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Background. Self-stigma is a major issue in serious mental illness (SMI) and is negatively associated with patient outcomes. Most studies have been conducted in schizophrenia (SZ). Less is known about self-stigma in other SMI and autism spectrum disorder (ASD). The objectives of this study are: (i) to assess the frequency of self-stigma in a multicentric nonselected psychiatric rehabilitation SMI and ASD sample; and (ii) to investigate the correlates of elevated self-stigma in different SMI conditions and in ASD. Methods. A total of 738 SMI or ASD outpatients were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluations included sociodemographic data, illness characteristics, and standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, personal recovery, a large cognitive battery, and daily functioning assessment. Results. 31.2%of the total sample had elevated self-stigma. The highest prevalence (43.8%) was found in borderline personality disorder and the lowest (22.2%) in ASD. In the multivariate analysis, elevated self-stigma was best predicted by early stages of personal recovery (moratorium, p = 0.001, OR = 4.0 [1.78-8.98]; awareness, p = 0.011, OR = 2.87 [1.28-6.44]), history of suicide attempt (p = 0.001, OR = 2.27 [1.37-3.76]), insight (p = 0.002, OR = 1.22 [1.08-1.38]), wellbeing (p = 0.037, OR = 0.77 [0.60-0.98]), and satisfaction with interpersonal relationships (p < 0.001, OR = 0.85 [0.78-0.93]). Conclusions. The present study has confirmed the importance of addressing self-stigma in SMI and ASD patients enrolled in psychiatric rehabilitation. The effectiveness of psychiatric rehabilitation on self-stigma and the potential mediating effects of changes in self-stigma on treatment outcomes should be further investigated. [ABSTRACT FROM AUTHOR]

Nowadays, rural tourism is one of the important aspects of economic, social, cultural and environmental activities of human community that have a so many positive and negative effects on human's life and is appreciable based on effects on accessing to sustainable development. Thus, the purpose of this study is, measuring the sustainable development level in tourism destination rural of Darb Gonbad rural district (Koohdasht province) from the local community attitude. This practical study is based on descriptive- annalistic methodology and had been used of document and field study method through of questionnaires for data gathering. The statistical approach (sample T-test, regression and path analyze) had been used for analyzing the collected data. Sample community of this survey calculated 3751people in the villages that with 0.05 errors, 154 questioners had been designed and randomly filled by sample community. The results of study explain that the changes become meaningful and become up than moderate level. Also, there is the positive relation between all of aspect (economic, social, cultural, environmental and physical) so the statistical tests result show that in totally, economic effects are most effective and environmental effects are less effective aspect in rural destinations sustainable development. In final, for ranking the rural sustainability had been used of VICOR technique that based that, Darb Gonbad village with 0.11 lay in best position and Baghleh Sofla village with 0.87 laid in worse condition of sustainability. [ABSTRACT FROM AUTHOR]

Background: The present study evaluated the therapeutic efficacy and tolerability of 10 transcranial direct current stimulation (tDCS) sessions in treatment-resistance obsessive-compulsive disorder (OCD) patients using a multisite double-blind sham-controlled design., Methods: Eighty treatment-resistance outpatients suffering from obsessive-compulsive disorder were randomized to receive either active or sham transcranial direct current stimulation. The cathode was positioned over the supplementary motor area and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment (day 14), one-month follow-up (day 45), and three-month follow-up (day 105) on the Yale-Brown Obsessive Compulsive Scale., Results: Although a significant interaction between time and treatment was observed, the primary endpoint-measuring the change in Yale-Brown obsessive compulsive scale scores after two weeks-was not achieved. Conversely, the secondary endpoint, which concerned the change in Yale-Brown obsessive compulsive scale scores after three months, was successfully met. It is important to note, however, that there were no significant differences in the percentage of responders and remitters at any of the post-treatment assessments. This suggests that the treatment may not have had a clinically relevant impact. Patients well received the transcranial direct current stimulation treatment, indicating its good tolerability., Conclusion: This is the largest controlled trial using transcranial direct current stimulation in treatment-resistance obsessive-compulsive disorder patients. Our results indicate the importance of studying the placebo effect in transcranial direct current stimulation and the necessity to consider a long follow-up time to best evaluate the effects of the intervention., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03304600., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Harika-Germaneau, Heit, Drapier, Sauvaget, Bation, Chatard, Doolub, Wassouf, Langbour and Jaafari.)

Resistance to punishment is commonly used to measure the difficulty in refraining from rewarding activities when negative consequences ensue, which is a hallmark of addictive behavior. We recently developed a progressive shock strength (PSS) procedure in which individual rats can titrate the amount of punishment that they are willing to tolerate to obtain food rewards. Here, we investigated the effects of a range of delays (0-12 s) on resistance to punishment measured by PSS break points. As expected from delay discounting principles, we found that delayed shock was less effective as a punisher, as revealed by higher PSS breakpoints. However, this discounting effect was not equally distributed in the population of rats, and the introduction of a delay highlighted the existence of two populations: rats that were sensitive to immediate punishment were also sensitive to delayed shock, whereas rats that were resistant to immediate punishment showed strong temporal discounting of delayed punishment. Importantly, shock-sensitive rats suppressed responding even in subsequent non-punishment sessions, and they differed from shock-resistant rats in anxiety-like behavior, but not in sensitivity to pain. These results show that manipulation of temporal contingencies of punishment in the PSS procedure provides a valuable tool to identify individuals with a double vulnerability to addiction: low sensitivity to aversion and excessive discounting of negative future consequences. Conversely, the shock-sensitive population may provide a model of humans who are vulnerable to opportunity loss due to excessive anxiety., (© 2024. The Author(s).)

