Search

Recent literature concerning attention-deficit/hyperactivity disorder (ADHD) underlines the persistence of this neurodevelopmental illness in older patients. Comorbidity with a neurodegenerative disease is thus possible. However, few studies have investigated this topic. To our knowledge, this is the first case report of such a possible association, which raises important questions about clinical presentation, symptoms, diagnosis, and treatment. A 72-year-old man, without any psychiatric history, presented with depression, subjective memory loss, and attention deficit and anxious symptoms, and was diagnosed with mild neurocognitive disorder due to Alzheimer's disease. However, the patient's attentional symptoms appeared to have been present since childhood. A formalized diagnostic interview assessing for ADHD did not allow for a clear diagnosis, possibly due to recall bias. The patient's anxiety symptoms also did not respond well to cognitive behavioral therapy coupled with different antidepressants. We hypothesized the presence of ADHD, with the symptoms balanced until now by the patient's high cognitive capacities, and we postulated that the onset of a neurogenerative process may have disrupted this balance. In this case report, we discuss symptom dimensionality, the interplay between neurodegenerative and neurodevelopmental diseases, and various treatment options. Attentional deficits and anxiety symptoms are frequent in mild neurocognitive disorders due to neurodegenerative illnesses. It is important to explore the time of onset of such symptoms since neurodegenerative processes can worsen neurodevelopmental conditions. Moreover, identification of a pre-existing neurodevelopmental condition can lead to alternative care and treatment options. In addition, the unexplained worsening of ADHD symptoms should prompt clinicians to assess for a neurodegenerative process.

Psychosocial rehabilitation (PSR) is a practice focused on recovery of the personal processes in which the elderly subject works to maintain his autonomy for as long as possible, and to remain in control of his life and his decisions. The belief that once old, the person loses his ability to act, is often linked to cognitive biases and can have negative impacts on recovery. Indeed, compared to adults, the elderly subject is doubly stigmatized, both by mental disorders and the consequences of aging. Thus, the geriatric population requires, in the recovery process, to take into account the specificities related to aging. Moreover, PSR must go beyond the control of symptoms and aim to improve the quality of life and well-being. We thus propose to describe in this article the RPS tools adapted to the psychiatry of the elderly subject.La réhabilitation psychosociale (RPS) est une pratique axée sur le rétablissement des processus personnels dans lesquels le sujet âgé chemine pour maintenir son autonomie le plus longtemps possible, et rester maitre de sa vie et de ses décisions. La croyance qu'une fois âgée, la personne perd de sa capacité à agir, est souvent liée à des biais cognitifs et peut avoir des impacts négatifs sur le rétablissement. En effet, par rapport à l'adulte, le sujet âgé est doublement stigmatisé, à la fois par les troubles mentaux, et les conséquences du vieillissement. Ainsi, la population gériatrique nécessite, dans le processus de rétablissement, une prise en compte des spécificités liées au vieillissement. Par ailleurs, la RPS doit aller au-delà de la maîtrise des symptômes et viser l'amélioration de la qualité de vie et du bien-être. Nous proposons ainsi de décrire dans cet article les outils de RPS adaptés à la psychiatrie du sujet âgé.

The ‘Frontotemporal dementia–Amyotrophic lateral sclerosis Spectrum’ (FAS) encompasses different phenotypes, including cognitive disorders (frontotemporal dementia, FTD) and/or motor impairments (amyotrophic lateral sclerosis, ALS). The aim of this study was to apprehend the specific uses of neurofilaments light chain (NfL) and phosphorylated neurofilaments heavy chain (pNfH) in a context of FAS. First, NfL and pNfH were measured in 39 paired cerebrospinal fluid (CSF) and plasma samples of FAS and primary psychiatric disorders (PPD) patients, considered as controls. Secondly, additional plasma samples were included to examine a larger cohort of 81 samples composed of symptomatic FAS and PPD patients, presymptomatic and non-carrier relatives individuals. The measures were performed using Simoa technology. There was a positive correlation between CSF and plasma values for NfL (p

Background: Facial emotion recognition (FER) and gaze direction (GD) identification are core components of social cognition, possibly impaired in many psychiatric or neurological conditions. Regarding Alzheimer’s disease (AD), current knowledge is controversial. Objective: The aim of this study was to explore FER and GD identification in mild AD compared to healthy controls. Methods: 180 participants with mild AD drawn from the PACO study and 74 healthy elderly controls were enrolled. Participants were asked to complete three socio-cognitive tasks: face sex identification, recognition of facial emotions (fear, happiness, anger, disgust) expressed at different intensities, and GD discrimination. Multivariate analyses were conducted to compare AD participants and healthy controls. Results: Sex recognition was preserved. GD determination for subtle deviations was impaired in AD. Recognition of prototypically expressed facial emotions was preserved while recognition of degraded facial emotions was impacted in AD participants compared to controls. Use of multivariate analysis suggested significant alteration of low-expressed fear and disgust recognition in the AD group. Conclusion: Our results showed emotion recognition and GD identification in patients with early-stage AD compared to elderly controls. These impairments could be the object of specific therapeutic interventions such as social cognition remediation or raising awareness of primary caregivers to improve the quality of life of patients with early AD.

