Family psychoeducation in schizophrenia and schizophrenia related disorder, treatment compliance, and suicidal risk reduction: questions about their relationship from a naturalistic observation.

Introduction: The Profamille V3.2 multi-family psycho-educational program directed at caregivers of relatives with schizophrenia or schizophrenia related disorder has been shown to decrease the annual prevalence of suicide attempts. It has been reported that psychoeducation of families can sometimes improve compliance with treatment. This study investigates whether the Profamille program improves compliance and thus reduces the risk of suicide among patients. Method: This is a retrospective study of 179 groups of family caregivers, encompassing 1946 participants enrolled in Module 1 of the Profamille program and followed up one year after completion of the module. Evaluations were conducted using questionnaires filled out by family caregivers at three distinct times: prior to beginning the program, upon its completion, and again one year following its conclusion. The annual prevalence of suicide attempts was measured both before the program began and one year after its conclusion, while compliance to treatment was evaluated at the start and end of the program. Result: After the Profamille program, the annual prevalence of suicide attempts fell by a factor of 2 (p-value = 0.00002) and patient compliance improved (p-value <0.000001). This reduction in suicide attempts was observed independently of improved compliance. Compliance seems to have an additional effect, but only after participation in the program. Conclusion: The Profamille program reduces patients' risk of suicide even when patients are not taking the treatment. When family psychoeducation is not proposed in schizophrenia or schizophrenia related disorder, this can represent a loss of chance for patients.

Diminished capacity to make treatment decision for COVID-19 vaccination in schizophrenia.

Recent evidence suggests that people with schizophrenia are at high risk for severe COVID-19 and should be prioritized for vaccination. However, impaired decision-making capacities could negatively affect the uptake of COVID-19 vaccination in this population. Capacity to consent to COVID-19 vaccination was assessed in 80 outpatients with schizophrenia. Using the MacArthur Competence Assessment Tool for Treatment, 56.3% of the sample were classified as having diminished capacity to consent to the vaccination. Diminished capacity to consent to COVID-19 vaccination was associated with lower vaccination rates, poorer cognition and higher level of psychotic symptoms. Developing interventions for enhancing informed consent for vaccination is urgent within this population.

Attitudes towards Vaccines, Intent to Vaccinate and the Relationship with COVID-19 Vaccination Rates in Individuals with Schizophrenia.

Schizophrenia patients are at high risk of developing severe COVID-19 outcomes but recent evidence suggests that they are under-vaccinated. This study explored the role of potential attitudinal barriers by comparing schizophrenia patients with participants from the general population regarding COVID-19 vaccination rates, general attitudes towards vaccines, and willingness to take a COVID-19 vaccine. We conducted a cross-sectional study between April 2021 and October 2021. A total of 100 people with schizophrenia and 72 nonclinical controls were recruited. In our study, individuals with schizophrenia were under-vaccinated, despite similar general attitudes towards vaccination and higher willingness to be vaccinated against COVID-19 compared to nonclinical participants. In patients, negative attitudes toward vaccines were related to higher levels of negative psychotic symptoms and higher levels of paranoid ideation. As a whole, participants with more negative attitudes towards vaccines were less likely to be vaccinated against COVID-19 and had lower levels of trust in institutions. Vaccine hesitancy does not appear to be a major barrier for COVID-19 vaccine uptake amongst people with schizophrenia. This study suggests that disparities in COVID-19 vaccination rates in schizophrenia do not seem related to attitudinal but rather structural barriers.

Validation of the French Clinical Assessment Interview for Negative Symptoms in a Sample of Stable French Individuals With Schizophrenia.

