Structural and functional changes associated with functional/dissociative seizures: A review of the literature.

INTRODUCTION: The term 'functional/dissociative seizures (FDS)' refers to a paroxysmal, transient clinical manifestation that may include motor, sensory, vegetative, psychological and cognitive signs, similar to the manifestations observed in epileptic seizures. In recent years, there has been an increase of literature in the field of brain imaging research on functional neurological disorders and, more specifically, on FDS. However, most of the studies have been carried out on limited samples. We propose an update of this review work by performing a systematic review of studies performed since 2017 in the field of neuroimaging in patients with FDS. METHODS: We conducted a systematic review of the literature using the PRISMA methodology and reproduced most of the methodological elements of the latest systematic literature review. RESULTS: Our work over the last five years has identified 14 articles. It is still difficult to isolate a distinct structure or network specifically involved in the mechanism of FDS. However, certain structures are recurrently involved in imaging studies, notably the amygdala, the orbitofrontal cortex, and the anterior cingulate cortex. CONCLUSION: The contribution of neuroimaging may allow a more precise explanation of the disorder for patients, avoiding the stigma frequently associated with this diagnosis. as with other 'conversion' phenomena which have traditionally been considered only as 'medically unexplained'. In the longer term and beyond a better understanding of the physiopathology of the disorder, the challenge of this neuroimaging work would be to identify specific imaging biomarkers for a diagnosis of FDS.

Repetitive transcranial magnetic stimulation for functional tremor: A randomized, double-blind, controlled study.

OBJECTIVES: The objective of this study was to compare the effect on functional tremor of active versus sham repetitive transcranial magnetic stimulation and investigate whether the addition of hypnosis might help to prolong any repetitive transcranial magnetic stimulation-induced therapeutic effect. METHODS: We compared the effect of 5 consecutive daily sessions of active/sham repetitive transcranial magnetic stimulation on functional tremor, at 1 and 2 months, in a randomized, double-blind, 2-arm, parallel-controlled study. In a second open-label phase, all patients underwent 3 weekly sessions of hypnosis combined with single sessions of real repetitive transcranial magnetic stimulation. The primary outcome was a change in the Psychogenic Movement Disorder Rating Scale at month 1 when compared with baseline. Secondary outcomes were changes in the Psychogenic Movement Disorder Rating Scale and Tremor subscores, the 36-item Short Form Health Survey, the Self-Report Hospital Anxiety and Depression Scale, the Hamilton Depression Rating Scale, and the Clinical Global Impression Scale assessed at months 1, 2, 6, and 12. RESULTS: A total of 33 outpatients affected by functional tremor were screened, and 18 outpatients fulfilling the inclusion criteria (8 men, 10 women) were randomized. One month after the intervention, the mean Psychogenic Movement Disorder Rating Scale score had decreased in both groups, but the differences from baseline were only significant in the active repetitive transcranial magnetic stimulation group (P < .001). This remained significant at month 2 (P < .001). The significant decrease of the Psychogenic Movement Disorder Rating Scale and Tremor subscores were maintained at months 6 and 12 for the active repetitive transcranial magnetic stimulation group. For the control group, the Psychogenic Movement Disorder Rating Scale score had returned almost to its baseline value by month 2 and remained unchanged at months 6 and 12. CONCLUSION: Repetitive transcranial magnetic stimulation could represent a valuable therapeutic option in the management of functional tremor. © 2019 International Parkinson and Movement Disorder Society.

Traumatic Hystero-Neurasthenia in Professor Charcot's Leçons du Mardi.

At the end of the 19th century, several authors became interested in the physical and psychological symptoms resulting from traumatic life events. Oppenheim presented 42 detailed clinical observations. He suggested the term "traumatic neurosis." Charcot, who was interested in male hysteria, published over 20 cases of traumatic hysteria between 1878 and 1893. The symptoms were considered to have a dynamic or functional origin. The role of horror and terror during the trauma was emphasized. However, Charcot opposed the idea of traumatic neuroses as specific syndromes as he considered them to be only an etiological form of hystero-neurasthenia. In The Tuesday Lessons (Les Leçons du Mardi), he presents several observations. They are surprising when compared with the current criteria for posttraumatic stress disorder (PTSD). Although he had rejected this new entity, a hundred years before the appearance of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, Charcot described most of the symptoms mentioned for a diagnosis of PTSD such as intrusion (reliving the trauma, nightmares, and severe emotional distress), avoidance, negative changes in thinking and mood (negative thoughts, lack of interest, etc.), arousal, and reactivity (trouble sleeping, trouble concentrating, being easily startled or frightened, irritability, etc.).

