Pr Mohamed Saoud
Adult psychiatry department
The neuro-psychiatry department is responsible for the assessment and management of patients hospitalized or consulting at the HCL and suffering from psychiatric or psychological difficulties related to, or prior to, their illness. The teams, made up of psychiatrists and psychologists, intervene in all the departments of the establishment, at the request of the patient, relayed by the care team or at the request of the care team, after having informed the patient. Support for the patient’s family can also be offered depending on the situation.
Themes
The research areas of Professor SAOUD and his teams concern Functional Neurological Disorders (FND)
These different axes are:
In the Clinic: clinical characterization of the different TNF phenotypes by collecting a database.
In Psychopathology: Process-TNF (Doctoral subject in neuropsychology, Ms. Annabelle BOUAMMARI)
The main objective of the project is to compare the psychometric properties (scores on psychological process measurement tools) of the main TNF phenotypes.
The secondary objective(s) are to study the relationship between these scores (psychological processes) and the intensity scores of functional neurological symptoms, and to study the relationship between these scores (psychological processes) and the quality of life scores. life reported by patients.
In Neuropsychology: Comparative study of source memory disorders in patients with TNF with other populations (healthy volunteers and patients with neuropsychiatric pathologies), in collaboration with the PsyR2 Team, CRNL.
On a therapeutic axis:
- Associate investigator in the PHRCN 2018 CONVERSTIM: Effectiveness of dorsolateral prefrontal cortex stimulation by tDCS in patients with motor conversion disorder. Randomized, double-blind multicenter trial. RIPH Category 2, interventional, randomized, safety/efficacy, parallel allocation, double-blind study (Principal Investigator: Dr Ismael Conejero, Nîmes)
- Feasibility study: Mirror therapy in TNF in collaboration with Professor Jacques LUAUTE
- Collaboration with C2Care for the development of mirror therapy in virtual reality.
Support structure and research team
- Rattachement à l’Equipe PsyR2, CRNL
- Cellule Mutualisée de Recherche Clinique (CMRC)
- Membre du programme de recherche Axe neurologie, handicap & santé mentale ; Axe génétique & maladies rares
- Membre de l’Institut Pierre Wertheimer (IPW)
Publications
1. Albatrellus confluens (Alb. & Schwein.) Kotl. & Pouz.: Natural Fungal Compounds and Synthetic Derivatives with In Vitro Anthelmintic Activities and Antiproliferative Effects against Two Human Cancer Cell Lines
Dube M, Llanes D, Saoud M, Rennert R, Imming P, Häberli C, Keiser J, Arnold N.
Molecules (2022) — Abstract
Neglected tropical diseases affect the world’s poorest populations with soil-transmitted helminthiasis and schistosomiasis being among the most prevalent ones. Mass drug administration is currently the most important control measure, but the use of the few available drugs is giving rise to increased resistance of the parasites to the drugs. Different approaches are needed to come up with new therapeutic agents against these helminths. Fungi are a source of secondary metabolites, but most fungi remain largely uninvestigated as anthelmintics. In this report, the anthelmintic activity of Albatrellus confluens against Caenorhabditis elegans was investigated using bio-assay guided isolation. Grifolin (1) and neogrifolin (2) were identified as responsible for the anthelmintic activity. Derivatives 4-6 were synthesized to investigate the effect of varying the prenyl chain length on anthelmintic activity. The isolated compounds 1 and 2 and synthetic derivatives 4-6, as well as their educts 7-10, were tested against Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum. Prenyl-2-orcinol (4) and geranylgeranyl-2-orcinol (6) showed promising activity against newly transformed schistosomula. The compounds 1, 2, 4, 5, and 6 were also screened for antiproliferative or cytotoxic activity against two human cancer lines, viz. prostate adenocarcinoma cells (PC-3) and colorectal adenocarcinoma cells (HT-29). Compound 6 was determined to be the most effective against both cell lines with IC50 values of 16.1 µM in PC-3 prostate cells and 33.7 µM in HT-29 colorectal cells.
2. Anthelmintic Activity and Cytotoxic Effects of Compounds Isolated from the Fruits of Ozoroa insignis Del. (Anacardiaceae).
Dube M, Saoud M, Rennert R, Fotso GW, Andrae-Marobela K, Imming P, Häberli C, Keiser J, Arnold N.
Biomoleucles (2021) — Abstract
Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 1-3 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1µM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC50 value of 43.2 µM, compound 3 was found to be the most active of the 3 investigated compounds.
