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International audience; Patients with schizophrenia are often unaware of their condition and the consequences of their illness. This lack of insight results in impaired functioning, treatment non-adherence and poor prognosis. Here, we aimed to investigate the effects of non-invasive brain stimulation (NIBS) on two forms of insight, clinical and cognitive, in patients with schizophrenia. We conducted a systematic review of the literature registered in the PROSPERO database (CRD42020220323) according to PRISMA guidelines. The literature search was conducted in Medline and Web of Science databases based on studies published up until October 2020 that included pre-NIBS and post-NIBS measurements of clinical and/or cognitive insight in adults with schizophrenia. A total of 14 studies were finally included, and their methodological quality was assessed by using the QualSyst tool. Despite the lack of well-conducted large randomized-controlled studies using insight as the primary outcome, the available findings provide preliminary evidence that NIBS can improve clinical insight in patients with schizophrenia, with a majority of studies using transcranial direct current stimulation with a left frontotemporal montage. Further studies should investigate the effect of NIBS on insight as a primary outcome and how these effects on insight could translate into clinical and functional benefits in patients with schizophrenia.

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.

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.

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.

Background: Obsessive-compulsive disorder (OCD) is a severe mental disorder with poor response to the available treatments. Neuroimaging studies have identified dysfunctions within the orbito-fronto-striato-pallido-thalamic network in patients with OCD. Here, we assessed the efficacy and safety of transcranial direct current stimulation (tDCS) applied with the cathode over the orbitofrontal cortex (OFC) and the anode over the right cerebellum to decrease OCD symptoms in patients with treatment-resistant OCD. Methods: In a randomized sham-controlled double-blind study, 21 patients with OCD were assigned to receive ten 20-min sessions (two sessions per day) of either active (2 mA) or sham tDCS. The clinical symptoms were measured using the Yale-Brown Obsessive and Compulsive Scale (YBOCS). Acute effects on the symptoms were measured from baseline to immediately after the 10 tDCS sessions. Long-lasting effects were measured 1 and 3 months after the 10th tDCS session. Results: Compared with the sham tDCS, active tDCS significantly decreased OCD symptoms immediately after the 10th tDCS session (F(1,19) = 5.26, p = 0.03). However, no significant differences were observed between the active and sham groups in terms of changes in YBOCS score or the number of responders one and 3 months after tDCS. Conclusion: Despite significant acute effects, tDCS with the cathode placed over the left OFC and the anode placed over the right cerebellum was not significantly effective in inducing a long-lasting reduction of symptoms in patients with treatment-resistant OCD.

Non-selective and irreversible MAOI have become as third or fourth-line strategy for the management of treatment-resistant depression. Non-selective and irreversible MAOI requires careful monitoring of drug interactions and dietary restrictions. Nutritional supplements such as omega-3 have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment. The glutamate antagonist ketamine has been found to produce beneficial effects in the management of treatment-resistant depression while administered alone. Dopamine and/or norepinephrine agonists, such as methylphenidate, modafinil or pramipexole, have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment.

The most largely used definition of the treatment-resistant depression relies on the failure of two successive trials of antidepressant treatment at an adequate dose and duration. The absence of response to previous antidepressant treatments should be assessed using specific and appropriate clinical instruments enabling a correct staging of the therapeutic resistance. A wide range of socio-demographic and clinical factors (i.e. psychiatric/somatic comorbidities) are classically associated with the therapeutic resistance. The aim of the treatment of major depression is to achieve a complete clinical remission. The presence of residual symptoms increases the risk for the subsequent occurrence of relapses and recurrences, hence facilitating the development of therapeutic resistance. The treatment-resistant depression has a deleterious impact on the social, familial or professional functioning, thereby leading to an impaired quality of life with serious socioeconomic consequences and costs.

Background Obsessive–compulsive disorder (OCD) is a severe mental illness. OCD symptoms are often resistant to available treatments. Abnormalities within the orbitofronto-striato-pallido-thalamic circuitry, especially orbitofrontal cortex (OFC) hyperactivity and cerebellar hypoactivity have been observed in patients. Non-invasive brain stimulation studies have indicated that transcranial direct current stimulation (tDCS) may be a useful alternative to alleviate treatment-resistant symptoms in various neuropsychiatric conditions. Methods In an open-label pilot study, 8 patients with treatment-resistant OCD received 10 sessions (twice a day) of 2 mA tDCS applied with the cathode over the left OFC and the anode over the right cerebellum. OCD (Y-BOCS and OCD-VAS) as well as depressive (MADRS) symptoms were measured 4 times: one time before tDCS and 3 times after (immediately after, 1 and 3 months after the 10th tDCS session). Results We reported a significant 26.4% (± 15.8) decrease of Y-BOCS score (p = 0.002). The beneficial effect lasted during the 3 month follow-up. No effect of tDCS was observed on depressive symptoms. At end point, 5 out of 8 patients had a decrease of ≥ 25%; and 3 out of 8 patients had a decrease of ≥ 35% in Y-BOCS score. tDCS was well tolerated. Conclusion tDCS with the cathode placed over the left OFC combined with the anode placed over the right cerebellum is a suitable and safe approach to decrease OCD symptoms in patients with treatment-resistant OCD. Large scale randomized controlled studies are needed to confirm this promising result.