Neuroimaging Biomarkers at Baseline Predict Electroconvulsive Therapy Overall Clinical Response in Depression: A Systematic Review.

OBJECTIVE: Major depressive disorder is a frequent and disabling disease and can be treated with antidepressant drugs. When faced with severe or resistant major depressive disorder, however, psychiatrists may resort to electroconvulsive therapy (ECT). Although very effective, the response falls short of 100%. A recent meta-analysis established clinical and biological predictive factors of the response to ECT. We decided to explore neuroimaging biomarkers that could be predictors of the ECT response. METHODS: We performed a systematic literature review up to January 1, 2018, using a Boolean combination of MeSH terms. We included 19 studies matching our inclusion criteria. RESULTS: Lower hippocampal, increased amygdala, and subgenual cingulate gyrus volumes were predictive for a better ECT response. Functional magnetic resonance imaging also found that the connectivity between the dorsolateral prefrontal cortex and posterior default-mode network is predictive of increased efficacy. Conversely, deep white matter hyperintensities in basal ganglia and Virchow-Robin spaces, medial temporal atrophy, ratio of left superior frontal to left rostral middle frontal cortical thickness, cingulate isthmus thickness asymmetry, and a wide range of gray and white matter anomalies were predictive for a poorer response. CONCLUSIONS: Our review addresses the positive or negative predictive value of neuroimaging biomarkers for the ECT response, indispensable in a personalized medicine dynamic. These data could reduce the risk of nonresponders or resistance with earlier effective management. It might also help researchers elucidate the complex pathophysiology of depressive disorders and the functioning of ECT.

Reconsidering the seizure threshold? A retrospective study about seizure quality among patients with maintenance ECT.

OBJECTIVES: Electroconvulsive therapy (ECT) is a safe and validated technique used to treat various psychiatric conditions. It triggers an artificially-induced seizure. This seizure is defined using several parameters such as the amount of energy, duration, frequency, pulse width and intensity. Efficacy and adverse events depend on the amount of energy delivered. Due to technical control, the amount of energy delivered by our unit's ECT device was limited to 614 mC, 60% of the maximum possible output of the device. We wondered if lowering the dose would lead to better seizure quality among maintenance ECT patients. METHODS: We assessed seizure quality based on the EEG, using a validated tool created by MacPherson. Two evaluators independently rated the seizures. Pre- and post-control scores were compared using Student's t-test for paired samples. RESULTS: We analysed data from 15 patients. Mean age was 65 years old. Twelve had depressive disorder, two had schizophrenia and one had schizo-affective disorder. Mean duration of seizure before control was 41.1 s [95% confidence interval (95CI)=26.1, 51.1]. The mean MacPherson's score was 20.3 (95CI=16.2, 24.4). After control, the mean MacPherson's score was 28.2 (23.1, 33.3), showing a significant difference with the pre-control dataset (p=0.032; t=-2.4; df=14). Specifically, peak mid-ictal amplitude increased from 6.9 (95CI=5.1, 8.7) to 10.0 (95CI=7.2, 12.8). Other sub-scores remained unchanged. CONCLUSION: Lowering the energy delivered led to an overall increase of seizure quality among our sample. This highlights the necessity and utility of retitration during ECT maintenance, possibly leading to better management of our patients.

