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Only survey studies have linked specific individual psychiatric disorders such as anxiety, depression and schizophrenia to Restless Legs Syndrome (RLS), Periodic Limb Movements in Sleep (PLMS) or both. We therefore aim to polysomnographically characterize sleep in a sample of physician-based, newly diagnosed cases of RLS with various ICD-10 psychiatric diagnoses. Retrospective analysis of data from a convenience sample of psychiatric patients (n = 43) per standard clinical sleep disorder cut-offs was conducted. Next, a cluster analysis was performed on the sleep data, taking into account the psychiatric diagnosis, comorbid non-psychiatric somatic problems and medication. We found that 37.2% of our sample showed clinically significant PLMS ≥ 15 and 76.5% exhibited an apnea hypopnea index (AHI) ≥ 5. Sleep structure was unaltered apart from the PLMS-related parameters. Two clusters were statistically identified: Cluster 1 primarily representing recurrent major depressive issues and Cluster 2 representing present but not predominant mood symptomatology as well as mixed disorders with personality problems. The known confounders were controlled. A PLMS index ≥ 15 was differentially distributed among the two clusters with Cluster 1: 10 out of 17 with PLMS index ≥ 15, Cluster 2: 1 out of 16 with PLMS index ≥15, whilst AHI was not different. Patients in Cluster 1 have a higher rate of periodic leg movements than patients in Cluster 2. This suggests that the high association with PLMS is primarily driven by affective disorders. Our findings warrant questioning of RLS symptomatology in patients with psychiatric conditions.

Background: In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial Direct Current Stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Further, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear.Method: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham controlled, 4-centers trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS.Discussion: Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a Randomized Controlled Trial (RCT) with follow-up assessments up to 3 months and a large sample size. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia.Trial registration: ClinicalTrials.gov NCT05440955. Prospectively registered on July 1st, 2022

Noninvasive brain stimulation has emerged in the last three decades as a promising treatment for patients with antipsychotic-resistant symptoms of schizophrenia. This review updates the latest progress in the use of noninvasive brain stimulation to treat schizophrenia symptoms.Several recently published randomized-controlled trials support a long-lasting clinical effect of stimulation techniques on schizophrenia symptoms. In addition, efforts have been made in recent months to improve efficacy through several optimization strategies. Studies have tested new parameters of stimulation, such as theta burst stimulation, and alternative cortical or subcortical targets and have reported encouraging results. New forms of electrical stimulations such as alternating and random noise stimulation, have also been studied and have shown clinical and cognitive usefulness for patients. Accelerated stimulation protocols, and prospects could arise with deeper stimulation strategies.Using brain stimulation to treat symptoms of schizophrenia seems promising and the great flexibility of the stimulation parameters leaves much room for developing optimization strategies and improving its effectiveness. Further studies need to identify the optimal parameters to maximize response rate.

Stress is an adaptive response with repercussions on the human health. The dorsolateral prefrontal cortex (DLPFC) is thought to be involved in stress regulation by contributing to limit its biological and behavioral pejorative consequences. Here, to investigate the contribution of the DLPFC in stress response, we applied transcranial Direct Current Stimulation (tDCS) over the DLPFC during acute stress exposure in healthy participants. We hypothesized that active tDCS compared to sham would impact top-down control of the DLPFC on goal-directed behavior and hypothalamo–pituitary–adrenal (HPA) axis activity. In a double-blind sham-controlled study, 30 healthy subjects were randomly allocated to receive either active (2 mA, n = 15) or sham tDCS (n = 15) with the anode over the left DLPFC and the cathode over the right DLFPC. During the 30-min stimulation period, participants faced an experimental acute stress paradigm. Changes in goal-directed behavior were measured with a decision-making task. HPA axis reactivity was assessed by repeated measures of salivary cortisol. Acute stress decreased appetite for immediate reward in the sham group (mean - 4.40%; p = 0.017) whereas no significant effect of stress was observed in the active group. During stress exposure, we observed a significant larger elevation of salivary cortisol (p = 0.045; Cohen's d = 0.431) in the sham tDCS group (+179.8%; Standard error of the mean (SEM) = 20.6) than in the active group (+138.5%; SEM = 14.2). Stimulating the DLPFC using bifrontal tDCS may prevent stress-induced acute effects on both biological and behavioral outcomes.