Objectives: The Clinical Assessment Interview for Negative Symptoms (CAINS) is an interview-based instrument evaluating the existence and severity of negative symptoms in people diagnosed with schizophrenia or schizoaffective disorder. The aim of this study is to translate and validate a French version of the CAINS in a French sample of outpatients diagnosed with schizophrenia or schizoaffective disorder. Methods: In this study, we included 84 outpatients with a diagnosis of schizophrenia from the University Department of Adult Psychiatry in Montpellier, France. All participants were assessed for the severity of negative symptoms as well as level of depression. Psychometric properties of the French CAINS were investigated including its factor structure, internal consistency, and interrater and test-retest reliabilities. We also determined the discriminant and convergent validity. Results: Exploratory factor analysis and parallel analysis reproduced the two-factor model, and explained 43.55% of the total score variation with good internal consistency (Cronbach α of 0.87). Both interrater and test-retest reliabilities were high for the CAINS and its subscales (intraclass correlation coefficient range, 0.89-0.99). The standard errors of measurement and minimal detectable change were also investigated. Convergent validity of the CAINS was underpinned by correlations obtained with various measures of negative symptoms. Adequate discriminant validity was established by showing that the CAINS did not correlate with positive symptoms. Conclusion: Overall, our results obtained were similar to those found in the original study of the CAINS. Structural analyses also replicated the two-factor model of the CAINS. Our results indicate that the French CAINS has robust psychometric properties and is a valid tool for evaluating negative symptoms in French-speaking individuals diagnosed with schizophrenia.

Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM'Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial.

BACKGROUND: One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. METHODS: In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100-500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients' symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. DISCUSSION: The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016.

The Patient, Investigator, Nurse, Carer Questionnaire (PINC-Q): a cross-sectional, retrospective, non-interventional study exploring the impact of less frequent medication administration with paliperidone palmitate 3-monthly as maintenance treatment for schizophrenia.

BACKGROUND: To understand the implications of switching from paliperidone palmitate 1-monthly (PP1M) to paliperidone palmitate 3-monthly (PP3M) treatment of schizophrenia from the perspective of four key stakeholders: patients, physicians, nurses and carers. METHODS: This was a cross-sectional, retrospective, non-interventional study comprising a one-time questionnaire (PINC-Q) for adult patients (aged ≥18 years) with schizophrenia (International Classification of Diseases; ICD-10) and their physician, nurse and carer. Questionnaires were developed in association with patient and carer advocacy groups (GAMIAN and EUFAMI) and following an advisory board formed of psychiatrists and nurses. The degree of alignment between stakeholders was also examined. RESULTS: Responses were received from a total of 224 evaluable patients. For most patients (88.4%), responses were received from at least two other stakeholders. Patients were moderately ill with mild-to-moderate lack of insight and had received PP1M for a mean (standard deviation [SD]) of 23.9 (21.28) months before switching to PP3M (duration mean [SD] 12.8 [3.72] months). The most frequently reported reasons to switch from PP1M to PP3M were 'to live life as normally as possible' and 'patient convenience'. Over 79% of responses within each stakeholder group stated that PP3M helped the patients, with increased patient activity and social involvement, improved frequency and quality of physician-patient and nurse-patient communication and decreased perceived stigma. CONCLUSIONS: The results of this study add to the increasing body of evidence supporting the benefits of PP3M in a population of patients with schizophrenia representative of real-world clinical practice.

The French Version of the Revised Ritvo Autism and Asperger Diagnostic Scale: A Psychometric Validation and Diagnostic Accuracy Study.

The early recognition of ASD in adults is challenging, in particular due to the lack of appropriate and robust diagnostic tools. We performed a psychometric validation and diagnostic accuracy study of the French version of the RAADS-R on a sample of 305 adults: 105 with ASD without ID, 99 with psychiatric disorders, and 103 non-psychiatric control groups. The French version of the RAADS-R demonstrates good reliability and diagnostic validity, suggesting that it can help clinicians during the diagnostic process in adults with ASD without ID. However, the finding that a two-factor structure better fits the results requires further validation. This study point out the need of further study of RAADS in psychiatric disorders group due to the relatively high false positive rate (55.6%) of ASD.

Apathy in Obsessive-Compulsive Disorder and Its Psychological Correlates: Comparison With Individuals With Schizophrenia.