The current scientific literature has extensively explored the potential role of proteasome inhibitors (PIs) in the NF-κB pathway of leukemia and lymphoma. The ubiquitin-proteasome system (UPS) is a critical component in regulating protein degradation in eukaryotic cells. PIs, such as BTZ, are used to target the 26S proteasome in hematologic malignancies, resulting in the prevention of the degradation of tumor suppressor proteins, the activation of intrinsic mitochondrial-dependent cell death, and the inhibition of the NF-κB signaling pathway. NF-κB is a transcription factor that plays a critical role in the regulation of apoptosis, cell proliferation, differentiation, inflammation, angiogenesis, and tumor migration. Despite the successful use of PIs in various hematologic malignancies, there are limitations such as resistant to these inhibitors. Some reports suggest that PIs can induce NF-κB activation, which increases the survival of malignant cells. This article discusses the various aspects of PIs' effects on the NF-κB pathway and their limitations. Video Abstract., (© 2024. The Author(s).)

Introduction: Alcohol use disorder (AUD) ranks among the most prevalent psychiatric disorders worldwide. Despite current treatments, more than half of patients relapse within weeks after treatment. In animal models, exposure to environmental enrichment (EE) has been shown to be a promising approach to reduce relapse. However, controlled, multimodal EE is difficult to transpose to humans. To address this gap, this study aims at assessing the effectiveness of exposure to a newly designed EE protocol during AUD treatment in reducing relapse to alcohol use. Our EE will allow an enhancement of the standard intervention, and will combine several promising enrichment factors identified in the literature-physical activity, cognitive stimulation, mindfulness and virtual reality (VR)., Methods and Analysis: A randomised controlled trial involving 135 participants receiving treatment for severe AUD will be conducted. Patients will be randomised to an intervention enhancement group or a control group. The enhanced intervention will consist of six 40-min sessions of EE spread over 9 days. During the first 20 min of these sessions, patients will practise mindfulness in multisensory VR, in virtual environments designed to practise mindfulness and use it to regulate craving induced by virtual cues or stress. Then, participants will practise indoor cycling combined with cognitive training exercises. The control group will undergo standard management for AUD. The primary outcome is relapse assessed at 2 weeks after treatment, using a questionnaire and biological indicators. Relapse will be defined as drinking at least five drinks per occasion or drinking at least five times a week. It is predicted that the group receiving the EE intervention will have a lower relapse rate than the control group. The secondary outcomes are relapse at 1 month and 3 months after treatment, craving and drug-seeking behaviour, mindfulness skills acquisition and the effect of the intervention enhancement on the perceived richness of the daily environment, assessed by questionnaires and neuropsychological tasks., Ethics and Dissemination: All participants have to give written informed consent to the investigator. This study is approved by the Ethics Committee Nord Ouest IV of Lille (reference number 2022-A01156-37). Results will be disseminated through presentations, peer-reviewed journals and seminar conferences. All information on ethical considerations and open science practices can be accessed at https://osf.io/b57uj/ TRIAL REGISTRATION NUMBER: NCT05577741., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Around 50% of the patients with obsessive-compulsive disorder (OCD) are resistant to treatment, and patients with OCD show alterations in a broad range of cognitive abilities. The present study investigated the links between treatment-resistance, executive and working memory abilities, and the severity of OCD symptoms among 66 patients with OCD. The patients performed seven tests gauging their executive functions and working memory and filled in questionnaires for OCD severity and insight into their pathology. In addition, the executive and working memory abilities of a subset of these patients were compared with those of individually matched control participants. In contrast with previous studies, patients' treatment resistance was evaluated by considering the clinical outcomes of all the treatments that they received during the course of their disease. Higher treatment resistance was associated with lower performance in one particular executive test, the Stroop test, which assessed patients' ability to inhibit prepotent/automatic responses. Older age and more severe OCD symptoms were also associated with higher treatment resistance. Regardless of OCD severity, the patients displayed small to moderate deficits across most components of executive functions compared to control participants. Interestingly, patients with OCD took more time than control participants to perform speeded neuropsychological tests but never made more errors. Altogether, this study shows that the treatment-resistance of patients with OCD may be reliably quantified over the course of years and treatments using Pallanti and Quercioli's (2006) treatment resistance-related scales. The data suggest that the Stroop test could be used clinically to anticipate treatment outcomes in to-be-treated patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Doolub, Vibert, Botta, Razmkon, Bouquet, Wassouf, Millet, Harika-Germaneau and Jaafari.)