Schizophrenia is associated with early neurodevelopmental disorders, including most frequently learning disorders (LD), among them dyslexia and dyspraxia. Despite the demonstrated links between schizophrenia and LD, specific clinical patterns of the schizophrenia with a history of LD subgroup remain unknown. The aim of the present study was to investigate cognitive impairment, symptoms and functional outcome associated with a history of LD in a large cross-sectional, multicentric, sample of schizophrenia subjects. 492 community-dwelling subjects with schizophrenia (75.6% male, mean age 30.8 years) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. The 51 (10.4%) subjects identified with a history of LD had significantly impaired general cognitive ability (Wechsler Adult Intelligence Scale Full Scale Total IQ: Cohen's d = 0.50, p = 0.001), processing speed (d = 0.19), verbal comprehension (d = 0.29), working memory (d = 0.31), cognitive inhibition and flexibility (d = 0.26), central executive functioning (d = 0.26), phonemic verbal fluency (d = 0.22) and premorbid intellectual ability (d = 0.48), as well as with a worse functional outcome (Global Assessment of Functioning, d = 0.21), independently of age, sex, education level, symptoms, treatments, and addiction comorbidities. These results indicate that a history of LD is associated with later cognitive impairment and functional outcome in schizophrenia. This suggests that history of LD is a relevant clinical marker to discriminate subgroups of patients with schizophrenia with different profiles in a precision psychiatry framework.

International audience; Background: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes.Aim: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life.Methods: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits.Results: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235(41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR =2.141, p = 0.021), severe nicotine dependence (aOR =2.906, p < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR =2.297, p = 0.001), positive symptoms (aOR =1.052, p = 0.006), current major depressive episode (aOR =2.627, p < 0.001), sleep disorders (aOR =1.474, p = 0.024) and lower medication adherence (aOR =0.836, p = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder.Interpretation: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia.

International audience; Background: Peripheral inflammation is associated with impaired prognosis in schizophrenia (SZ). Highly sensitive C-reactive protein (hs-CRP) is the most used inflammatory biomarker in daily practice. However, no consensual cut-off has been determined to date to discriminate patients with peripheral inflammation from those without.Aims: To determine if patients with peripheral inflammation between 1 and 3 mg/L had poorer outcomes compared to those with undetectable CRP ( 1 mg/L is a reliable marker to detect peripheral inflammation in patients with schizophrenia.

Cross-sectional studies highlighted changes in autonomic nervous system (ANS) activity in geriatric depression. However, few longitudinal studies assessed this link which remains still debated. We examined the longitudinal association between lifetime depression history, current depressive disorders, and the evolution of ANS activity in older community women.The present data stemmed from the PROOF study, a population-based cohort of 1011 community-dwellers followed-up at 2-year intervals for 10 years. Only data from female participants was analyzed (n = 508, mean age 68.5 ± 0.88 years), as very few men had depression in our population. Depressive symptoms and depression history were collected at baseline. Participants were classified in four groups according to presence or absence of history of depression (HD) or current depressive symptomatology (CD): HD+/CD+, HD-/CD+, HD+/CD- and HD-/CD-. ANS activity was assessed during the follow-up through 24-h heart rate variability (HRV). Longitudinal associations between depressive status and HRV indices during the follow-up were investigated using multivariate linear mixed models.Compared to HD-/CD- group, women belonging to HD-/CD+ group had greater baseline parasympathetic tone, as measured by lower LF index and LF/HF balance. The longitudinal analysis exhibited a significant enhancement of LF/HF balance with time, measuring an increase of sympathetic tone in HD-/CD+ group.Our findings suggest that late-onset depressive symptoms may be associated with subsequent autonomic dysregulation in older women. These results highlight the importance of detecting and managing depressive symptoms to limit their consequences on ANS functioning, and the risk of cardiovascular events.

The prevalence of paradoxical reactions to benzodiazepines is estimated to be approximately 1% in the general population. The semiology can be very varied, diverse and misleading. Advanced age as well as cognitive disorders are classically described in the literature as risk factors for developing paradoxical reactions. However, this literature review only identified a limited number of articles focusing on the elderly and only one article on patients with neurocognitive disorders. This paradoxical situation raises questions as to whether these are unpublished clinical observations or whether the elderly population is really at risk, especially patients with neurocognitive disorders. Semiology can be confused with underlying neurocognitive disorders. Paradoxical reactions are ultimately only rarely or not evoked, leading to a very high risk of iatrogeny. It is therefore important to be aware of these paradoxical effects in order to be able to evoke them rapidly. The most striking semiological element would be the suddenness of onset of self-aggressive or hetero-aggressive behaviours.

