Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study.

Nitrous oxide (N2O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 with a major depressive episode resistant to at least one antidepressant and 10 healthy controls-HC, aged 25-50, only females) were exposed to a 1-h single session of EMONO and followed for 1 week. We defined response as a reduction of at least 50% in the MADRS score 1 week after exposure. Cerebral connectivity of the Anterior Cingulate Cortex (ACC), using ROI-based resting state fMRI, and BTP, using ultrasound Tissue Pulsatility Imaging, were compared before and rapidly after exposure (as well as during exposure for BTP) among HC, non-responders and responders. We conducted analyses to compare group × time, group, and time effects. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the three groups between baseline and gas exposure, but the increase in BTP within the first 10 min was only significant in responders. We found that a single session of EMONO can rapidly modify the functional connectivity in the subgenual ACC-precuneus, nodes within the default mode network, in depressed participants responders to EMONO. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of N2O, as well as potential markers for treatment response with this fast-acting antidepressant.

Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study.

BACKGROUND: Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors. METHODS: This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed. RESULTS: Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034). CONCLUSION: Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03991611, registered on June 19, 2019.

Post-epileptic seizure posttraumatic stress Disorder: A mediation analysis.

OBJECTIVE: Previous studies investigated the varying prevalence of post-epileptic seizure posttraumatic stress disorder (PS-PTSD). The current study aimed first to compare the profiles of patients with and without PS-PTSD and, second, to study the interaction between other past traumatic experiences, subjective ictal anxiety, psychiatric comorbidities, and PS-PTSD in people with epilepsy (PWE). METHODS: We conducted an observational study, investigating past traumatic experiences and PS-PTSD through standardized scales (CTQ-28, LEC-5 and PCL-5). We used semi-structured interviews and validated psychometric scales (NDDIE for depression and GAD-7 for anxiety) to collect data on general psychiatric comorbidities. We also assessed epilepsy specific psychiatric symptoms (interictal and peri-ictal). We performed a mediation analysis through PROCESS for SPSS to evaluate the effect of history of past trauma and subjective ictal anxiety on PS-PTSD through interictal depression and anxiety symptoms. RESULTS: We enrolled 135 PWE, including 35 patients with PS-PTSD (29.5 %). Patients with PS-PTSD had significantly higher depression (12.87 vs 10; p = 0.005) and anxiety (7.74 vs 5.01; p = 0.027) scores and higher prevalence of peri-ictal psychiatric symptoms, compared to patients without PS-PTSD. The relationship between other past traumatic experiences and PS-PTSD was totally mediated by interictal depression and anxiety. We found a significant indirect effect of interictal anxiety symptoms on the path between subjective ictal anxiety and PS-PTSD. SIGNIFICANCE: Our results showed that patients with PS-PTSD have a more severe psychopathological profile (more peri ictal and inter ictal depressive and anxiety symptoms). Both inter ictal and subjective ictal anxiety appear to have a significant role in PS-PTSD.

Right temporoparietal junction transcranial direct current stimulation in the treatment of functional dissociative seizures: a case series.

Functional dissociative seizures (FDSs) are clinical events that resemble epileptic seizures but are not associated with abnormal brain electrical discharges or other physiological problems. In this pilot case series, ten adults with FDSs were recruited from our psychiatry department after being referred by a neurologist who made the diagnosis of FDS based on video EEG results. Each subject received ten sessions of cathodal tDCS focused on the right temporoparietal junction. A significant decrease in weekly seizure frequency was seen in all participants between baseline (30.2 ± 70.3 events) and 1 month after tDCS treatment (0.2 ± 0.3events) (p = 0.006). Main predisposing factors were unchanged after treatment.

Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients.

OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. METHODS: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. CONCLUSION: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

The association between post-traumatic stress disorder (PTSD) and executive functioning.

Introduction: Post-Traumatic Stress Disorder (PTSD) is a condition characterised by several disturbances in an individual's executive functioning. We were interested in the link between executive functions and the presence of anxiety and depression in a clinical population with post-traumatic stress disorder.Methods: Our sample comprised 180 participants divided into three groups: 60 with PTSD, 60 trauma-exposed without PTSD, and 60 controls. All participants were assessed on the following dimensions: PTSD, dissociation, executive functions, anxiety, and depression.Results: Consistent with the literature, the results of our study suggest that individuals with PTSD have difficulties in executive functioning. These disturbances are related to levels of anxiety and depression.Conclusion: The severity of PTSD is positively correlated with executive function disturbances, but the observed disturbances, especially in working memory updating, can be explained mainly by the high level of depression, rather than by PTSD alone.