Optimal noninvasive brain stimulation parameters for the treatment of negative symptoms of schizophrenia remain unclear. Here, we aimed to investigate the clinical and biological effects of intermittent theta burst transcranial magnetic stimulation (iTBS) in patients with treatment-resistant negative symptoms of schizophrenia (NCT00875498). In a randomized sham-controlled 2-arm study, 22 patients with schizophrenia and treatment-resistant negative symptoms received 20 sessions of either active (n = 12) or sham (n = 10) iTBS. Sessions were delivered twice a day on 10 consecutive working days. Negative symptom severity was assessed 5 times using the Scale for the Assessment of Negative Symptoms (SANS): before iTBS, after iTBS, and 1, 3, and 6 months after iTBS. As a secondary objective, we explored the acute effects of iTBS on functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) using seed-based resting-state functional connectivity MRI (rsFC fMRI) images acquired before and after iTBS. Active iTBS over the left DLPFC significantly decreased negative symptoms severity compared to sham iTBS (F(3,60) = 3.321, p = 0.026). Post hoc analyses revealed that the difference between groups was significant 6 months after the end of stimulation sessions. Neuroimaging revealed an increase in rsFC between the left DLPFC and a brain region encompassing the right lateral occipital cortex and right angular gyrus and a right midbrain region that may encompass dopamine neuron cell bodies. Thus, iTBS over the left DLPFC can alleviate negative symptoms of schizophrenia. The effect might be driven by significant modulation of dopamine transmission.

In recent years noninvasive brain stimulation (NIBS) applications have emerged as a third and novel treatment option alongside psychopharmacology and psychotherapy in the treatment of mental diseases. It is assumed that NIBS could represent a supplement or (in some indications) even replacement to established therapeutic strategies, e.g. in disorders with high resistance to current treatment regimens, such as negative symptoms or cognitive impairments in schizophrenia. Although positive symptoms in schizophrenia can be treated sufficiently with antipsychotic drugs, patients with negative symptoms frequently suffer from persistent lack of impetus, cognitive decline, social withdrawal and loss of global functioning in the activities of daily life; however, in these cases, current treatment strategies exert only moderate effects, and new treatment options are urgently needed. This review article provides a summary of the clinical effects of new electrical NIBS methods, e.g. transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) for the treatment of negative symptoms in schizophrenia. These new NIBS methods could help restore the disrupted neuronal networks and improve disturbed connectivity, especially of the left dorsolateral prefrontal cortex and left temporoparietal junction. Promising results are reported for the treatment of negative symptoms with tDCS, tACS and tRNS and could thus represent new therapeutic options in the treatment of schizophrenia.Über die letzten Jahre entwickelten sich Neuromodulationsverfahren zu einer dritten Säule neben Pharmakotherapie und Psychotherapie in der Behandlung psychischer Erkrankungen. Besonders in der Behandlung von Menschen mit einer Schizophrenie könnten Hirnstimulationsverfahren eine Alternative oder Ergänzung zu den etablierten Therapiestrategien darstellen. Die meist vorhandenen Positivsymptome können zumeist mit Antipsychotika adäquat behandelt werden. Gerade bei Patienten mit Schizophrenie besitzen jedoch Negativsymptome einen überdauernden Krankheitswert und beeinflussen den Verlauf durch globale Antriebsverarmung und beeinträchtigte Kognition im alltäglichen Leben negativ. Dieser Übersichtsartikel stellt eine Zusammenfassung über die verschiedenen nichtinvasiven Hirnstimulationsverfahren transkranielle Gleichstromstimulation (transcranial direct current stimulation, tDCS), Wechselstromstimulation (transcranial alternating current stimulation, tACS) sowie Rauschstromstimulation (transcranial random noise stimulation, tRNS) zur Behandlung der Negativsymptomatik bei Schizophrenie dar. Die neuen transkraniellen Hirnstimulationsverfahren könnten dabei helfen, gestörte neuronale Vernetzungen wieder herzustellen und die Konnektivität vor allem der dorsolateralen präfrontalen Anteile des Kortex zu verbessern. Einige Studien weisen auf eine Verbesserung der Negativsymptome durch Behandlung mit tDCS, tACS bzw. tRNS hin und könnten so neue Therapiemöglichkeiten in der Behandlung der Schizophrenie darstellen.

Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES.Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided.Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity.Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials. (C) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

International audience; No abstract available

Transcranial direct current stimulation (tDCS) has been proposed as a therapeutic option for treatment-resistant auditory verbal hallucinations (AVH) in schizophrenia. In such cases, repeated sessions of tDCS are delivered with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. Despite promising findings, the clinical response to tDCS is highly heterogeneous among patients. Here, we explored baseline differences between responders and nonresponders to frontotemporal tDCS using electric field modeling. We hypothesized that responders would display different tDCS-induced electric field strength in the brain areas involved in AVH compared to nonresponders. Using baseline structural MRI scans of 17 patients with schizophrenia and daily AVH who received 10 sessions of active frontotemporal tDCS, we constructed individual realistic whole brain models estimating electric field strength. Electric field maps were compared between responders (n = 6) and nonresponders to tDCS (n = 11) using an independent two-sample t test. Clinical response was defined as at least a 50% decrease of AVH 1 month after the last tDCS session. Results from the electric field map comparison showed that responders to tDCS displayed higher electric field strength in the left transverse temporal gyrus at baseline compared to nonresponders (T = 2.37; p = 0.016; 32 voxels). These preliminary findings suggested that the strength of the tDCS-induced electric field reaching the left transverse temporal gyrus could play an important role in the response to frontotemporal tDCS. In addition, this work suggests the interest of using electric field modeling to individualize tDCS and increase response rate.

Obsessive-compulsive disorder (OCD) is a severe mental illness characterized by persistent, intrusive and distressing obsessions and/or compulsions. Such symptoms have been conceptualized as resulting from a failure in source-monitoring processes, suggesting that patients with OCD fail to distinguish actions they perform from those they just imagine doing. In this study, we aimed to provide an updated and exhaustive review of the literature examining the relationship between source-monitoring and OCD. A systematic search in the literature through January 2019 allowed us to identify 13 relevant publications investigating source-monitoring abilities in patients with OCD or participants with subclinical compulsive symptoms. Most of the retrieved studies did not report any source-monitoring deficits in clinical and subclinical subjects compared with healthy volunteers. However, most of the studies reported that patients with OCD and subclinical subjects displayed reduced confidence in source-monitoring judgments or global cognitive confidence compared to controls. The present review highlighted some methodological and statistical limitations. Consequently, further studies are needed to explore source monitoring with regard to the subcategories of OCD symptoms (i.e., symmetry-ordering, contamination-washing, hoarding, aggressive obsession-checking, sexual-religious thoughts) and to clarify the relationship between source-monitoring subtypes (i.e., reality or internal source-monitoring) and confidence in these populations.

Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Device appraisal showed moderate digitalization readiness, with high safety and the possibility of trial implementation, but low connectivity. Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; although they reached no consensus about aspects regarding methodological biases. We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.Graphical Abstract. Consensus Roadmap(A) Recruitment process. The study procedure started with defining the components of the research problem by the core research team. After defining the problems, two different sets of participants (the steering committee (SC) including key leaders of the field identified by the core team and the expert panel (EP) as a more diverse group of experts identified based on the number of publications based on a systematic review) were identified and were invited to participate in a Delphi study. The study facilitators (first and last authors) led the communications with the SC to design the initial questionnaire through an iterative approach. (B) Evidence synthesis: To collect the available evidence, companies producing portable tES (ptES) devices were contacted, based on the companies suggested by the SC and EP to provide details about the available devices. For mapping methodological processes of digitizing tES trials, two distinct strategies were performed and embedded into the questionnaire, namely SIPOC (Suppliers, Inputs, Process, Outputs, and Customer) and SWOT (Strengths, Weaknesses, Opportunities, and Threats) assessment were performed and embedded into the questionnaire. (C) Consensus development: In the next phase, the questionnaire was validated and finalized via collecting and summarizing opinions. Afterward, the SC and EP responded to the final questionnaire, and results were analyzed providing a list of recommendations for running tES digital trials based on a pre-registered consensus threshold.

