Effects of web-based adapted physical activity on hippocampal plasticity, cardiorespiratory fitness, symptoms, and cardiometabolic markers in patients with schizophrenia: a randomized, controlled study.

Among the lifestyle interventions, the physical activity (PA) has emerged as an adjuvant non-pharmacological treatment improving mental and physical health in patients with schizophrenia (SZPs) and increasing the hippocampus (HCP) volume. Previously investigated PA programs have been face-to-face, and not necessary adapted to patients' physiological fitness. We propose an innovative 16-week adapted PA program delivered by real-time videoconferencing (e-APA), allowing SZPs to interact with a coach and to manage their physical condition. The primary goal was to demonstrate a greater increase of total HCP volumes in SZPs receiving e-APA compared to that observed in a controlled group. The secondary objectives were to demonstrate the greater effects of e-APA compared to a controlled group on HCP subfields, cardiorespiratory fitness, clinical symptoms, cognitive functions, and lipidic profile. Thirty-five SZPs were randomized to either e-APA or a controlled group receiving a health education program under the same conditions (e-HE). Variables were assessed at pre- and post-intervention time-points. The dropout rate was 11.4%. Compared to the e-HE group, the e-APA group did not have any effect on the HCP total volumes but increased the left subiculum volume. Also, the e-APA group significantly increased cardiorespiratory fitness (VO2max), improved lipidic profile and negative symptoms but not cognitive functions. This study demonstrated the high feasibility and multiple benefits of a remote e-APA program for SZPs. e-APA may increase brain plasticity and improve health outcomes in SZPs, supporting that PA should be an add-on therapeutic intervention. ClinicalTrial.gov on 25 august 2017 (NCT03261817).

EPA guidance on treatment of negative symptoms in schizophrenia.

Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.

EPA guidance on assessment of negative symptoms in schizophrenia.

BACKGROUND: During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent. METHODS: In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice. RESULTS: Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings. CONCLUSIONS: The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

[Accountability of anti-cholinergic drugs in increase of psychotic episodes: A case of tropatepine overdose]. / Imputabilité des traitements anticholinergiques dans l'exacerbation d'épisodes psychotiques : à propos d'un cas de surdosage en tropatépine.

INTRODUCTION: Corrective treatments for some neurological side effects due to antipsychotic treatments can induce anticholinergic adverse effects. However, the risk of triggering or increasing psychotic symptoms induced by these drugs is unknown with only one case-report concerning the tropatepine. In addition, recommendations for the use of these drugs remain imprecise regarding the management of this type of adverse effect. CASE REPORT: We report the case of a psychotic episode in an 18-year-old patient potentially acutised after an auto-intoxication with tropatepine. CONCLUSION: At high doses, anticholinergic treatments, including tropatepine, might increase psychotic episodes. In addition, the available epidemiological data reveal an inappropriate and excessive prescription of these drugs. Their use and risks should be better known and need an update of the available recommendations.

A new toolbox to compare target localizations for non-invasive brain stimulation: An application of rTMS treatment for auditory hallucinations in schizophrenia.

BACKGROUND: Most repetitive transcranial magnetic stimulation (rTMS) studies aiming to reduce auditory verbal hallucinations (AVH) in schizophrenia target the left temporo-parietal junction (TPJ), but the efficacy of this approach remains controversial. The observed differences in efficacy could be attributed to inaccurate target localization. Here, to precisely quantify anatomical bias induced by localization method, we developed a free open-source software (GeodesicSlicer) that computes shortest curved path (i.e. geodesic) between rTMS targets. Here we compare a personalized target with accurate anatomical criteria with a standardized target based on the 10-20 EEG system (the middle between T3 and P3 electrodes: T3P3). METHODS: We compare in 69 patients with schizophrenia the geodesic distances of two approaches for rTMS target localization within the left TPJ. In addition, we characterize the personalized target according to the 10-20 EEG system. RESULTS: A differential of 3 cm in term of geodesic distance between rTMS localization approaches was observed. Moreover, this personalized target to treat AVH is located at 25% in the T3-P3 axis. CONCLUSIONS: This software for rTMS localization comparison demonstrates the difference between standardized and personalized rTMS target. This difference has the potential to explain a part of the dissonant clinical results found in previous rTMS studies.