Objectives To estimate the attributable fraction of nursing home placement associated with cognitive impairment, neuropsychiatric symptoms, behavioral disorders, functional limitations, and caregiver burden. Design Longitudinal study conducted on the “MEMORA cohort” linked with both regional public health insurance and hospital discharge databases. Setting Memory center at the University Hospital of Lyon, France. Participants A sample of 2456 outpatients attending the memory center between 2012 and 2017. Measures Cognitive impairment, functional limitations, neuropsychiatric symptoms/behavioral disorders, and caregiver burden were measured with the Mini-Mental State Examination, the Instrumental Activities of Daily Living scale, the Neuropsychiatric Inventory (NPI), and a short version of the Zarit Burden Inventory, respectively. Sociodemographics characteristics were collected during the first visit. Comorbidities were gathered from the hospital discharge database. Dates of nursing home placement were obtained from the public health insurance database. Results More than 38% of nursing home placements were attributable to caregiver burden, and the attributable fraction associated with functional limitations exceeded 35%. Between 20% and 25% of nursing home placements were due to cognitive impairment whereas less than 16% were attributable to neuropsychiatric symptoms or behavioral disorders. The associations between anxiety or agitation and nursing home placement were mediated by caregiver burden. Apathy or aberrant motor behaviors were associated with a higher risk of nursing home placement independently of caregiver burden. Conclusions/Implications Our findings suggest that a high proportion of nursing home placements are attributable to caregiver burden and functional limitations in outpatients attending a memory center. Cognitive impairment and neuropsychiatric symptoms or behavioral disorders contribute less to nursing home placements. Interventions directed to delay nursing home placement should emphasize actions toward reducing caregiver burden and functional limitations of patients.

International audience; BACKGROUND: People with dementia (PWD) and their caregivers are populations highly vulnerable to COVID-19 pandemic and its consequences. A better knowledge of the living conditions during the first lockdown is necessary to prevent the risk of poor mental health (PMH) in this population. OBJECTIVE: The present study aimed to compare the mental health of caregivers of PWD living at home or in nursing-homes and to identify specific factors influencing their mental health. METHODS: We conducted an anonymous cross-sectional online survey in France from March 17 to May 11, 2020. Three hundred and eighty-nine caregivers accompanying a PWD living at home (HC) and 159 accompanying a PWD living in a nursing home (NHC) participated in the study. Caregivers' mental health including anxiety, depression, stress, and burden was assessed with self-reported standardized scales. RESULTS: Half of the caregivers exhibited PMH, including depression, anxiety, or self-reported stress. Similar PMH rates were provided whatever the PWD place of residence. Regarding HC, our results also highlighted a number of risk factors for PMH, including the fact that caregiver live with PWD, to give increased support to PWD, and to feel more isolated for managing PWD since lockdown. CONCLUSION: PMH was observed for caregivers of PWD during lockdown, whatever PWD living place, suggesting that concern for PWD may explain more of caregiver distress than increased material tasks. In the future, it will be necessary to pay attention to caregivers after the crisis by estimating the longer-term impact on their mental health.

The 'Frontotemporal dementia-Amyotrophic lateral sclerosis Spectrum' (FAS) encompasses different phenotypes, including cognitive disorders (frontotemporal dementia, FTD) and/or motor impairments (amyotrophic lateral sclerosis, ALS). The aim of this study was to apprehend the specific uses of neurofilaments light chain (NfL) and phosphorylated neurofilaments heavy chain (pNfH) in a context of FAS.First, NfL and pNfH were measured in 39 paired cerebrospinal fluid (CSF) and plasma samples of FAS and primary psychiatric disorders (PPD) patients, considered as controls. Secondly, additional plasma samples were included to examine a larger cohort of 81 samples composed of symptomatic FAS and PPD patients, presymptomatic and non-carrier relatives individuals. The measures were performed using Simoa technology.There was a positive correlation between CSF and plasma values for NfL (p 0.0001) and for pNfH (p = 0.0036). NfL values were higher for all phenotypes of symptomatic FAS patients compared to PPD patients (p = 0.0016 in CSF; p = 0.0003 in plasma). On the contrary, pNfH values were solely increased in FAS patients exhibiting motor impairment. Unlike symptomatic FAS patients, presymptomatic cases had comparable concentrations with non-carrier individuals.NfL, but not pNfH, appeared to be useful in a context of differential diagnosis between FTD and psychiatric patients. Nevertheless, pNfH seem more specific for the diagnosis and follow-up of motor impairments. In each specific indication, measures in CSF and plasma will provide identical interpretations.

Opioid analgesic (OA) addiction occurs frequently among the elderly, and results in high morbidity and mortality due to geriatric pathologies associated with pharmacokinetic modifications. However, patients with this type of addiction are under-identified and specific screening tools should be more widely used to detect the risk factors for OA addiction. Before initiating an opioid prescription, exhaustive research into associated treatments (to track drug interaction) and opioid prescriptions by other clinicians (a phenomenon known as "doctor shopping") is required. Specific specialist care, as has been developed in the United States, is still scarce in France and treatment is provided through collaboration between geriatricians and psychiatrists. Optimisation of the treatment of somatic and psychiatric comorbidities is key to effective management.