Objective: The aim of this study was to validate the French version of the 7-item Auditory Hallucination Rating Scale (AHRS) so as to facilitate fine-grained assessment of auditory hallucinations (AH) in native French-speaking patients with schizophrenia (SZ) in clinical settings and studies. Method: Patients ( N = 66) were diagnosed with SZ according to the Diagnostic and Statistical Manual of Mental Disorders. The French version of the AHRS was developed using a forward–backward translation procedure. Psychometric properties of the French version of the AHRS were tested including (i) construct validity with a confirmatory one-factor analysis, (ii) internal validity with Pearson correlations and Cronbach α coefficients, and (iii) external validity by correlations with the Scale for Assessment of Positive Symptoms (SAPS-H1), the Positive and Negative Syndrome Scale (PANSS-P3; concurrent), the PANSS-Negative subscale and age of subjects (divergent), and inter-rater intraclass correlation coefficients (ICCs). Results: (i) The confirmatory one-factor analysis found a root mean square error of approximation (RMSEA) = 0.00, 90% confidence interval = [0.000 to 0.011], and a comparative fit index = 0.994. (ii) Correlations between AHRS total score and individual items were mostly ≥0.4. Cronbach α coefficient was 0.61. (iii) Correlations with PANSS-P3 and SAPS-H1 were 0.42 and 0.53, respectively. In a subset of participants ( N = 16), ICC values were extremely high and significant for AHRS total and individual item scores (ICCs range 0.899 to 0.996) Conclusion: The French version of the AHRS is a psychometrically acceptable instrument for the evaluation of AH severity in French-speaking patients with SZ.

The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n=12) or sham (n=14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.

Auditory and visual dysfunctions are key pathophysiological features of schizophrenia (Sz). Therefore, remedial interventions that directly target such impairments could potentially drive gains in higher-order cognition (e.g., memory, executive functions, emotion processing), symptoms and functional outcome, in addition to improving sensory abilities in this population. Here, we reviewed available sensory-targeted cognitive training (S-TCT) programs that were investigated so far in Sz patients. Area covered: A systematic review of the literature was conducted following PRISMA guidelines. Twenty-seven relevant records were included. The superiority of S-TCT over control conditions on higher-order cognition measures was repeatedly demonstrated, but mostly lost significance at later endpoints of evaluation. Clinical symptoms and functional outcome were improved in a minority of studies. S-TCT interventions were associated with the relative normalization of several neurobiological biomarkers of neuroplasticity and sensory mechanisms. Expert commentary: S-TCT, although time-intensive, is a cost-efficient, safe and promising technique for Sz treatment. Its efficacy on higher-order cognition opens a critical window for clinical and functional improvement. The biological impact of S-TCT may allow for the identification of therapeutic biomarkers to further precision-medicine. Additional research is required to investigate the long-term effects of S-TCT, optimal training parameters and potential confounding factors associated with the illness.

Although transcranial direct current stimulation (tDCS) shows promise as a treatment for auditory verbal hallucinations in patients with schizophrenia, mechanisms through which tDCS may induce beneficial effects remain unclear. Evidence points to the involvement of neuronal plasticity mechanisms that are underpinned, amongst others, by brain-derived neurotrophic factor (BDNF) in its two main forms: pro and mature peptides. Here, we aimed to investigate whether tDCS modulates neural plasticity by measuring the acute effects of tDCS on peripheral mature BDNF levels in patients with schizophrenia. Blood samples were collected in 24 patients with schizophrenia before and after they received a single session of either active (20 min, 2 mA, n = 13) or sham (n = 11) frontotemporal tDCS with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. We compared the tDCS-induced changes in serum mature BDNF (mBDNF) levels adjusted for baseline values between the two groups. The results showed that active tDCS was associated with a significantly larger decrease in mBDNF levels (mean −20% ± standard deviation 14) than sham tDCS (−8% ± 21) (F = 5.387, p = 0.030, η2 = 0.205). Thus, mature BDNF may be involved in the beneficial effects of frontotemporal tDCS observed in patients with schizophrenia.