Auditory verbal hallucinations (AVH) in patients with schizophrenia are linked to abnormalities within a large cerebral network including frontal and temporal regions. Whilst abnormalities of frontal speech production and temporal speech perception regions have been extensively studied, alterations of the dorsolateral prefrontal cortex (DLPFC), a region critically involved in the pathophysiology of schizophrenia, have rarely been studied in relation to AVH. Using 1.5 T proton magnetic resonance spectroscopy, this study examined the relationship between right and left DLPFCs N-AcetylAspartate (NAA) levels and the severity of AVH in patients with schizophrenia. Twenty-seven male patients with schizophrenia were enrolled in this study, 15 presented daily treatment-resistant AVH (AVH+) and 12 reported no AVH (no-AVH). AVH+ patients displayed higher NAA levels in the right DLPFC than no-AVH patients (p = 0.033). In AVH+ patients, NAA levels were higher in the right DLPFC than in the left (p = 0.024). No difference between the right and left DLPFC was observed in no-AVH patients. There was a positive correlation between NAA levels in the right DLPFC and the severity of AVH (r = 0.404, p = 0.037). Despite limited by magnetic field strength, these results suggest that AVH may be associated with increased NAA levels in the right DLPFC in schizophrenia.

Amongst the most disabling psychiatric disorders, obsessive-compulsive disorder (OCD) is a prevalent, and chronic condition, burdened by an early onset, frequently in pre-adult age, and a pervasive limitation of patients interpersonal and occupational functioning. Nevertheless, as OCD treatment rarely results in complete remission, residual symptoms represent an on-going challenge for clinicians and researchers in the field. Non-invasive brain stimulation (rTMS/tDCS) has emerged as a promising tool to treat OCD resistant patients. Several randomized control trials using repeated transcranial magnetic stimulation (rTMS) to treat OCD have been published in the last 20 years but their results are inconclusive. We will try to present an updated review on the data on rTMS in OCD to provide a framework for its clinical use. tDCS has been more recently proposed as an useful add-on treatment for resistant patient. We will present the most updated data available on the treatment of OCD by tDCS and discuss the perspective in this field. DBS is as a reversible, non- ablative neurosurgical treatment option, approved by the FDA and the EMA for the treatment of refractory OCD patients. DBS clinical studies have permit a better insight on the physiopathology of OCD. Clinical experience with DBS in OCD suggest that brain stimulation should be implemented alongside intensive psychoeducation and psychotherapeutic interventions to reach optimal outcome. rTMS in treatment resistant OCD and related disorders: Where do we stand, where do we go? by Pr Bernardo Maria Dell’Osso; tDCS in anxiety and obsessive compulsive disorders by Dr Roberta Ferrucci; tDCS in SSRI resistant OCD? A randomized trial by Dr Remy Bation; What can DBS teach us on OCD physiopathology and treatment? by Dr Anne-Helene Clair.

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.

Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 μUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.

Lithium is among the most classically recommended add-on therapeutic a strategy for the management of depressive patients showing unsuccessful a response to standard antidepressant medications. a The effectiveness of the add-on strategy with lithium requires achieving a plasma levels above 0.5 mEq/L. a Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate a derivatives or lamotrigine have not demonstrated conclusive therapeutic a effects for the management of depressive patients showing unsuccessful a response to standard antidepressant medications. a Thyroid hormones are considered among the currently recommended add-on a therapeutic strategy for the management of depressive patients showing a unsuccessful response to standard antidepressant medications. a The effectiveness of the add-on strategy with thyroid hormones requires a achieving plasma concentration of TSH close to the lower limits at the a normal range (0.4 mUI/L) or even below it. Second-generation a antipsychotics such as aripiprazole or quetiapine have consistently a demonstrated significant therapeutic effects for the management of a depressive patients showing unsuccessful response to standard a antidepressant medications. a Second-generation antipsychotics however require the careful monitoring a of both cardiovascular and metabolic adverse effects.