The serotonin syndrome is a potentially deadly complication resulting from drug adverse effect, drug-drug interaction or overdose involving one or more serotonergic molecules, e.g., antidepressants, psychostimulants and sometimes an "ignored" serotonergic compound. The serotonin syndrome typically consists of a clinical triad including cognitive/behavioral, neurovegetative and neuromuscular features. However, this syndrome is characterized by major clinical heterogeneity, making the diagnosis difficult in practice. Moreover, many practitioners are quite unaware of this syndrome. Available scores and classifications can help physicians in their diagnosis approach. Knowing the responsible molecules, their potential interactions and mechanisms of action can help preventing this complication allowing therapeutic education among patients. This updated article reviews the clinical presentation, prevention, management, and pathophysiology of the serotonin syndrome, and addresses the most recent advances in pharmacogenetics regarding this syndrome.

International audience; Introduction: Deficits in theory of mind (ToM) can vary depending on the predominant schizophrenia symptoms, and though most neurocognitive functions are involved in ToM, all may not be associated with the same symptoms. With consideration to the relationships between symptoms, neurocognition and ToM, the aim of the present study is to identify the neurocognitive functions influencing ToM capacities according to symptomatic profile. Methods: The study is based on a sample of 124 adults with schizophrenia from a French national cohort. Patients were divided into two groups according to their scores on the five Wallwork factors of the Positive and Negative Syndrome Scale using hierarchical clustering before carrying out multivariable analyses. Results: The “disorganised group” (n = 89) showed high scores on the disorganised factor, and had a ToM associated with reasoning, visual recognition and speed of processing. The “positive group” (n = 35) showed high scores on the positive and depressive factors, and had a ToM associated with working memory. Conclusions: These results suggest that neurocognitive predictors of ToM in schizophrenia are different according to the predominant clinical dimension, thus refining our knowledge of the relationship between symptoms, neurocognition and ToM, and acknowledging their status as important predictors of patients’ functional status. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

In schizophrenia, altered transcription in brain and peripheral tissues may be due to altered expression of the microRNA biogenesis machinery genes. In this study, we explore the expression of these genes both at the cerebral and peripheral levels. We used shinyGEO application to analyze gene expression from ten Gene Expression Omnibus datasets, in order to perform differential expression analyses for eight genes encoding the microRNA biogenesis machinery. First, we compared expression of the candidate genes between control subjects and individuals with schizophrenia in postmortem cerebral samples from seven different brain regions. Then, we compared the expression of the candidate genes between control subjects and individuals with schizophrenia in three peripheral tissues. In brain and peripheral tissues of individuals with schizophrenia, we report distinct altered expression patterns of the microRNA biogenesis machinery genes. In the dorsolateral prefrontal cortex, associative striatum and cerebellum of individuals with schizophrenia, we observed an overexpression pattern of some candidate genes suggesting a heightened miRNA production in these brain regions. Additionally, mixed transcriptional abnormalities were identified in the hippocampus. Moreover, in the blood and olfactory epithelium of individuals with schizophrenia, we observed distinct aberrant transcription patterns of the candidate genes. Remarkably, in individuals with schizophrenia, we report DICER1 overexpression in the dorsolateral prefrontal cortex, hippocampus and cerebellum as well as a congruent DICER1 upregulation in the blood compartment suggesting that it may represent a peripheral marker. Transcriptional disruption of the miRNA biogenesis machinery may contribute to schizophrenia pathogenesis both in brain and peripheral tissues.

International audience; Objective: Existing staging models have not been fully validated. Thus, after classifying patients with schizophrenia according to the staging model proposed by McGorry et al. (2010), we explored the validity of this staging model and its stability after one-year of follow-up.Method: Using unsupervised machine-learning algorithm, we classified 770 outpatients into 5 clinical stages, the highest being the most severe. Analyses of (co)variance were performed to compare each stage in regard to socio-demographics factors, clinical characteristics, co-morbidities, ongoing treatment and neuropsychological profiles.Results: The precision of clinical staging can be improved by sub-dividing intermediate stages (II and III). Clinical validators of class IV include the presence of concomitant major depressive episode (42.6% in stage IV versus 3.4% in stage IIa), more severe cognitive profile, lower adherence to medication and prescription of >3 psychotropic medications. Follow-up at one-year showed good stability of each stage.Conclusion: Clinical staging in schizophrenia could be improved by adding clinical elements such as mood symptoms and cognition to severity, relapses and global functioning. In terms of therapeutic strategies, attention needs to be paid on the factors associated with the more stages of schizophrenia such as treatment of comorbid depression, reduction of the number of concomitant psychotropic medications, improvement of treatment adherence, and prescription of cognitive remediation.

While the literature regarding the existence of difficulties in inhibition in schizophrenia is relatively consistent, it is not clear whether these difficulties reflect any specific deficit in an inhibitory control process or whether they are the result of deficits in the systems that regulate inhibitory control, such as attentional resources. This also raises the issue of attentional resources in schizophrenia, which offers a somewhat puzzling and sometimes contradictory picture. In this study, these issues were investigated by means of a paradigm in which the need for inhibitory control and the need for correct allocation of attentional resources varied parametrically. Twenty-six outpatients with a diagnosis of schizophrenia and 26 matched controls completed a visual search task during which distractors were presented and had to be inhibited. At the same time, they also completed an auditory target detection task of varying difficulty. The results show that the patients had difficulties both in inhibiting distractors and in correctly allocating attention to the two tasks. The results also show that these two difficulties were not related. This leads to the conclusion that schizophrenia involves both defective inhibitory control and faulty management of attentional resources, and that the former does not result from the latter. Furthermore, these effects seem to be neither dependent on processing speed, nor related to medication.