Background Suicide is a major public health issue and the majority of those who attempt suicide suffer from mental disorders. Beyond psychopharmacotherapy, seizure therapies and noninvasive brain stimulation interventions have been used to treat such patients. However, the effect of these nonpharmacological treatments on the suicidal ideation and incidence of suicidality remains unclear. Here, we aimed to provide an update on the effects of seizure therapies and noninvasive brain stimulation on suicidality. Methods We conducted a systematic review of the literature in the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Elsevier ScienceDirect, and Wiley Online Library databases using the MeSH terms “Electroconvulsive Therapy”, “Magnetic Seizure Stimulation”, “repetitive Transcranial Magnetic Stimulation”, “transcranial Direct Current Stimulation”, “Cranial Electrostimulation” and “suicide”. We included studies using seizure therapies and noninvasive brain stimulation as a main intervention that evaluated suicidality, regardless of diagnosis. Results Among 1,019 records screened, 26 studies met the inclusion criteria using either electroconvulsive therapy (n = 14), magnetic seizure therapy (n = 2), repetitive transcranial magnetic stimulation (n = 9), or transcranial direct current stimulation (n = 1). We observed that studies reported significant results, suggesting these techniques can be effective on the suicidal dimension of mental health pathologies, but a general statement regarding their efficacy is premature due to limitations. Conclusions Future enquiry is necessary to address methodological limitations and evaluate the long‐term efficacy of these methods both alone and in combination with pharmacotherapy and/or psychotherapy., We provided an update of current evidence on the effects of seizure therapies (electroconvulsive therapy and magnetic seizure therapy) and noninvasive brain stimulations (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial electrostimulation) on suicidality. The antisuicidal effect of ECT could be supported, but magnetic seizure therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial electrostimulation were not consistently recommended for treating suicidality. Long‐term antisuicidal effect of seizure therapies and noninvasive brain stimulations should be further investigated both alone and in combination with pharmacotherapy or psychotherapy.

Background Reality-monitoring process enables to discriminate memories of internally generated information from memories of externally derived information. Studies have reported impaired reality-monitoring abilities in schizophrenia patients with auditory hallucinations (AHs), specifically with an exacerbated externalization bias, as well as alterations in neural activity within frontotemporoparietal areas. In healthy subjects, impaired reality-monitoring abilities have been associated with reduction of the paracingulate sulcus (PCS). The current study aimed to identify neuroanatomical correlates of reality monitoring in patients with schizophrenia. Methods Thirty-five patients with schizophrenia and AHs underwent a reality-monitoring task and a 3D anatomical MRI scan at 1.5 T. PCS lengths were measured separately for each hemisphere, and whole-brain voxel-based morphometry analyses were performed using the Computational Anatomy Toolbox (version 12.6) to evaluate the gray-matter volume (GMV). Partial correlation analyses were used to investigate the relationship between reality-monitoring and neuroanatomical outcomes (PCS length and GMV), with age and intracranial volume as covariates. Results The right PCS length was positively correlated with reality-monitoring accuracy (Spearman’s ρ = 0.431, p = 0.012) and negatively with the externalization bias (Spearman’s ρ = −0.379, p = 0.029). Reality-monitoring accuracy was positively correlated with GMV in the right angular gyrus, whereas externalization bias was negatively correlated with GMV in the left supramarginal gyrus/superior temporal gyrus, in the right lingual gyrus and in the bilateral inferior temporal/fusiform gyri (voxel-level p p Conclusions Reduced reality-monitoring abilities were significantly associated with shorter right PCS and reduced GMV in temporal and parietal regions of the reality-monitoring network in schizophrenia patients with AHs.

Schizophrenia is a debilitating disease affecting about 1% of the general population and auditory verbal hallucinations (AVHs) are common symptoms of this disease. In 25–30% of cases, AVHs fail to respond to antipsychotic treatments. Transcranial direct current stimulation (tDCS) has recently been proposed as a novel therapeutic solution for medication-resistant hallucinations. This chapter proposes an overview of the randomized sham-controlled trials investigating the effect of tDCS on AVHs in schizophrenia patients. Eleven available studies from the PubMed database were included in this chapter. Results suggest that tDCS can be used to reduce AVHs if a certain design is respected. Twice-daily 20 min sessions of tDCS at 2 mA over 5 consecutive days would be the most appropriate, with anode over the left dorsolateral prefrontal cortex and cathode over the left temporoparietal junction. Other randomized controlled studies with larger sample sizes are needed to confirm the usefulness of tDCS for medication-resistant AVHs in schizophrenia.

