Modulation of Visually Induced Self-motion Illusions by α Transcranial Electric Stimulation over the Superior Parietal Cortex.

The growing popularity of virtual reality systems has led to a renewed interest in understanding the neurophysiological correlates of the illusion of self-motion (vection), a phenomenon that can be both intentionally induced or avoided in such systems, depending on the application. Recent research has highlighted the modulation of α power oscillations over the superior parietal cortex during vection, suggesting the occurrence of inhibitory mechanisms in the sensorimotor and vestibular functional networks to resolve the inherent visuo-vestibular conflict. The present study aims to further explore this relationship and investigate whether neuromodulating these waves could causally affect the quality of vection. In a crossover design, 22 healthy volunteers received high amplitude and focused α-tACS (transcranial alternating current stimulation) over the superior parietal cortex while experiencing visually induced vection triggered by optokinetic stimulation. The tACS was tuned to each participant's individual α peak frequency, with θ-tACS and sham stimulation serving as controls. Overall, participants experienced better quality vection during α-tACS compared with control θ-tACS and sham stimulations, as quantified by the intensity of vection. The observed neuromodulation supports a causal relationship between parietal α oscillations and visually induced self-motion illusions, with their entrainment triggering overinhibition of the conflict within the sensorimotor and vestibular functional networks. These results confirm the potential of noninvasive brain stimulation for modulating visuo-vestibular conflicts, which could help to enhance the sense of presence in virtual reality environments.

Exploring the spatial resolution of TMS-EEG coupling on the sensorimotor region.

The use of TMS-EEG coupling as a neuroimaging tool for the functional exploration of the human brain recently gained strong interest. If this tool directly inherits the fine temporal resolution from EEG, its spatial counterpart remains unknown. In this study, we explored the spatial resolution of TMS-EEG coupling by evaluating the minimal distance between two stimulated cortical sites that would significantly evoke different response dynamics. TMS evoked responses were mapped on the sensorimotor region in twenty participants. The stimulation grid was composed of nine targets separated between 10 and 15 mm on average. The dynamical signatures of TMS evoked activity were extracted and compared between sites using both local and remote linear regression scores and spatial generalized mixed models. We found a significant effect of the distance between stimulated sites on their dynamical signatures, neighboring sites showing differentiable response dynamics. Besides, common dynamical signatures were also found between sites up to 25-30 mm from each other. This overlap in dynamical properties decreased with distance and was stronger between sites within the same Brodmann area. Our results suggest that the spatial resolution of TMS-EEG coupling might be at least as high as 10 mm. Furthermore, our results reveal an anisotropic spatial resolution that was higher across than within the same Brodmann areas, in accordance with the TMS induced E-field modeling. Common cytoarchitectonic leading to shared dynamical properties within the same Brodmann area could also explain this anisotropy. Overall, these findings suggest that TMS-EEG benefits from the spatial resolution of TMS, which makes it an accurate technique for meso-scale brain mapping.

The Impact of Wearing a Face Mask on the Psychiatric Interview: a National Survey During the COVID-19 Pandemic.

The COVID-19 pandemic has forced to rapidly encourage the use of face masks during medical consultations, with significant implication for psychiatry. This study examined the opinions and attitudes of psychiatrists toward the impact of wearing a face mask on the psychiatric interview. 513 psychiatrists and trainee psychiatrists completed an electronic survey about the impact of wearing a face mask on the psychiatric interview. Less efficiency in capturing clinical signs/symptoms, emergence of false inferences in patients and altered patient-clinician interactions were commonly reported negative impacts of face mask (66-96%). The quality of the therapeutic alliance was reported as affected by the mask by 47% of the sample. Results were mixed on the use of telepsychiatry as a potential solution to mask-related inconvenience. The use of face masks has significant negative effects on the psychiatric interview. Providing specific training to clinicians could be a potential solution for masks-induced biases.

Four Questions Nurses Can Ask to Predict PTSD 1 Year After a Motor Vehicle Crash.