Neural correlates of mindfulness meditation and hypnosis on magnetic resonance imaging: similarities and differences. A scoping review.

BACKGROUND: Mindfulness meditation (MM) and hypnosis practices are gaining interest in mental health, but their physiological mechanisms remain poorly understood. This study aimed to synthesize the functional, morphometric and metabolic changes associated with each practice using magnetic resonance imaging (MRI), and to identify their similarities and differences. METHODS: MRI studies investigating MM and hypnosis in mental health, specifically stress, anxiety, and depression, were systematically screened following PRISMA guidelines from four research databases (PubMed, Web of Science, Embase, PsycINFO) between 2010 and 2022. RESULTS: In total, 97 references met the inclusion criteria (84 for MM and 13 for hypnosis). This review showed common and divergent points regarding the regions involved and associated brain connectivity during MM practice and hypnosis. The primary commonality between mindfulness and hypnosis was decreased default mode network intrinsic activity and increased central executive network - salience network connectivity. Increased connectivity between the default mode network and the salience network was observed in meditative practice and mindfulness predisposition, but not in hypnosis. CONCLUSIONS: While MRI studies provide a better understanding of the neural basis of hypnosis and meditation, this review underscores the need for more rigorous studies.

The bifocal model: A two-level clinical model of psychiatric disorders integrating diagnostic and transdiagnostic approaches.

Nowadays, two distinct conceptualizations are available to classify, label and guide the treatment of psychiatric disorders: the diagnostic approach and the transdiagnostic approach. There are pros and cons to both approaches. We propose here to link these two conceptualizations by creating a two-level clinical model that takes advantages of both approaches, named the bifocal model (BFM). This two-tier clinical model consists of a double level of analysis: the first step is to identify transdiagnostic mechanisms involved in multiple disorders and then to recognize specific mechanisms identified in a given disorder or cluster of symptoms. Such a process would bring the diagnostic and transdiagnostic approaches together and offer a more flexible way to understand mental disorders and ultimately to improve medical outcomes.

Cerebral Metabolic Signature of Chronic Benzodiazepine Use in Nondemented Older Adults: An FDG-PET Study in the MEMENTO Cohort.

OBJECTIVE: We sought to examine the association between chronic Benzodiazepine (BZD) use and brain metabolism obtained from 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in the MEMENTO clinical cohort of nondemented older adults with an isolated memory complaint or mild cognitive impairment at baseline. METHODS: Our analysis focused on 3 levels: (1) the global mean brain standardized uptake value (SUVR), (2) the Alzheimer's disease (AD)-specific regions of interest (ROIs), and (3) the ratio of total SUVR on the brain and different anatomical ROIs. Cerebral metabolism was obtained from 2-deoxy-2-fluoro-D-glucose-FDG-PET and compared between chronic BZD users and nonusers using multiple linear regressions adjusted for age, sex, education, APOE ε 4 copy number, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant use. RESULTS: We found that the SUVR was significantly higher in chronic BZD users (n = 192) than in nonusers (n = 1,122) in the whole brain (beta = 0.03; p = 0.038) and in the right amygdala (beta = 0.32; p = 0.012). Trends were observed for the half-lives of BZDs (short- and long-acting BZDs) (p = 0.051) and Z-drug hypnotic treatments (p = 0.060) on the SUVR of the right amygdala. We found no significant association in the other ROIs. CONCLUSION: Our study is the first to find a greater global metabolism in chronic BZD users and a specific greater metabolism in the right amygdala. Because the acute administration of BZDs tends to reduce brain metabolism, these findings may correspond to a compensatory mechanism while the brain adapts with global metabolism upregulation, with a specific focus on the right amygdala.

Posttraumatic Stress Symptoms Increase the Efficiency of Memory Functioning for Trauma-Related Information.