The current COVID-19 pandemic is the most severe pandemic of the 21st century, on track to having a rising death toll. Beyond causing respiratory distress, COVID-19 may also cause mortality by way of suicide. The pathways by which emerging viral disease outbreaks (EVDOs) and suicide are related are complex and not entirely understood. We aimed to systematically review the evidence on the association between EVDOs and suicidal behaviors and/or ideation. An electronic search was conducted using five databases: Medline, Embase, Web of Science, PsycINFO and Scopus in April 2020. A rapid systematic review was carried out, which involved separately and independently extracting quantitative data of selected articles. The electronic search yielded 2480 articles, of which 9 met the inclusion criteria. Most of the data were collected in Hong Kong (n = 3) and the USA (n = 3). Four studies reported a slight but significant increase in deaths by suicide during EVDOs. The increase in deaths by suicide was mainly reported during the peak epidemic and in older adults. Psychosocial factors such as the fear of being infected by the virus or social isolation related to quarantine measures were the most prominent factors associated with deaths by suicide during EVDOs. Overall, we found scarce and weak evidence for an increased risk of deaths by suicide during EVDOs. Our results inform the need to orient public health policies toward suicide prevention strategies targeting the psychosocial effects of EVDOs. High-quality research on suicide risk and prevention are warranted during the current pandemic., Highlights • Few studies assessed the association between suicidal behaviors or ideation and emerging viral outbreaks. • The literature reports weak evidence for increased suicide rates during emerging viral outbreaks. • Psychosocial factors are associated with deaths by suicide during emerging viral outbreaks. • Suicide prevention strategies are needed during emerging viral outbreaks.

International audience; Nicotine use, which is mostly done through smoking tobacco, is among the most burdensome comorbidities of schizophrenia. However, the ways in which nicotine affects the cognitive and early sensory alterations found in this illness are still debated. After conducting a systematic literature search, 29 studies were selected. These studies involve individuals with schizophrenia who underwent cognitive and/or early sensory function assessments after acute nicotine administration and include 560 schizophrenia subjects and 346 non-schizophrenia controls. The findings highlight that a single dose of nicotine can improve a range of cognitive functions in schizophrenia subjects, such as attention, working memory, and executive functions, with attention being the most responsive domain. In addition, nicotine can modulate early detection of changes in the sensory environment at both the auditory and visual levels. Nevertheless, effects vary strongly depending on the type of neuropsychological assessment and nicotine intake conditions used in each study. The current findings suggest the need to consider a potential decrease of cognitive and early sensory performance when patients with schizophrenia quit smoking.

Noninvasive brain stimulation techniques are safe tools to modulate the brain activity and connectivity in vivo. They offer promise to alleviate psychotic symptoms, mainly in patients with schizophrenia. Evidence suggests that low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the left temporoparietal junction may decrease auditory verbal hallucinations with a moderate effect size. High-frequency rTMS targeting the left dorsolateral prefrontal cortex yields encouraging results to alleviate negative symptoms of schizophrenia, but recent findings have diminished the enthusiasm raised by the first studies. Transcranial direct current stimulation (tDCS) is an emerging field that shows promises to decrease hallucinations and negative symptoms in schizophrenia, but it suffers from a lack of large randomized controlled studies to confirm its interest in psychosis. Overall, electromagnetic techniques are promising techniques, offering new perspectives for treating psychotic symptoms but further studies are needed to draw a clear-cut conclusion.

International audience; Objective: DSM-5 Substance Use Disorders (SUD) are frequent and debilitating comorbidities displayed by patients with schizophrenia spectrum disorders (SZ). One crucial feature of SUD is drug craving, an intense desire to consume a substance, commonly divided into reward and relief dimensions. Here, we conducted a meta-analysis of studies investigating craving in individuals with both SUD and SZ in order to examine whether these patients exhibit a distinct pattern of craving as compared to patients with SUD without SZ.Method: Meta-analysis based on the PRISMA guidelines.Results: Sixteen relevant publications were identified by a systematic search of databases, which included 1219 individuals (589 SUD-SZ and 630 SUD-without-SZ). Of the 16 studies, 11 focused on tobacco, 3 on cannabis and 2 on cocaine. When considered across all studies, SUD-SZ had significantly higher scores than SUD-without-SZ for global craving with medium effect size (knumber of studies = 16, Zr = 0.20 [0.15, 0.26], equivalent d = 0.41, P < 0.001). Discrete patterns emerged for reward (k = 7, Zr = 0.10 [0.02, 0.17], equivalent d = 0.20, P < 0.05) and relief (k = 7, Zr = 0.25 [0.17, 0.33], d = 0.52, P < 0.001) craving, and the direct comparison revealed a significantly greater effect for relief than reward (χ2(1) = 7.40 P = 0.007).Conclusion: These results suggest that SUD-SZ cases experience higher craving, more specifically for relief, in comparison to patients with SUD-without-SZ. These clinical findings can foster the development of tailored addiction therapies for this specific comorbid population.

