Caroline Demily

Cognitive remediation: a promising tool for the treatment of schizophrenia

Cognitive remediation is a type of treatment added recently to the range of tools available to therapists. It includes a number of miscellaneous methods that aim to correct some of the cognitive impairments observed in schizophrenia. These cover the fields of target attention, memory and executive deficits, as well as impaired social cognition. Cognitive remediation acts as a complement to medication and psychological therapies, which constitute the core methods of treatment for schizophrenia. The present paper reviews the state of the art in cognitive remediation. The principle underlying this innovative therapeutic approach is the enhancement of the cognitive resources of patients with schizophrenia in order to improve their cognitive functions, social skills and in some cases alleviate some of the symptoms of the disease. Several programs developed within the past two decades (e.g., IPT, CRT, NEAR, CET, NET, CRT and CAT) are becoming more widely used. Their efficacy on neurocognition and on functional outcome has been demonstrated, with inconstant continuation of benefit after completion of treatment. The sustainability of the cognitive and functional improvements following completion of these programs has to be further studied. Other programs aimed at acting upon altered social cognition (one of the critical facets of schizophrenia) are still in the experimental stages, but the results obtained so far are encouraging. A preliminary study has also demonstrated the effectiveness of board games in improving cognitive functioning, which seems to be a highly promising therapeutic avenue owing to its ease of use.

Brain-derived neurotrophic factor in schizophrenia and its relation with dopamine.

The brain-derived neurotrophic factor (BDNF) belongs to the neurotrophins family and has a role in proliferation, differentiation of neurons but also as a neurotransmitter. This neurotrophin has received much attention during the last year in regard of the pathophysiology of schizophrenia. Results of genetic studies conducted in schizophrenia support a role for BDNF in schizophrenia and in brain function associated with the disorder. The changes of BDNF observed in the brain and in the plasma of patients with schizophrenia have generated results that can be interpreted either as a hallmark of the disease or a consequence of antipsychotic drugs. Antipsychotic drugs act by blocking the dopamine transmission at the dopamine D2-like receptors. BDNF controls the expression of one of these D2-like receptors, the dopamine D3 receptor. This raises the hypothesis of a link between cortical area, via BDNF, and the dopamine neurotransmission pathway in schizophrenia and its treatment.

Delusions and metacognition in patients with schizophrenia.

Introduction. The aim of the present study was to explore the basis of the strong feeling of conviction and the high resistance to change characteristic of delusions and to test whether patients with schizophrenia suffering from delusions have specific metacognitive impairments when compared to both patients without delusions and healthy controls. Methods. 14 actively delusional patients with schizophrenia, 14 nondelusional patients, and 14 healthy subjects were administered two measures assessing different aspects of metacognition: an emotional metacognitive version of the WCST adapted from Koren et al. (2004) and the Beck Cognitive Insight Scale. Results. Relative to both healthy controls and nondelusional patients, delusional participants were specifically impaired on metacognitive measures of free choice improvement and global monitoring. This was correlated with high self-certainty on the BCIS relative to nondelusional patients. Conclusions. Our results suggest that metacognitive impairments play an important role in the maintenance of delusional beliefs. It may therefore be important to adapt remediation strategies to the metacognitive profiles of patients.

The Odor Context Facilitates the Perception of Low-Intensity Facial Expressions of Emotion

It has been established that the recognition of facial expressions integrates contextual information. In this study, we aimed to clarify the influence of contextual odors. The participants were asked to match a target face varying in expression intensity with non-ambiguous expressive faces. Intensity variations in the target faces were designed by morphing expressive faces with neutral faces. In addition, the influence of verbal information was assessed by providing half the participants with the emotion names. Odor cues were manipulated by placing participants in a pleasant (strawberry), aversive (butyric acid), or no-odor control context. The results showed two main effects of the odor context. First, the minimum amount of visual information required to perceive an expression was lowered when the odor context was emotionally congruent: happiness was correctly perceived at lower intensities in the faces displayed in the pleasant odor context, and the same phenomenon occurred for disgust and anger in the aversive odor context. Second, the odor context influenced the false perception of expressions that were not used in target faces, with distinct patterns according to the presence of emotion names. When emotion names were provided, the aversive odor context decreased intrusions for disgust ambiguous faces but increased them for anger. When the emotion names were not provided, this effect did not occur and the pleasant odor context elicited an overall increase in intrusions for negative expressions. We conclude that olfaction plays a role in the way facial expressions are perceived in interaction with other contextual influences such as verbal information.

Cognitive remediation therapy (CRT) benefits more to patients with schizophrenia with low initial memory performances.