BACKGROUND: The role of nurses in screening for posttraumatic stress disorder is crucial in trauma units. OBJECTIVES: To create and evaluate an easy and brief tool for nurses to predict chronic posttraumatic stress disorder 1 year after a motor vehicle crash. METHODS: We performed a 1-year follow-up multicenter study from 2007 to 2015, including 274 patients injured in a motor vehicle crash who were hospitalized in an orthopedic trauma unit. Nurses administered the DEPITAC questionnaire. Posttraumatic stress disorder was measured by the Post-Traumatic Stress Disorder Checklist of symptoms during the first year following the crash. A multivariable logistic regression model was implemented to select items significantly associated with posttraumatic stress disorder to improve the DEPITAC questionnaire. Predictive performance to predict posttraumatic stress disorder 1 year after the motor vehicle crash was examined for these different models. RESULTS: Of 274 patients studied, a total of 75.9% completed the questionnaire at 1 year of follow-up. We found that only two questions and two simple elements of the patient's medical record (other injury or a person dying during the crash, perception of vital threat, number of children, and length of stay in trauma) predicted posttraumatic stress disorder 1 year after a motor vehicle crash. CONCLUSIONS: The brevity of this evaluation, simple scoring rules, and screening test performance suggest that this new screening tool can be easily administered in the acute care setting by nurses.

Longitudinal relationships between cognition and functioning over 2 years in euthymic patients with bipolar disorder: a cross-lagged panel model approach with the FACE-BD cohort.

BACKGROUND: Longitudinal studies of the relationship between cognition and functioning in bipolar disorder are scarce, although cognition is thought to be a key determinant of functioning. The causal structure between cognition and psychosocial functioning in bipolar disorder is unknown. AIMS: We sought to examine the direction of causality between cognitive performance and functional outcome over 2 years in a large cohort of euthymic patients with bipolar disorder. METHOD: The sample consisted of 272 adults diagnosed with bipolar disorder who were euthymic at baseline, 12 and 24 months. All participants were recruited via the FondaMental Advanced Centers of Expertise in Bipolar Disorders. We used a battery of tests, assessing six domains of cognition at baseline and 24 months. Residual depressive symptoms and psychosocial functioning were measured at baseline and 12 and 24 months. The possible causal structure between cognition and psychosocial functioning was investigated with cross-lagged panel models with residual depressive symptoms as a covariate. RESULTS: The analyses support a causal model in which cognition moderately predicts and is causally primary to functional outcome 1 year later, whereas psychosocial functioning does not predict later cognitive performance. Subthreshold depressive symptoms concurrently affected functioning at each time of measure. CONCLUSIONS: Our results are compatible with an upward causal effect of cognition on functional outcome in euthymic patients with bipolar disorder. Neuropsychological assessment may help specify individual prognoses. Further studies are warranted to confirm this causal link and evaluate cognitive remediation, before or simultaneously with functional remediation, as an intervention to improve functional outcome.

Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study.

BACKGROUND: As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention. METHODS: For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion. RESULTS: Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment. CONCLUSIONS: The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.

Probing regional cortical excitability via input-output properties using transcranial magnetic stimulation and electroencephalography coupling.

The modular organization of the cortex refers to subsets of highly interconnected nodes, sharing specific cytoarchitectural and dynamical properties. These properties condition the level of excitability of local pools of neurons. In this study, we described TMS evoked potentials (TEP) input-output properties to provide new insights into regional cortical excitability. We combined robotized TMS with EEG to disentangle region-specific TEP from threshold to saturation and describe their oscillatory contents. Twenty-two young healthy participants received robotized TMS pulses over the right primary motor cortex (M1), the right dorsolateral prefrontal cortex (DLPFC) and the right superior occipital lobe (SOL) at five stimulation intensities (40, 60, 80, 100, and 120% resting motor threshold) and one short-interval intracortical inhibition condition during EEG recordings. Ten additional subjects underwent the same experiment with a realistic sham TMS procedure. The results revealed interregional differences in the TEPs input-output functions as well as in the responses to paired-pulse conditioning protocols, when considering early local components (<80 ms). Each intensity in the three regions was associated with complex patterns of oscillatory activities. The quality of the regression of TEPs over stimulation intensity was used to derive a new readout for cortical excitability and dynamical properties, revealing lower excitability in the DLPFC, followed by SOL and M1. The realistic sham experiment confirmed that these early local components were not contaminated by multisensory stimulations. This study provides an entirely new analytic framework to characterize input-output relations throughout the cortex, paving the way to a more accurate definition of local cortical excitability.

