Management of depression in patients with schizophrenia spectrum disorders: a critical review of international guidelines.

OBJECTIVES: Depression is a frequent but potentially treatable clinical dimension in patients with schizophrenia spectrum disorders (PWS). However, there is a lack of consensual recommendations regarding the optimal strategy to manage depression in PWS. In this study, we aimed to compare the various proposed strategies to define a core set of valid care recommendations for depression management in PWS. METHODS: After a systematic search of the literature, the methodological quality of 10 international guidelines from four continents was compared using a validated guideline appraisal instrument (AGREE II). Key recommendations for the management of depression in PWS were subsequently reviewed and discussed. RESULTS: The methodological quality of the guidelines was heterogeneous. Although all guidelines proposed pharmacotherapy, psychosocial interventions were a minor concern. Waiting for antipsychotic effects mostly was recommended during the acute phase of schizophrenia. During the postpsychotic phase of the illness, a switch to a second-generation antipsychotic and/or the adjunction of an antidepressant were the primary recommendations. Cognitive behavioural therapy and other medications were considered with strong variations. CONCLUSIONS: Further studies are needed to strengthen the level of evidence for antidepressive approaches in PWS. The inclusion of PWS as stakeholders is also considered to be a major issue for future guideline development.

The effects of oxytocin on social cognition in borderline personality disorder.

INTRODUCTION: Deficits in social cognition and interpersonal difficulties are key features in borderline personality disorder. Social cognition refers to the function of perceiving and adequately dealing with social signals, leading to the establishment and maintenance of healthy and positive social relationships. Evidence suggests that oxytocin (OT) may improve social cognition and human social behavior. Recently, several studies have highlighted the beneficial effects of oxytocin in several psychiatric conditions involving social cognition deficits such as schizophrenia, autism or social phobia. However, despite growing interest, the effects of oxytocin in patients with borderline personality disorder are far from being clearly demonstrated. OBJECTIVE: The objective of this work was to review and discuss studies investigating the interest of oxytocin in alleviating social cognition deficits in patients with borderline personality disorder (recognition of emotion, trust and cooperation, affective and cognitive empathy, emotional expression and social problem-solving). METHOD: A systematic review of the literature was conducted up to September 31, 2016 on the Pubmed, Science direct, Medline and Scopus databases using "borderline personality disorder" and "oxytocin" as keywords. To be included, studies were to include patients with borderline personality disorder; to investigate social cognition and to investigate the effect of oxytocin on social cognition in patients with TPB. RESULTS: The initial search yielded 52 articles. Among them, 11 studies were selected according to the PRISMA criteria. The effect of oxytocin on social cognition in patients with borderline personality disorder was mainly investigated in relation to recognition of emotions and trust and cooperation. We did not find any studies investigating the effect of oxytocin on affective and cognitive empathy, emotional expression or social problem-solving abilities. In patients with borderline personality disorder, oxytocin had a beneficial impact on recognition and discrimination of emotions and on hypervigilance towards social threats. However, oxytocin could hinder trust and cooperation. CONCLUSIONS: These data lead us to consider oxytocin as a treatment for emotion recognition deficit and hypervigilance towards social threats in borderline personality disorder. A beneficial effect of oxytocin of this nature may be obtained only in patients without deficits in trust and cooperation because of a risk of aggravating relational instability. There was no current evidence for the interest of oxytocin in enhancing affective and cognitive empathy in borderline personality disorder. Further studies are needed to evaluate the clinical interest of combining oxytocin with psychotherapeutic approaches such as dialectical behavioral therapy or mentalisation-based treatment.

A single session of repetitive transcranial magnetic stimulation of the prefrontal cortex reduces cue-induced craving in patients with gambling disorder.

BACKGROUND: Gambling disorder (GD) is common and disabling addictive disorder. In patients with substance use disorders, the application of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers promise to alleviate craving. We hypothesized that applying real compared to sham rTMS over the left DLPFC would reduce gambling craving in patients with GD. METHODS: In a randomized sham-controlled crossover design, 22 treatment-seeking patients with GD received real or sham treatment with high frequency rTMS over the left DLPFC followed a week later by the other type of treatment. Before and after each rTMS session, participants rated their gambling craving (from 0 to 100) before and after viewing a gambling video used as a cue. We used the Yale-Brown Obsessive Compulsive Scale adapted for Pathological Gambling to assess gambling behavior before and 7 days after each rTMS session. RESULTS: As compared to sham (mean +0.74; standard deviation±3.03), real rTMS significantly decreased cue-induced craving (-2.12±3.39; F(1,19)=4.87; P=0.04; partial η2=0.05; 95% CI: 0.00-0.21). No significant effect of rTMS was observed on gambling behavior. CONCLUSIONS: Patients with GD reported decreased cue-induced craving following a single session of high frequency rTMS applied over the left DLPFC. Further large randomized controlled studies are needed to determine the usefulness of rTMS in GD.