INTRODUCTION Pain is underdiagnosed and undertreated in patients with Alzheimer's disease (AD). Pain management is of major importance in this population to limit behavioural and functional consequences. Our study aimed to assess the capacity of AD patients to represent pain using a questionnaire exploring daily painful situations and to determine the most appropriate pain scale assessment. METHODS Twenty-eight patients with mild AD, 21 with moderate AD and 28 matched controls underwent the Situation Pain Questionnaire (SP-Q) and assessed imaginary pain with four pain scales. Two scores were compared between the three groups: the P(A) discrimination score and the response bias β score. P(A) reflects the degree of discrimination between high-pain and low-pain events, whereas the β score means the degree to which situations are considered as painful. RESULTS Our results showed that AD patients hardly discriminated the high- from low-pain events. Compared to controls, the mean P(A) score was significantly lower for Mild AD (p

Background In schizophrenia, abnormal synaptic pruning during adolescence may be due to altered expression of the Complement component 4 (C4). Overexpression of C4 genes has been identified in the total cerebral cortex and in 6 different brain regions of schizophrenic patients compared to controls. These alterations should be replicated and extended to other brain regions relevant to schizophrenia. Moreover, it remains unknown whether cerebral and peripheral C4 expression levels are related. Methods We explored C4 genes expression both at the cerebral and peripheral levels. Using shinyGEO application we analyzed C4 expression from eight Gene Expression Omnibus datasets obtained from 196 schizophrenic patients and 182 control subjects. First, we compared C4 expression between schizophrenic patients and controls in postmortem cerebral samples from 7 different brain regions. Then, we compared C4 expression between schizophrenic patients and controls in 4 peripheral tissues. Results At the cerebral level, we provide further evidence of C4 overexpression in schizophrenic patients. Consistently with a previous report, we found C4 overexpression in the dorsolateral prefrontal cortex and in the parietal cortex of schizophrenic patients. The observation of C4 overexpression was further extended to the superior temporal cortex and the associative striatum of schizophrenic patients. Conversely, no significant alteration of C4 expression was observed in peripheral tissues. Conclusions Our results support the hypothesis of an excessive Complement activity in various brain regions of schizophrenic patients which may disrupt the synaptic pruning process occurring during adolescence. C4 overexpression may be specific to the cerebral tissue while other alterations of the Complement system may be detected at the systemic level.

Background Although electroconvulsive therapy (ECT) is a highly effective, safe, and well-tolerated antidepressant treatment for late-life depression (LLD), there is large variability in response rates across individuals. We hypothesized that these variations would be in part explained by the level of vascular risk in this population. We therefore compared response rates to ECT in patients with LLD presenting with or without vascular risk factors (VRF). Methods 52 patients with LLD (age > 55) who received a course of ECT were separated into 2 groups according to the presence of VRF (n = 20) or not (n = 32). Framingham score (10-year risk for developing a coronary heart disease) was calculated for each patient. Our primary outcome was the number of responders to ECT in each group (defined as at least 50% decrease of the Montgomery–Asberg Depression Rating Scale score following ECT course). Scores at the self-rated Beck Depression Inventory are also reported. Results Patients with VRF presented significant lower response rates to ECT (12 out of 20; 60%) than patients without VRF (30 out of 32; 94%; p = 0.004). A negative correlation was found between Framingham score and changes in depression scores pre/post ECT (r = -0.42; p = 0.0039). Limitations Our study was limited by sample size and retrospective design. Conclusion Patients with LLD and VRF showed lower response rates to ECT than those without VRF. The more the VRF increased, the less the antidepressant effect of ECT was observed. Results are discussed in light of the role of apathy in clinical response to ECT.

Background Behavioral and psychological symptoms of dementia (BPSD) are frequent and troublesome for patients and caregivers. Considering possible preventive approaches, a better understanding of underlying neural correlates of BPSD is crucial. Objective The aim is to assess whether brain regional volume predicts behavioral changes in mild AD. Methods This work took part from the PACO study, a multicenter and prospective study that included 252 patients with mild AD from 2009 to 2014. Fifty-three patients were retained. Forty healthy matched control subjects from the ADNI cohort were included as controls. Voxel-based morphometry analysis was conducted to assess regional brain volume using baseline MRI scans as a predictor of future behavioral changes over a period of 18 months. Behavior was assessed at baseline and longitudinally at 6-month intervals using the shortened form of the Neuropsychiatric Inventory (NPI). Results The volume of 23 brain structures in frontal, temporal, parietal, occipital, subcortical regions and cerebellum predicted the evolution of NPI scores. Frontal volume was the most powerful predictor with frontal gyri, anterior cingulate cortex, and orbital gyri being particularly involved. Conclusion To our knowledge, this is the first study assessing regional brain volumes as predictors of behavioral changes considered at earlier stages of AD. Up to 23 brain structures were associated with an increased risk of developing BPSD. Frontal lobe volume was the strongest predictor of future evolution of NPI. The involvement of multiple structures in the prediction of behavior suggests a role of the main large-scale networks involved in cognition.

