Stigma resistance is associated with advanced stages of personal recovery in serious mental illness patients enrolled in psychiatric rehabilitation.

BACKGROUND: Stigma resistance (SR) is defined as one's ability to deflect or challenge stigmatizing beliefs. SR is positively associated with patient's outcomes in serious mental illness (SMI). SR appears as a promising target for psychiatric rehabilitation as it might facilitate personal recovery. OBJECTIVES: The objectives of the present study are: (i) to assess the frequency of SR in a multicentric non-selected psychiatric rehabilitation SMI sample; (ii) to investigate the correlates of high SR. METHODS: A total of 693 outpatients with SMI were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluation included standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, and personal recovery and a large cognitive battery. SR was measured using internalized stigma of mental illness - SR subscale. RESULTS: Elevated SR was associated with a preserved executive functioning, a lower insight into illness and all recovery-related outcomes in the univariate analyses. In the multivariate analysis adjusted by age, gender and self-stigma, elevated SR was best predicted by the later stages of personal recovery [rebuilding; p = 0.004, OR = 2.89 (1.36-4.88); growth; p = 0.005, OR = 2.79 (1.30-4.43)). No moderating effects of age and education were found. CONCLUSION: The present study has indicated the importance of addressing SR in patients enrolled in psychiatric rehabilitation. Recovery-oriented psychoeducation, metacognitive therapies and family interventions might improve SR and protect against insight-related depression. The effectiveness of psychiatric rehabilitation on SR and the potential mediating effects of changes in SR on treatment outcomes should be further investigated in longitudinal studies.

Being parent is associated with suicidal history in people with serious mental illness enrolled in psychiatric rehabilitation.

Parenting is a central life experience that could promote recovery in people with Serious Mental Illness (SMI). It could also be challenging for parents with SMI and result in poor recovery-related outcomes. Parenting is often overlooked in psychiatric rehabilitation. The objectives of the present study were to identify the characteristics and needs for care of mothers and fathers with SMI enrolled in a multicentric non-selected psychiatric rehabilitation SMI sample. We consecutively recruited 1436 outpatients from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). The evaluation included standardized scales for clinical severity, psychosocial function, quality of life and satisfaction with life, wellbeing, personal recovery and a broad cognitive battery. We found that parenting was associated to suicidal history in mothers and fathers with SMI. In the multivariate analysis, being mother was best explained by insight (p < 0.015, adjusted OR = 0.76 [0.59-0.90]), current age (p < 0.001, aOR = 1.13 [1.07-1.21]), education level (p = 0.008; aOR = 0.12 [0.02-0.53]) and family accommodation (p = 0.046, aOR = 0.19 [0.03-0.84]). Being father was best explained by suicidal history (p = 0.005, aOR = 3.85 [1.51-10.10]), marital status (in relationship, p < 0.001; aOR = 7.81 [2.73-23.84]), satisfaction with family relationships (p = 0.032, aOR = 1.22 [1.02-1.47]) and current age (p < 0.001, aOR = 1.16 [1.10-1.23]). In short, parenting was associated to increased history of suicide attempt in mothers and fathers with SMI. Mothers and fathers with SMI may have unique treatment needs relating to parenting and recovery-related outcomes. The implementation of interventions supporting the needs of parents with SMI in psychiatric rehabilitation services could improve parent and children outcomes.

Cognitive remediation and professional insertion of people with schizophrenia: RemedRehab, a randomized controlled trial.