3. Cisplatin-cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA-MB-468 breast cancer cell line.
Predarska I, Saoud M, Morgan I, Eichhorn T, Kaluđerović GN, Hey-Hawkins E.
Dalton Trans (2022) — Abstract
For the development of anticancer drugs with higher activity and reduced toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II) counterparts and loading them into mesoporous silica SBA-15 with the aim to utilise the passive enhanced permeability and retention (EPR) effect of nanoparticles for accumulation in tumour tissues. Three conjugates based on a cisplatin scaffold bearing the anti-inflammatory drugs naproxen, ibuprofen or flurbiprofen in the axial positions (1, 2 and 3, respectively) were synthesised and loaded into SBA-15 to afford the mesoporous silica nanoparticles (MSNs) SBA-15|1, SBA-15|2 and SBA-15|3. Superior antiproliferative activity of both free and immobilised conjugates in a panel of four breast cancer cell lines (MDA-MB-468, HCC1937, MCF-7 and BT-474) with markedly increased cytotoxicity with respect to cisplatin was demonstrated. All compounds exhibit highest activity against the triple-negative cell line MDA-MB-468, with conjugate 1 being the most potent. However, against MCF-7 and BT-474 cell lines, the most notable improvement was found, with IC50 values up to 240-fold lower than cisplatin. Flow cytometry assays clearly show that all compounds induce apoptotic cell death elevating the levels of both early and late apoptotic cells. Furthermore, autophagy as well as formation of reactive oxygen species (ROS) and nitric oxide (NO) were elevated to a similar or greater extent than with cisplatin.
4. Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies.
Drača D, Edeler D, Saoud M, Dojčinović B, Dunđerović D, Đmura G, Maksimović-Ivanić D, Mijatović S, Kaluđerović GN.
J Inorg Biochem (2021) — Abstract
Adolescebat autem obstinatum propositum erga haec et similia multa scrutanda, stimulos admovente regina, quae abrupte mariti fortunas trudebat in exitium praeceps, cum eum potius lenitate feminea ad veritatis humanitatisque viam reducere utilia suadendo deberet, ut in Gordianorum actibus factitasse Maximini truculenti illius imperatoris rettulimus coniugem.
5. Need for systematic screening for IGD in adolescent psychiatric inpatients.
Gauthier B, Rolland B, Berthiller J, Tatou M, Charvet D, Gansel Y, Fleury R, Saoud M, Laconi S.
Encephale (2020) — Abstract
Psychiatric comorbidities are frequent in adolescents with internet gaming disorder (IGD). In contrast, the proportion of IGD among adolescents hospitalized for a psychiatric disorder has not been documented yet. In addition, parental ratings of IGD could be useful for diagnosis, but very few data exist on this issue. The objectives of this study were to: (1) assess the prevalence of IGD among adolescent psychiatric inpatients, using the Ten-Item Internet Gaming Disorder Test (IGDT-10), and (2) assess the parental version developed for this study (IGDT-10-P). A total of 102 patients, aged from 12 to 17 years old, were included from four psychiatric units of the French region Auvergne-Rhône-Alpes, during a 6-month inclusion period. Adolescents completed the IGDT-10 while one of their parents completed the IGDT-10-P. The inclusion rate among the eligible population was 57.95%. The prevalence of IGD in the sample, based on the IGDT-10 and IGDT-10-P, was 6.00% and 12.79%, respectively. Psychometric features of the IGDT-10-P indicated excellent internal consistency, a good model fit to the one factor model in confirmatory factor analysis, a strong correlation with gaming time, and a moderate correlation with the IGDT-10. Our results support the need for a systematic screening of IGD among adolescents hospitalized for a psychiatric disorder. Future studies should aim to confirm and explain the prevalence gap between self- and parent-reported criteria.
6. Early Detection of Patients at Risk of Developing a Post-Traumatic Stress Disorder After an ICU Stay.
Wawer E, Viprey M, Floccard B, Saoud M, Subtil F, Wafa H, Rheims E, Rimmelé T, Poulet E.