The dysfunctional patterns of microstates dynamics in obsessive-compulsive disorder (OCD) remain uncertain. Using high-density electrical neuroimaging (EEG) at rest, we explored microstates deterioration in OCD and whether abnormal microstates patterns are associated with a dysregulation of the resting-state networks interplay. We used EEG microstates analyses, TESS method for sources reconstruction, and General Linear Models to test for the effect of disease severity on neural responses. OCD patients exhibited an increased contribution and decreased duration of microstates C and D, respectively. Activity was decreased in the Salience Network (SN), associated with microstate C, but increased in the Default Mode Network (DMN) and Executive Control Network (ECN), respectively, associated with microstates E and D. The hyperactivity of the right angular gyrus in the ECN correlated with the symptoms severity. The imbalance between microstates C and D invalidates the hypothesis that this electrophysiological pattern is specific to psychosis. Demonstrating that the SN-ECN dysregulation manifests as abnormalities in microstates C and D, we confirm that the SN deterioration in OCD is accompanied by a failure of the DMN to deactivate and aberrant compensatory activation mechanisms in the ECN. These abnormalities explain typical OCD clinical features but also detachment from reality, shared with psychosis., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is a lack of knowledge regarding the actionable key predictive factors of homelessness in psychiatric populations. Therefore, we used a machine learning model to explore the REHABase database (for rehabilitation database- n = 3416), which is a cohort of users referred to French psychosocial rehabilitation centers in France., Methods: First, we analyzed whether the different risk factors previously associated with homelessness in mental health were also significant risk factors in the REHABase. In the second step, we used unbiased classification and regression trees to determine the key predictors of homelessness. Post hoc analyses were performed to examine the importance of the predictors and to explore the impact of cognitive factors among the participants., Results: &nbsp;First, risk factors that were previously found to be associated with homelessness were also significant risk factors in the REHABase. Among all the variables studied with a machine learning approach, the most robust variable in terms of predictive value was the nature of the psychotropic medication (sex/sex relative mean predictor importance: 22.8, σ = 3.4). Post hoc analyses revealed that first-generation antipsychotics (15.61%; p < 0.05 FDR corrected), loxapine (16.57%; p < 0.05 FWER corrected) and hypnotics (17.56%; p < 0.05 FWER corrected) were significantly associated with homelessness. Antidepressant medication was associated with a protective effect against housing deprivation (9.21%; p < 0.05 FWER corrected)., Conclusions: Psychotropic medication was found to be an important predictor of homelessness in our REHABase cohort, particularly loxapine and hypnotics. On the other hand, the putative protective effect of antidepressants confirms the need for systematic screening of depression and anxiety in the homeless population.

Exosomes, known as a type of extracellular vesicles (EVs), are lipid particles comprising heterogeneous contents such as nucleic acids, proteins, and DNA. These bi-layered particles are naturally released into the extracellular periphery by a variety of cells such as neoplastic cells. Given that exosomes have unique properties, they can be used as vectors and carriers of biological and medicinal particles like drugs for delivering to the desired areas. The proteins and RNAs being encompassed by the circulating exosomes in B-cell malignancies are deemed as the promising sources for diagnostic and prognostic biomarkers, as well as therapeutic agents. Exosomes can also provide a "snapshot" view of the tumor and metastatic landscape at any particular time. Further, clinical research has shown that exosomes are produced by immune cells such as dendritic cells can stimulate the immune system, so these exosomes can be used in antitumor vaccines. Despite the great potential of exosomes in the fields of diagnostic and treatment, further studies are in need for these purposes to reach a convergence notion. This review highlights the applications of exosomes in multiple immune-related diseases, including chronic lymphocytic leukemia, multiple sclerosis, and arthritis rheumatoid, as well as explaining sundry aspects of exosome therapy and the function of exosomes in diagnosing diseases., (© 2022. The Author(s).)

Background: Schools are ideal for promoting the mental health of school-age children, but the teachers' current knowledge is insufficient to play an influential role in mental health services at schools. Fortunately, however, teachers have a high sense of responsibility, interest, and talent to receive knowledge and the ability to participate in this field. This study aimed to examine whether a protocol focused on the role of teachers could identify, guide, and care for school-age children with behavioral and mental health problems., Method: The current research was a "before and after" pilot quasi-experimental study conducted in three elementary, secondary, and high schools. The main intervention consisted of a 5-h workshop based on a ready-to-use booklet for teachers conducted separately in each school. A total of 58 teachers and 872 school-age children were included using a judgmental sampling technique., Results: The pre-and post-workshop mean scores of teachers' knowledge about common mental disorders in school-age children were 6.21 ± 4.58 and 12.50 ± 7.27, respectively. According to the Strengths and Difficulties Questionnaire (SDQ), the teachers made 127 referrals, of whom 102 school-age children had problems. Consultants diagnosed 114 school children who reflected 90% of all teachers' recommendations needing psychological care and counseling. Finally, only 50 diagnosed school-age children were followed up and attended therapy sessions at counseling centers. The sensitivity and specificity of this brief intervention in detecting school-age children with psychological problems were respectively 80.3 and 98.0%., Conclusions: This study's results support teacher empowerment training's effectiveness in identifying and guiding school-age children needing mental health care. Psychological counseling programs in schools in various quantitative and qualitative dimensions, including responding to school-age children's needs and psychological problems, should be adequately evaluated, and appropriate measures should be taken to promote mental health services. Collaboration between health systems and the education department will increase the effectiveness of mental health programs' promotion and drug abuse prevention. These pilot data lead the way to designing scientifically sound follow-up studies that will concretely ascertain the benefit of this program., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Afshari, Kaveh, Lankarani, Doolub, Jaafari and Ostovarfar.)

Aim: The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a trial. This assumption of additivity was tested by Kleijnen et al in 1994 but the data produced since then have not been synthetized. In this review, we aimed to systematically review the literature to determine whether additivity held., Methods: We searched Medline and PsychInfo up to 10 January 2019. Studies using the balanced placebo design (BPD), testing two different strengths of placebos, were included. The presence of interaction was evaluated by comparing each group in the BPD with analysis of variance or covariance., Results: Thirty studies were included and the overall risk of bias was high: four found evidence of additivity and 16 studies found evidence of interaction (seven had evidence of positive additivity)., Conclusion: Evidence of additivity between placebo and specific features of treatments was rare in included studies. We suggest interventions for placebo-sensitive ailments should be tested in trials designed to take interactions seriously once an exploratory RCTs has proven their efficacy with sufficient internal validity., (© 2022 British Pharmacological Society.)

