Opinions of French psychiatrists on the regulatory status of cannabis: Results from the "PsyCan - Encéphale" national online survey.

OBJECTIVE: To explore the opinions of French psychiatrists toward the legalization of medical or recreational use of cannabis in France. METHODS: Psycan was an anonymous Internet survey conducted between September 28, 2021 and March 29, 2022, among subscribers of the Encéphale Online community, i.e., approximately 4000 French psychiatrists. Participants were asked to complete a structured questionnaire, collecting their socio-demographic features, clinical experience, opinions toward cannabis legalization, and perceived impact of cannabis derivatives for psychiatric disorders. Logistic regression models were used to identify factors associated with being for or against cannabis legalization. RESULTS: In total, 413 psychiatrists answered the survey, of whom 253 (61.3%) declared being in favour of recreational cannabis, and 349 (84.4%) of medical cannabis. Being in favour of legalization of recreational cannabis was negatively associated with being female (odd ratio [OR]=0.61; 95% confidence interval [CI]=0.41-0.93), and with the frequency of meeting patients with cannabis use disorder (OR=0.60; 95%CI=0.43-0.83). Most respondents were concerned about the development of psychotic disorders. The most frequent pro-legalization arguments were improved prevention, better control of product content, and better protection of youth, respectively. Arguments against legalization were increased societal damages, increased impact on health, including mental health. CONCLUSIONS: A majority of French psychiatrists were in favour of the marketing of medical cannabis, and, to a lesser extent, the legalization of recreational cannabis. For recreational cannabis, the proportion of pro-legalization psychiatrists was slightly more elevated than that found in the French general population.

A recovery-oriented day hospital in psychiatry: A springboard for reintegration.

Psychiatric disorders are common and can cause psychological disabilities. While the creation of day hospitals (DHs) was intended to direct psychiatric care towards community settings, they may have paradoxically contributed to a form of chronicity. Furthermore, the heterogeneity and lack of evaluation of care within DHs prevent the availability needed to collect objective data on users outcomes. In this article, we aim to describe and measure the effects of a transformation of practice within a sector-based DH initially focused on traditional institutional psychiatry towards a rehabilitation model of care which offers different therapeutic tools, structured in three stages, and whose main objective is professional integration. This retrospective mirror study compares, before and after the transformation of this DH, several indicators including the rate of professional integration and its maintenance after two years. We found that this psychosocial rehabilitation model for care allowed a very clear increase in the professional integration rate and its maintenance at two years while reducing the length of stay to around 18 months. These promising results therefore highlight the pivotal role of DHs as "stepping stones" in addressing psychological disabilities towards recovery.

Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study.

BACKGROUND: Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19. METHODS: This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis. RESULTS: In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9-59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. CONCLUSION: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.

Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity.

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.

Association Between Anxiety and New Organ Failure, Independently of Critical Illness Severity and Respiratory Status: A Prospective Multicentric Cohort Study.

OBJECTIVES: Anxiety results from the anticipation of a threat and might be associated with poor outcome in the critically ill. This study aims at showing that anxiety at admission in critically ill patients is associated with new organ failure over the first 7 days of ICU hospitalization independently of baseline organ failure at admission. DESIGN: Prospective multicenter cohort study. SETTING: Three mixed ICU from April 2014 to December 2017. PATIENTS: Coma-, delirium-, and invasive mechanical ventilation-free patients admitted to the ICU were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: "State anxiety" was assessed using the state component of the State-Trait Anxiety Inventory State. Severity of illness was measured using Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. Primary endpoint was a composite of occurrence of death or new organ failure in the first 7 days after admission. Three hundred ninety-one patients were included; 159 of 391 women (40.7%); median age 63 years (49-74 yr); median Simplified Acute Physiology Score II 28 (19-37). Two hundred three out of 391 patients (51.9%) reported moderate to severe anxiety (State-Trait Anxiety Inventory State ≥ 40). One hundred two out of 391 patients (26.1%) developed a new organ failure. After adjustment to Simplified Acute Physiology Score II and Sequential Organ Failure Assessment, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with the primary endpoint (odds ratio, 1.94; 95% CI, 1.18-3.18; p = 0.009) and respiratory failure. In post hoc analysis, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with new organ failure independently and notably of respiratory status at admission (dyspnea-Visual Analogic Scale and PaCO2 ≥ 45 mm Hg). CONCLUSIONS: Moderate to severe anxiety at ICU admission is associated with early occurrence of new organ failure in critically ill patients, independently of respiratory status and severity of critical illness. The causality link could be addressed in an interventional trial.