Objective To compare the clinical symptomatology in patients with Early‐Onset Schizophrenia (EOS, N = 176), especially the subgroup Very Early Onset Schizophrenia (VEOS) and Adult Onset Schizophrenia (AOS, N = 551). Method In a large French multicentric sample, 727 stable schizophrenia patients, classified by age at onset of the disorder, were assessed using standardized and extensive clinical and neuropsychological batteries: AOS with onset ≥ 18 years and EOS with onset, To describe schizophrenia from childhood to adulthood is complex and patients with early‐onset schizophrenia (EOS) remain undiagnosed or misclassified, especially the subgroup with very early‐onset schizophrenia (VEOS). In patients with VEOS, the DUP which exceeds 8 years, almost eight times higher than in patients with AOS, objective the problem of early diagnosis and the need to develop diagnostic programs and management cares.

International audience; Background Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. Method The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. Results The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. Conclusion These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

BACKGROUND The 2008-2012 French Alzheimer's Plan has provided hospital Cognitive and Behavioral Units (CBU) to improve the management of patients with productive behavioral and psychological symptoms of dementia (BPSD). Little is known concerning the behavioral outcome of these patients after discharge. OBJECTIVE The present study investigated the long-term evolution of BPSD over one year after CBU discharge. METHODS The EVITAL cohort included 221 participants admitted to the CBUs of 3 French hospitals. BPSD were collected using the Neuropsychiatric Inventory (NPI) at admission and 3, 6, and 12 months after hospitalization. The global NPI score evolution was assessed using a linear mixed-effect model. A four-factor model of the NPI including behavioral dyscontrol, psychosis, mood, and agitation subscores was also analyzed. RESULTS Our analysis focused on 148 patients followed up during 12 months and evaluated at each visit. The global NPI score was 48.5 (SD 21.7) at baseline, 28.8 (SD 18.7) at 3-month, 23.2 (SD 16.4) at 6-month and 20.9 (SD 15.9) at 12-month follow-up. The score significantly decreased from baseline to follow-up (F = 109.3 p

Background A link between personality traits and cognitive performance has been shown in normal adults and elderly individuals. Very few studies have evaluated this link in Alzheimer's disease (AD). Objective To better understand cognitive performance as regards to personality traits, our study was aimed to evaluate the role of premorbid personality on cognitive functioning in a population of patients presenting prodromal or mild AD. Methods 181 elderly with prodromal or mild AD participated in a cross-sectional, prospective cohort study. The participants completed a personality inventory and a neuropsychological battery exploring memory, attention, executive function, language, and praxis. Cognitive performance were compared according to the level of each personality trait, using multivariate MANOVA models. Results A higher level of neuroticism was associated with lower performance at similarities test (D = 9.49, p = 0.003), delayed Free and Cued Selective Reminding test (D = 5.22, p = 0.02), and digit span score (D = 7.99, p = 0.006). A higher level of openness was related to better performance at similarities (D = 4.33, p = 0.04), letter fluency (D = 11.45, p = 0.001), and category fluency test (D = 5.85, p = 0.02). Neuroticism interfered negatively with cognitive functioning at the prodromal stage; the association between openness and cognitive function was observed at both prodromal and mild AD stage. Conclusion These results suggest that personality traits, in particular neuroticism and openness, modulate cognitive abilities in patients with early AD. These results encourage the development of stress management programs to prevent its negative effects on cognitive aging.

Objective: The present report aims to evaluate whether singing intervention can bring an immediate benefit that is greater than the one provided by painting intervention on pain and well-being. Methods: Fifty-nine mild patients with Alzheimer disease were randomized to a 12-week singing (n = 31) or painting group (n = 28). In the present analysis, the immediate evolution of pain and well-being was compared across sessions between the 2 groups using mixed-effects models. Results: We observed a significant improvement in well-being for both singing and painting groups immediately after sessions, compared to the assessment before the sessions. We did not observe this improvement across the sessions for pain intensity measurement. Discussion: Our results revealed that both painting and singing interventions provide an immediate benefit on the patients’ well-being.

Background Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. Method Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians’ opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. Results The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. Conclusion The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations. Electronic supplementary material The online version of this article (10.1186/s12888-019-2237-x) contains supplementary material, which is available to authorized users.