Background: Cognitive impairments are prevalent in patients with unipolar and bipolar depressive disorder (UDD and BDD, respectively). Considering the fact assessing cognitive functions is increasingly feasible for clinicians and researchers, targeting these problems in treatment and using them at baseline as predictors of response to treatment can be very informative., Method: In a naturalistic, retrospective study, data from 120 patients (Mean age: 33.58) with UDD ( n = 56) and BDD ( n = 64) were analyzed. Patients received 20 sessions of bilateral rTMS (10 Hz over LDLPFC and 1 HZ over RDLPFC) and were assessed regarding their depressive symptoms, sustained attention, working memory, and executive functions, using the Beck Depression Inventory (BDI-II) and Neuropsychological Test Automated Battery Cambridge, at baseline and after the end of rTMS treatment course. Generalized estimating equations (GEE) and logistic regression were used as the main statistical methods to test the hypotheses., Results: Fifty-three percentage of all patients ( n = 64) responded to treatment. In particular, 53.1% of UDD patients ( n = 34) and 46.9% of BDD patients ( n = 30) responded to treatment. Bilateral rTMS improved all cognitive functions (attention, working memory, and executive function) except for visual memory and resulted in more modulations in the working memory of UDD compared to BDD patients. More improvements in working memory were observed in responded patients and visual memory, age, and sex were determined as treatment response predictors. Working memory, visual memory, and age were identified as treatment response predictors in BDD and UDD patients, respectively., Conclusion: Bilateral rTMS improved cold cognition and depressive symptoms in UDD and BDD patients, possibly by altering cognitive control mechanisms (top-down), and processing negative emotional bias., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rostami, Kazemi, Nasiri, Ataei, Hadipour and Jaafari.)

Background: Repetitive transcranial magnetic stimulation (rTMS) has proven to be an efficient treatment option for patients with treatment-resistant depression (TRD). However, the success rate of this method is still low, and the treatment outcome is unpredictable. The objective of this study was to explore clinical and structural neuroimaging factors as potential biomarkers of the efficacy of high-frequency (HF) rTMS (20 Hz) over the left dorso-lateral pre-frontal cortex (DLPFC)., Methods: We analyzed the records of 131 patients with mood disorders who were treated with rTMS and were assessed at baseline at the end of the stimulation and at 1 month after the end of the treatment. The response is defined as a 50% decrease in the MADRS score between the first and the last assessment. Each of these patients underwent a T1 MRI scan of the brain, which was subsequently segmented with FreeSurfer. Whole-brain analyses [Query, Design, Estimate, Contrast (QDEC)] were conducted and corrected for multiple comparisons. Additionally, the responder status was also analyzed using binomial multivariate regression models. The explored variables were clinical and anatomical features of the rTMS target obtained from T1 MRI: target-scalp distance, DLPFC gray matter thickness, and various cortical measures of interest previously studied., Results: The results of a binomial multivariate regression model indicated that depression type ( p = 0.025), gender ( p = 0.010), and the severity of depression ( p = 0.027) were found to be associated with response to rTMS. Additionally, the resistance stage showed a significant trend ( p = 0.055). Whole-brain analyses on volume revealed that the average volume of the left part of the superior frontal and the caudal middle frontal regions is associated with the response status. Other MRI-based measures are not significantly associated with response to rTMS in our population., Conclusion: In this study, we investigated the clinical and neuroimaging biomarkers associated with responsiveness to high-frequency rTMS over the left DLPFC in a large sample of patients with TRD. Women, patients with bipolar depressive disorder (BDD), and patients who are less resistant to HF rTMS respond better. Responders present a lower volume of the left part of the superior frontal gyrus and the caudal middle frontal gyrus. These findings support further investigation into the use of clinical variables and structural MRI as possible biomarkers of rTMS treatment response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Harika-Germaneau, Wassouf, Le Tutour, Guillevin, Doolub, Rostami, Delbreil, Langbour and Jaafari.)

In psychiatry, recent years have seen a change of focus from a clinician- to a patient-centered perspective that emphasizes quality of life as a treatment target. As a complex construct, quality of life is composed of multiple dimensions that interact with one-another (e.g. physical and psychological well-being, relationships, autonomy, self-esteem). Here, we used data from the REHABase cohort, which includes N = 2180 patients from 15 psychosocial rehabilitation centers in France, to explore networks of quality-of-life dimensions among six psychiatric disorders: schizophrenia, neurodevelopmental, bipolar, depressive, anxiety, and personality disorders. Stronger connections (edges) involved the Self-Esteem dimension, such as Self-Esteem-Physical Well-Being, Self-Esteem-Autonomy, Self-Esteem-Psychological Well-Being, and Self-Esteem-Resilience. Self-esteem was also consistently retrieved as the most central node (the dimension with the most connections within each network). Between-group tests did not reveal any differences regarding network structure, overall connectivity, edge-weights, and nodes' centrality. Despite presenting with different symptom profiles, various psychiatric disorders may demonstrate similar inter-relationships among quality-of-life dimensions. In particular, self-esteem may have a crucial inter-connecting role in patients' quality of life. Our findings could support treatment programmes that specifically target self-esteem to improve patients' quality of life in a cost-effective way., (© 2022. The Author(s).)