OBJECTIVE: The present study explored the resources reallocation explanation for memory biases in posttraumatic stress disorder (PTSD), whereby a preferential allocation of cognitive resources to the processing of threatening stimuli could result in both improvements in their memorization and deficits for other types of information. METHOD: To this end, 25 participants presenting significant symptoms of PTSD (i.e., total PCL-5 score ≥33) and 32 participants presenting low levels of symptoms (i.e., total PCL-5 score <20) took part in a Remember/Know recognition procedure associated with a dual-task encoding of positive, neutral, negative, and trauma-related words. In order to manipulate the availability of cognitive resources, the encoding of each word was associated with a simultaneous encoding of series of letters and numbers. RESULTS: Results replicated the increased production of Remember recognitions for trauma-related words in participants with significant PTSD symptoms. However, the dual-task load only impaired remember recognitions for non-trauma-related words. CONCLUSIONS: Contrary to expectations, these findings suggest that the encoding of trauma-related information in PTSD is relatively independent from the availability of cognitive resources. Thus, rather than reflecting an increased allocation of cognitive resources to the processing of threatening information, memory biases in PTSD appeared to be supported by an enhanced efficiency of their processing.

The mental health impact of the COVID-19 pandemic and exposure to other potentially traumatic events up to old age.

We investigated whether the impact of potentially traumatic events (PTEs) on trauma-related symptoms changes across the transitional adult lifespan (i.e., 16-100 years old) and if this association differs for self-reported COVID-19-related PTEs compared to other PTEs. A web-based cross-sectional study was conducted among 7,034 participants from 88 countries between late April and October 2020. Participants completed the Global Psychotrauma Screen (GPS), a self-report questionnaire assessing trauma-related symptoms. Data were analyzed using linear and logistic regression analyses and general linear models. We found that older age was associated with lower GPS total symptom scores, B = -0.02, p < .001; this association remained significant but was substantially weaker for self-reported COVID-19-related PTEs compared to other PTEs, B = 0.02, p = .009. The results suggest an association between older age and lower ratings of trauma-related symptoms on the GPS, indicating a blunted symptom presentation. This age-related trend was smaller for self-reported COVID-19-related PTEs compared to other PTEs, reflecting the relatively higher impact of the COVID-19 pandemic on older adults.

Development of the Transdiagnostic Skills Scale (T2S).

INTRODUCTION: Psychotherapy has proved its efficacy for treating a wide range of psychological disorders. Most types of psychotherapy have been developed to treat specific disorders and validated through controlled-randomized trials. In recent years, researchers have developed a new way to conceptualize patients' difficulties, focusing on processes instead of diagnoses. However, there is no simple scale that evaluates transdiagnostic processes, and the development of such a tool is thus the aim of this study. METHOD: We identified 12 processes that can be targeted in cognitive behavior therapy and created the Transdiagnostic Skills Scale (T2S) to evaluate them. We measured its internal consistency, factor structure and convergent validity in clinical and non-clinical samples. RESULTS: We found a 6-factor structure composed of emotion regulation, behavioral activation/planning, emotional identification, assertiveness, problem solving and emotional confrontation. The T2S has high internal consistency (Cronbach's alpha = 0.95). We found negative associations between skills and symptoms of anxiety, depression and eating disorders. We found no association between these processes and symptoms of either alcohol or cannabis use disorder. CONCLUSIONS: The T2S is a useful and valid tool to identify the skills that clinicians should work on with their patients. It offers a complementary way to understand patients' difficulties when categorical assessment is complicated.

Bullying and self-harming behavior in universities - A cross-sectional study of a sample of 327 university students.

INTRODUCTION: Bullying is a widespread public health issue, found in different contexts (e.g. schools, universities, workplaces, families), and it has negative consequences on both the perpetrator and the victim. There is a lack of studies addressing bullying among university students in Arab countries and more specifically in Lebanon. The objective of our study was to determine the prevalence of bullying among a sample of university students in Lebanon, its forms, and associated factors. METHODS: The study consists of a cross-sectional online survey addressed to university students in Lebanon that evaluates sociodemographic data, presence and type of bullying, history of bullying during childhood, adverse childhood experiences, daily life functioning, and mental health status (reported psychiatric disorders, substance use, self-harming behaviors, and suicidal attempts). Chi-Square and Fisher's exact tests were used to compare the results between victims of bullying and the rest of the sample. RESULTS: Three hundred and twenty-seven university students participated in this study. The prevalence of bullying was 14.1%. The main forms of reported bullying were verbal (58.7%) and social bullying (65.2%). The main associated factors were being a witness of bullying at university (84.8% vs. 56.2% - P<.001) and history of cyberbullying (13% vs. 4.6% - P=.024). Among students who reported current bullying, 28.3% had a psychiatric diagnosis, 19.6% reported substance use, 15.2% had self-harming behaviors, and 8.7% had suicide attempts. Victims of bullying in the university reported a significant negative impact on their daily lives (lack of interest in daily activities, academic decline) (83.7%) and mental health concerns (psychiatric disorders, substance use, suicide attempts) (88.4%). CONCLUSION: Even though bullying is an event less experienced in university than in school, it is nevertheless still present with potential negative impact on the victims. Bullying in a university setting is a public health issue that could benefit from more studies as well as prevention and intervention programs.