Deep brain stimulation of the subthalamic nucleus in obsessive-compulsives disorders: long-term follow-up of an open, prospective, observational cohort.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a major cause of disability in western country and responsible for severe impairment of quality of life. About 10% of patients present with severe OCD symptoms and require innovative treatment such as deep brain stimulation (DBS). Among possible targets, the non-motor subthalamic nucleus (STN) is a key node of the basal ganglia circuitry, strongly connected to limbic cortical areas known to be involved in OCD. METHOD: We analysed, in a prospective, observational, monocentric, open label cohort, the effect of chronic non-motor STN-DBS in 19 patients with treatment-resistant OCD consecutively operated in a single centre. Severity of OCD was evaluated using the Yale and Brown Obsessive-Compulsive Scale (YBOCS). YBOCS scores at 6, 12 and 24 months postoperatively were compared with baseline. Responders were defined by >35% improvement of YBOCS scores. Global Assessment Functioning (GAF) scale was used to evaluate the impact of improvement. RESULTS: At a 24-month follow-up, the mean YBOCS score improved by 53.4% from 33.3±3.5 to 15.8±9.1 (95% CI 11.2-20.4; p<0.0001). Fourteen out of 19 patients were considered as responders, 5 out of 19 being improved over 75% and 10 out of 19 over 50%. GAF scale improved by 92% from 34.1±3.9 to 66.4±18.8 (95% CI 56.7-76.1; p=0.0003). The most frequent adverse events consisted of transient DBS-induced hypomania and anxiety. CONCLUSION: Chronic DBS of the non-motor STN is an effective and relatively safe procedure to treat severe OCD resistant to conventional management.

Allostatic load, emotional hyper-reactivity, and functioning in individuals with bipolar disorder.

OBJECTIVES: Diagnosis and management of bipolar disorder (BD) are limited by the absence of available biomarkers. Allostatic load (AL) represents the strain that stress, including the effects of acute phases and inter-episode chronic mood instability, exerts on interconnected biological systems. This study aimed to operationalize an AL index and explore whether it could be relevant to better characterize BD patients with and without emotional hyper-reactivity particularly those at higher risk of immune-cardiometabolic dysregulation and functional impairment. METHODS: Levels of biomarkers of chronic inflammation (hsCRP and albumin), cardiovascular (systolic/diastolic blood pressure) and metabolic functions (fasting glucose, glycosylated hemoglobin, total cholesterol, LDL, HDL, and triglycerides) were measured in 1072 adult BD outpatients. Patients were classified in two groups (with/without emotional hyper-reactivity) assessed by the Multidimensional Assessment of Thymic States scale. An Allostatic Load Index for BD (BALLI), comprising six biomarkers, was constructed using data-driven biomarker selection. RESULTS: BALLI showed 81.1% accuracy with good sensitivity (81%) and specificity (81.2%) for characterizing BD patients presenting emotional hyper-reactivity, elevated risk of inflammation (increased hsCRP, hypoalbuminemia) and cardiometabolic disturbances (hypertension, hyperglycemia, and hypertriglyceridemia). Patients classified by the BALLI as presenting emotional hyper-reactivity had significantly lower global and cognitive functioning than those without emotional hyper-reactivity (P < .0001). CONCLUSIONS: A multidimensional approach based on a simple AL score (eg, BALLI) and dimensions of behavior (eg, emotional hyper-reactivity) alongside mood is clinically relevant. AL index could be a useful tool to detect multisystemic physiological dysregulations in BD patients with/without emotional hyper-reactivity particularly those at higher risk of immune-cardiometabolic disturbances and functional impairment.

Childhood maltreatment and clinical severity of treatment-resistant depression in a French cohort of outpatients (FACE-DR): One-year follow-up.