Background: Posttraumatic stress disorder (PTSD) has been hailed by some as the emblematic mental disorder of the COVID-19 pandemic, assuming that PTSD's life-threat criterion was met de facto. More plausible outcomes like adjustment disorder (AD) have been overlooked., Methods: An online cross-sectional survey was launched in the initial stage of the pandemic using a convenience sample of 5 913 adults to compare the prevalence of COVID-related probable PTSD versus probable AD. The abridged Impact of Event Scale - Revised (IES-6) assessed the severity of trauma- and stressor-related symptoms over the previous week. Demographic and pandemic-related data (e.g., receiving a formal diagnosis of COVID-19, job loss, loss of loved one, confinement, material hardship) were collected. A Classification and Regression Tree analysis was conducted to uncover the pandemic experiences leading to clinical 'caseness'. Caseness was defined by a score > 9 on the IES-6 symptom measure and further characterized as PTSD or AD depending on whether the Peritraumatic Distress Inventory's life-threat item was endorsed or not., Results: The participants were predominantly Caucasian (72.8%), women (79.2%), with a university degree (85%), and a mean age of 42.22 (SD = 15.24) years; 3 647 participants (61.7%; 95%CI [60.4, 63.0]) met the threshold for caseness. However, when perceived life-threat was accounted for, only 6.7% (95%CI [6.1, 7.4]) were classified as PTSD cases, and 55% (95%CI [53.7, 56.2]) as AD cases. Among the AD cases, three distinct profiles emerged marked by the following: (i) a worst personal pandemic experience eliciting intense fear, helplessness or horror (in the absence, however, of any life-threat), (ii) a pandemic experience eliciting sadness/grief, and (iii) worrying intensely about the safety of significant others., Conclusions: Studies considering the life-threat criterion as met de facto during the pandemic are confusing PTSD for AD on most counts. This misconception is obscuring the various AD-related idioms of distress that have emerged during the pandemic and the actual treatment needs., (© 2022. The Author(s).)

Background: The severity of symptoms represents an important source of distress in patients with a psychiatric disease. However, the extent to which this endogenous stress factor interacts with genetic vulnerability factors for predicting suicide risks remains unclear., Methods: We evaluated whether the severity of symptoms interacts with a genetic vulnerability factor (the serotonin transporter gene-linked promoter region variation) in predicting the frequency of lifetime suicide attempts in patients with a psychiatric disease. Symptom severity and 5-HTTLPR polymorphism were collected from a sample of 95 patients with obsessive-compulsive disorder (OCD). Lifetime suicide attempt was the primary outcome, and antecedent of multiple suicide attempts was the secondary outcome., Results: The gene-by-symptoms interaction was associated with an excess risk of suicide attempts (OR = 4.39, 95CI[1.44, 13.38], p < 0.009) and of multiple suicide attempts (OR = 4.18, 95CI[1.04, 16.77], p = 0.043). Symptom severity (moderate, severe, or extreme) was associated with an approximately five-fold increase in the odds of a lifetime suicide attempt in patients carrying one or two copies of the short allele of 5-HTTLPR. No such relationship was found for patients carrying the long allele., Conclusion: This study provides preliminary evidence for the gene-by-stress interaction on suicide attempt when stress is operationalized as symptom severity. Progress in suicide research may come from efforts to investigate the gene-by-symptoms interaction hypothesis in a variety of diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Harika-Germaneau, Lafay-Chebassier, Langbour, Thirioux, Wassouf, Noël, Jaafari and Chatard.)

(1) Background: Precarious patients are more difficult to care for due to low literacy rates and poor adherence to treatment and hospitalization. These difficulties have detrimental effects on general practitioners (GPs), deteriorating medical communication, advice, diagnoses, and drug prescriptions. To better understand how precariousness affects primary care, we tested whether, among GPs, exposure to high precariousness prevalence more severely impacts drug prescriptions to precarious and non-precarious populations compared to low precariousness prevalence. Materials and methods: This pharmaco-epidemiological study, using linear regression analyses, compared the defined daily dose of 20 drugs prescribed by GPs to precarious and non-precarious patients in four French regions with low and high precariousness prevalence in 2015. (2) Findings: Exposure to high precariousness prevalence significantly impacted the prescriptions of nine medications to precarious patients and two medications to non-precarious patients, and distributed into three interaction patterns. (3) Interpretation: The selective over-prescription of drugs with easy intake modalities to precarious patients probably reflects GPs' attempts to compensate for poor patient compliance. In contrast, the under-prescription of drugs targeting fungal infections in precarious populations and diabetes and cardiovascular diseases in non-precarious populations was seemingly due to a breakdown of empathy and professional exhaustion, causing medical neglect.

Background: Perception of treatment need (PTN), a component of clinical insight, is associated to negative addiction treatment outcomes when low. Our hypothesis was that lower PTN was associated with less craving when reported retrospectively, the most common measure of craving in clinical settings., Objective: To explore the association between PTN and craving among a dataset of subjects with severe substance use disorders., Methods: Participants were recruited from outpatient addiction clinic admissions or harm reduction program services. Good and low PTN were based on consistency between severe addiction (at least six DSM-5 criteria) and self-report need for addiction treatment from the Addiction Severity Index. Craving was retrospectively characterized over the past 30 days. Multiple regression analyses were conducted., Results: Participants with low PTN ( n = 97) retrospectively reported less frequent and intense episodes of craving, compared with participants with good PTN ( n = 566) after controlling for sociodemographic factors, addiction type, and severity ( p < 0.0001)., Conclusion: Low perception of treatment need among subjects with severe addictions is associated to less retrospective report of craving, which may contribute to reduced efficiency of treatment. Further studies are needed to explore the mechanisms of the association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lambert, Serre, Thirioux, Jaafari, Roux, Jauffret-Roustide, Lalanne, Daulouède and Auriacombe.)