BACKGROUND: People suffering from schizophrenia cannot easily access employment in European countries. Different types of vocational programs coexist in France: supported employment, sheltered employment (ShE), and hybrid vocational programs. It is now acknowledged that the frequent cognitive impairments constitute a major obstacle to employment for people with schizophrenia. However, cognitive remediation (CR) is an evidence-based nonpharmacological treatment for these neurocognitive deficits. METHODS: RemedRehab was a multicentric randomized comparative open trial in parallel groups conducted in eight centers in France between 2013 and 2018. Participants were recruited into ShE firms before their insertion in employment (preparation phase). They were randomly assigned to cognitive training Cognitive Remediation for Schizophrenia (RECOS) or Treatment As Usual (TAU). The aim of the study was to compare with the benefits of the RECOS program on access to employment and work attendance for people with schizophrenia, measured by the ratio: number of hours worked on number of hours stipulated in the contract. RESULTS: Seventy-nine patients were included in the study between October 2018 and September 2019. Fifty-three patients completed the study. Hours worked / planned hours equal to 1 or greater than 1 were significantly higher in the RECOS group than in the TAU group. CONCLUSIONS: Participants benefited from a RECOS individualized CR program allows a better rate of work attendance in ShE, compared to the ones benefited from TAU. Traditional vocational rehabilitation enhanced with individualized CR in a population of patients with schizophrenia is efficient on work attendance during the first months of work integration.

Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti.

BACKGROUND: Incontinentia pigmenti (IP) is a rare multisystemic X-linked dominant genetic disorder characterized by highly diagnostic skin lesions. The disease can be misdiagnosed in infants, and complications affecting the eyes and/or the brain can be severe. Our objective was to highlight the urgency of an appropriate diagnosis and management strategy, as soon as the first symptoms appear, and the need for a well-codified monitoring strategy for each child. METHODS: An in-depth literature review using a large number of databases was conducted. The selection criteria for articles were literature review articles on the disease, case series and retrospective studies based on the disease, clinical studies (randomized or not) on treatment, articles discussing patient care and management (treatment, diagnosis, care pathways), and recommendations. The research period was from 2000 until 2018. A group of multidisciplinary experts in IP management was involved, issued from different healthcare providers of the European Network for Rare Skin Diseases (ERN-Skin). The final recommendations have been submitted to two patient representative associations and to a general practitioner and a neonatal specialist prior to their finalization. RESULTS AND CONCLUSION: The diagnosis of IP must be promptly performed to detect potential extracutaneous manifestations, thus allowing the timely implementation of specific therapeutic and monitoring strategies. Eye involvement can be a therapeutic urgency, and central nervous system (CNS) involvement requires a very rigorous long-term follow-up. Assessments and patient support should take into account the possible co-occurrence of various symptoms (including motor, visual and cognitive symptoms).

Self-stigma in serious mental illness and autism spectrum disorder: Results from the REHABase national psychiatric rehabilitation cohort.

BACKGROUND: Self-stigma is a major issue in serious mental illness (SMI) and is negatively associated with patient outcomes. Most studies have been conducted in schizophrenia (SZ). Less is known about self-stigma in other SMI and autism spectrum disorder (ASD). The objectives of this study are: (i) to assess the frequency of self-stigma in a multicentric nonselected psychiatric rehabilitation SMI and ASD sample; and (ii) to investigate the correlates of elevated self-stigma in different SMI conditions and in ASD. METHODS: A total of 738 SMI or ASD outpatients were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluations included sociodemographic data, illness characteristics, and standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, personal recovery, a large cognitive battery, and daily functioning assessment. RESULTS: 31.2% of the total sample had elevated self-stigma. The highest prevalence (43.8%) was found in borderline personality disorder and the lowest (22.2%) in ASD. In the multivariate analysis, elevated self-stigma was best predicted by early stages of personal recovery (moratorium, p = 0.001, OR = 4.0 [1.78-8.98]; awareness, p = 0.011, OR = 2.87 [1.28-6.44]), history of suicide attempt (p = 0.001, OR = 2.27 [1.37-3.76]), insight (p = 0.002, OR = 1.22 [1.08-1.38]), wellbeing (p = 0.037, OR = 0.77 [0.60-0.98]), and satisfaction with interpersonal relationships (p < 0.001, OR = 0.85 [0.78-0.93]). CONCLUSIONS: The present study has confirmed the importance of addressing self-stigma in SMI and ASD patients enrolled in psychiatric rehabilitation. The effectiveness of psychiatric rehabilitation on self-stigma and the potential mediating effects of changes in self-stigma on treatment outcomes should be further investigated.