GeodesicSlicer: a Slicer Toolbox for Targeting Brain Stimulation.

NonInvasive Brain Stimulation (NIBS) is a potential therapeutic tool with growing interest, but neuronavigation-guided software and tools available for the target determination are mostly either expensive or closed proprietary applications. To address these limitations, we propose GeodesicSlicer, a customizable, free, and open-source NIBS therapy research toolkit. GeodesicSlicer is implemented as an extension for the widely used 3D Slicer medical image visualization and analysis application platform. GeodesicSlicer uses cortical stimulation target from either functional or anatomical images to provide functionality specifically designed for NIBS therapy research. The provided algorithms are tested and they are accessible through a convenient graphical user interface. Modules have been created for NIBS target determination according to the position of the electrodes in the 10-20 system electroencephalogram and calculating correction factors to adjust the repetitive Transcranial Magnetic Stimulation (rTMS) dose for the treatment. Two illustrative examples are processing with the module. This new open-source software has been developed for NIBS therapy: GeodesicSlicer is an alternative for laboratories that do not have access to neuronavigation system. The triangulation-based MRI-guided method presented here provides a reproducible and inexpensive way to position the TMS coil that may be used without the use of a neuronavigation system.

Social cognition in schizophrenia: Validation of an ecological fMRI task.

Neuroimaging studies have revealed brain regions involved in social cognition, which reportedly show functional alterations in schizophrenia. However, the social neural network has not been investigated with regards to language perception and social interactions in daily life. Here we developed and validated an integrative fMRI task to explore the neural basis of social cognition with regards to language perception in schizophrenia. The task comprised listening to film extracts and inferring mental states to characters. We first identified the functional network activated during the task in 28 healthy controls (HC). Next, we evaluated the reproducibility of Blood-Oxygen-Level Dependent (BOLD) variations in 14 HC participants. Finally, we investigated network impairment in 20 patients with schizophrenia (SZ) compared to HC. The HC group exhibited bilateral activation in the superior and middle temporal gyri (including the poles and the temporo-parietal junction). Overall, our novel integrative task induced activation of a functional network with good reproducibility and involved in language conveying social information. Compared to the HC group, the SZ group showed decreased recruitment of the right temporo-parietal junction. These findings may be useful for testing the impact of remediation on the brain, particularly on the network of language conveying social information.

Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study.

The fronto-striato-thalamic circuitry is a key network in patients with schizophrenia (SZPs). We use diffusion tensor imaging (DTI) to investigate the integrity of white matter (WM) pathways involved in this network in SZPs relative to healthy controls (HCs). We also evaluate the differential impact of chronic exposure to clozapine as well as other atypical and typical antipsychotics. 63 HCs and 41 SZPs were included. Of the SZPs, 16 were treated with clozapine (SZPsC), 17 with atypical antipsychotics (SZPsA), and 8 with typical antipsychotics (SZPsT). Three tracts were reconstructed in the left hemisphere using tractography: one fronto-subcortical tract, one prefronto-subcortical tract, and one prefronto-frontal tract. Diffusion parameters were individually extracted in each tract. SZPs exhibited lower integrity in both the fronto-subcortical and prefronto-subcortical tracts relative to HCs, and SZPsT showed altered integrity compared to SZPsC. There were no WM integrity differences in the prefronto-frontal tract between SZP groups or between SZPs and HCs. SZPs exhibit structural connectivity abnormalities in the prefronto-fronto-subcortical network that are specifically and differentially impacted by the type of antipsychotic treatment. Additional studies are needed to separate the contributions of clozapine-mediated neuroprotection, neurotoxicity related to typical antipsychotics, and the illness itself to observed differences.

[Physical activity in patients with schizophrenia: From neurobiology to clinical benefits]. / L'activité physique chez les patients atteints de schizophrénie : de la neurobiologie aux bénéfices cliniques.