International audience; The most largely used definition of the treatment-resistant depression relies on the failure of two successive trials of antidepressant treatment at an adequate dose and duration. The absence of response to previous antidepressant treatments should be assessed using specific and appropriate clinical instruments enabling a correct staging of the therapeutic resistance. A wide range of socio-demographic and clinical factors (i.e. psychiatric/somatic comorbidities) are classically associated with the therapeutic resistance. The aim of the treatment of major depression is to achieve a complete clinical remission. The presence of residual symptoms increases the risk for the subsequent occurrence of relapses and recurrences, hence facilitating the development of therapeutic resistance. The treatment-resistant depression has a deleterious impact on the social, familial or professional functioning, thereby leading to an impaired quality of life with serious socioeconomic consequences and costs.

Switching antidepressant medication may be helpful in depressed patients a having no benefit from the initial antidepressant treatment. a Before considering switching strategy, the initial antidepressant a treatment should produce no therapeutic effect after at least 4 weeks of a administration at adequate dosage. a Choosing an antidepressant of pharmacologically distinct profile fails a to consistently demonstrate a significant superiority in terms of a effectiveness over the switching to another antidepressant within the a same pharmacological class. a Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most a recommended strategy of antidepressant combinations. a Augmenting SSRI with tricyclic drugs is now a less recommended strategy a of antidepressant combinations given the increased risk for the a occurrence of pharmacokinetic drug-drug interactions and adverse a effects.

Despite the advances in psychopharmacology and established psychotherapeutic interventions, more than 40% of patients with obsessive-compulsive disorder (OCD) do not respond to conventional treatment approaches. Transcranial direct current stimulation (tDCS) has been recently proposed as a therapeutic tool to alleviate treatment-resistant symptoms in patients with OCD. The aim of this review was to provide a comprehensive overview of the current state of the art and future clinical applications of tDCS in patients with OCD. A literature search conducted on the PubMed database following PRISMA guidelines and completed by a manual search yielded 12 results: eight case reports, three open-label studies (with 5, 8, and 42 participants), and one randomized trial with two active conditions (12 patients). There was no sham-controlled study. A total of 77 patients received active tDCS with a large diversity of electrode montages mainly targeting the dorsolateral prefrontal cortex, the orbitofrontal cortex or the (pre-) supplementary motor area. Despite methodological limitations and the heterogeneity of stimulation parameters, tDCS appears to be a promising tool to decrease obsessive-compulsive symptoms as well as comorbid depression and anxiety in patients with treatment-resistant OCD. Further sham-controlled studies are needed to confirm these preliminary results.

Electroconvulsive therapy (ECT) is a safe and highly effective treatment for certain major mental disorders, including major depressive disorder, bipolar disorder, and certain forms of schizophrenia. The most frequently reported side effects are anterograde amnesia, post-ictal confusion, nausea, headache, myalgia, oral lacerations, and dental injuries. Hyperthermia is not commonly described as a side-effect of ECT. Examination of older texts find reports of fevers occurring after seizures, 1 but the occurrence of hyperthermia after ECT has not been reported since then. We report the case of a patient who experienced four transient high-grade fever episodes following ECT. We provide a differential diagnosis of fever in this particular clinical setting and raise the hypothesis of a neurogenic fever induced by ECT.

Objective There is considerable interest in cognitive remediation for schizophrenia. Our study aimed to evaluate, in a large sample of patients with schizophrenia, the interest of a computer-assisted cognitive remediation program on cognitive performances of patients as well as in clinical and functional outcome. Method Seventy-seven patients with remitted schizophrenia were randomly assigned to 14 2-hours individual sessions of computer-assisted cognitive remediation (n = 39) or a control condition (n = 38). Remediation was performed using RehaCom ® software. Four procedures were chosen to train four cognitive functions involved in different stages of the information processing: attention/concentration, working memory, logic, and executive functions. Primary outcomes were remediation exercise metrics, neuropsychological composites (episodic memory, working memory, attention, executive functioning, and processing speed), clinical and community functioning measures. Results Cognitive performances concerning Attention/vigilance, verbal working memory and verbal learning memory and reasoning/problem solving improved significantly in the remediation condition when no difference was reported in the control condition between the 2 assessments. However, there were no significant benefits of cognitive remediation on non-verbal working memory and learning and speed of processing or functional outcome measures. Conclusions Cognitive remediation for people with schizophrenia was effective in improving performance, but the benefits of training did not generalize to functional outcome measures. Long term follow-up studies are needed to confirm the maintenance of such improvements.