[Preventing violence in schizophrenia with cognitive remediation]. / Prévenir la violence associée à la schizophrénie avec la remédiation cognitive.

OBJECTIVES: The association between schizophrenia and violence represents an important issue in psychiatry. Often highly publicized, violent acts raise the question of their detection, prevention, management and treatment. There is no single, direct and exclusive link between aggressiveness and the underlying psychiatric disorder. On the contrary, the processes underlying this violence are multiple and interlinked. In addition to static and dynamic risk factors, cognitive deficits play an important role in the genesis and maintenance of violent and aggressive behavior. METHODS: Using recent data from the international literature and the main databases, we first clarify the role played by cognitive deficits in the violence of patients with schizophrenia. We then evaluate the place of psychosocial interventions such as cognitive remediation and social cognitive training in managing the violent and aggressive behavior of these patients. RESULTS: Executive functions and working memory are the most studied neurocognitive functions in the field of violence in schizophrenia. Impulsivity, lack of cognitive flexibility, lack of adaptation and inhibition of automatic motor responses, and altered anger regulation may explain this relationship. Three main components of social cognition are associated with violent behaviors in schizophrenia: (1) the recognition of facial emotions through the inoperability of systems of "emotional monitoring", violent inhibition and recognition of informative facial zones; (2) the theory of the mind through the erroneous interpretation of the intentions of others; (3) the attributional style through the preferentially aggressive over interpretation of social situations and weak capacities of introspection. Overall, cognitive biases inhibit response in a socially acceptable manner and increase the risk of responding impulsively and aggressively to a stressful or provocative situation. In this context, we studied the place held by psychosocial interventions in the management of the violent and aggressive behaviors of these patients. Various cognitive remediation programs have shown their feasibility in people with schizophrenia and neurocognitive deficits with a history of violence as well as their effectiveness in reducing violence, mainly by reducing impulsivity. Similarly, specific programs dedicated to social cognitive training such as Social Cognition and Interaction Training (SCIT), Reasoning and Rehabilitation Mental Health Program (R&R2 MHP) and Metacognitive Training (MCT) have shown their positive impact on the control and reduction of global aggressive attitudes and on the numbers of physical and verbal aggressive incidents in schizophrenia. The improvement of social cognition would be achieved through the amendment of interpersonal relationships and social functioning. These interventions are effective at different stages of disease progression, in patients with varied profiles, on violent attitudes in general and on the number of verbal and physical attacks, whether for in-patients or out-patients. Beneficial effects can last up to 12months after termination of the study program. The interest of these interventions is preventive if the subject never entered in a violent register or curative in case of a personal history of violence. This type of care can be considered from a symptomatic point of view by limiting downstream the heavy consequences of such acts, but also etiologically by acting on one of the causes of violent behavior. Compliance with the eligibility criteria, carrying out a prior functional analysis and confirmation of the major impulsive part of the patient's violence are prerequisites for the use of these programs. Similarly, the early introduction of such therapies, their repetition over time and the integration of the patient into a comprehensive process of psychosocial rehabilitation will ensure the best chance of success. CONCLUSIONS: Some cognitive impairments appear to have their place in the genesis, progression and maintenance of violent acts of individuals with schizophrenia. Their management thus opens new therapeutic perspectives such as cognitive remediation, still rarely used in this aim, to complement the action of the traditional care tools. However, further therapeutic trials are needed before considering cognitive remediation and social cognitive training as central care modalities in the therapeutic control of violence in schizophrenia.

[Social cognition in children with neurogenetic syndromes: A literature review]. / Cognition sociale dans les troubles neuro-génétiques de l'enfant : revue de la littérature.