Schizophrenia is a severe chronic mental disorder that mainly manifests by positive symptoms, negative symptoms, disorganized behavior and thought and cognitive impairments. Taken together, these symptoms have substantial impact on quality of life, well-being and functional outcome. Patients with schizophrenia have dramatically higher levels of cardiovascular and metabolic morbidity than the general population due to poor physical fitness and to sedentary lifestyle. They have a reduced life expectancy, and an excess mortality being two or three times more than that in the general population. Moreover, despite major therapeutic advances in the overall management of these patients, some symptomatic dimensions, and more specifically the negative and cognitive ones, remain to be resistant to the usual pharmacological approaches. Moreover, antipsychotics can also reinforce the global cardiovascular risk due to side effects and low neurometabolic tolerance. The benefits of physical activity on health are now well described in the general population and in many medical diseases. More recently, physical activity has also found its place as an adjuvant therapy in severe mental illnesses, particularly in schizophrenia. In the literature physical activity programs, in addition to pharmacological treatments, appear to be feasible in patients and improve both physical and mental health as well as functional outcome. Clinical benefits of physical activity would be underpinned by biological and cerebral mechanisms, which remain unclear. In this review, we propose to present a state of the art and to present an update of the interests of physical activity in the management of patients with schizophrenia. We emphasize the clinical benefits of physical activity regarding the different symptomatic dimensions and its impact specifically on cognitive deficits. Finally, we describe the various underlying pathophysiological mechanisms in particular in the neurobiological, cerebral and physiological fields. We then discuss the barriers, facilitators and motivating factors towards physical activity to enhance health promotion initiatives, to optimize resource allocation when delivering physical activity programs in clinical practice, and to maximize physical activity participation. Physical activity appears to be an original and novel adjunctive therapeutic approach in the management of patients with schizophrenia and would both reduce schizophrenic symptoms and act like pro-cognitive therapy, improve quality of life and long-term functioning in daily life and reduce cardiovascular comorbidities. However, efforts are still needed to increase the motivating factors and adherence towards physical activity participation for people with schizophrenia.

[Validation of the French version of the self-evaluation of negative symptoms (SNS)]. / Validation de la version française de l'échelle autoévaluation des symptômes négatifs (SNS).

INTRODUCTION: Schizophrenia is a disorder affecting 1% of the population and is associated with severe functional impairment. Negative symptoms are responsible for the majority of this impairment, and many patients with schizophrenia have negative symptoms. However, their evaluation is still a challenge. Thus, standardized assessments are needed to facilitate identification of these symptoms. Many tools have been developed, but most are based on observer ratings. Self-evaluation can provide an additional outcome measure and allow patients to be more engaged in their treatment. The Self-evaluation of Negative Symptoms (SNS) has been developed recently. This is a remarkably understandable instrument for patients with schizophrenia as it allows them to readily complete it without assistance, providing information with respect to their own perception of negative symptoms. The SNS is a self-assessment that permits patients to evaluate themselves in 5 dimensions of negative symptoms. This validation study for the SNS revealed good psychometric properties alongside satisfactory acceptance by patients. AIM: This study was to confirm the validation of the French version of the self-evaluation of negative symptoms (SNS). METHODS: Patients with schizophrenia or schizoaffective disorder according to the DSM-IV-R, with a stable regimen of anti-psychotic drugs for the last two months, aged more than 18 years old were eligible for the study. Symptoms were rated using the SNS, the Scale for the Assessment of Negative Symptoms (SANS), the Calgary Depression Scale for Schizophrenics (CDSS), the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression and Parkinsonism. Patients were asked to fulfill the SNS twice, 6 weeks apart. RESULTS: Sixty patients were evaluated. Cronbach's coefficient (α=0.8) showed good internal consistency. The SNS significantly correlated with the SANS (r=0.6), the negative sub-score of the BPRS (r=0.6) and the Clinician Global Impression on the severity of negative symptoms (r=0.7). SNS scores did not correlate with level of insight (r=0.08) or Brief Psychiatric Rating Scale positive sub-scores (r=0.2). SNS scores correlated with CDSS scores. However, we did not find correlation between the first item of the CDSS which evaluates depression and the "diminished emotional range" sub-score of SNS. The test-retest of SNS revealed no changes of scores at two evaluations 6 weeks apart. CONCLUSION: The acceptance by patients of the SNS was excellent. The French version of the SNS demonstrated a good internal consistency, good convergent validity and good discriminant validity. The study demonstrates the ability of patients with schizophrenia to accurately report their own experiences. Self-assessments of negative symptoms should be more widely employed in clinical practice because they may allow patients with schizophrenia to develop appropriate coping strategies.