OBJECTIVE: Apathy, defined as reduced goal-directed behavior, is a frequent symptom in mental and neurological disorders but has been poorly studied in individuals with obsessive-compulsive disorder (OCD). The primary aim of this study was to examine levels of apathy between individuals with OCD, healthy control subjects, and individuals with schizophrenia, a mental disorder with high levels of apathy. The second aim was to assess whether the psychological factors that have been previously shown as underlying apathy in other mental disorders were associated with apathy in patients with OCD. METHODS: This exploratory study included 25 individuals with OCD, 24 individuals with schizophrenia, and 24 healthy control subjects. Apathy was assessed using the Lille Apathy Rating Scale. Measures of depression, sensibility to punishment and reward, defeatist performance beliefs, and cognitive functioning were also assessed. RESULTS: Individuals diagnosed with OCD and schizophrenia scored significantly higher than healthy control subjects on the apathy total score. Levels of apathy among OCD patients were mainly associated with depression but also dysexecutive functioning and defeatist beliefs. CONCLUSIONS: These findings suggest that motivational deficits could play a central role in disability caused by OCD. Similar to other mental disorders, various psychological factors, including depression, defeatist beliefs, and dysexecutive functioning, are involved in apathetic manifestations. However, the fact that depression is the variable most associated with apathy indicates that apathetic symptoms in patients with OCD must be considered mainly as secondary rather than primary symptoms.

[Mood disorders: When should we use repetitive transcranial magnetic stimulation?] / Troubles de l'humeur : quand recourir à la stimulation magnétique transcrânienne ?

Repeated transcranial magnetic stimulation (rTMS) is still a recent treatment in psychiatry. This article aims at updating the clinicians'knowledge about rTMS in the treatment of mood disorders (uni and bipolar depressive disorders, manic/mixed states, suicidal risk, catatonia). It is intended for clinicians who are required to indicate and/or use rTMS in their current practice. rTMShas the highest level of evidence for the treatment of unipolar depression, provided that effective parameters are used, that is to say, for classical high frequency protocols: 20 to 30 sessions, 1000 pulses/session, 5 to 20Hz, and 110 % of the motor threshold. Low frequency protocol are also efficient and well tolerated. The duration of the efficacy varies with relapses rates around 50 % at one year. Pharmacological treatment generally remains associated. With regard to manic states, and mixed states the results are preliminary and limited to a possible reduction in symptoms. In the suicidal risk associated with mood disorders, the interest of rTMS is still to demonstrate, as well as in catatonia. The current place of the rTMS is no longer disputed in the curative treatment of major depressive disorder, preferentially used after one or two lines of antidepressants upstream. Further studies are needed to confirm preliminary positive findings in other aspects of mood disorders.

Improving decision-making and cognitive impulse control in bulimia nervosa by rTMS: An ancillary randomized controlled study.

OBJECTIVE: Impaired decision-making and inhibitory control may be involved in the pathophysiology of psychiatric disorders like bulimia nervosa (BN). Their improvement after neuromodulation may underpin clinical improvement. We assessed the effects of rTMS on these cognitive functions in a sample of women with BN. METHODS: Thirty-nine participants (22 in a sham group and 17 in an rTMS group) were assessed before and after 10 high frequency rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). RESULTS: The between-group analyses revealed no differences in the final neuropsychological performances. The within-group analyses showed that inhibitory control improved in both the go/no-go task (p = .03) and the BIS cognitive impulsivity subscale (p = .01) in the rTMS group only. Switches toward good choices on the Iowa gambling task significantly improved in the rTMS group only (p = .002), and understanding of the task contingencies increased between the two assessments, also in the rTMS group only (p = .03). DISCUSSION: This preliminary evidence suggests that modulation of left DLPFC might improve two putative cognitive biomarkers of BN.

Success of tardive electroconvulsive therapy sessions after loxapine-induced malignant syndrome in the context of very poor metabolisation.