[Understanding functional neurological disorders: From biological markers to pathophysiological models]. / Étiopathogénie des troubles neurologiques fonctionnels : marqueurs biologiques et modèles théoriques.

OBJECTIVES: Functional neurological disorders have witnessed intense research activity in the fields of structural and functional neuroimaging for more than twenty years. Thus, we propose a synthesis of recent research findings and etiological hypotheses that have been proposed so far. This work should help clinicians to better understand the nature of the mechanisms involved, but also help patients to increase their knowledge about the biological features underlying their functional symptoms. METHODS: We carried out a narrative review of international publications dealing with neuroimaging and biology of functional neurological disorders, from 1997 to 2023. RESULTS: Several brain networks underlie functional neurological symptoms. These networks play a role in the management of cognitive resources, in attentional control, emotion regulation, in agency and in the processing of interoceptive signals. The mechanisms of the stress response are also associated with the symptoms. The biopsychosocial model helps to better understand predisposing, precipitating, and perpetuating factors involved. The functional neurological phenotype results from the interaction between: i) a specific pre-existing vulnerability resulting from biological background and epigenetic modifications, and ii) exposure to stress factors, according to the stress-diathesis model. This interaction causes emotional disturbances including hypervigilance, lack of integration of sensations and affects, and emotional dysregulation. These characteristics in turn impact the cognitive, motor and affective control processes related with the functional neurological symptoms. CONCLUSIONS: A better knowledge of the biopsychosocial determinants of brain network dysfunctions is necessary. Understanding them would help developing targeted treatments, but is also critical for patients care.

[Validated care programs for patients with functional neurological disorders]. / Modèles de soins validés pour les patients souffrant de troubles neurologiques fonctionnels.

Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. Diagnostic delay may lead to no treatment, inappropriate treatment or even iatrogenic symptoms. Yet, several treatments significantly reduce physical symptoms and improve functioning in FND patients even though not all patients respond to the currently available treatments. This review aims to describe the range of evidence-based rehabilitative and/or psychological therapeutic approaches available for FND patients. The most effective treatments are multidisciplinary and coordinated; using an outpatient or inpatient setting. Building a network of FND-trained healthcare professionals around the patient is an essential aspect of optimal patient management. Indeed, a supportive environment coupled with a collaborative therapeutic relationship improves understanding of FND and appears to help patients engage in appropriate treatments. Patients need to be invested in their own care and have to understand that recovery may depend on their commitment. The conventional treatment combines psychoeducation, physical rehabilitation and psychotherapy (cognitive and behavioral therapy, hypnosis, psychodynamic interpersonal therapy). Early referral of patients to physical therapy is recommended; however, the optimal parameters of treatment, duration and intensity are unknown and seem to vary with the severity and chronicity of symptoms. The goal is to minimize self-awareness by diverting attention or by stimulating automatically generated movements with non-specific and gradual exercises. The use of compensatory technical aids should be avoided as much as possible. Psychotherapeutic management should encourage self-evaluation of cognitive distortions, emotional reactions and maladaptive behaviors while empowering the patient in managing symptoms. Symptom management can use anchoring strategies to fight against dissociation. The aim is to connect to the immediate environment and to enrich one's sensoriality. The psychological interventions should then be adapted to the individual psychopathology, cognitive style and personality functioning of each patient. There is currently no known curative pharmacological treatment for FND. The pharmacological approach rather consists of progressively discontinuing medication that was introduced by default and that could lead to undesirable side effects. Finally, neurostimulation (transcranial magnetic stimulation, transcranial direct current stimulation) can be effective on motor FND.

[Psychological impact of involvement of medical and psychological emergency unit professionals in the medical and psychological care system of the COVID-19 epidemic]. / Impact psychologique de l'implication des professionnels des CUMP dans le dispositif de soins médico-psychologique face à l'épidémie COVID-19.