Brain imaging in catatonia: systematic review and directions for future research.

BACKGROUND: Catatonia is a frequent, complex and severe identifiable syndrome of motor dysregulation. However, its pathophysiology is poorly understood. METHODS: We aimed to provide a systematic review of all brain imaging studies (both structural and functional) in catatonia. RESULTS: We identified 137 case reports and 18 group studies representing 186 individual patients with catatonia. Catatonia is often associated with brain imaging abnormalities (in more than 75% of cases). The majority of the case reports show diffuse lesions of white matter, in a wide range of brain regions. Most of the case reports of functional imaging usually show frontal, temporal, or basal ganglia hypoperfusion. These abnormalities appear to be alleviated after successful treatment of clinical symptoms. Structural brain magnetic resonance imaging studies are very scarce in the catatonia literature, mostly showing diffuse cerebral atrophy. Group studies assessing functional brain imaging after catatonic episodes show that emotional dysregulation is related to the GABAergic system, with hypoactivation of orbitofrontal cortex, hyperactivation of median prefrontal cortex, and dysconnectivity between frontal and motor areas. CONCLUSION: In catatonia, brain imaging is abnormal in the majority of cases, and abnormalities more frequently diffuse than localised. Brain imaging studies published so far suffer from serious limitations and for now the different models presented in the literature do not explain most of the cases. There is an important need for further studies including a better clinical characterisation of patients with catatonia, functional imaging with concurrent catatonic symptoms and the use of novel brain imaging techniques.

Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3.

BACKGROUND: Elderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment. METHODS: This phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Analyses included a preplanned analysis by age (65-74 versus ≥75 years) and post-hoc analyses including age at depression onset. RESULTS: For the primary endpoint, the median-unbiased estimate of the treatment difference (95% CI) was -3.6 (-7.20, 0.07); weighted combination test using MMRM analyses z = 1.89, two-sided p = 0.059. Adjusted mean (95% CI) difference for change in MADRS score between treatment groups was -4.9 (-8.96, -0.89; t = -2.4, df = 127; two-sided nominal p = 0.017) for patients 65 to 74 years versus -0.4 (-10.38, 9.50; t = -0.09, two-sided nominal p = 0.930) for those ≥75 years, and -6.1 (-10.33, -1.81; t = -2.8, df = 127; two-sided nominal p = 0.006) for patients with depression onset <55 years and 3.1 (-4.51, 10.80; t = 0.8, two-sided nominal p = 0.407) for those ≥55 years. Patients who rolled over into the long-term open-label study showed continued improvement with esketamine following 4 additional treatment weeks. CONCLUSIONS: Esketamine/antidepressant did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen for younger patients (65-74 years) and patients with earlier onset of depression (<55 years).

Predicting the individual risk of psychosis conversion in at-risk mental state (ARMS): a multivariate model reveals the influence of nonpsychotic prodromal symptoms.

To improve the prediction of the individual risk of conversion to psychosis in UHR subjects, by considering all CAARMS' symptoms at first presentation and using a multivariate machine learning method known as logistic regression with Elastic-net shrinkage. 46 young individuals who sought help from the specialized outpatient unit at Sainte-Anne hospital and who met CAARMS criteria for UHR were assessed, among whom 27 were reassessed at follow-up (22.4 ± 6.54 months) and included in the analysis. Elastic net logistic regression was trained, using CAARMS items at baseline to predict individual evolution between converters (UHR-P) and non-converters (UHR-NP). Elastic-net was used to select the few CAARMS items that best predict the clinical evolution. All validations and significances of predictive models were computed with non-parametric re-sampling strategies that provide robust estimators even when the distributional assumption cannot be guaranteed. Among the 25 CAARMS items, the Elastic net selected 'obsessive-compulsive symptoms' and 'aggression/dangerous behavior' as risk factors for conversion while 'anhedonia' and 'mood swings/lability' were associated with non-conversion at follow-up. In the ten-fold stratified cross-validation, the classification achieved 81.8% of sensitivity (P = 0.035) and 93.7% of specificity (P = 0.0016). Non-psychotic prodromal symptoms bring valuable information to improve the prediction of conversion to psychosis. Elastic net logistic regression applied to clinical data is a promising way to switch from group prediction to an individualized prediction.