Social cognitive impairments may largely contribute to reduced social skills and adaptive problems in individuals with microdeletion syndromes associated with behavioral and psychiatric phenotypes. Understanding the role of social information processing deficits in the emergence of psychotic disorders is a crucial challenge in the management of these patients. Each neurogenetic disorder is characterized by a specific social cognition phenotype. Clarifying the social ability profile of each population may help adjust patient care according to their key strengths and weaknesses. The main objective of this article is to review the social cognitive skills of various neurogenetic disorders and shed light on the specific mechanisms that may underlie these skills in each syndrome. After detailing the different processes unified under the generic term "social cognition", we present these processes in the most frequent microdeletion syndromes presenting with social interaction deficits: 22q11.2 deletion syndrome, Angelman syndrome, fragile X syndrome, Klinefelter syndrome, Prader-Willi syndrome, Rett syndrome, Smith-Magenis syndrome, Turner syndrome, and Williams syndrome. Finally, we highlight future approaches that may have a significant influence on the development of adapted therapeutic interventions, such as cognitive remediation therapies. The importance of connecting neurocognitive and social cognition remediations is also emphasized.

Cognitive remediation and social cognitive training for violence in schizophrenia: a systematic review.

A significant correlation exists between violence and schizophrenia (SCZ). Recent studies matched some cognitive deficits like strong risk factors for violence with interesting applications in terms of treatment. Our objective was to conduct a systematic review of the effectiveness of cognitive remediation (CR) and social cognitive training (SCT) in the management of violent and aggressive behaviors in SCZ. METHODS: The electronic databases Pubmed, Web of Science, Cochrane Library and ScienceDirect were searched in, using combinations of terms relating to SCZ, CR and violence. Studies were selected and data were extracted using a PRISMA statement. Inclusion criteria were adults with SCZ and a documented collection of disruptive and violent behaviors, for whom researchers had used a CR or SCT program. RESULTS: Eleven studies were identified, two related to non-specific CR intervention and nine to codified CR or SCT programs. Results showed that these programs had a positive impact on the control and reduction of global aggressive attitudes and physical assaults. Therapeutic targets were social cognition and executive functions through the improvement of interpersonal relationships and impulsivity feature respectively. Effectiveness was proved at various stages of the illness, in different types of patients and units, with effects persisting for up to 12 months after interruption of CR. Conclusions are limited by some methodological restrictions. CONCLUSION: Although current evidences need to be completed with further randomized studies, CR and SCT appear to be promising approaches in the management of violence in SCZ.

[Social cognition disorders in Klinefelter syndrome: A specific phenotype? (KS)]. / Troubles de la cognition sociale dans le syndrome de Klinefelter : un trait phénotypique ?

INTRODUCTION: The Klinefelter syndrome (KS) is a genetic condition characterized by an X supernumerary sex chromosome in males. The syndrome is frequently associated with cognitive impairment. Indeed, the different areas of the executive sphere can be affected such as inhibition, cognitive flexibility but also attentional and visual-spatial domain. Social cognition disorders, predominantly on emotional recognition processes, have also been documented. In addition, the syndrome may be associated with psychiatric symptoms. MATERIAL AND METHOD: Our study aims to characterize of the various components of social cognition in the SK: facial emotional recognition, theory of mind and attributional style. For this two groups (SK group versus control group) of participants (n=16) matched for age and sociocultural level were recruited. Participants with intellectual disabilities, psychiatric or neurological disorders were excluded. Three social cognition tests were available: the TREF, the MASC, the AIHQ. Neurocognitive functions were assessed by the fNart, the subtest "logical memory" of the MEM-III, the subtests of the two VOSP battery, the d2, the TMT and the Stroop test. RESULTS: The SK group had specific social cognition disorders in comparison to the control group. Two emotions in particular were less well recognized: fear and contempt. In addition, the SK group had significantly lower results in theory of mind. Regarding the hostile attribution bias, no significant difference was found. Finally, the results showed correlations between specific attentional disorders and facial emotional recognition. DISCUSSION-CONCLUSION: Our study emphasizes social cognition disorders in SK. These disorders could be considered as a phenotypic trait in the syndrome. The interest of better characterizing the cognitive phenotype of genetic disorders that can affect the neurodevelopment is to offer specific cognitive remediation strategies.