Abstract Purpose: Cognitive deficits in schizophrenia mainly affect memory, attention and executive functions. Cognitive remediation is a technique derived from neuropsychology, which aims to improve or compensate for these deficits. Working memory, verbal learning, and executive functions are crucial factors for functional outcome. Our purpose was to assess the impact of the cognitive remediation therapy (CRT) program on cognitive difficulties in patients with schizophrenia, especially on working memory, verbal memory, and cognitive flexibility. Methods: We collected data from clinical and neuropsychological assessments in 24 patients suffering from schizophrenia (Diagnostic and Statistical Manual of mental Disorders-Fourth Edition, DSM-IV) who followed a 3-month (CRT) program. Verbal and visuo-spatial working memory, verbal memory, and cognitive flexibility were assessed before and after CRT. Results: The Wilcoxon test showed significant improvements on the backward digit span, on the visual working memory span, on verbal memory and on flexibility. Cognitive improvement was substantial when baseline performance was low, independently from clinical benefit. Conclusions: CRT is effective on crucial cognitive domains and provides a huge benefit for patients having low baseline performance. Such cognitive amelioration appears highly promising for improving the outcome in cognitively impaired patients. Implications for Rehabilitation Cognitive impairment is observed in 70–80% of patients with schizophrenia a devastating disorder with high direct and indirect social costs and cognitive alterations are a crucial predictive factor for an inability to work. Cognitive remediation is an efficient technique to improve cognition, autonomy, and social functioning in patients. Individual structure programs are successful to improve working memory, verbal learning and flexibility in this study.

Facial emotion perception by intensity in children and adolescents with 22q11.2 deletion syndrome

Difficulties in the recognition of emotions in expressive faces have been reported in people with 22q11.2 deletion syndrome (22q11.2DS). However, while low-intensity expressive faces are frequent in everyday life, nothing is known about their ability to perceive facial emotions depending on the intensity of expression. Through a visual matching task, children and adolescents with 22q11.2DS as well as gender- and age-matched healthy participants were asked to categorise the emotion of a target face among six possible expressions. Static pictures of morphs between neutrality and expressions were used to parametrically manipulate the intensity of the target face. In comparison to healthy controls, results showed higher perception thresholds (i.e. a more intense expression is needed to perceive the emotion) and lower accuracy for the most expressive faces indicating reduced categorisation abilities in the 22q11.2DS group. The number of intrusions (i.e. each time an emotion is perceived as another one) and a more gradual perception performance indicated smooth boundaries between emotional categories. Correlational analyses with neuropsychological and clinical measures suggested that reduced visual skills may be associated with impaired categorisation of facial emotions. Overall, the present study indicates greater difficulties for children and adolescents with 22q11.2DS to perceive an emotion in low-intensity expressive faces. This disability is subtended by emotional categories that are not sharply organised. It also suggests that these difficulties may be associated with impaired visual cognition, a hallmark of the cognitive deficits observed in the syndrome. These data yield promising tracks for future experimental and clinical investigations.

Améliorer le pronostic fonctionnel de la schizophrénie avec la remédiation cognitive

The functional outcome of schizophrenia is partly conditioned by cognitive disorders associated with this disease. The functional outcome of schizophrenia depends not only on psychotropic medications, but also on non-pharmacological measures and in particular on cognitive remediation. All patients suffering from schizophrenia should benefit from a multidisciplinary functional evaluation including neuropsychological assessment. The restitution of the functional evaluations results values preserved skills rather than deficits. Cognitive remediation should be considered when cognitive disorders have a functional impact. It reduces the impact of the patients cognitive disorders and improves the success of his/her concrete projects.

Perspectives actuelles dans la microdélétion 22q11.2 : prise en charge du phénotype neurocomportemental

INTRODUCTION The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22. 22q11.2DS has several presentations including Di Georges syndrome, velo-cardio-facial syndrome or Shprintzens syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). The inheritance of the syndrome (10%) is autosomal dominant. Most people with 22q11.2DS are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. A small percentage of affected individuals have shorter deletions in the same region (contiguous gene deletion syndrome). The general features of 22q11.2DS vary widely (more than 180 phenotypic presentations) and the syndrome is under diagnosed. Characteristic symptoms may include congenital heart disease, defects in the palate, neuromuscular problems, velo-pharyngeal insufficiency, hypoparathyroidism, craniofacial features and problems with the immune system T-cell mediated response (caused by hypoplasia of the thymus). COGNITIVE PHENOTYPE The neurocognitive phenotype of the 22q11.2DS is complex. Cognitive deficits are seen in the majority (80-100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory and visual-spatial perception. Borderline intellectual function (IQ: 70-75) is most common, mild intellectual disability (IQ: 55-75) is slightly less frequent and a small percentage of children fall into the low average intelligence range. Most children with 22q11.2DS achieve higher scores in verbal tasks than in non-verbal tasks, although this pattern of dysfunction being not universal. Brain MRI studies have shown volumetric changes in multiple cortical and subcortical regions in individuals with 22q11DS that could be related to both cognition and psychoses. PSYCHIATRIC PHENOTYPE General psychiatric features included anxiety disorders, attention deficit disorder and poor social skills (40-50%). An elevated risk of bipolar disorder and major depression occurs in adolescence and young adulthood. A strong and specific relationship exists between the presence of the 22q11.2 microdeletion and schizophrenia (30-40%). This risk is not associated with any other neurogenetic syndrome. Social cognition is impaired in 22q11.2 DS and this observation is correlated with psychotic features. So, long-term medical care is increasingly being directed towards the treatment and recognition of these symptoms. TREATMENT Required pharmacological treatment strategies have to be adapted to the syndrome. Moreover, cognitive remediation is a promising tool for treating neuro- and social cognitive deficits in 22q11.2DS. However, these new therapeutic strategies have to be developed to improve quality of life.