The next psychoactive drugs: From imipramine to ketamine.

Since the 1950s, the therapeutic arsenal against depression has grown considerably. From the discovery of mono-amine oxidase inhibitors (MAOIs) to the antidepressant effect of ketamine, several pharmacological breakthroughs made the history of psychiatry. These discoveries oriented the research about the pathophysiology of depression, which is one of the most disabling diseases worldwide affecting 10 to 20% of general population. In this article, we offer a short historical review of the various therapeutic options developed over the past century and the consequences of these innovations. We then review the discovery of the antidepressant effects of ketamine (and its S-enantiomer, esketamine), the lastest development in depression treatment. Ketamine's effects are spectacular both in terms of their very short onset time, and because they are observed even in treatment-resistant depression. Just as MAOIs and tricyclic antidepressants allowed the "monoaminergic hypothesis of depression" to emerge, unravelling the mechanisms of ketamine's antidepressant effects should highlight the role of glutamatergic system and neuro-inflammation in the neurobiology of depression. Ketamine might also help to refine our understanding of the cognitive pathophysiology of depression and to deeply transform the clinical representations of depressive disorder.

Depuis les années 1950, l'arsenal thérapeutique permettant de lutter contre la dépression s'est considérablement enrichi. De la découverte des inhibiteurs de la mono-amine oxydase (IMAO) à celle de la kétamine, ces percées pharmacologiques ont marqué l'histoire de la psychiatrie et guidé la recherche sur la physiopathologie de la dépression, cette pathologie dévastatrice affectant entre 10 et 20 % de la population mondiale. Nous proposons dans cet article une courte revue historique des différentes options thérapeutiques développées au cours du siècle passé et des conséquences qu'ont eues ces innovations. Nous réalisons ensuite un état des lieux de la plus récente de ces découvertes, celle des effets antidépresseurs de la kétamine (et de son énantiomère S, l'eskétamine), spectaculaires de par leur délai d'action et leur efficacité même dans les formes les plus résistantes de dépression. De même que la découverte des IMAO et des tricycliques a permis de concevoir une théorie monoaminergique de la dépression, l'étude des mécanismes d'actions de la kétamine pourrait permettre de comprendre le rôle de la transmission glutamatergique ou de la neuro-inflammation dans la neurobiologie de cette pathologie, d'affiner nos connaissances sur sa physiopathologie cognitive, ou encore de transformer en profondeur les représentations des cliniciens sur cette maladie.

Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1).

BACKGROUND: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression. METHODS: This Phase 3, double-blind, multicenter study enrolled adults with moderate-to-severe depression and nonresponse to ≥2 antidepressants in the current depression episode. Eligible patients (N = 346) were randomized (1:1:1) to twice-weekly nasal spray treatment (esketamine [56 or 84 mg] or placebo) plus a newly initiated, open-label, oral antidepressant taken daily for 4 weeks. The primary efficacy endpoint was change from baseline to day 28 in the Montgomery-Asberg Depression Rating Scale total score, performed by blinded, remote raters. Based on the predefined statistical testing sequence, esketamine 84 mg/antidepressant had to be significant for esketamine 56 mg/antidepressant to be formally tested. RESULTS: Statistical significance was not achieved with esketamine 84 mg/antidepressant compared with antidepressant/placebo (least squares [LS] means difference [95% CI]: -3.2 [-6.88, 0.45]; 2-sided P value = .088). Although esketamine 56 mg/antidepressant could not be formally tested, the LS means difference was -4.1 [-7.67, -0.49] (nominal 2-sided P value = .027). The most common (>20%) adverse events reported for esketamine/antidepressant were nausea, dissociation, dizziness, vertigo, and headache. CONCLUSIONS: Statistical significance was not achieved for the primary endpoint; nevertheless, the treatment effect (Montgomery-Asberg Depression Rating Scale) for both esketamine/antidepressant groups exceeded what has been considered clinically meaningful for approved antidepressants vs placebo. Safety was similar between esketamine/antidepressant groups and no new dose-related safety concerns were identified. This study provides supportive evidence for the safety and efficacy of esketamine nasal spray as a new, rapid-acting antidepressant for patients with treatment-resistant depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02417064.