Background Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. Objective We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson’s disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. Methods Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. Results Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson’s disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). Conclusion All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.

International audience; Background: Evidence suggests that individuals with psychopathy display difficulties to adapt their behavior in accordance with the demands of the environment and show altered performance monitoring. However, studies investigating electrophysiological markers of error monitoring (e.g., the error-related negativity (ERN) and the error-positivity (Pe)) in this population reported mixed results. To explain discrepancies observed between studies, we hypothesized that psychopathy dimensions influence electrophysiological outcomes and we predicted that individuals with impulsive-antisocial features would display abnormal ERN compared to individuals with interpersonal-affective features. Methods: Based on the PRISMA guidelines, we conducted a systematic review and meta-analysis of studies investigating ERN and Pe components in individuals with psychopathy compared to controls. A factorial analysis was undertaken to investigate the role of psychopathy dimensions on ERN. Results: Among the 206 retrieved studies, 15 were included in the meta- analysis. Individuals with psychopathy (n = 817) showed a reduced ERN (Cohen's d = 0.18) and Pe amplitude (d = -0.22) compared to control. The factorial analysis indicates a dissociation regarding the dimensional construct of psychopathy. The impulsive-antisocial dimension was linked to reduced ERN amplitude (d = 0.22) whereas the interpersonal-affective dimension was related to increased ERN amplitude compare to controls (d = -0.17). Conclusion: Individuals with psychopathy displayed abnormal ERN and Pe amplitudes following error commission. In addition, models reported that individuals with psychopathic traits relating more specifically to the interpersonal-affective dimension shows efficient error-monitoring systems and increased ERN component while those with marked impulsive-antisocial dimension displayed decreased ERN and altered performance monitoring.

BackgroundImpairments in self-recognition (i.e. recognition of own thoughts and actions) have been repeatedly shown in individuals with schizophrenia. According to classical clinical characterizations, schizophrenia is included in a continuum encompassing a large range of genetic statuses, psychotic states and symptoms. The current meta-analysis aims to determine whether self-recognition is affected by individuals within the psychosis continuum.MethodThree populations were considered: people with an at-risk mental state for psychosis (ARMS), hallucination-prone individuals and unaffected relatives of patients with schizophrenia. Eleven studies contrasted self-recognition between these three populations (n = 386) and healthy controls (n = 315) and four studies used correlational analysis to estimate comparable effects (n = 629). Eligible studies used experimental paradigms including source-monitoring and self-monitoring.ResultsWe observed significantly reduced self-recognition accuracy in these populations [g = −0.44 (−0.71 to −0.17), p = 0.002] compared to controls. No influence of the type of population, experimental paradigm or study design was observed.ConclusionThe present analysis argues for self-recognition deficits in populations with no full-blown psychotic symptoms represented across the continuum of psychosis.

Background:Based on the observed clinical overlap between obsessive–compulsive disorder (OCD) and schizophrenia (SCZ), both conditions may share, at least in part, common cognitive underpinnings. Among the cognitive deficits that could be involved, it has been hypothesized that patients share a failure in their abilities to monitor their own thoughts (source monitoring), leading to confusion between what they actually did or perceived and what they imagined. Although little is known regarding source-monitoring performances in patients with OCD, numerous studies in patients with SCZ have observed a relationship between delusions and/or hallucinations and deficits in both internal source- and reality-monitoring abilities.Methods:The present work compared source-monitoring performances (internal source and reality monitoring) between patients with OCD (n= 32), patients with SCZ (n= 38), and healthy controls (HC;n= 29).Results:We observed that patients with OCD and patients with SCZ displayed abnormal internal source-monitoring abilities compared to HC. Only patients with SCZ displayed abnormalities in reality monitoring compared to both patients with OCD and HC.Conclusions:Internal source-monitoring deficits are shared by patients with OCD and SCZ and may contribute to the shared cognitive deficits that lead to obsessions and delusions. In contrast, reality-monitoring performance seems to differentiate patients with OCD from patients with SCZ.