BACKGROUND: Childhood maltreatment is associated with major depressive disorder (MDD). It not only increases the risk of lifetime MDD, but it also aggravates its course. Among depressed patients, 20-30% of them experience treatment-resistance depression (TRD). We aimed to assess the association between childhood maltreatment, severity of depression in a unipolar TRD sample, and patient outcomes after one-year of follow-up. METHODS: Patients were recruited for a prospective cohort from the French network of TRD expert centers. Depressive symptom severity was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology self-report (QIDS-SR). Childhood maltreatment was evaluated with the Childhood Trauma Questionnaire (CTQ). RESULTS: In total, 256 patients filled in the CTQ at baseline between 2012 and 2019. At baseline, the MADRS score was associated with CTQ score (ß = .185; p = .004). QIDS was also associated with CTQ scores (ß = .27; p < .001). Regarding the different subtypes of childhood maltreatment, MADRS was associated with physical (ß = .21; p = .005) and sexual abuse (ß = .22; p = .002), while QIDS with physical abuse (ß = .304; p < .001) and physical neglect (ß = .254; p < .001). However, we did not find any significant association focusing on the other types of traumas. During a 1-year follow-up focusing on remission, CTQ scores (baseline) were less important in remittent patients [n = 38; CTQ score = 39.26 (9.68)] than in nonremittent ones [n = 92; CTQ score = 46.02 (17.53)] (p = .027). There was no significant difference among remitters and nonremitters based on trauma subtypes. At baseline, CTQ scores had a significant influence on remission at 1 year (χ2 (1) = 5.57; p < .05). We lost this influence adding MADRS scores at baseline in the model (p = .063). CONCLUSION: We highlighted a significant association between the severity of depressive disorders and childhood maltreatment in the TRD population. Information about a history of childhood maltreatment helps in identifying individuals who could be less likely to go into remission after treatment.

Prevalence and determinants of cognitive impairment in the euthymic phase of bipolar disorders: results from the FACE-BD cohort.

BACKGROUND: Cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, but risk factors associated with cognitive deficits in euthymic BD are still poorly understood. We aimed to validate classification criteria for the identification of clinically significant cognitive impairment, based on psychometric properties, to estimate the prevalence of neuropsychological deficits in euthymic BD, and identify risk factors for cognitive deficits using a multivariate approach. METHODS: We investigated neuropsychological performance in 476 euthymic patients with BD recruited via the French network of BD expert centres. We used a battery of tests, assessing five domains of cognition. Five criteria for the identification of neuropsychological impairment were tested based on their convergent and concurrent validity. Uni- and multivariate logistic regressions between cognitive impairment and several clinical and demographic variables were performed to identify risk factors for neuropsychological impairment in BD. RESULTS: One cut-off had satisfactory psychometric properties and yielded a prevalence of 12.4% for cognitive deficits in euthymic BD. Antipsychotics use were associated with the presence of a cognitive deficit. CONCLUSIONS: This is the first study to validate a criterion for clinically significant cognitive impairment in BD. We report a lower prevalence of cognitive impairment than previous studies, which may have overestimated its prevalence. Patients with euthymic BD and cognitive impairment may benefit from cognitive remediation.

Decisional impulsivity and the associative-limbic subthalamic nucleus in obsessive-compulsive disorder: stimulation and connectivity.

Why do we make hasty decisions for short-term gain? Rapid decision-making with limited accumulation of evidence and delay discounting are forms of decisional impulsivity. The subthalamic nucleus is implicated in inhibitory function but its role in decisional impulsivity is less well-understood. Here we assess decisional impulsivity in subjects with obsessive compulsive disorder who have undergone deep brain stimulation of the limbic and associative subthalamic nucleus. We show that stimulation of the subthalamic nucleus is causally implicated in increasing decisional impulsivity with less accumulation of evidence during probabilistic uncertainty and in enhancing delay discounting. Subthalamic stimulation shifts evidence accumulation in subjects with obsessive-compulsive disorder towards a functional less cautious style closer to that of healthy controls emphasizing its adaptive nature. Thus, subjects with obsessive compulsive disorder on subthalamic stimulation may be less likely to check for evidence (e.g. checking that the stove is on) with no difference in subjective confidence (or doubt). In a separate study, we replicate in humans (154 healthy controls) using resting state functional connectivity, tracing studies conducted in non-human primates dissociating limbic, associative and motor frontal hyper-direct connectivity with anterior and posterior subregions of the subthalamic nucleus. We show lateralization of functional connectivity of bilateral ventral striatum to right anterior ventromedial subthalamic nucleus consistent with previous observations of lateralization of emotionally evoked activity to right ventral subthalamic nucleus. We use a multi-echo sequence with independent components analysis, which has been shown to have enhanced signal-to-noise ratio, thus optimizing visualization of small subcortical structures. These findings in healthy controls converge with the effective contacts in obsessive compulsive disorder patients localized within the anterior and ventral subthalamic nucleus. We further show that evidence accumulation is associated with anterior associative-limbic subthalamic nucleus and right dorsolateral prefrontal functional connectivity in healthy controls, a region implicated in decision-making under uncertainty. Together, our findings highlight specificity of the anterior associative-limbic subthalamic nucleus in decisional impulsivity. Given increasing interest in the potential for subthalamic stimulation in psychiatric disorders and the neuropsychiatric symptoms of Parkinson's disease, these findings have clinical implications for behavioural symptoms and cognitive effects as a function of localization of subthalamic stimulation.