Reconnaître les symptômes psychiatriques iatrogènes liés aux antipsychotiques

INTRODUCTION This article proposes a review of atypical multicentre studies for drug-induced movement disorders (and related psychiatric symptoms) and supersensitivity psychosis. A well-conducted antipsychotic treatment consists of regular attempts to reduce the dose by finding the minimal therapeutic dose. To achieve optimal antipsychotic treatment, it is important to distinguish psychiatric symptoms associated with drug-induced movement disorder(s) (DIMD) or supersensitivity psychosis from true relapse. LITERATURE FINDINGS Persistent DIMD have been found to be a predictor of supersensitivity psychosis or tardive dyskinesia (DT). DIMD-associated psychiatric symptoms can be classified into three types: directly induced by DIMD; resulting from confounding DIMD with psychiatric symptoms; and supersensitivity symptoms associated with DIMD. Without this distinction, the beneficial effects of antipsychotics are masked by emergent DIMD psychiatric symptoms (as was confounded in the CATIE study). DISCUSSION A constant decline in the prevalence of TD (hyperkinetic, involuntary and purposeless movement disorder) has been observed since the introduction of atypical antipsychotics. The neurotoxic effects of classical antipsychotics are well documented and their discontinuation is required. However, the risk of TD still exits with atypical antipsychotics and continued surveillance of emerging cases is very important for clinicians. Moreover, a regular evaluation of DIMD and associated psychiatric symptoms is crucial. It is important to underline the fact that DIMD persists with antipsychotics, with significantly higher total PANSS scores than in patients without DIMD. CONCLUSION Supersensitivity psychosis is a drug-induced psychotic relapse (6 weeks following the decrease or withdrawal of an antipsychotic). Discontinuation syndromes can produce psychiatric symptoms (and be confounded with true relapse), but can be improved more quickly after reintroduction of treatment. Interestingly, various data suggest that lower doses of antipsychotics could prevent such symptoms. Anticonvulsants can be efficient adjuvants in the treatment of psychosis. In the United States, many patients received valproate or gabapentin treatment. These adjuvants, by antikindling effect, can facilitate minimal maintenance drug treatment and be efficient for anxiety. Resistant schizophrenia can be related to supersensitivity psychosis; gabapentin and lamotrigine are effective in this case.

Overview of Social Cognitive Dysfunctions in Rare Developmental Syndromes With Psychiatric Phenotype

Rare neurodevelopmental syndromes often present social cognitive deficits that may underlie difficulties in social interactions and increase the risk of psychosis or autism spectrum disorders. However, little is known regarding the specificities of social cognitive impairment across syndromes while it remains a major challenge for the care. Our review provides an overview of social cognitive dysfunctions in rare diseases associated with psychiatric symptoms (with a prevalence estimated between 1 in 1,200 and 1 in 25,000 live births: 22q11.2 deletion syndrome, Angelman syndrome, Fragile X syndrome, Klinefelter syndrome, Prader–Willi syndrome, Rett syndrome, Smith–Magenis syndrome, Turner syndrome, and Williams syndrome) and shed some light on the specific mechanisms that may underlie these skills in each clinical presentation. We first detail the different processes included in the generic expression “social cognition” before summarizing the genotype, psychiatric phenotype, and non-social cognitive profile in each syndrome. Then, we offer a systematic review of the social cognitive abilities and the disturbed mechanisms they are likely associated with. We followed the PRISMA process, including the definition of the relevant search terms, the selection of studies based on clear inclusion, and exclusion criteria and the quality appraisal of papers. We finally provide insights that may have considerable influence on the development of adapted therapeutic interventions such as social cognitive training (SCT) therapies specifically designed to target the psychiatric phenotype. The results of this review suggest that social cognition impairments share some similarities across syndromes. We propose that social cognitive impairments are strongly involved in behavioral symptoms regardless of the overall cognitive level measured by intelligence quotient. Better understanding the mechanisms underlying impaired social cognition may lead to adapt therapeutic interventions. The studies targeting social cognition processes offer new thoughts about the development of specific cognitive training programs, as they highlight the importance of connecting neurocognitive and SCT techniques.