We report the success of tardive electroconvulsive therapy in a case of loxapine malignant syndrome with catatonia. Loxapine and its metabolites were measured in biological samples by liquid chromatography coupled to tandem mass spectrometry. Genes were studied by sequencing and quantitative polymerase chain reaction (PCR). Plasmatic drug concentrations showed a supratherapeutic concentration of loxapine with a very low 8-hydroxyloxapine/loxapine ratio (range from 0.32 to 0.66, normal value>2 for 100mg) and a very long elimination half-life of loxapine (half-life>140h, normal value from 1 to 4hours). We tried to explain this kinetics by exploring the main pharmacogenes implicated in the metabolism of loxapine. No genetic abnormality for CYP1A2 was observed. The study of associated treatments showed the potential contribution of valproate. Pharmacokinetics and pharmacogenetics investigations revealed a blockade of the CYP1A2 metabolic pathway without genetic abnormalities, probably due to valproate co-medication. Toxicological monitoring of loxapine and its metabolites helped to explain the persistence of symptoms and to adapt the therapeutic management.

Mirror self-face perception in individuals with schizophrenia: Feelings of strangeness associated with one's own image.

Self-face recognition is crucial for sense of identity and for maintaining a coherent sense of self. Most of our daily life experiences with the image of our own face happen when we look at ourselves in the mirror. However, to date, mirror self-perception in schizophrenia has received little attention despite evidence that face recognition deficits and self abnormalities have been described in schizophrenia. Thus, this study aims to investigate mirror self-face perception in schizophrenia patients and its correlation with clinical symptoms. Twenty-four schizophrenia patients and twenty-five healthy controls were explicitly requested to describe their image in detail during 2min whilst looking at themselves in a mirror. Then, they were asked to report whether they experienced any self-face recognition difficulties. Results showed that schizophrenia patients reported more feelings of strangeness towards their face compared to healthy controls (U=209.5, p=0.048, r=0.28), but no statistically significant differences were found regarding misidentification (p=0.111) and failures in recognition (p=0.081). Symptoms such as hallucinations, somatic concerns and depression were also associated with self-face perception abnormalities (all p-values>0.05). Feelings of strangeness toward one's own face in schizophrenia might be part of a familiar face perception deficit or a more global self-disturbance, which is characterized by a loss of self-other boundaries and has been associated with abnormal body experiences and first rank symptoms. Regarding this last hypothesis, multisensorial integration might have an impact on the way patients perceive themselves since it has an important role in mirror self-perception.

A Lack of Clinical Effect of High-frequency rTMS to Dorsolateral Prefrontal Cortex on Bulimic Symptoms: A Randomised, Double-blind Trial.

Studies suggest that stimulation of the left dorsolateral prefrontal cortex (DLPFC) reduces food craving in bulimic patients, but evidence supporting repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool is lacking. We investigated the safety and therapeutic efficacy of an adjunct high-frequency rTMS programme targeting the left DLPFC. Forty-seven women with bulimia nervosa were randomised to a real or sham stimulation group. The real group underwent 10 rTMS sessions, each consisting of 20 trains of 5 seconds with 55-second intervals between trains, at a frequency of 10 Hz. The main outcome was the number of binge episodes in the 15 days following the end of stimulation. Overall, no significant improvement in bingeing and purging symptoms was noted after the programme. rTMS was well tolerated. This suggests that 10 sessions of high-frequency rTMS to the left DLPFC provide no greater benefit than placebo. Future studies should consider methodological issues as well as alternative targets. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

The efficacy and safety of low frequency repetitive transcranial magnetic stimulation for treatment-resistant depression: the results from a large multicenter French RCT.

CONTEXT: The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD). METHOD: In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n = 55), active rTMS combined with placebo venlafaxine (n = 60) or sham rTMS combined with active venlafaxine (n = 55). The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS17 score <8. RESULTS: We reported a similar significant antidepressant effect in the 3 groups (P < 10(-6)), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; P = 0.59). CONCLUSION: Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 min) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.

Social motor coordination in unaffected relatives of schizophrenia patients: a potential intermediate phenotype.