[Association between the violence in the community and the aggressive behaviors of psychotics during their hospitalizations]. / Relation entre la violence intra-hospitalière des patients avec psychoses et la violence dans la communauté.

BACKGROUND: Violence is a common issue in psychiatry and has multiple determiners. The aim of this study is to assess the psychotic inpatients' violence in association with the violence of the neighborhood from which the patients are drawn and to estimate the impact of this environmental factor with regard to other factors. METHOD: A prospective multicenter study was led in nine French cities. Eligible patients were psychotic involuntary patients hospitalized in the cities' psychiatric wards. During their treatments, any kind of aggressive behavior by the patients has been reported by the Overt Aggression Scale (OAS). RESULTS: From June 2010 to May 2011, 95 patients have been included. Seventy-nine per cent of the patients were violent during their hospitalizations. In a bivariate analysis, inpatient violence was significantly associated with different factors: male gender, patient violence history, substance abuse, manic or mixed disorder, the symptoms severity measured by the BPRS, the insight degree and the city crime rate. In a multivariate analysis, the only significant factors associated with the patients' violence were substance abuse, the symptoms severity and the crime rates from the different patients' cities. CONCLUSION: These results suggest that violence within the psychotic patients' neighborhood could represent a risk of violence during their treatments.

Impact of rTMS on functional connectivity within the language network in schizophrenia patients with auditory hallucinations.

This exploratory study investigated the functional connectivity (FC) in the language network in schizophrenia patients (SZ) with auditory verbal hallucinations (AVHs), and the therapeutic efficacy of rTMS on it. Eleven SZ with AVHs and 10 healthy controls (HC) underwent two fMRI sessions using a speech listening paradigm. SZ received 20Hz rTMS following the first fMRI session. Compared to HC, SZ showed a reduced FC in the language network. While AVHs improved after 12days, no changes in FC were observed. This suggests the efficacy of high-frequency rTMS on AVH without any impact for rTMS on FC within the language network.

Catatonic syndrome: From detection to therapy.

INTRODUCTION: Catatonia is a psychomotor syndrome which can include motor, mental, behavioral and vegetative symptoms. Exclusively associated with schizophrenia until the 1970s, catatonia still remains an under-diagnosed syndrome with significant morbidity and mortality. LITERATURE FINDINGS: As a result of its different forms and developments, catatonic syndrome can be associated with many organic and psychiatric etiologies and confused with a variety of diagnoses. In addition to its organic complications, malignant catatonia can also be extremely severe. Several diagnostic scales are described, those of Bush and Peralta being the most widely used. Despite the recent development of the DSM-5, we can regret the lack of progress in the international classifications concerning both the recognition of the etiological diversity of this syndrome and in the clinical and therapeutic approaches to it. The diagnosis is based solely on clinical data, and needs to be completed by information from paraclinical settings, particularly with respect to detecting organic etiology. The first-line treatment is still based on the use of certain benzodiazepines or benzodiazepine-like agents such as lorazepam, diazepam and zolpidem. If the first or second line fails, or in case of malignant catatonia, electroconvulsive therapy is recommended. For the periodic form, no large-sample study has been performed on long-term treatment. A few case reports suggest the use of lithium in periodic catatonia, specifically to prevent recurrent episodes or at least to extend the inter-episode intervals. Other studies are in favor of the use of benzodiazepines, with disagreement between gradual discontinuation and long-term treatment. Concerning the management of catatonia in patients with schizophrenia, for whom first-line benzodiazepines are often insufficient, certain atypical antipsychotics such as clozapine or quetiapine appear efficient. These data are also applicable to children and adolescents. CONCLUSION: Often neglected by practitioners, catatonic syndrome remains a common entity of which it is important to be aware, especially in case of rapid installation of the symptoms. Diagnostic scales should be used and a lorazepam test should be performed to avoid delaying the diagnosis. Second-line therapy requires further study. This concerns in particular diazepam, anti-NMDA (N-methyl-D-aspartate) and rTMS (repetitive transcranial magnetic stimulation). Some specificities of catatonia, such as the periodic form and cases in patients with schizophrenia, also require further evaluations.