Effects of smoking status and MADRS retardation factor on response to low frequency repetitive transcranial magnetic stimulation for depression.

BACKGROUND: Despite growing evidence supporting the clinical interest of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD), little is known regarding the effects of clinical and sociodemographic factors on the clinical outcome in patients. METHODS: We retrospectively investigated the effects of clinical (using the 3-factor model of the Montgomery-Åsberg depression rating scale [MADRS] encompassing dysphoria, retardation and vegetative symptoms) and sociodemographic characteristics of participants on clinical outcome in a sample of 54 TRD patients receiving low frequency rTMS (1Hz, 360 pulses) applied over the right dorsolateral prefrontal cortex combined with sham venlafaxine. RESULTS: Responders (n=29) displayed lower retardation baseline scores (13.6±2.9) than non-responders (15.6±2.9; n=25; P=0.02). We also observed a significant difference between the numbers of ex-smokers in responders and non-responders groups; all ex-smokers (n=8) were responders to rTMS (P=0.005). CONCLUSION: Low MADRS retardation factor and ex-smoker status is highly prevalent in responders to low frequency rTMS. Further studies are needed to investigate the predictive value of these factors.

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel.

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials.

Deviations in cortex sulcation associated with visual hallucinations in schizophrenia.

Hallucinations, and auditory hallucinations (AH) in particular, constitute the most typical and disabling schizophrenia symptoms. Although visual hallucinations (VH) have been largely neglected in psychiatric disorders, a recent review reported a 27% mean prevalence of VH in schizophrenia patients. The pathophysiology underlying VH in schizophrenia remains elusive. Several schizophrenia studies reported a significant effect of age on VH; therefore, we tested the hypothesis that the neurodevelopmental model of schizophrenia may explain VH occurrence. We analyzed cortex sulcation, a marker of brain development, in healthy controls (HCs) and two subgroups of carefully selected schizophrenia patients suffering from hallucinations: patients with only AH (that is, patients who never reported VH) and patients with audio-visual hallucinations (A+VH). Different cortical sulcation and left-right sulcal asymmetry were found between A+VH and AH patients, with decreased sulcation in both A+VH and AH patients in comparison with the HCs. Although a specific association between VH and neurodegenerative mechanisms, for example, in Body-Lewy Dementia or Parkinson's Disease, has previously been reported in the literature, the current study provides the first neuroimaging evidence of an association between VH and neurodevelopmental mechanisms.

[Validation of the French translation of the impulsive nonconformity scale]. / Traduction et validation de la version française de l'échelle d'impulsivité non conformité de Chapman.

INTRODUCTION: Impulsive traits are key characteristics in a lot of psychiatric disorders and are part of the "normal" behaviour spectrum. Although impulsivity is a controversial concept, some questionnaires have focused on its "dysfunctional" aspect. The Barratt Impulsive Scale (BIS-10) is the scale the most used to explore impulsiveness, but it does not explore antisocial or nonconform behaviour. The Chapman Impulsive and Nonconformity Scale (INCS) is a questionnaire of 51 items that measures the impulsivity and nonconformism. The INCS reflects "failure to internalize societal norms, lack of empathy for the pain of others, and an unrestrained yielding to impulse and self-gratification" and was originally designed to assess psychosis proneness. It has been validated in the USA, but has not yet been validated in France. Interestingly, although it was not predictive of psychosis, high scorers on INCS exceeded controls on depression, and on rates of substance abuse. Furthermore, participants scoring high on hypomanic personality scale and INCS were found to have an especially heightened risk for bipolar disorders. OBJECTIVE: To translate and determine reliability and validity of the French version of the Chapman Impulsive and Nonconformity Scale in young adults by comparison with the BIS. METHOD: Chapman Impulsive and Nonconformity Scale has been back-translated into French, and filled out by 237 students (males: 104; females: 133; mean age: 20.4 [range 19-25]). BIS-10 was used for convergent validity. Each participant completed the two scales. Reliability and validity of the French form of INCS were assessed with the internal consistency (coefficient alpha of Cronbach and the split half reliability) and the convergent validity. RESULTS: In the French version of the INCS, the 51 items have high internal reliability (Cronbach's alpha=0.81 and split half reliability=0.80). Concerning the BIS, internal reliability is good (Cronbach's alpha=0.72 and split half reliability=0.66). Moreover, Pearson's r of the INCS/BIS is statistically significant (0.65) and underlines the concomitant validity of the INCS with the BIS. CONCLUSION: The psychometric properties of the French version of the INCS are very similar to those of the English version. Hence, the INCS could provide a way to explore the two related dimensions: impulsivity and nonconformism.

[Efficacy of repetitive transcranial magnetic stimulation (rTMS) in major depression: a review]. / Efficacité de la stimulation magnétique transcrânienne (rTMS) dans le traitement de la dépression: revue de la littérature.