Stimulation of subgenual cingulate area decreases limbic top-down effect on ventral visual stream: A DBS-EEG pilot study.

Deep brain stimulation (DBS) of the subgenual cingulate gyrus (area CG25) is beneficial in treatment resistant depression. Though the mechanisms of action of Cg25 DBS remain largely unknown, it is commonly believed that Cg25 DBS modulates limbic activity of large networks to achieve thymic regulation of patients. To investigate how emotional attention is influenced by Cg25 DBS, we assessed behavioral and electroencephalographic (EEG) responses to an emotional Stroop task in 5 patients during ON and OFF stimulation conditions. Using EEG source localization, we found that the main effect of DBS was a reduction of neuronal responses in limbic regions (temporal pole, medial prefrontal and posterior cingulate cortices) and in ventral visual areas involved in face processing. In the dynamic causal modeling (DCM) approach, the changes of the evoked response amplitudes are assumed to be due to changes of long range connectivity induced by Cg25 DBS. Here, using a simplified neural mass model that did not take explicitly into account the cytoarchitecture of the considered brain regions, we showed that the remote action of Cg25 DBS could be explained by a reduced top-down effective connectivity of the amygdalo-temporo-polar complex. Overall, our results thus indicate that Cg25 DBS during the emotional Stroop task causes a decrease of top-down limbic influence on the ventral visual stream itself, rather than a modulation of prefrontal cognitive processes only. Tuning down limbic excitability in relation to sensory processing might be one of the biological mechanisms through which Cg25 DBS produces positive clinical outcome in the treatment of resistant depression.

Associations between residual depressive symptoms, cognition, and functioning in patients with euthymic bipolar disorder: results from the FACE-BD cohort.

BackgroundThe relationship between residual depressive symptoms, cognition and functioning in patients with euthymic bipolar disorder is a subject of debate.AimsTo assess whether cognition mediates the association between residual depressive symptoms and functioning in patients with bipolar disorder who were euthymic.MethodWe included 241 adults with euthymic bipolar disorder in a multicentre cross-sectional study. We used a battery of tests to assess six cognition domains. A path analysis was then used to perform a mediation analysis of the relationship between residual depressive symptoms, cognitive components and functioning.ResultsOnly verbal and working memory were significantly associated with better functioning. Residual depressive symptoms were associated with poorer functioning. No significant relationship was found between residual depressive symptoms and any cognitive component.ConclusionsCognition and residual depressive symptoms appear to be two independent sources of variation in the functioning of people with euthymic bipolar disorder.

Cognitive profiles in euthymic patients with bipolar disorders: results from the FACE-BD cohort.

OBJECTIVES: Although cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, little is known about cognitive phenotype heterogeneity among patients with BD. METHODS: We investigated neuropsychological performance in 258 euthymic patients with BD recruited via the French network of expert centers for BD. We used a test battery assessing six domains of cognition. Hierarchical cluster analysis of the cross-sectional data was used to determine the optimal number of subgroups and to assign each patient to a specific cognitive cluster. Subsequently, subjects from each cluster were compared on demographic, clinical functioning, and pharmacological variables. RESULTS: A four-cluster solution was identified. The global cognitive performance was above normal in one cluster and below normal in another. The other two clusters had a near-normal cognitive performance, with above and below average verbal memory, respectively. Among the four clusters, significant differences were observed in estimated intelligence quotient and social functioning, which were lower for the low cognitive performers compared to the high cognitive performers. CONCLUSIONS: These results confirm the existence of several distinct cognitive profiles in BD. Identification of these profiles may help to develop profile-specific cognitive remediation programs, which might improve functioning in BD.

Emotional reactivity, functioning, and C-reactive protein alterations in remitted bipolar patients: Clinical relevance of a dimensional approach.