OBJECTIVE: Medication nonadherence is one of the most important, and potentially modifiable, prognostic factors in the outcome of patients with schizophrenia. The aim of this article is to propose a new classification of adherence profiles according to the Medication Adherence Rating Scale (MARS) in a large community-dwelling sample of French patients with schizophrenia to provide a new tool to help clinicians in daily practice. METHODS: 319 community-dwelling patients from a national network of 10 Schizophrenia Expert Centers were interviewed between January 2009 and January 2014. Assessments were conducted with a dedicated electronic medical record including the Structured Clinical Interview for DSM-IV Disorders. A cluster analysis was performed to explore clinical variables associated with poor adherence. RESULTS: Two distinct groups of patients were identified relative to their main adherence style. Items about medications' subjective negative effects constituted the greatest discriminating factor between the 2 clusters. Patients with poor adherence (n = 117) were significantly younger (adjusted OR [aOR] = 1.036; 95% CI, 1.004-1.069) and had higher levels of current depression (aOR = 0.894; 95% CI, 0.829-0.964) and lower insight (aOR = 0.820; 95% CI, 0.693-0.970). CONCLUSIONS: The MARS provides a useful tool for clinicians and can also aid in the evaluation of adherence styles and their determinants in patients with schizophrenia. The element providing the greatest discriminative power between the 2 clusters was a subjective negative attitude toward medication. The findings also suggest that depression is more frequent in schizophrenia patients with poor adherence and that improving insight into illness might be suggested as a first-line intervention to improve adherence in this population.

International audience; INTRODUCTION:The primary objective of this study was to determine if second-generation antipsychotic (SGA) administration was associated with lower aggressiveness scores compared to first-generation (FGA) in schizophrenia (SZ). The secondary objective was to determine if antidepressants, mood stabilizers, and benzodiazepines administration were respectively associated with lower aggressiveness scores compared to patients who were not administered these medications.METHODS:Three hundred thirty-one patients with schizophrenia (N = 255) or schizoaffective disorder (N = 76) (mean age = 32.5 years, 75.5 % male gender) were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with the structured clinical interview for DSM-IV Axis I disorders and validated scales for psychotic symptomatology, insight, and compliance. Aggressiveness was measured by the Buss-Perry Aggression Questionnaire (BPAQ) score. Ongoing psychotropic treatment was recorded.RESULTS:Patients who received SGA had lower BPAQ scores than patients who did not (p = 0.01). More specifically, these patients had lower physical and verbal aggression scores. On the contrary, patients who received benzodiazepines had higher BPAQ scores than patients who did not (p = 0.04). No significant difference was found between BPAQ scores of patients respectively being administered mood stabilizers (including valproate), antidepressant, and the patients who were not. These results were found independently of socio-demographical variables, psychotic symptomatology, insight, compliance into treatment, daily-administered antipsychotic dose, the way of antipsychotic administration (oral vs long acting), current alcohol disorder, and daily cannabis consumption.CONCLUSION:The results of the present study are in favor of the choice of SGA in SZ patients with aggressiveness, but these results need further investigation in longitudinal studies. Given the potent side effects of benzodiazepines (especially dependency and cognitive impairment) and the results of the present study, their long-term prescription is not recommended in patients with schizophrenia and aggressive behavior.

Background Alzheimer's disease (AD) mainly occurs in elderly individuals. Comorbidities and chronic pain are frequent in this population. Previous studies revealed that personality modulates both chronic pain (CP) andADoccurrence and evolution. Moreover, as pain treatments can induce side-effects, non-drugs treatments, such as art interventions, are interesting alternative therapies for decreasing CP in these patients. Objective Our aim was to assess the potential role of personality traits on art intervention efficacy for reducing CP in a population of patients with mild AD. Methods Design: multicenter randomized controlled trial. Fifty mild AD patients underwent a 12-week art intervention including singing and painting groups. Personality was assessed with the Big Five Inventory before the sessions. CP was measured with Numeric Rating Scale (NRS) [Usual pain (NRS-U) and most Intense pain (NRS-I)], Simple Visual Scale [Usual pain (SVS-U) and most Intense pain (SVS-I)] and Brief Pain Inventory (BPI) before and after the sessions. The influence of personality traits on CP evolution before and after art intervention was assessed with multiple linear regression models. Results A positive association was observed between neuroticism and the evolution of three CP measures including NRS-U (B = 0.34, p = 0.01), SVS-U (B = 0.20, p = 0.04), and BPI-U (B = 0.46, p = 0.02) evolution. No significant relationship was observed between neuroticism and NRS-I, SVS-I and BPI-R evolution. Conclusions Our findings suggest that neuroticism can decrease the efficacy of group art intervention on pain in patients with mild AD. Individual therapies could be more appropriate for these patients. These results emphasize the interest of taking into account patients' personality before proposing them to participate to a group therapy.

Dementia with Lewy bodies (DLB) is a common neurodegenerative disease, second in terms of prevalence after Alzheimer's disease (AD). DLB may be suspected according to three core features which are cognitive and motor fluctuations, early visual hallucinations and parkinsonism; and more recently, according to the new criteria, REM sleep behavior disorder (RBD). Behavorial and psychological symptoms associated with DLB are more frequent, more severe and appear earlier than those found in other neurodegenerative diseases. They may be at the forefront and are a major diagnostic and therapeutic challenge. An improved knowledge of the pathophysiology and phenomenology associated to these symptoms can facilitate their identification as well as eliminating differential diagnoses. Managing these symptoms may require drugs when hallucinations are overwhelming and induce behavorial disorders. However, psychotropic medications are not well tolerated in this specific population and some antipsychotic drugs cannot be prescribed due to their side effects. Although further studies are needed on this subject, non-interventional treatments such as therapeutic strategies based on the patients and their caregivers appear to be essential. This paper offers a review which aims to help clinicians to identify behavioral and psychological symptoms in DLB and treat them in their daily practice.