Objectives: COVID-19 pandemic and its consequences have put into great difficulty health professionals, and the general population, fostering the emergence of various psychological and psychiatric disorders. Medical and psychological emergency units' mission is the medical and psychological emergency care of people impacted during a traumatic event. Given their expertise in crisis management, they set up an important medical and psychological support system adapted to the health crisis' characteristics. The unusual modalities of intervention, the specific clinic that these professionals faced in this context of great tension may have unsettled workers and generate a psychological impact. This study aims to assess the existence of such repercussions among medical and psychological emergency unit professionals involved in this new system. Method: In all, 313 medical and psychological emergency unit professionals agreed to participate at the online survey. They filled surveys and visual analog scales assessing the difficulties encountered in the system, as well as their level of satisfaction, post-traumatic stress, burnout, level of anxiety and depression and coping strategies put in place. Results: Results show few significant emotional difficulties. However higher scores are found among women, among professionals who felt a negative impact on their personal lives, as well as for those who thought they had been infected with COVID-19. The establishment of coping strategies such as active coping, planning, expressing feelings, positive reinterpretation and acceptance helped to decrease the level of emotional complexities and brought more compassionate satisfaction. We note that participants with more medical and psychological emergency unit experience tend to show less emotional hardship and more compassionate satisfaction. It appears that older as well as younger professionals have lower burnout scores, as do workers who conducted more interviews for the same person. Likewise, participants who were satisfied of the system organization and of the support - a majority in this study - report less emotional challenges and more compassionate satisfaction. Conclusion: Psychological impact in this new system among medical and psychological emergency unit professionals is overall low. It appears that some coping strategies, perceived usefulness, satisfaction with the organization and the received support are associated with a lower level of emotional difficulties. A supportive framework and an operative organization of the medical and psychological emergency unit system in times of crisis has a protective effect on the participants.

Functional (psychogenic non-epileptic/dissociative) seizures: why and how?

Functional seizures (FS) known also as psychogenic non-epileptic seizures or dissociative seizures, present with ictal semiological manifestations, along with various comorbid neurological and psychological disorders. Terminology inconsistencies and discrepancies in nomenclatures of FS may reflect limitations in understanding the neuropsychiatric intricacies of this disorder. Psychological and neurobiological processes of FS are incompletely understood. Nevertheless, important advances have been made on underlying neuropsychopathophysiological mechanisms of FS. These advances provide valuable information about the underlying mechanisms of mind-body interactions. From this perspective, this narrative review summarises recent studies about aetiopathogenesis of FS at two levels: possible risk factors (why) and different aetiopathogenic models of FS (how). We divided possible risk factors for FS into three categories, namely neurobiological, psychological and cognitive risk factors. We also presented different models of FS based on psychological and neuroanatomical understanding, multilevel models and integrative understanding of FS. This work should help professionals to better understand current views on the multifactorial mechanisms involved in the development of FS. Shedding light on the different FS profiles in terms of aetiopathogenesis will help guide how best to direct therapy, based on these different underlying mechanisms.

Heterogeneity of patients with functional/dissociative seizures: Three multidimensional profiles.

OBJECTIVE: Current concepts highlight the neurological and psychological heterogeneity of functional/dissociative seizures (FDS). However, it remains uncertain whether it is possible to distinguish between a limited number of subtypes of FDS disorders. We aimed to identify profiles of distinct FDS subtypes by cluster analysis of a multidimensional dataset without any a priori hypothesis. METHODS: We conducted an exploratory, prospective multicenter study of 169 patients with FDS. We collected biographical, trauma (childhood and adulthood traumatic experiences), semiological (seizure characteristics), and psychopathological data (psychiatric comorbidities, dissociation, and alexithymia) through psychiatric interviews and standardized scales. Clusters were identified by the Partitioning Around Medoids method. The similarity of patients was computed using Gower distance. The clusters were compared using analysis of variance, chi-squared, or Fisher exact tests. RESULTS: Three patient clusters were identified in this exploratory, hypothesis-generating study and named on the basis of their most prominent characteristics: A "No/Single Trauma" group (31.4%), with more male patients, intellectual disabilities, and nonhyperkinetic seizures, and a low level of psychopathology; A "Cumulative Lifetime Traumas" group (42.6%), with clear female predominance, hyperkinetic seizures, relatively common comorbid epilepsy, and a high level of psychopathology; and A "Childhood Traumas" group (26%), commonly with comorbid epilepsy, history of childhood sexual abuse (75%), and posttraumatic stress disorder, but also with a high level of anxiety and dissociation. SIGNIFICANCE: Although our cluster analysis was undertaken without any a priori hypothesis, the nature of the trauma history emerged as the most important differentiator between three common FDS disorder subtypes. This subdifferentiation of FDS disorders may facilitate the development of more specific therapeutic programs for each patient profile.