How Does Repetitive Transcranial Magnetic Stimulation Influence the Brain in Depressive Disorders?: A Review of Neuroimaging Magnetic Resonance Imaging Studies.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological technique used to stimulate the brain. It is a safe and proven alternative tool to treat resistant major depressive disorders (MDDs). Neuroimaging studies suggest a wide corticolimbic network is involved in MDDs. We researched observable changes in magnetic resonance imaging induced by rTMS to clarify the operational mechanism. METHODS: A systematic search of the international literature was performed using PubMed and Embase, using papers published up to January 1, 2017. The following MESH terms were used: (depression or major depressive disorder) and (neuroimaging or MRI) and (rTMS or repetitive transcranial magnetic stimulation). We searched the databases using a previously defined strategy to identify potentially eligible studies. RESULTS: Both structural and functional changes were observed on magnetic resonance imagings performed before and after rTMS. Various areas of the brain were impacted when rTMS was used. Although the results were very heterogeneous, a pattern that involved the anterior cingulate cortex and the prefrontal cortex emerged. These are known to be regions of interest in MDDs. However, the various parameters used in rTMS make any generalization difficult. CONCLUSIONS: Repetitive transcranial magnetic stimulation helps to treat MDDs with good efficacy. Its effect on the brain, as observed in several neuroimaging studies, seems to impact on the structural and functional features of several networks and structures involved in major depressive disorders.

What are the neural correlates of dissociative amnesia? A systematic review of the functional neuroimaging literature.

Aim: Dissociative amnesia is an emblematic psychiatric condition in which patients experience massive memory loss ranging from focal to global amnesia. This condition remains poorly understood and this review aims to investigate the neuroanatomical feature of this disease. Methods: We conducted a systematic review of the scientific literature available on PubMed, up to December 1, 2022, using a combination of keywords referring to dissociative amnesia. We included every scientific report involving patients undergoing a functional imaging procedure. Results: Twenty-two studies met our inclusion criteria (gathering 49 patients). Only one was a controlled study with a large sample. The other 21 were case reports and case series. In resting state, neuroimaging studies mostly showed a hypo-activated right inferolateral prefrontal cortex, associated with limbic hypoactivity and lesser activation of the hippocampal and para-hippocampal structures. The patients also presented abnormal patterns of cerebral activation when performing memory tasks. When testing recognition of memories from the amnestic period, patients showed increased activation across temporal areas (hippocampal and para-hippocampal gyri) and the limbic network. When trying to recollect memories from an amnestic period compared to a non-amnestic period, patients failed to activate these structures efficiently. Most of these patterns tended to return to normal when symptoms resolved. Conclusion: This review identified a paucity of controlled studies in the field of dissociative amnesia neuroimaging, which restricts the extrapolation of results. Patients with dissociative amnesia present a broad prefronto-temporo-limbic network dysfunction. Some of the brain areas implicated in this network might represent potential targets for innovative treatments.

What clinical analysis of antipsychotic-induced catatonia and neuroleptic malignant syndrome tells us about the links between these two syndromes: A systematic review.

OBJECTIVES: Antipsychotic-induced catatonia (AIC) and neuroleptic malignant syndrome (NMS) are life-threatening adverse reactions to antipsychotic medication. We conducted a systematic review of literature following the PRISMA statement guidelines to obtain a description of these syndromes (population, context of occurrence, antipsychotic agents implicated) and draw conclusions about their links. METHODS: We searched Medline and Web of science databases from January 1951 to May 2019 (further restricted from 2000 to 2019) using search terms including "catatonia", "neuroleptic malignant syndrome" and "antipsychotic agents" for case reports, case series and analytic studies. After screening 4082 records, 410 full-text articles (describing 555 events) were assessed for eligibility. We included events of AIC and/or NMS according to Diagnostic and Statistical Manual (DSM) criteria and extracted data about patients' characteristics, context of occurrence, antipsychotic agent(s) involved and treatment outcomes. RESULTS: We included 165 events (16 AIC, 129 NMS and 20 AIC + NMS) from 144 case reports and case series. The most reported diagnosis was schizophrenia. Comorbid pre-existing conditions such as central nervous system diseases and acute medical events were common. Most of the events (63.3 %) occurred during antipsychotic monotherapy. Second-generation antipsychotics (SGAs, 63.8 %) were overall more implicated than first-generation antipsychotics (FGAs, 36.2 %). DISCUSSION: Our findings highlight that any antipsychotic medication, even SGA monotherapy prescribed at recommended dose, is at risk for these side effects. FGAs and polypharmacy seem to represent risk factors for malignant catatonia in AIC. The clinical overlap observed between AIC and NMS events in our review suggests a clinical continuum between catatonia and NMS.

Efficacy of traumatic memory reactivation with or without propranolol in PTSD with high dissociative experiences.