[Can men be included in the population subjected to puerperal psychosis? A case report]. / Psychose puerpérale chez l'homme : une entité diagnostique ?

INTRODUCTION: Puerperal psychosis (PP) is a psychiatric disorder that occurs in 1 out of 1000 pregnancies. Well known since antiquity, its symptoms have often been described in mothers, but few studies have successfully investigated a related disorder in fathers. The characteristic of this pathology is more related to its appearance than to its semiological description which is why its nosographic place is always discussed. The objective here is to focus on the definition of PP and to suggest an entity for both genders. CASE REPORT: Our case report focused on the clinical description of an eighteen-year-old man suffering from an acute psychosis episode that occurred around the birth of his first child. Delusion followed a sudden decline in mood that lasted for a short period of time during the course of the third trimester of his wife's pregnancy. The delirium was rich with auditory and cenesthesic hallucinations, pregnancy and birth denial, feeling movements and hearing voices in his stomach. The symptoms disappeared after one month of treatment via an antipsychotic drug, risperidone. CONCLUSION: We can confirm that the symptomatic description of the disorder in this patient fits the classical descriptions of PP. Two elements make the PP different from other acute psychoses: the context of pregnancy and delirium focused on the child which can lead to a child murder. The absence of a framework precisely defining the PP does not improve its prevention and can lead to legal attitudes rather than medical care. Men suffering from acute psychosis in a context of pregnancy are submitted to the same risks as women. It is necessary to emphasize descriptions of PP in men to redefine the disease and consider that this entity involves both men and women.

[Scale for assessing negative symptoms in schizophrenia: A systematic review]. / Symptômes négatifs de la schizophrénie: une revue des instruments d'évaluation.

INTRODUCTION: Negative symptoms are a fundamental dimension of schizophrenia despite their limited role in the international diagnostic classification. Although a consensual definition seems to be attempted regarding the main negative dimensions (anhedonia, alogia, social withdrawal, blunted affect, avolition), several standardized assessment scales have been created. OBJECTIVES: The objective of this study was to identify a set of unidimensional instruments which allows an assessment of negative symptoms in schizophrenia and also to identify their general characteristics and the items included. METHODS: Inclusion criteria were: (a) the unidimensional assessment scales of negative symptoms of schizophrenia; (b) instruments in English (with French versions if possible); (c) all assessment instruments, the oldest and the most recent. The investigation ended in February 2013. RESULTS: Twelve unidimensional instruments were identified with only one of them based on a self-administered survey (MAP-SR). The number of items included is from 6 (SDS) to 25 (SANS). The fastest instrument is the HEN (5-10min) and the longest is the SANS (30min). The MASS needs an evaluation by another person (family or care-giver). Most instruments need to be handled and take place during a semi-structured or structured psychiatric interview. The SANS allows an assessment of the most important number of negative domains (11 domains). On the other side, we have the MAP-SR (3 domains). The most frequently evaluated domains are emotional blunting, alogia, social withdrawal, anhedonia and avolition. On the other side, we have mood and thought disorders. Only SDS allows to distinguish the primary and secondary negative symptoms. DISCUSSION: The oldest instruments (SANS, NSA-16, SDS) are more complicated to handle and to use. The SANS is the most complete instrument but there are more recent instruments which are easier to use and handle (BNSS, CAINS). Using a self-evaluation survey, MAP-SR is judicious as this type of evaluation is reliable. However, in this case, the assessment covers only a limited part of the negative symptoms. CONCLUSION: Despite some progress in the definition, assessment and treatment of negative symptoms and despite new scales further instruments which are easy to use in clinical practice and integrating the patient's self-report are needed.

[Pseudo-pheochromocytoma due to iproniazid: A case report]. / Pseudo-phéochromocytome médicamenteux sous iproniazide : à propos d'un cas.