[Smith-Magenis syndrome is an association of behavioral and sleep/wake circadian rhythm disorders]. / Le syndrome de Smith-Magenis, une association unique de troubles du comportement et du cycle veille/sommeil.

Smith-Magenis syndrome (SMS) is a genetic disorder characterized by the association of facial dysmorphism, oral speech delay, as well as behavioral and sleep/wake circadian rhythm disorders. Most SMS cases (90%) are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases stem from mutations of the RAI1 gene. Behavioral issues may include frequent outbursts, attention deficit/hyperactivity disorders, self-injuries with onychotillomania and polyembolokoilamania (insertion of objects into bodily orifices), etc. It is noteworthy that the longer the speech delay and the more severe the sleep disorders, the more severe the behavioral issues are. Typical sleep/wake circadian rhythm disorders associate excessive daytime sleepiness with nocturnal agitation. They are related to an inversion of the physiological melatonin secretion cycle. Yet, with an adapted therapeutic strategy, circadian rhythm disorders can radically improve. Usually an association of beta-blockers in the morning (stops daily melatonin secretion) and melatonin in the evening (mimics the evening deficient peak) is used. Once the sleep disorders are controlled, effective treatment of the remaining psychiatric features is needed. Unfortunately, as for many orphan diseases, objective guidelines have not been drawn up. However, efforts should be focused on improving communication skills. In the same vein, attention deficit/hyperactivity disorders, aggressiveness, and anxiety should be identified and specifically treated. This whole appropriate medical management is underpinned by the diagnosis of SMS. Diagnostic strategies include fluorescent in situ hybridization (FISH) or array comparative genomic hybridization (array CGH) when a microdeletion is sought and Sanger sequencing when a point mutation is suspected. Thus, the diagnosis of SMS can be made from a simple blood sample and should be questioned in subjects of any age presenting with an association of facial dysmorphism, speech delay with behavioral and sleep/wake circadian rhythm disorders, and other anomalies including short stature and mild dysmorphic features.

[Neurocognitive and psychiatric management of the 22q11.2 deletion syndrome]. / 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 George's syndrome, velo-cardio-facial syndrome or Shprintzen's 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.

[Iatrogenic psychiatric-like symptoms recognition]. / 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.

The Emotional Stroop task: a comparison between schizophrenic subjects and controls.

The colour-word Emotional Stroop task (ES task) has been proposed to assess the interferences between emotion and attention. Using this task, first, we examined how attention (using reaction times) can be modified by emotionally relevant words in schizophrenics as compared with controls as a function of the emotional significance of the word; second, we tested the assumption that schizophrenics with the most negative symptoms will show higher impairment in relationship to negative emotional words. In general, schizophrenics were slower to react. In both groups, mean reaction times were slower for emotional as compared with neutral words. No significant differences were observed between negative and positive words either in schizophrenics (n=21) or in controls (n=20). Even in the most negative schizophrenic patients, there were no differences between negative and positive words. There were no significant interactions between type of stimulus and any clinical variables (PANSS negative or non negative categorization, etc.). Also, there were no statistically significant correlations between reaction times and neuroleptic dosage or anhedonia scores. In conclusion, schizophrenia patients showed the same degree of interference from emotional words as compared with controls. Moreover, patients with a higher level of negative symptoms did not differently experience positive and negative words.

[How to differentiate schizophrenia from bipolar disorder using cognitive assessment?]. / L'évaluation cognitive permet-elle de distinguer la schizophrénie du trouble bipolaire ?