Background: Post-traumatic stress disorder (PTSD) with dissociative symptoms is now a full-fledged subtype of this disorder. The dissociative subtype is associated with a greater number of psychiatric comorbidities. To date, the impact of dissociation on the efficacy of PTSD treatment remains unclear.Objective: The aim of this study was to compare the efficacy of a traumatic memory reactivation procedure with the administration of propranolol or a placebo once a week for six consecutive weeks in reducing PTSD and MDE symptoms between PTSD subjects with or without high dissociative symptoms.Method: For that, we conducted a randomized clinical trial in 66 adults diagnosed with longstanding PTSD and measured the SCID PTSD module, the PTSD Checklist (PCL-S), Beck's Depression Inventory-II (BDI-II), and the Dissociative Experiences Scale (DES).Results: Patients with and without high dissociative experience had significant improvement in their PCL-S scores over the 6 treatment sessions, and PCL-S scores continued to decline in all patients during the post-treatment period. However, there was no correlation between the presence/absence of high dissociative experiences and no specific effect of propranolol treatment. We found exactly the same results for MDE symptoms. Interestingly, patients with high dissociative experiences before treatment exhibited very significant improvement in their DES scores after the 6 treatment sessions, and patients maintained this improvement 3 months post-treatment.Conclusions: The traumatic memory reactivation procedure is an effective way to treat dissociative symptoms in patients with PTSD, and improvement of these dissociative symptoms was associated with a decrease in both PTSD and depression severity.

Traumatic memory reactivation procedure is an effective way to treat dissociative symptoms in patients with PTSD.The improvement of these dissociative symptoms was associated to a decrease of both PTSD and depression severity.Dissociative symptoms do not seem to mitigate the efficacy of traumatic memory reactivation during the treatment of PTSD.

Prevalence and prediction of PTSD and depression in mothers of children surviving a motor vehicle crash.

Introduction: Few studies have examined the psychopathological consequences for parents of children who were survivors of a motor vehicle crash (MVC). This study assessed the impact of dissociation and peritraumatic distress on the severity of PTSD and post-traumatic major depressive episode (MDE) symptoms in mothers during the first years after the MVC and the role that cortisol response might play in this association. Methods: 125 mothers were included. Peritraumatic distress and dissociation were assessed. Morning salivary cortisol was tested at the baseline. Participants were assessed for a probable diagnosis of PTSD and MDE at 5 weeks, 6 months and 12 months. Results: At 5 weeks, 12 (13.6%) mothers exhibited probable PTSD. During the first year, the PCL score was higher when the (i) Peritraumatic Distress Inventory (PDI) score increased and (ii) the Peritraumatic Dissociation Experience Questionnaire (PDEQ) score increased. Cortisol levels were lower when the PDI score increased. Conclusion: This is the first study to assess the mothers of MVC survivors for one year following the trauma. We confirm that peritraumatic responses are useful for predicting the severity of PTSD symptoms. These results could encourage the implementation of follow-up programmes not only for survivors but also for their mothers. HIGHLIGHTS Mothers of children involved in motor vehicle accident are at risk for developing PTSD.Peritraumatic responses (distress and dissociation) are associated to the severity of PTSD symptoms.Low salivary cortisol levels were associated with high peritraumatic distress.

Antecedentes: Pocos estudios han examinado las consecuencias psicopatológicas para los padres de niños que fueron sobrevivientes de un accidente automovilístico (MVC, por sus siglas en inglés).Objetivo: Este estudio evaluó el impacto de la disociación y la angustia peritraumática en la gravedad del TEPT y los síntomas del episodio depresivo mayor (EDM) postraumático en las madres durante los primeros años después del MVC y el papel que podría desempeñar la respuesta del cortisol en esta asociación.Métodos: Se incluyeron 125 madres. Se evaluó la angustia peritraumática y la disociación. El cortisol salival matutino se analizó al inicio del estudio. Los participantes fueron evaluados para un diagnóstico probable de TEPT y EDM a las 5 semanas, 6 meses y 12 meses.Resultados: A las 5 semanas, 12 (13,6%) madres exhibieron TEPT probable. Durante el primer año, la puntuación PCL (lista de chequeo para TEPT) fue mayor cuando i) aumentó la puntuación del Inventario de angustia peritraumática (PDI, por sus siglas en inglés) y ii) aumentó la puntuación del Cuestionario de experiencias de disociación peritraumática (PDEQ, por sus siglas en inglés). Los niveles de cortisol fueron más bajos cuando aumentó la puntuación PDI.Conclusión: Este es el primer estudio que evalúa a las madres de sobrevivientes de MVC un año después del trauma. Confirmamos que las respuestas peritraumáticas son útiles para predecir la gravedad de los síntomas del TEPT. Estos resultados podrían incentivar la implementación de programas de seguimiento no solo para las sobrevivientes sino también para sus madres.