Intermediate endophenotypes emerge as an important concept in the study of schizophrenia. Although research on phenotypes mainly investigated cognitive, metabolic or neurophysiological markers so far, some authors also examined the motor behavior anomalies as a potential trait-marker of the disease. However, no research has investigated social motor coordination despite the possible importance of its anomalies in schizophrenia. The aim of this study was thus to determine whether coordination modifications previously demonstrated in schizophrenia are trait-markers that might be associated with the risk for this pathology. Interpersonal motor coordination in 27 unaffected first-degree relatives of schizophrenia patients and 27 healthy controls was assessed using a hand-held pendulum task to examine the presence of interpersonal coordination impairments in individuals at risk for the disorder. Measures of neurologic soft signs, clinical variables and neurocognitive functions were collected to assess the cognitive and clinical correlates of social coordination impairments in at-risk relatives. After controlling for potential confounding variables, unaffected relatives of schizophrenia patients had impaired intentional interpersonal coordination compared to healthy controls while unintentional interpersonal coordination was preserved. More specifically, in intentional coordination, the unaffected relatives of schizophrenia patients exhibited coordination patterns that had greater variability and in which relatives did not lead the coordination. These results show that unaffected relatives of schizophrenia patients, like the patients themselves, also present deficits in intentional interpersonal coordination. For the first time, these results suggest that intentional interpersonal coordination impairments might be a potential motor intermediate endophenotype of schizophrenia opening new perspectives for early diagnosis.

Treating patients with schizophrenia deficit with erythropoietin?

This systematic review summarizes and critically appraises the literature on the effect of erythropoietin (EPO) in schizophrenia patients and the pathophysiological mechanisms that may explain the potential of its use in this disease. EPO is mainly known for its regulatory activity in the synthesis of erythrocytes and is frequently used in treatment of chronic anemia. This cytokine, however, has many other properties, some of which may improve the symptoms of psychiatric illness. The review follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Three databases (Medline, Web of Science, and Cochrane) were searched combining the search terms 'erythropoietin AND (psychotic disorders OR schizophrenia)'. Seventy-eight studies were included in qualitative synthesis, a meta-analytic approach being prohibited. The findings suggest that several EPO cerebral potential properties may be relevant for schizophrenia treatment, such as neurotransmission regulation, neuroprotection, modulation of inflammation, effects on blood-brain barrier permeability, effects on oxidative stress and neurogenesis. Several potentially detrimental side-effects of EPO therapy, such as increased risk of thrombosis, cancer, increased metabolic rate and mean arterial blood pressure leading to cerebral ischemia could severely limit or halt the use of EPO. Overall, because the available data are inconclusive, further efforts in this field are warranted.

Insight is not associated with insensitivity to future consequences in schizophrenia.

In this study, we examined the association between insight and decision-making capacity in schizophrenia using the Iowa Gambling Task (IGT). No association was found between insight and IGT scores. Our results suggest that impaired decision-making ability in schizophrenia patients cannot be solely predicted by lack of insight.

[Post-traumatic stress disorder and acute stress disorder]. / Etat de stress post-traumatique et etat de stress aigu.

Post-traumatic stress disorder (PTSD) is a disabling chronic disorder, which is often under-diagnosed, difficult to treat and to predict. The emotional and physical symptoms occur in three clusters: re-experiencing the trauma, avoidance of reminders of the event and hyperarousal for at least one month. Up to 80% of patients with PTSD have another psychiatric disorder. The main risk factors of PTSD are psychiatric and trauma history, trauma severity, peritraumatic dissociation and lack of social support. Treatment relies on psychotherapies like cognitive behavior therapy or EMDR and pharmacologic treatment like selective serotonin reuptake inhibitors without neglecting the forensic aspect.

[Rationalizing the prescription of antidepressants]. / Optimiiser la prescription des antidépresseurs.

The prescription of antidepressant drugs should only concern depressed patients fulfilling diagnostic criteria for a major depressive episode. This prescription should remain as simple as possible and the association of other psychotropic drugs should not be systematic. Optimal doses should be reached rapidly but the therapeutic efficacy will only become obvious after 2-4 weeks and complete after 6-8 weeks. As most antidepressants display a similar therapeutic efficacy, the choice will depend on tolerability, patient characteristics and the result of previous therapeutic attempts. Prescribing an antidepressant requires a thorough supervision and repeated visits during the first weeks of treatment. The recommended duration of treatment for a depressive episode is six months and the medication should he tapered off progressively in order to avoid withdrawal symptoms.