BACKGROUND: Historical aspects of the dichotomy between manic-depressive disorders and schizophrenia raise the question of a continuum between the two entities. Griesinger (1817-1868) proposed a unitary concept of psychosis: "Einheitspsychose", adaptations of which have survived until the present day. Although Kraepelin's traditional dichotomy is still a common base for clinicians every day: diagnosis, prognosis and treatment of psychotic disorders, recent epidemiological and neurobiological data are congruent with a dimensional aspect of psychosis. Epidemiological data are consistent with the existence of an individual and a familial overlap between bipolar disorder and schizophrenia. Schizophrenia is probably the most debilitating psychological disorder. It was primarily considered as a behavioural disorder, characterized by socially inappropriate and bizarre behaviour, but much attention has been focussed nowadays on the cognitive component and the cognitive pathology underlying schizophrenia. On the other hand, bipolar, or manic depressive disorder has been primarily considered as a mood or affective disorder, characterized by excessive swings of emotion and motivation. Manic depression is more about recurrent dimensions. However, symptoms associated with the diagnosis of schizophrenia can be associated with psychotic mood disorders: hallucinations and delusions (50%), disorganised speech and behaviour (all patients with moderate to severe mania or mixed episode), negative symptoms (all patients with moderate to severe depression). The social and job dysfunction may be due to disturbances in the volitional system in patients with schizophrenia or severe bipolar disorder. LITERATURES FINDINGS: A considerable body of literature exists concerning the relationship between cognitive impairment in schizophrenia, but there is less data about cognition in bipolar disorder. However, there are some notable similarities between data observed in schizophrenia and bipolar disorder. Many domains of cognition are disrupted in schizophrenia with varying degrees of deficit. Concerning mood disorders, cognitive dysfunction could be considered as a state marker. Globally some studies indicate that, compared with schizophrenia, those with bipolar disorder display a similar but less severe neuropsychological pattern of impairment. However, it is only recently that cognitive dysfunction has been recognized as a primary and enduring core deficit in schizophrenia and further studies in bipolar disorder are needed. DISCUSSION: In this way, it has been suggested that psychotic symptoms may be distributed along a continuum that extends from schizophrenia to psychotic mood disorders with increasing level of severity. An explicative theory has to explain the evolution and the similarities between those affections including genetic and environmental liability. Some individuals, who are at high risk for psychosis, can even develop bipolar disorder or schizophrenia. Likewise, common factors can explain cognitive and social disorders in psychosis. So, there are various arguments for the dimensional approach of psychosis. These data are not completely in contradiction with Kraepelin: schizophrenia is a chronic affection and bipolar disorder is a cyclic pathology. However, common symptoms are not in favour of a strict categorization.

Hyperprolinemia is a risk factor for schizoaffective disorder.

DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case-control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P=0.02, Odds ratio=4.6, 95% confidence interval 1.3-16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and we found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an intermediate phenotype associated with certain forms of psychosis.

The promoter -194 C polymorphism of the nicotinic alpha 7 receptor gene has a protective effect against the P50 sensory gating deficit.

As suggested by several studies, abnormal sensory gating measured by the P50 paradigm could be an endophenotype predisposing to schizophrenia. In a previous work, we have shown a significant association between the presence of at least one -2 bp deletion located within exon 6 of the CHRNA7-like gene and the P50 abnormality in the general population. A recent study involved polymorphisms located in the core promoter region of the CHRNA7 gene as risk factors for the P50 inhibitory deficit. Screening for promoter variants in a large population of schizophrenic patients (n=111) and control subjects (85), for whom auditory-evoked potentials had been recorded did not allow us to replicate these results. By contrast, we showed a significant association between the -194 C allele and a T/C ratio <0.45, thus demonstrating a protective effect of this variant for the sensory gating deficit. Such conflicting results can be reconciled if we consider that the -194 C polymorphism has no causative effect, but is in linkage disequilibrium with other causal variations for the P50 sensory gating deficit, and that different alleles are in disequilibrium in different populations.