Background: Approximately half of all people with alcohol use disorder (AUD) relapse into alcohol reuse in the next few weeks after a withdrawal treatment. Brain stimulation and cognitive training represent recent forms of complementary interventions in the context of AUD., Objective: To evaluate the clinical efficacy of five sessions of 2 mA bilateral transcranial direct current stimulation (tDCS) for 20 min over the dorsolateral prefrontal cortex (DLPFC) (left cathodal/right anodal) combined with alcohol cue inhibitory control training (ICT) as part of rehabilitation. The secondary outcomes were executive functioning (e.g. response inhibition) and craving intensity, two mechanisms strongly related to abstinence., Methods: A randomized clinical trial with patients (n = 125) with severe AUD at a withdrawal treatment unit. Each patient was randomly assigned to one of four conditions, in a 2 [verum vs. sham tDCS] x 2 [alcohol cue vs. neutral ICT] factorial design. The main outcome of treatment was the abstinence rate after two weeks or more (up to one year)., Results: Verum tDCS improved the abstinence rate at the 2-week follow-up compared to the sham condition, independently of the training condition (79.7% [95% CI = 69.8-89.6] vs. 60.7% [95% CI = 48.3-73.1]; p = .02). A priori contrasts analyses revealed higher abstinence rates for the verum tDCS associated with alcohol cue ICT (86.1% [31/36; 95% CI = 74.6-97.6]) than for the other three conditions (64% [57/89; 95% CI = 54-74]). These positive clinical effects on abstinence did not persist beyond two weeks after the intervention. Neither the reduction of craving nor the improvement in executive control resulted specifically from prefrontal-tDCS and ICT., Conclusions: AUD patients who received tDCS applied to DLPFC showed a significantly higher abstinence rate during the weeks following rehabilitation. When combined with alcohol specific ICT, brain stimulation may provide better clinical outcomes., Trial Registration: ClinicalTrials.gov number NCT03447054 https://clinicaltrials.gov/ct2/show/NCT03447054., Competing Interests: Declaration of competing interest This study is part of Macha Dubuson Ph.D thesis. Dr Kornreich reported receiving grants from the King Baudouin Foundation and the CHU Brugmann Foundation during the study. Dubuson reported receiving salary support through grants of the King Baudouin Foundation and the Brugmann Foundation during the study. There are no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Many patients with major depressive disorder (MDD) are reported to have higher levels of multiple inflammatory cytokines including interleukin 6 (IL-6). Recent studies both pre-clinical and clinical have advocated for the functional role of IL-6 in development of MDD and suggested a great potential for targeting this cytokine to open new avenues in pharmacotherapy of depression. The purpose of the present narrative review was to provide an integrated account of how IL-6 may contribute to development of depression. All peer-reviewed journal articles published before July 2020 for each area discussed were searched by WOS, PubMed, MEDLINE, Scopus, Google Scholar, for original research, review articles, and book chapters. Publications between 1980 and July 2020 were included. Alterations in IL-6 levels, both within the periphery and the brain, most probably contribute to depression symptomatology in numerous ways. As IL-6 acts on multiple differing target tissues throughout the body, dysregulation of this particular cytokine can precipitate a multitude of events relevant to depression and blocking its effects can prevent further escalation of inflammatory responses, and potentially pave the way for opening new avenues in diagnosis, treatment, and prevention of this debilitating disorder.

There is a debate over whether actions that resist devaluation (i.e., compulsive alcohol consumption) are primarily habit- or goal-directed. The incentive habit account of compulsive actions has received support from behavioral paradigms and brain imaging. In addition, the self-reported Creature of Habit Scale (COHS) has been proposed to capture inter-individual differences in habitual tendencies. It is subdivided into two dimensions: routine and automaticity. We first considered a French version of this questionnaire for validation, based on a sample of 386 undergraduates. The relationship between two dimensions of habit and the risk of substance use disorder and impulsive personality traits was also investigated. COHS has good psychometric properties with both features of habits positively associated with an Obsessive-Compulsive Inventory score. Besides, the propensity to rely more on routines was associated with lower levels of alcohol abuse and nicotine use, suggesting that some degree of routine might act as a protective factor against substance use. In contrast, a high automaticity score was associated with an increased risk of harmful alcohol use. These results demonstrate that the COHS is a valid measure of habitual tendencies and represents a useful tool for capturing inter-individual variations in drug use problems in undergraduates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wyckmans, Chatard, Saeremans, Kornreich, Jaafari, Fantini-Hauwel and Noël.)

Background: Application of repetitive transcranial magnetic stimulation (rTMS) for treating obsessive-compulsive disorder (OCD) has been promising and approved by the Food and Drug Administration in 2018, but effects differ between patients. Knowledge about clinical predictors of rTMS response may help to increase clinical efficacy but is not available so far., Methods: In a retrospective study, we investigated the efficacy of rTMS over the dorsolateral prefrontal cortex (DLPFC) or supplementary motor area (SMA) in 65 pharmaco-resistant OCD outpatients recruited for rTMS treatment from July 2015 to May 2017. Patients received either SMA rTMS (n = 38) or bilateral DLPFC rTMS (n = 27) in case of reporting higher affective and depressive symptoms in addition to the primary OCD symptoms. OCD symptoms and depression/anxiety states were measured at baseline (before the 1st session) and after the 20th session of rTMS. Additionally, we performed a binary logistic regression analysis on the demographic and clinical variables based on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) 3-factor and 2-factor models and individual items to investigate potential predictors of rTMS response., Results: Patients' scores in Y-BOCS and Beck anxiety/depression inventories were significantly decreased following rTMS treatment. 46.2% of all patients responded to rTMS, based on the criterion of at least a 30% reduction in Y-BOCS scores. There was no significant difference between response rates of patients in DLPFC and SMA groups. No significant demographic predictors of rTMS efficacy were identified. The factors "obsession severity", "resistance" and "disturbance" and the "interference due to obsessions" and "resistance against compulsions" items of the Y-BOCS significantly predicted response to rTMS., Conclusions: In patients with less intrusive/interfering thoughts, and low scores in the "obsession severity", "disturbance", and "resistance" factors, rTMS might have superior effects. Identifying clinical and non-clinical predictors of response is relevant to personalize and adapt rTMS protocols in pharmaco-resistant OCD patients. Interpretation of rTMS efficacy should be done with caution due to the lack of a sham intervention condition.