OBJECTIVES: Inter-episode mood instability has increasingly been considered in bipolar disorder. This study aimed to investigate emotional reactivity as a major dimension for better characterizing remitted bipolar patients with subthreshold mood symptoms and functional status. This study also aimed to investigate whether high-sensitivity C-reactive protein, a marker of low-grade inflammation, could be a biological marker of emotional dysregulation in bipolar disorder (BD). METHODS: Cross-sectional study of 613 subjects who met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for BD recruited from the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort from 2009 to 2014. All patients had been in remission for at least 3 months before assessment. Patients were classified into three groups according to levels of emotional reactivity. Emotional reactivity was assessed by using the Multidimensional Assessment of Thymic States, and functional status was assessed by the Functioning Assessment Short Test. Clinical characteristics and blood sample were collected from all patients. RESULTS: In total, 415 (68%) patients had abnormal emotional reactivity. Independent of potential confounders, including age, gender and subthreshold mood symptoms, serum levels of high-sensitivity C-reactive protein were significantly higher in patients with emotional hyper-reactivity (median = 4.0 mg/L, interquartile range = 2.7-5.6), and with emotional hypo-reactivity (median = 3.0 mg/L, interquartile range = 1-4) compared with patients with normal emotional reactivity (median = 0.95 mg/L, interquartile range = 0.4-1.9, p < 0.001). Patients with emotional hyper-reactivity showed significant cognitive functioning impairment ( p < 0.001). CONCLUSIONS: Emotional reactivity appears to be a relevant dimension for better characterizing remitted bipolar patients with subthreshold mood symptoms. Levels of high-sensitivity C-reactive protein may be an objective marker of emotional dysregulation in BD. Further studies are needed to confirm our findings.

[Cyamemazine (Tercian®): Exploration of extrapyramidal syndrome cases contained in the French pharmacovigilance database]. / Cyamémazine (Tercian®) et syndromes extrapyramidaux : exploration des cas contenus dans la base nationale de pharmacovigilance.

PURPOSE: Cyamemazine (Tercian®) is currently the most widely prescribed neuroleptic in France. This widespread use is due to its anxiolytics properties and to a claimed good safety profile. Although, prescription of cyamemazine is not devoid of the risks associated with the use of neuroleptics: extrapyramidal syndromes. This study aims at describing extrapyramidal syndromes induced by cyamemazine registered in the French pharmacovigilance database. METHODS: All spontaneous reports of extrapyramidal syndromes in the French pharmacovigilance database between 1st January 1985 and 31th December 2015 were described and analyzed. RESULTS: During this period 132 cases following cyamemazine intake were reported in the French pharmacovigilance database. The extrapyramidal syndromes were considered as "serious" in 77% of cases. More than 80% of the cases were described with a dosage of cyamemazine under 100mg/day and no correlation between drug dose and seriousness of the cases were found. Thirty-six cases were described with a monotherapy of cyamemazine. CONCLUSION: We should keep in mind that despite its widespread use in various indications (e.g. anxiolytic) cyamemazine remains a neuroleptic and could induce extrapyramidal syndromes even with low dosage. Careful monitoring should be performed when introducing and with long-term use of cyamemazine, mostly in elderly patients or patient already being treated with neuroleptics.

Bipolar patients referred to specialized services of care: Not resistant but impaired by sub-syndromal symptoms. Results from the FACE-BD cohort.

OBJECTIVE: A national network of expert centers for bipolar disorders was set up in France to provide support, mainly for psychiatrists, who need help for managing bipolar disorder patients. The aims of this article are to present the main characteristics of the patients referred to an expert center in order to highlight the major disturbances affecting these patients and to understand the most significant difficulties encountered by practitioners dealing with bipolar disorder patients. METHODS: Patients were evaluated by trained psychiatrists and psychologists, with standardized and systematic assessment using interviews and self-report questionnaires. RESULTS: All patients (n = 839) met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for bipolar disorder I (48.4%), bipolar disorder II (38.1%) or bipolar disorder-not otherwise specified (13.5%). Mean illness duration was 17 years (±11.3), with 41.9% of patients having a history of suicide attempts. Lifetime comorbidities were 43.8% for anxiety disorders and 32.8% for substance abuse. At the point of inclusion, most patients (76.2%) were not in an acute phase, being considered to have a syndromal remission, but which still required referral to a tertiary system of care. Among these patients, 37.5% had mild to moderate residual depressive symptoms (Montgomery and Asberg Depression Rating Scale ranging from 7 to 19) despite 39% receiving an antidepressant. However, 47.8% were considered to be poorly adherent to medication; 55% showed evidence of sleep disturbances, with half being overweight; 68.1% of patients showed poor functioning (Functioning Assessment Short Test ⩾ 12) with this being linked to residual depressive symptoms, sleep disturbances and increased body mass index. CONCLUSIONS: It appears that bipolar disorder patients referred to an expert center in most cases do not suffer from a severe or resistant illness but they rather have residual symptoms, including subtle but chronic perturbations that have a major impact on levels of functioning. The longitudinal follow-up of these patients will enable a better understanding of the evolution of such residual symptoms.