Microglial production of quinolinic acid as a target and a biomarker of the antidepressant effect of ketamine.

Major depressive disorder is a complex multifactorial condition with a so far poorly characterized underlying pathophysiology. Consequently, the available treatments are far from satisfactory as it is estimated that up to 30% of patients are resistant to conventional treatment. Recent comprehensive evidence has been accumulated which suggests that inflammation may be implied in the etiology of this disease. Here we investigated ketamine as an innovative treatment strategy due to its immune-modulating capacities. In a murine model of LPS-induced depressive-like behavior we demonstrated that a single dose of ketamine restores the LPS-induced depressive-like alterations. These behavioral effects are associated with i/ a reversal of anxiety and reduced self-care, ii/ a decrease in parenchymal cytokine production, iii/ a modulation of the microglial reactivity and iv/ a decrease in microglial quinolinic acid production that is correlated with plasmatic peripheral production. In a translational approach, we show that kynurenic acid to quinolinic acid ratio is a predictor of ketamine response in treatment-resistant depressed patients and that the reduction in quinolinic acid after a ketamine infusion is a predictor of the reduction in MADRS score. Our results suggest that microglia is a key therapeutic target and that quinolinic acid is a biomarker of ketamine response in major depressive disorder.

The impact of the Paris terrorist attacks on the mental health of resident physicians.

BACKGROUND: On November 13, 2015, terrorist attacks took place in Paris. One hundred and twenty-nine people were immediately killed and 302 needed emergency care. Many resident physicians were on the front line of the medical response. Our aim was to report the frequency of symptoms of post-traumatic stress disorder (PTSD), anxiety and depression among resident physicians after the Paris terrorist attacks. METHODS: Anonymous questionnaires, including the Impact of Event Scale- Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS), were emailed two months after the attacks to 2413 Parisian resident physicians. Exposure to the attacks was defined as having direct clinical contact with one of the victims up to one week after the attacks, being one of the victims, or having one among close relatives. RESULTS: The questionnaire was completed by 680 (28.2%) residents. Eighty-four (12.4%) reported symptoms of PTSD (IES-R ≥ 33), 76 (11.2%) reported symptoms of anxiety (HADS anxiety score > 10) and 16 (2.4%) reported symptoms of depression (HADS depression score > 10). Exposed residents had higher IES-R scores than non-exposed residents (18.8 ± 16.6 versus 14.2 ± 12.0, p = 0.001), and 40 (18.5%) of them reported symptoms of PTSD, compared to 44 (9.5%) of the non-exposed residents (p = 0.001). CONCLUSIONS: There was a high frequency of symptoms of mental distress among our respondents. Dedicated screening and care strategies must be considered in the event of new attacks.

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study.