Background: Obsessive-compulsive disorder (OCD) is a complex disorder with 40%-60% of patients' refractory to treatment. Transcranial direct current stimulation (tDCS) has been shown to induce potent and long-lasting effects on cortical excitability. The aim of the present clinical trial was to evaluate the therapeutic efficacy and tolerability of cathodal tDCS over the supplementary motor area (SMA) in treatment-resistant OCD patients., Methods: Twenty-one treatment-resistant OCD outpatients received 10 sessions of tDCS. Each treatment session consisted of 2 mA stimuli for 30 min. The cathode was positioned over the bilateral SMA and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment, one-month follow-up, and three-month follow-up. Response to treatment was defined as at least a decrease of 35% on the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and a score of 2 or less on the Clinical Global Impressions-Improvement (CGI-I) between baseline and 1-month follow-up., Results: There was a significant decrease of YBOCS scores between baseline and one-month assessment. At one month, five patients (24%) were considered as responders and 3 (15%) at 3 months. We also observed concomitant changes in depressive symptoms, and insight. The treatment was well tolerated. Short-lasting side effects were reported as localized tingling sensation and skin redness., Conclusion: Our results suggest that the use of cathodal tDCS over the SMA and anodal tDCS over the right supraorbital area in OCD treatment-refractory patients is safe and promising to improve obsessive and compulsive symptoms. Large randomized controlled trials are needed to confirm this positive result., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Aims: Recent research suggests that evaluative conditioning (EC) can change implicit evaluations of alcohol and reduce drinking behaviors among college students (Houben et al., 2010a). This research has been conceptually replicated in two previous studies. To date, however, no direct and independent replication of the original study has been performed. In this paper, we report a high-powered direct replication of Houben et al.'s (2010a) study., Method: About 168 French college students took part in this preregistered study. Drinking behavior was assessed before and 2 weeks after the intervention. The intervention consisted of 120 trials of words related to alcoholic beverages or soft drinks paired with neutral, positive or negative pictures. The two conditions were factually equivalent and differed only in the repeated pairing between alcohol-related words and negative pictures; in the EC condition, but not in the control condition, alcohol-related words were systematically paired with negative pictures., Results: EC did not change participants' implicit evaluations of alcohol and drinking behaviors. However, EC reduced drinking behaviors among hazardous drinkers. Yet, further non-preregistered Bayesian analysis did not provide much support for this hypothesis., Conclusion: This high-powered preregistered direct replication of Houben et al.'s (2010a) study suggests that the original effects are more fragile than initially thought. The effect of EC on drinking behaviors may be restricted to heavy drinkers, and we found no evidence that this effect is mediated by a change in implicit attitudes. It is necessary to perform further studies to test the original effects in clinical populations., (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Lack of insight, i.e., unawareness of one's mental illness, is frequently encountered in psychiatric conditions. Insight is the capacity to recognize (psychical insight) and accept one's mental illness (emotional insight). Insight growth necessitates developing an objective perspective on one's subjective pathological experiences. Therefore, insight has been posited to require undamaged self-reflexion and cognitive perspective-taking capacities. These enable patients to look objectively at themselves from the imagined perspective of someone else. Preserved theory-of-mind performances have been reported to positively impact insight in psychosis. However, some patients with schizophrenia or obsessive-compulsive disorders, although recognizing their mental disease, are still not convinced of this and do not accept it. Hence, perspective-taking explains psychical insight (recognition) but not emotional insight (acceptance). Here, we propose a new conceptual model. We hypothesize that insight growth relies upon the association of intact self-reflexion and empathic capacities. Empathy (feeling into someone else) integrates heterocentered visuo-spatial perspective (feeling into ), embodiment, affective ( feeling into) and cognitive processes, leading to internally experience the other's thought. We posit that this subjective experience enables to better understand the other's thought about oneself and to affectively adhere to this. We propose that the process of objectification, resulting from empathic heterocentered, embodiment, and cognitive processes, generates an objective viewpoint on oneself. It enables to recognize one's mental illness and positively impacts psychical insight. The process of subjectification, resulting from empathic affective processes, enables to accept one's illness and positively impacts emotional insight. That is, affectively experiencing the thought of another person about oneself reinforces the adhesion of the emotional system to the objective recognition of the disease. Applying our model to different psychiatric disorders, we predict that the negative effect of impaired self-reflexion and empathic capacities on insight is a transnosographic state and that endophenotypical differences modulate this common state, determining a psychiatric disease as specific., (Copyright © 2020 Thirioux, Harika-Germaneau, Langbour and Jaafari.)

Compulsive behaviors (e.g., addiction) can be viewed as an aberrant decision process where inflexible reactions automatically evoked by stimuli (habit) take control over decision making to the detriment of a more flexible (goal-oriented) behavioral learning system. These behaviors are thought to arise from learning algorithms known as "model-based" and "model-free" reinforcement learning. Gambling disorder, a form of addiction without the confound of neurotoxic effects of drugs, showed impaired goal-directed control but the way in which problem gamblers (PG) orchestrate model-based and model-free strategies has not been evaluated. Forty-nine PG and 33 healthy participants (CP) completed a two-step sequential choice task for which model-based and model-free learning have distinct and identifiable trial-by-trial learning signatures. The influence of common psychopathological comorbidities on those two forms of learning were investigated. PG showed impaired model-based learning, particularly after unrewarded outcomes. In addition, PG exhibited faster reaction times than CP following unrewarded decisions. Troubled mood, higher impulsivity (i.e., positive and negative urgency) and current and chronic stress reported via questionnaires did not account for those results. These findings demonstrate specific reinforcement learning and decision-making deficits in behavioral addiction that advances our understanding and may be important dimensions for designing effective interventions.