INTRODUCTION: In 1985, Barker et al. showed that it was possible to stimulate both nerves and brain using external magnetic stimulation without significant pain. During the past 10 years, therapeutic effects of repeated Transcranial Magnetic Stimulation (rTMS) have been widely studied in psychiatry and its efficacy has been demonstrated in the treatment of major depressive disorders, particularly as an alternative to electroconvulsivotherapy (ECT). Facing the large range of studies, we found necessary to propose an up-to-date review in French of the methodological and therapeutic variations among them. METHOD: Based on an exhaustive consultation of Medline data and the Avery-George-Holtzheimer Database of rTMS Depression-Studies, supplemented by a manual research, only works evaluating the therapeutic efficacy of rTMS on depressive symptoms were retained, excluding all studies exclusively investigating the stimulation parameters or the tolerance as well as case reports. RESULTS: Out the 66 available reports we retained 30 studies. After a description of the main results of these 30 studies, several elements of the 66 will be discussed. Open studies demonstrated that short courses rTMS (5 to 10 sessions) produced a decrease in the mean Hamilton Depression Ratting Scale (HDRS) scores, although significant remission of depression in individuals was rare. Most authors had used high frequency rTMS applied to the left Dorso Lateral Prefrontal Cortex (left DLPFC). However, low frequency rTMS applied to the right DLPFC was also followed by significant reduction of HDRS scores. Parallel arm, double blind versus placebo studies are designed to clarify the therapeutic efficacy of rTMS therapy but conclude in contradicting results. Literature data globally confirms a greater efficacy of rTMS compared to placebo (37% responders in the active group vs 20% in the sham). This efficacy could in fact be even greater because the sham procedure is disputable in most studies. Indeed, positioning rTMS coil at 45 or 90 from the scalp may not represent an accurate sham procedure and the use of real sham coil is to be recommended. Only one study has suggested that associating rTMS and ECT could decrease the number of general anesthesia required. Therapeutic efficacy has been shown by either inhibiting the right DLPFC or by stimulating the left DLPFC, although some patients exhibit paradoxical responses. High frequency rTMS (>5 Hz) increases cortical excitability and metabolism, while low-frequency rTMS stimulation ( 1 Hz) has the opposite effect. Other parameters are: relevant: intensity (from 80 to 110% of motor threshold), total number of stimulations (from 120 to 2 000) and total number of rTMS sessions (from 5 to 20). As suggested in most recent studies, higher-intensity pulses, higher number of stimulation or longer treatment courses may be more effective. Greater responsiveness to rTMS may be predicted by several patients' factors, including the absence of psychosis, younger age and previous response to rTMS therapy. DISCUSSION: Conclusions on these factors and others, such as the importance of anatomically accurate coil placement and the distance from the coil to the brain, await further investigation. Despite heterogeneity of these reports according to methodology and treatment parameters, the antidepressive properties of rTMS now appear obvious, opening interesting prospects, in particular in the treatment of pharmacoresistant major depressive patients and, we hope, administered as adjuvant therapy in non-resistant depression. CONCLUSION: Thus, many questions remain unanswered concerning the optimal stimulation parameters, privileged indications and maintenance sessions. This justifies the development of structured evaluation trials on larger samples.

Impaired fronto-temporal processing of emotion in schizophrenia.

AIMS: Abnormal emotion processing in schizophrenia affects social and functional outcome. Spatiotemporal brain mechanisms underlying this deficit are unclear. MATERIALS AND METHODS: Event-related potential (ERP) responses to emotional and neutral face processing during an implicit (gender detection) and an explicit (expression detection) task were compared between a group of healthy volunteers (n=10) and a group of patients with schizophrenia (n=10). RESULTS: Whereas patients had normal primary visual cortex responses, the early modulation of occipital, temporal, and frontal responses by emotional expression observed in controls was absent in patients. The occipito-temporal N170 amplitude was reduced in patients relative to controls during expression detection, but not during gender detection. Frontal activity within 180-250ms was reduced in patients compared to controls. As opposed to controls, no significant difference was seen in patients at the right temporal electrode (T6) between amplitudes of long-latency ERPs elicited by distinct emotions during the expression detection task. CONCLUSION: In patients with schizophrenia, abnormal early extraction of expression-related information in the occipito-temporal cortex (before 170ms) impairs structural encoding of facial expressions (N170) and may disrupt motivation- and task-dependent context processing (180-250ms time window) of expression-related facial features. Moreover, top-down neuromodulation from frontal and limbic structures to visual occipito-temporal cortex may not be sufficient to optimize the extraction of expression-specific face features.

Repetitive transcranial magnetic stimulation does not potentiate antidepressant treatment.

In a double blind controlled study, rTMS results in a similar antidepressant effect to sham in combination with paroxetine. Both groups had the same delay in scale's scores improvement. rTMS seems not to be efficient as an add-on treatment to pharmacological medication in non-resistant major depression.