INTRODUCTION: Pheochromocytoma is suggested by the presence of severe and paroxysmal hypertension associated with hyperadrenergy clinical signs. If the diagnosis of pheochromocytoma is ruled out, a pseudo-pheochromocytoma should be considered. We report a clinical observation of pseudo-pheochromocytoma due to iproniazid, a non-selective irreversible monoamine oxidase (MAO) A and B inhibitor in a patient with bipolar disorder. CASE REPORT: A 78-year-old Caucasian male patient treated by iproniazid was hospitalized for depressive relapse. After several episodes of syncopes related to orthostatic hypotension, the patient presented hypertensive crisis. Urinary normetanephrines were increased to twice the upper limit of the normal range. Iproniazid was discontinued. Patient hemodynamic was rapidly stabilized and sympathetic hypertonia diminished. The urinary measurements normalized within two months. The abdominal imaging eliminated an adrenal tumor. CONCLUSION: Iproniazid could be responsible for severe irregular blood pressure associated with abnormal catecholamine metabolism (i.e. pseudo-pheochromocytoma).

[Cognitive deficits in first episode psychosis patients and people at risk for psychosis: from diagnosis to treatment]. / Troubles cognitifs des sujets présentant un premier épisode psychotique et à haut risque de transition vers la psychose: du repérage à la prise en charge.

BACKGROUND: Up to now, studies have not demonstrated significant efficacy of antipsychotics on cognitive impairments in patients with psychotic disorders. These cognitive deficits are of particular interest since they traditionally start early before the diagnosis of psychosis. They are observed during premorbid and prodromal stages, and during the first episode of psychosis. Moreover, cognitive impairments may be detected without any psychotic symptoms (such as positive symptoms) suggesting their development independently of the psychotic symptoms. Cognitive disturbances consist of impairments of episodic and working memories, intellectual functioning, executive functions (planning, inhibition, and cognitive flexibility), selective and sustained attentions and social cognition (emotion, recognition, theory of mind). The altered cognitive functions observed in schizophrenia are the same as in earlier stages but at a lower level of severity. LITERATURE FINDINGS: Data suggest that cognitive deficits can be considered as vulnerability markers of psychosis since they have been described in healthy relatives of psychotic patients with high genetic risk. Cognitive deficits might also be considered as predictive of the occurrence of the disease after the first episode of psychosis. Indeed, retrospective studies suggest cognitive impairments in patients with schizophrenia during premorbid and prodromal phases but not in bipolar patients. Cognitive assessment might be of particular interest in people at risk for psychosis, in order to differentiate diagnostic outcomes. Cognitive functioning impairs until the diagnosis of first episode psychosis, even though cognitive profiles are quite heterogeneous in these patients. Once the diagnosis of schizophrenia is considered, cognitive deficits may be stable, although the literature is still controversial. Several factors such as symptoms and gender can contribute in diversifying the cognitive profiles. Moreover, age of onset might worsen the prognosis because of a disruption of the cognitive development and the disturbance of scholarship in young individuals. DISCUSSION: Considering these results, the treatment of cognitive deficits should be initiated as soon as possible, e.g. in people at risk for psychosis in order to reinforce the normal cognitive development, prevent cognitive decline and to preserve the educational, professional and social status. Since antipsychotic medications do not impact on cognitive functioning, alternative therapeutics should be developed such as cognitive remediation. Several studies and meta-analyses have shown that cognitive remediation programs are particularly efficient in patients with schizophrenia or bipolar disorders. Contrary to antipsychotics, these techniques should be used in patients with a first psychotic episode, but also in individuals with subpsychotic symptoms, subthreshold to the diagnosis of schizophrenia.

Comorbid substance abuse in first-episode schizophrenia: effects on cognition and psychopathology in the EUFEST study.

UNLABELLED: Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients. METHOD: In a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N=119, consisting of N=88 patients with persisting SUD at baseline and N=31 patients with previous SUD) and without SUD (FE-non-SUD, N=204) were compared at baseline and 6 months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding. RESULTS: In total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p=0.033, Cohen's d=0.26) in patients with SUD at 6 months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p=0.008, Cohen's d=0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16 years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption. CONCLUSIONS: FE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6 months of antipsychotic treatment.