Experience Feedback Committee: a management tool to improve patient safety in mental health.

BACKGROUND: A management tool, called the Experience Feedback Committee, has been applied for patient safety and successfully used in medical departments. The purpose of this study was to analyse the functioning of an Experience Feedback Committee in a psychiatric department and to explore its contribution to the particular issues of patient safety in mental health. METHODS: We conducted a descriptive study based on all the written documents produced by the Experience Feedback Committee between March 2010 and January 2013. The study was conducted in Grenoble University Hospital in France. We analysed all reported incidents, reports of meetings and event analysis reports. Adverse events were classified according to the Conceptual Framework for the International Classification for Patient Safety. RESULTS: A total of 30 meetings were attended by 22 professionals including seven physicians and 12 paramedical practitioners. We identified 475 incidents reported to the Experience Feedback Committee. Most of them (92 %) had no medical consequence for the patient. Eleven incidents were investigated with an analysis method inspired by civil aviation security systems. Twenty-one corrective actions were set up, including eight responses to the specific problems of a mental health unit, such as training to respond to situations of violence or management of suicide attempts. CONCLUSIONS: The Experience Feedback Committee makes it possible to involve mental healthcare professionals directly in safety management. This tool seems appropriate to manage specific patient safety issues in mental health.

Changes of oscillatory brain activity induced by repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex in healthy subjects.

Repetitive transcranial magnetic stimulation (rTMS) modulates brain activity in different ways according to the stimulation parameters. Although the after-effects of rTMS over motor cortex are well documented in healthy individuals, less is known about the stimulation of dorso-lateral prefrontal cortex (DLPFC). Here, we studied in 20 healthy subjects how cortical oscillations are modulated by four different active rTMS protocols (1Hz, 10Hz, continuous and intermittent theta bursts - cTBS and iTBS) of the left DLPFC, and by a sham protocol used as a control condition, by comparing the spectral power of pre- and post-rTMS electroencephalographic (EEG) recordings of 15min duration. EEG spectrum was estimated with the fast Fourier transform (FFT) and partitioned using the common physiological frequency bands: delta (1-4Hz), theta (3.5-7Hz), alpha (7.5-13Hz), low beta (14-22Hz), high beta (22-30Hz) and gamma (30-45Hz). Statistical analyses of EEG changes induced by rTMS were computed with Statistical Parametric Mapping (SPM) for EEG, in every frequency band, at the scalp level and at the cortex level. We found for every active protocol a significant decrease of delta and theta power on left prefrontal electrodes, mainly localised in the left DLPFC. In higher frequency bands (beta and gamma), the decrease of power in the DLPFC was also observed contralaterally. Protocol-specific amplitude effects were found in the prefrontal cortex bilaterally in all frequency bands, but also in parietal and temporal regions in low EEG frequencies. In high frequencies, EEG power in the prefrontal cortex increased after rTMS for 10Hz and iTBS protocols, but this effect did not survive the comparison to Sham responses. Because large delta and theta activity is usually associated with cortical inhibition, observed rTMS-induced EEG changes in low frequencies suggest that rTMS of DLPFC transiently decreases local cortical inhibition. Importantly, local responses take place in association with other unknown mechanisms that modulate inter-hemispheric connectivity between homologous regions, resulting in the increase or decrease of fast activity in each prefrontal lobe, depending on the stimulation protocol. Only decreases of fast activity following active rTMS could be detected as significant when compared to Sham stimulation.