International audience; INTRODUCTION: There is a lack of data on health care consumption of patients suffering from schizophrenia, as well as on the related health care costs. Factors associated with health care costs have not been widely studied, whereas knowledge on this topic would allow identifying risk factors and delineating strategies to improve patients' health and follow-up, likely to also decrease health care costs. The aim of this study was to estimate the average direct health care cost of patients with schizophrenia in France and to identify the factors associated with this cost. METHODS: The study population included patients with schizophrenia enrolled in the FondaMental Advanced Centers of Expertise for Schizophrenia cohort. We accounted for the costs directly related to the treatment of schizophrenia. They included the costs of hospitalizations (full- and part-time), psychiatric ambulatory consultations and medications. We studied three categories of factors potentially associated with direct health care costs: demographic, socioeconomic and clinical characteristics. RESULTS: Three hundred and ninety five patients with schizophrenia were included. The mean (median) annual direct health care cost per patient amounted to \texteuro14,995 (\texteuro3,435). A lower level of functioning and being single were associated with a higher cost. A significant association between the expert center of inclusion and the direct health care cost of schizophrenia was also highlighted. CONCLUSION: Our results highlighted the significant cost of schizophrenia and suggest that improvement in patient care, based on well-validated targeted therapeutic interventions such as psycho-education and cognitive rehabilitation, could reduce worsening in symptom severity and therefore decrease health care costs.

Objective Predicting relapse is a major challenge in schizophrenia from a clinical and medico-economic point of view. During recent decades, major psychiatric disorders have been found to be extensively associated with metabolic disorders, even before the illness onset, with a prevalence estimated to be 35% in this population. However, no study to date has, to our knowledge, explored the potential impact of metabolic syndrome (MetS) on relapse. Methods From 2010 to 2016, 185 patients (mean age = 32 years) with a DSM-IV-TR diagnosis of schizophrenia were included in the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) cohort and followed up for 1 year. Multivariable logistic regression was performed to estimate the adjusted odds ratio for relapse. Results Thirty-seven percent of stabilized outpatients with schizophrenia (mean illness duration = 11 years) experienced a relapse at least once during the 1 year of follow-up. MetS strongly predicted relapse at 1 year, independently of illness severity, insight into illness, and treatment characteristics (including medication compliance). Patients with MetS at baseline had a 3 times higher risk (95% CI, 1.1-8.4) of experiencing a new episode of psychosis during the 12 months of follow-up. Conclusions Further studies should determine if reducing or preventing MetS could help to protect subjects with schizophrenia from relapse.

BACKGROUND Previous studies showed that a third of patients living at home entered an institution after hospitalization in Cognitive and Behavioral Units (CBUs). OBJECTIVE The main objective of this study was to identify predictors of discharge destination for these patients. The secondary objective was to estimate whether institutionalization can have an impact on a patient's long-term prognosis. METHODS The study population was selected from the EVITAL study and included 140 participants living at home before hospitalization in CBUs. Factors favoring nursing-home admission were investigated and the impact of discharge destinations (i.e., home or nursing home) on patients' prognosis was examined. RESULTS Institutionalized patients were more likely to be women (F = 4.7; p = 0.03), with a higher dementia severity (F = 9.82; p = 0.007), often living alone (F = 19.69; p = 0.001), with a caregiver other than spouse (F = 8.93; p = 0.003), and with a higher patient quality of life (QoL) according to the caregiver (F = 11.73; p = 0.001). When using multivariate logistic linear regressions, we showed a relationship between marital status (OR = 0.19, 95% CI: 0.08-0.43, p

Although Bipolar Disorder (BD) often affects young subjects, the number of elderly patients suf- fering from BD is rising as life expectancy increases. Few studies addressed the hospitalisation characteristics according to patient age. The goal of this preliminary study was to compare the hospitalisation characteristics of young and elderly patients suffering from BD admitted in a psy- chiatric hospital. The data were selected from the French nation-wide hospital database for psy- chiatry. The study included patients hospitalised in a French psychiatric hospital from January 2002 to December 2012. The hospitalisation characteristics were compared between young (YBD) and elderly bipolar patients (EBD). A total of 1842 patients were hospitalised during the 11-year period. Among them, 707 (38.4%) were 60 years old and over. The mean length of stay was signif- icantly longer for the EBD group than for the YBD group (48.1 vs 30.4 days, p < 0.0001). Among the patients first hospitalised in 2002, the readmission rate was significantly higher for the EBD (67.9%) than for the YBD (55.2%) group (p = 0.026). In contrast, the rate of compulsory hospitali- sations was higher among the YBD than among the EBD group. Our findings confirm that BD in old age remains a severe disease requiring longer hospitalisations than for BD in younger patients. Future prospective studies are needed to better understand the origin of these differences.