Comparative Effects of 30 Antipsychotics on Risk of Catatonia: An Analysis of the WHO Pharmacovigilance Database.

Objective: Catatonia is a life-threatening psychomotor syndrome that occurs in approximately 10% of patients with acute psychiatric illnesses. Although some case reports have argued that first generation antipsychotics (FGAs) are more likely to induce catatonia than second generation antipsychotics (SGAs), no large observational study has confirmed this hypothesis. We investigated whether FGAs were associated with an increased risk of reporting catatonia when compared with SGAs.Methods: A pharmacovigilance study was performed within VigiBase to compare the cases of catatonia syndromes reported in patients exposed to FGAs with those reported in patients exposed to SGAs. This approach is similar in concept to case-control study, but adapted to a pharmacovigilance database, and allows the estimation of reporting odds ratios (RORs) with 95% confidence intervals.Results: We identified 60,443 adverse effects reported in patients who received FGAs and 253,067 adverse effects reported in patients treated with SGAs. Compared with SGAs, the use of FGAs was associated with an increased risk of reporting catatonia syndromes (ROR = 2.2; 95% CI, 2.0-2.3). Consistent results were observed when the analysis was restricted to reports generated from physicians, reports from the US, and reports with the highest completeness score. The highest RORs were found for molindone (6.0; 95% CI, 3.1-10.4) and haloperidol (3.8; 95% CI, 3.5-4.0).Conclusions: In this large pharmacovigilance study of patients exposed to antipsychotics, the use of FGAs was associated with an increased risk of reporting catatonia syndromes compared to the use of SGAs. This increased risk is consistent with the pharmacodynamic hypothesis of antipsychotic-induced catatonia. Our results warrant replication in population-based studies.

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

The 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.

Suicidal Ideation and Traumatic Exposure Should Not Be Neglected in Epileptic Patients: A Multidimensional Comparison of the Psychiatric Profile of Patients Suffering From Epilepsy and Patients Suffering From Psychogenic Nonepileptic Seizures.

Introduction: Patients with psychogenic nonepileptic seizures (PNESs) have often been exposed to traumatic events, which is a risk factor for suicidal behavior. This would suggest that the severity of suicidal ideation is greater in PNES than in patients suffering only from epileptic seizures (ESs). However, these psychiatric symptoms may be underestimated in the ES population. The specific features or similarities between the psychiatric clinical profiles of these two groups should be elaborated to improve therapeutic management. Our study is the first to compare suicidal ideation, suicide risk, posttraumatic stress disorder (PTSD), and depression disorder simultaneously in both groups, in a tertiary care epilepsy center. Material and methods: We prospectively enrolled patients hospitalized for video-electroencephalography (EEG) monitoring to assess repeated seizures before an ES or a PNES diagnosis was made. During the psychiatric consultation that accompanied the video EEG, we rated the severity of suicidal ideation and depressive symptoms, suicidal risk, traumatic exposure history, and PTSD symptoms. Results: Eighteen subjects were enrolled and diagnosed with PNES, and 42, with ES. The PNES group reported more exposures to traumatic events and more intense PTSD symptoms (median: 17 vs. 27; p = 0.001). The severity of suicidal ideation did not differ significantly between the two groups. Conclusion: It is the severity of PTSD symptoms in PNES patients that differentiates them from ES patients, although exposure to traumatic events is also frequent in ES patients. We demonstrated that suicidal ideation and suicide risk are equally high in the ES and PNES groups. Therefore, both groups require extreme vigilance in terms of suicidal risk.

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

Introduction: 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.

Grey Matter changes in treatment-resistant depression during electroconvulsive therapy.

INTRODUCTION: 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.

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

Introduction: 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: ß = -2.78, t = -1.97, p = 0.04; ß = -2.56, t = -2, p = 0.04; ß = -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.

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=1.