Background: New technologies are set to profoundly change the way we understand and manage psychiatric disorders, including obsessive-compulsive disorder (OCD). Developments in imaging and biomarkers, along with medical informatics, may well allow for better assessments and interventions in the future. Recent advances in the concept of digital phenotype, which involves using computerized measurement tools to capture the characteristics of a given psychiatric disorder, is one paradigmatic example., Objective: The impact of new technologies on health professionals' practice in OCD care remains to be determined. Recent developments could disrupt not just their clinical practices, but also their beliefs, ethics, and representations, even going so far as to question their professional culture. This study aimed to conduct an extensive review of new technologies in OCD., Methods: We conducted the review by looking for titles in the PubMed database up to December 2017 that contained the following terms: [Obsessive] AND [Smartphone] OR [phone] OR [Internet] OR [Device] OR [Wearable] OR [Mobile] OR [Machine learning] OR [Artificial] OR [Biofeedback] OR [Neurofeedback] OR [Momentary] OR [Computerized] OR [Heart rate variability] OR [actigraphy] OR [actimetry] OR [digital] OR [virtual reality] OR [Tele] OR [video]., Results: We analyzed 364 articles, of which 62 were included. Our review was divided into 3 parts: prediction, assessment (including diagnosis, screening, and monitoring), and intervention., Conclusions: The review showed that the place of connected objects, machine learning, and remote monitoring has yet to be defined in OCD. Smartphone assessment apps and the Web Screening Questionnaire demonstrated good sensitivity and adequate specificity for detecting OCD symptoms when compared with a full-length structured clinical interview. The ecological momentary assessment procedure may also represent a worthy addition to the current suite of assessment tools. In the field of intervention, CBT supported by smartphone, internet, or computer may not be more effective than that delivered by a qualified practitioner, but it is easy to use, well accepted by patients, reproducible, and cost-effective. Finally, new technologies are enabling the development of new therapies, including biofeedback and virtual reality, which focus on the learning of coping skills. For them to be used, these tools must be properly explained and tailored to individual physician and patient profiles., (©Florian Ferreri, Alexis Bourla, Charles-Siegfried Peretti, Tomoyuki Segawa, Nemat Jaafari, Stéphane Mouchabac. Originally published in JMIR Mental Health (http://mental.jmir.org), 10.12.2019.)

Electrical stimulation studies have recently evidenced the involvement of orbitofrontal cortex (OFC) in obsessive-compulsive disorder (OCD). In addition, lateral OFC is activated in healthy subjects during delayed non-matching-to-sample task (DNMS). In the present study, we hypothesized that OCD results from a specific defect of lateral OFC processing that can be evidenced via a DNMS task. To this end, we compared the DNMS performances of 20 OCD patients vs 20 demographically matched healthy controls. As predicted, our results showed that OCD patients performed worse than healthy controls at DNMS task. To test for the specificity of this behavioral impairment, we furthermore compared OCD patients and healthy subjects on a different task not involving directly the lateral OFC: the delayed match-to-sample task (DMS). As expected, OCD patients are more impaired for both the DNMS and the DMS task, compared with healthy subjects. Moreover, OCD patients tend statistically to perform worse for the DNMS task than for DMS task. Our results suggest the DNMS task specifically target the malfunctioning areas in OCD, such as the lateral OFC. In light of these results, lateral OFC should therefore be the focus of future therapeutic interventions.

A historical review of the concepts of self-consciousness is presented, highlighting the important role of the body (particularly, body perception but also body action), and the social other in the construction of self-consciousness. More precisely, body perception, especially intermodal sensory perception including kinesthetic perception, is involved in the construction of a sense of self allowing self-other differentiation. Furthermore, the social other , through very early social and emotional interactions, provides meaning to the infant's perception and contributes to the development of his/her symbolization capacities. This is a necessary condition for body image representation and awareness of a permanent self in a time-space continuum (invariant over time and space). Self-image recognition impairments in the mirror are also discussed regarding a comprehensive developmental theory of self-consciousness. Then, a neuropsychological and neurophysiological approach to self-consciousness reviews the role of complex brain activation/integration pathways and the mirror neuron system in self-consciousness. Finally, this article offers new perspectives on self-consciousness evaluation using a double mirror paradigm to study self- and other- image and body recognition.

Objective: The REHABase project is a French observational, prospective, and multicenter cohort study of serious mental illness and autism spectrum disorder (ASD), launched in 2016 for a planned minimum duration of 15 years. The aim is to characterize the care and quality-of-life needs of participants. This article presents initial results from data collection., Methods: Psychosocial, cognitive, and functional data were collected at baseline, annually, and after rehabilitation care. Data from the baseline evaluation on diagnoses, medications, well-being, insight, life satisfaction, and care needs are presented. The clinical profiles of REHABase participants with serious mental illness or ASD were assessed in relation to their level of satisfaction with life and well-being in nine life dimensions and their needs, according to their stage of recovery in a five-stage model., Results: Baseline data were collected for 1,397 participants between January 2016 and August 2018. Main diagnoses were schizophrenia spectrum disorder (49%); ASD (13%); and personality (12%), bipolar (9%), and major depressive (6%) disorders. More than 50% of participants reported needs for care or interventions in four of nine dimensions: employment, cognitive functioning, symptom management, and interpersonal relationships. Nearly half of participants were not in the active stages of recovery (stages 4 and 5), and even those considered to have reached the final stage continued to require help in several areas., Conclusions: Most participants had already received psychiatric care for several years, and most remained dissatisfied with their social and emotional life and their psychological well-being.