Place of the partial dopamine receptor agonist aripiprazole in the management of schizophrenia in adults: a Delphi consensus study.

BACKGROUND: Aripiprazole is a second-generation antipsychotic, efficacious in patients with schizophrenia during acute episodes. Due to its pharmacological profile, aripiprazole may be of interest in patients with specific clinical profiles who have not been studied extensively in randomised clinical trials. OBJECTIVES: To capture experience with aripiprazole in everyday psychiatric practice using the Delphi method in order to inform decision-making on the use of aripiprazole for the treatment of patients with schizophrenia in clinical situations where robust evidence from clinical trials is lacking. METHODS: The scope of the survey was defined as the management of schizophrenia in adults. A systematic literature review was performed to identify the different clinical situations in which aripiprazole has been studied, and to describe the level of clinical evidence. Clinical profiles to include in the Delphi survey were selected if there was a clear interest in terms of medical need but uncertainty over the efficacy of aripiprazole. For each clinical profile retained, five to seven specific statements were generated and included in a questionnaire. The final 41-item questionnaire was proposed to a panel of 406 French psychiatrists with experience in the treatment of schizophrenia. Panellists rated their level of agreement using a Likert scale. A second round of voting on eleven items was organised to clarify points for which a consensus was not obtained in the first round. RESULTS: Five clinical profiles were identified in the literature review (persistent negative symptoms, pregnancy, cognitive dysfunction, addictive comorbidity and clozapine resistance). Sixty-two psychiatrists participated in the first round of the Delphi survey and 33 in the second round. A consensus was obtained for 11 out of 41 items in the first round and for 9/11 items in the second round. According to the panellists' clinical experience, aripiprazole can be used as maintenance treatment for pregnant women, is relevant to preserve cognitive function and can be considered an option in patients with a comorbid addictive disorder or with persistent negative symptoms. CONCLUSION: These findings may help physicians in choosing relevant ways to use aripiprazole and highlight areas where more research is needed to widen the evidence base.

Combining Trauma Script Exposure With rTMS to Reduce Symptoms of Post-Traumatic Stress Disorder: Randomized Controlled Trial.

BACKGROUND: Innovative therapeutic interventions for post-traumatic stress disorder (PTSD) are required. We opted to facilitate fear extinction by combining trauma script exposure with repetitive transcranial magnetic stimulation (rTMS) to reduce symptoms of PTSD. OBJECTIVE: The efficacy and safety of 10 Hz rTMS of the right dorsolateral prefrontal cortex simultaneously with exposure to personal traumatic narrative were studied in patients with PTSD. MATERIALS AND METHODS: This trial was a single-center randomized controlled trial (NCT02584894). Patients were randomly assigned 1:1 to receive eight daily sessions of 110% of motor threshold high frequency (HF) 10 Hz rTMS (110% HF rTMS) or 70% low frequency (LF) 1 Hz rTMS (70% LF rTMS) with trauma script exposure in both groups. Severity of PTSD, depression, and anxiety were assessed before and after study treatment (one month, three months) by an assessor masked to the trial group assignment. The primary outcome was the severity of PTSD assessed by the Clinician Administered PTSD Scale (CAPS). We used mixed linear regression models for statistical comparisons. RESULTS: Thirty-eight patients (65.8% females) were randomly assigned to 110% HF rTMS (n = 18, 31.3 ± 10.0 years, 13 females) or 70% LF rTMS (n = 20, 33.5 ± 11.1 years, 12 females). From baseline to three months, mean CAPS scores decreased by 51% in the 110% HF rTMS group (from 83.7 ± 14.4 to 41.8 ± 31.9) and by 36.9% in the 70% LF rTMS group (from 81.8 ± 15.6 to 51.6 ± 23.7), but with no significant difference in improvement (time by treatment interaction -3.61 [95% confidence interval (CI), -9.70 to 2.47]; p = 0.24; effect size 0.53). One serious adverse event occurred during the study (psychogenic nonepileptic seizure). CONCLUSION: We found no evidence of difference in clinical improvement or remission rates between the 110% HF and 70% LF stimulation. These findings may reflect the importance of exposure procedure and that larger number of participants is needed.