grey matter changes in patients with TRD undergoing bilateral ECT treatment at different points during and after treatment.Methods: Patients are recruited at the University Hospital of Toulouse. Eligibility criteria include a diagnosis of TRD and an age between 50 and 70 years old. Patients received clinical assessments (Hamilton Depression Rating Scale) and structural scans (MRI) at three points: baseline (within 48 h before the first ECT); V2 (after the first ECT considered effective); and V3 (within 1 week of completing ECT).Results: At baseline, controls had significantly higher cortical thickness than patients in the fusiform gyrus, the inferior, middle and superior temporal gyrus, the parahippocampal gyrus and the transverse temporal gyrus (respectively: t(35)=2.7, p = 0.02; t(35)=2.89, p = 0.017; t(35)=3.1, p = 0.015; t(35)=3.6, p = 0.009; t(35)=2.37, p = 0.031; t(35)=2.46, p = 0.03). This difference was no longer significant after ECT. We showed an increase in cortical thickness in superior temporal gyrus between (i) baseline and V3 (t(62)=-3.43 p = 0.009) and (ii) V2 and V3 (t(62)=-3.42 p = 0.009). We showed an increase in hippocampal volume between (i) baseline and V3 (t(62)=-5.23 p < 0.001) and (ii) V2 and V3 (t(62)=-5.3 p < 0.001).Conclusion: We highlight that there are grey matter changes during ECT treatment in a population with TRD compared to a healthy control population. These changes seem to occur after several rounds of ECT

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

International audienceBackground: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4-20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance. Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group-patients with current MDD (n = 20), (ii) remitted depressed group-patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups. Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice. Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=1

Des sources du savoir aux médicaments du futur

L'origine des pharmacopées traditionnelles L'élaboration des pharmacopées Les médicaments du XXIe siècle Comment les connaissances des savoirs thérapeutiques se sont-elles transmises au travers des différentes cultures ? Cet ouvrage innovant, qui réunit les travaux présentés au 4e Congrès européen d'ethnopharmacologie, fait remonter à la préhistoire les sources des connaissances thérapeutiques. Si les pharmacopées écrites jalonnent l'histoire des grandes médecines savantes, d'autres modes d'accès à la connaissance semblent exister dans l'univers chamanique des sociétés de tradition orale ainsi que dans la façon dont les animaux malades se soignent par les plantes. L'évaluation des propriétés pharmaco-toxicologiques et chimiques des plantes d'usage traditionnel devrait par ailleurs favoriser le développement futur des médicaments à base de plantes, l'un des thèmes porteurs abordés dans cet ouvrage. Mais l'objectif de ce livre est aussi de susciter, partout dans le monde, de nouvelles thématiques de recherche dans le domaine de la préhistoire du médicament et de la compréhension de l'acquisition et de la transmission du savoir. Le développement du phytomédicament non toxique destiné à l'homme et à l'animal figure également parmi les enjeux majeurs de demain.The origin of traditional pharmacopoeias The development of pharmacopoeias The medicines of the XXIth century How have the traditional Therapeutical knowledges been transmited to the différent cultures? This innovating book containing the proceedings of the 4th European Congress of Ethnopharmacology return to prehistory the sources of fherapeutical knowledge and asks how the animals cure themselves with plants. If the printing pharmacopoeias ponctuate the history of learning medicines other way of accessibility to the knowledge seems exist in the world of shaman in society with oral tradition. Ethnopharmacological evaluation of traditional médicinal plant should favour the development of phytomedicine. The purpose of this publication is also to provide dues to scientists in the whole world and help them identify new avenues for research in the field of the prehistory of drugs, for a better understanding of the way knowledge is acquired and then transmitted, and for the development of non-toxic herbal medicines for administration to human and animal beings