BACKGROUND: Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 study, we enrolled adults (aged 18-75 years) with indolent or smouldering systemic mastocytosis, according to WHO classification or documented mastocytosis based on histological criteria, at 50 centres in 15 countries. We excluded patients with cutaneous or non-severe systemic mastocytosis after a protocol amendment. Patients were centrally randomised (1:1) to receive either oral masitinib (6 mg/kg per day over 24 weeks with possible extension) or matched placebo with minimisation according to severe symptoms. The primary endpoint was cumulative response (≥75% improvement from baseline within weeks 8-24) in at least one severe baseline symptom from the following: pruritus score of 9 or more, eight or more flushes per week, Hamilton Rating Scale for Depression of 19 or more, or Fatigue Impact Scale of 75 or more. We assessed treatment effect using repeated measures methodology for rare diseases via the generalised estimating equation model in a modified intention-to-treat population, including all participants assigned to treatment minus those who withdrew due to a non-treatment-related cause. We assessed safety in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00814073. FINDINGS: Between Feb 19, 2009, and July 15, 2015, 135 patients were randomly assigned to masitinib (n=71) or placebo (n=64). By 24 weeks, masitinib was associated with a cumulative response of 18·7% in the primary endpoint (122·6 responses of 656·5 possible responses [weighted generalised estimating equation]) compared with 7·4% for placebo (48·9 of 656·5; difference 11·3%; odds ratio 3·6; 95% CI 1·2-10·8; p=0·0076). Frequent severe adverse events (>4% difference from placebo) were diarrhoea (eight [11%] of 70 in the masitinib group vs one [2%] of 63 in the placebo group), rash (four [6%] vs none), and asthenia (four [6%] vs one [2%]). The most frequent serious adverse events were diarrhoea (three patients [4%] vs one [2%]) and urticaria (two [3%] vs none), and no life-threatening toxicities occurred. One patient in the placebo group died (unrelated to study treatment). INTERPRETATION: These study findings indicate that masitinib is an effective and well tolerated agent for the treatment of severely symptomatic indolent or smouldering systemic mastocytosis. FUNDING: AB Science (Paris, France).

Everolimus induced mood changes in breast cancer patients: a case-control study.

Introduction The PI3K/Akt/mTOR pathway plays a critical role in cancer cell growth, proliferation and angiogenesis, but also in brain homeostasis and the pathophysiology of mood disorders. The impact of the mTOR inhibitor everolimus on the mood of breast cancer patients is unknown. Materials and methods Consecutive, post-menopausal metastatic breast cancer patients receiving hormone therapy +/- everolimus were prospectively followed-up using the Beck Depression Inventory (BDI) and the MADRS (Montgomery and Asberg Depression Rating Scale) questionnaires. Results Post hoc tests comparing everolimus + hormonotherapy to hormonotherapy alone demonstrated a significant effect of everolimus after 6 weeks of treatment on BDI scores (t(1,38) = -2.0716, p < 0.05), and after 3 weeks (t(1,38) = -3.9165, p < 0.001) and 6 weeks of treatment (t(1,38) = -2.0373, p < 0.05) on MADRS scores. Analysis within each treatment group showed that the effect of time since treatment initiation on BDI and MADRS scores was specifically observed in the everolimus + hormonotherapy group (F(2,34) = 11.875, p < 0.001 and F(2,34) = 7.820, p < 0.01 respectively), but not in the hormonotherapy alone group (F(2,34) = 1.671, p > 0.2 and F(2,34) = 0.830, p > 0.2 respectively). Conclusions The mTOR inhibitor everolimus induces significant mood alterations in breast cancer patients. The evaluation of psychiatric symptoms is not only mandatory in the context of phase 1, dose-finding studies of PI3K/Akt/mTOR inhibitors, but is also clinically relevant in daily practice.

Conscious and unconscious performance monitoring: Evidence from patients with schizophrenia.

The ability to detect our own errors is an essential component of action monitoring. Using a masking paradigm in normal adults, we recently discovered that some error-detection processes can proceed without awareness, while other markers of performance monitoring such as the Error-Related Negativity (ERN) are tightly linked to conscious perception. Interestingly, research on cognitive deficit in schizophrenia has shown that the ERN is altered in these patients. In the present study, we therefore tested if the error detection impairment in schizophrenia is specific to conscious perception or is also found under non-conscious conditions, probing whether these performance monitoring processes are truly distinct. Thirteen patients with schizophrenia and thirteen age-matched healthy control subjects performed a speeded number comparison task on masked stimuli while EEG and MEG signals were recorded. Conscious perception and error-detection were assessed on a trial-by-trial basis using subjective reports of visibility and confidence. We found that patients with schizophrenia presented altered cingulate error-detection responses in conscious trials, as reflected by a decreased ERN. By contrast, on unconscious trials, both controls and schizophrenia patients performed above chance in evaluating the likelihood of having made an error. This dissociation confirms the existence of two distinct performance monitoring systems, and suggests that conscious metacognition in schizophrenia is specifically altered while non-conscious performance monitoring remains preserved.

Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development.

BACKGROUND: Several clinical and radiological markers of early neurodevelopmental deviations have been independently associated with cognitive impairment in patients with schizophrenia. The aim of our study was to test the cumulative and/or interactive effects of these early neurodevelopmental factors on cognitive control (CC) deficit, a core feature of schizophrenia. METHODS: We recruited patients with first-episode schizophrenia-spectrum disorders, who underwent structural MRI. We evaluated CC efficiency using the Trail Making Test (TMT). Several markers of early brain development were measured: neurological soft signs (NSS), handedness, sulcal pattern of the anterior cingulate cortex (ACC) and ventricle enlargement. RESULTS: We included 41 patients with schizophrenia in our analysis, which revealed a main effect of ACC morphology (p = 0.041) as well as interactions between NSS and ACC morphology (p = 0.005), between NSS and handedness (p = 0.044) and between ACC morphology and cerebrospinal fluid (CSF) volume (p = 0.005) on CC measured using the TMT-B score - the TMT-A score. LIMITATIONS: No 3- or 4-way interactions were detected between the 4 neurodevelopmental factors. The sample size was clearly adapted to detect main effects and 2-way interactions, but may have limited the statistical power to investigate higher-order interactions. The effects of treatment and illness duration were limited as the study design involved only patients with first-episode psychosis. CONCLUSION: To our knowledge, our study provides the first evidence of cumulative and interactive effects of different neurodevelopmental markers on CC efficiency in patients with schizophrenia. Such findings, in line with the neurodevelopmental model of schizophrenia, support the notion that CC impairments in patients with schizophrenia may be the final common pathway of several early neurodevelopmental mechanisms.

History of psychosurgery at Sainte-Anne Hospital, Paris, France, through translational interactions between psychiatrists and neurosurgeons.

Sainte-Anne Hospital is the largest psychiatric hospital in Paris. Its long and fascinating history began in the 18th century. In 1952, it was at Sainte-Anne Hospital that Jean Delay and Pierre Deniker used the first neuroleptic, chlorpromazine, to cure psychiatric patients, putting an end to the expansion of psychosurgery. The Department of Neuro-psychosurgery was created in 1941. The works of successive heads of the Neurosurgery Department at Sainte-Anne Hospital summarized the history of psychosurgery in France. Pierre Puech defined psychosurgery as the necessary cooperation between neurosurgeons and psychiatrists to treat the conditions causing psychiatric symptoms, from brain tumors to mental health disorders. He reported the results of his series of 369 cases and underlined the necessity for proper follow-up and postoperative re-education, illustrating the relative caution of French neurosurgeons concerning psychosurgery. Marcel David and his assistants tried to follow their patients closely postoperatively; this resulted in numerous publications with significant follow-up and conclusions. As early as 1955, David reported intellectual degradation 2 years after prefrontal leucotomies. Jean Talairach, a psychiatrist who eventually trained as a neurosurgeon, was the first to describe anterior capsulotomy in 1949. He operated in several hospitals outside of Paris, including the Sarthe Psychiatric Hospital and the Public Institution of Mental Health in the Lille region. He developed stereotactic surgery, notably stereo-electroencephalography, for epilepsy surgery but also to treat psychiatric patients using stereotactic lesioning with radiofrequency ablation or radioactive seeds of yttrium-90. The evolution of functional neurosurgery has been marked by the development of deep brain stimulation, in particular for obsessive-compulsive disorder, replacing the former lesional stereotactic procedures. The history of Sainte-Anne Hospital's Neurosurgery Department sheds light on the initiation-yet fast reconsideration-of psychosurgery in France. This relatively more prudent attitude toward the practice of psychosurgery compared with other countries was probably due to the historically strong collaboration between psychiatrists and neurosurgeons in France.