Crit Care Med (2020) — Abstract
Objectives: To evaluate the diagnostic accuracy of the Impact Event Scale-Revisited assessed following ICU discharge to predict the emergence of post-traumatic stress disorder symptoms at 3 months. Design: Prospective cohort study. Setting: Three medical or surgical ICU of a French university hospital (Lyon, France). Patients: Patients greater than or equal to 18 years old, leaving ICU after greater than or equal to 2 nights of stay, between September 2017 and April 2018. Interventions: Patients completed the Impact Event Scale-Revisited and the Peritraumatic Dissociative Experiences Questionnaire within 8 days after ICU discharge and the Impact Event Scale-Revisited again at 3 months by phone. Patients having an Impact Event Scale-Revisited greater than or equal to 35 at 3 months were considered as having post-traumatic stress disorder symptoms. Measurements and main results: Among the 208 patients screened, 174 were included and 145 reassessed by phone at 3 months. Among the patients included at baseline, 43% presented symptoms of acute stress. At 3 months, 13% had an Impact Event Scale-Revisited greater than or equal to 35 and 17% had a score between 12 and 34. Regarding the performance of the Impact Event Scale-Revisited performed within 8 days after the ICU discharge to predict post-traumatic stress disorder symptoms at 3 months, the area under the curve was 0.90 (95% CI, 0.80-0.99), and an Impact Event Scale-Revisited greater than or equal to 12 had a sensitivity of 90%, a specificity of 71%, a positive predictive value of 32%, and a negative predictive value of 98%. History of anxiety disorder odds ratio = 3.7 (95% CI, 1.24-11.05; p = 0.02) and Impact Event Scale-Revisited greater than or equal to 12 odds ratio = 16.57 (95% CI, 3.59-76.46; p < 0.001) were identified as risk factors for post-traumatic stress disorder symptoms. Conclusions: Impact Event Scale-Revisited assessed at ICU discharge has a good ability for the detection of patients at risk of developing post-traumatic stress disorder symptoms. Patients with history of anxiety disorder and those presenting acute stress symptoms at ICU discharge are more at risk to develop post-traumatic stress disorder symptoms.
7. Transcranial direct current stimulation in patients with obsessive compulsive disorder: A randomized controlled trial.
Bation R, Mondino M, Le Camus F, Saoud M, Brunelin J.
Eur Psychiatry (2019) — Abstract
Background: Obsessive-compulsive disorder (OCD) is a severe mental disorder with poor response to the available treatments. Neuroimaging studies have identified dysfunctions within the orbito-fronto-striato-pallido-thalamic network in patients with OCD. Here, we assessed the efficacy and safety of transcranial direct current stimulation (tDCS) applied with the cathode over the orbitofrontal cortex (OFC) and the anode over the right cerebellum to decrease OCD symptoms in patients with treatment-resistant OCD. Methods: In a randomized sham-controlled double-blind study, 21 patients with OCD were assigned to receive ten 20-min sessions (two sessions per day) of either active (2 mA) or sham tDCS. The clinical symptoms were measured using the Yale-Brown Obsessive and Compulsive Scale (YBOCS). Acute effects on the symptoms were measured from baseline to immediately after the 10 tDCS sessions. Long-lasting effects were measured 1 and 3 months after the 10th tDCS session. Results: Compared with the sham tDCS, active tDCS significantly decreased OCD symptoms immediately after the 10th tDCS session (F(1,19) = 5.26, p = 0.03). However, no significant differences were observed between the active and sham groups in terms of changes in YBOCS score or the number of responders one and 3 months after tDCS. Conclusion: Despite significant acute effects, tDCS with the cathode placed over the left OFC and the anode placed over the right cerebellum was not significantly effective in inducing a long-lasting reduction of symptoms in patients with treatment-resistant OCD.
8. Transcranial Direct Current Stimulation for Obsessive-Compulsive Disorder: A Systematic Review.
Brunelin J, Mondino M, Bation R, Palm U, Saoud M, Poulet E.
Brain Sci (2018) — Abstract
Despite the advances in psychopharmacology and established psychotherapeutic interventions, more than 40% of patients with obsessive-compulsive disorder (OCD) do not respond to conventional treatment approaches. Transcranial direct current stimulation (tDCS) has been recently proposed as a therapeutic tool to alleviate treatment-resistant symptoms in patients with OCD. The aim of this review was to provide a comprehensive overview of the current state of the art and future clinical applications of tDCS in patients with OCD. A literature search conducted on the PubMed database following PRISMA guidelines and completed by a manual search yielded 12 results: eight case reports, three open-label studies (with 5, 8, and 42 participants), and one randomized trial with two active conditions (12 patients). There was no sham-controlled study. A total of 77 patients received active tDCS with a large diversity of electrode montages mainly targeting the dorsolateral prefrontal cortex, the orbitofrontal cortex or the (pre-) supplementary motor area. Despite methodological limitations and the heterogeneity of stimulation parameters, tDCS appears to be a promising tool to decrease obsessive-compulsive symptoms as well as comorbid depression and anxiety in patients with treatment-resistant OCD. Further sham-controlled studies are needed to confirm these preliminary results.
