Pilot study of the relationship between psychotic manifestations and living environment

The study of subclinical psychotic manifestations (quantitative schizotypy) represents clinical and public health issues. These manifestations are more common than schizophrenia or depression, but rarely identified while it impacts the quality of life. Screening schizotypy in the general population would make it possible to propose prevention strategies. The objectives of the present research is to better understand the determinants and mechanisms of schizotypy in order to identify population..

Handedness as a neurodevelopmental marker in schizophrenia: Results from the FACE-SZ cohort

Objectives: High rates of non-right-handedness (NRH) including mixed-handedness have been reported in neurodevelopmental disorders. In schizophrenia (SZ), atypical handedness has been inconsistently related to impaired features. We aimed to determine whether SZ subjects with NRH and mixed-handedness had poorer clinical and cognitive outcomes compared to their counterparts. Methods: 667 participants were tested with a battery of neuropsychological tests, and assessed for laterality using the Edinburg Handedness Inventory. Clinical symptomatology was assessed. Learning disorders and obstetrical complications were recorded. Biological parameters were explored. Results: The prevalence of NRH and mixed-handedness was high (respectively, 42.4% and 34.1%). In the multivariable analyses, NRH was associated with cannabis use disorder (p = 0.045). Mixed-handedness was associated with positive symptoms (p = 0.041), current depressive disorder (p = 0.005)), current cannabis use (p = 0.024) and less akathisia (p = 0.019). A history of learning disorder was associated with NRH. No association was found with cognition, trauma history, obstetrical complications, psychotic symptoms, peripheral inflammation. Conclusions: Non-right and mixed-handedness are very high in patients with SZ, possibly reflecting a neurodevelopmental origin. NRH is associated with learning disorders and cannabis use. Mixed-handedness is associated with positive symptoms, current depressive disorder, cannabis use and less akathisia. However, this study did not confirm greater cognitive impairment in these patients. © 2021 Informa UK Limited, trading as Taylor & Francis Group.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

Schizophrenia Bulletin Open

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific “immuno-metabolic” profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry. © 2022 The AuthorsImmuno-Génétique, Inflammation, retro-Virus, Environnement : de l'étiopathogénie des troubles psychotiques aux modèles animauxRéseau d'Innovation sur les Voies de Signalisation en Sciences de la Vi

Analyse d'admixture de l'âge de début de la schizophrénie

Dans la schizophrénie, les caractéristiques cliniques, familiales et biologiques en fonction de l'âge de début suggèrent que celui-ci puisse être un " symptôme candidat " pertinent pour les études génétiques recherchant les facteurs de vulnérabilité à cette maladie. Cependant, aucun des nombreux seuils utilisés dans la littérature pour définir des sous-groupes d'âge de début de la schizophrénie n'a été validé ! Le but de cette thèse est donc d'étudier la distribution de l'âge de début de la schizophrénie dans un échantillon de patients schizophrènes, afin de savoir si cet indicateur clinique permet de distinguer des sous-groupes plus homogènes de la maladie. Cent quarante et un sujets sont inclus lors d'admissions consécutives à l'hôpital. Nous avons utilisé une " analyse d'admixture " pour savoir si la distribution observée des âges de début correspondait à une courbe unique ou au mélange de plusieurs. Puis nous avons comparé les traits cliniques et les risques familiaux des différents groupes ainsi isolés. Le modèle traduisant le mieux la distribution observée des âges de début de notre population est l'assemblage de 2 courbes gaussiennes distinctes, d'age moyen : 19.92 3.56 et 33.48 8.21 ans avec un seuil à 28 ans. L'existence de ces 2 groupes d'âge de début est confirmée par l'étude de leurs profils démographiques, cliniques et familiaux, spécifiques. Nous avons donc validé mathématiquement l'existence de 2 sous-groupes définis par un âge de début de la schizophrénie avant ou après 28 ans avec des caractéristiques cliniques et familiales différentes. Ces résultats pourraient avoir d'importantes implications pour la recherche de facteurs de susceptibilité de la schizophrénie.PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

[The schizotypal personality disorder: Historical origins and current status.]

BACKGROUND: The schizotypal personality disorder is a recent psychiatric nosological concept developed by Spitzer at the end of the 1970s, based on the analysis of the characteristics of relatives of schizophrenic subjects included in the adoption studies carried out in the same decade by Kety, Wender and Rosenthal. HISTORICAL ASPECTS: However, this entity is based on older observations, at the beginning of the past century, showing common behavioural characteristics in relatives of schizophrenics. Its status within our current nosography remains dubious, sometimes classified among personality disorders, sometimes in the schizophrenia spectrum disorders. It is interesting to present the origins of this concept that stem from two complementary approaches: a family approach and a clinical approach of sporadic cases and then to redefine the framework within which the diagnostic approach was based and its continuity, up until our current classifications, the DSM and CIM. CURRENT STATUS: The historical origins cannot summarize the disorder and it appears important to redefine the multidimensional characteristics of the schizotypal personality disorder, generally a three-factor model. Indeed, dimensional models of psychosis are becoming established as conceptually and clinically useful. Recent studies on the dimensionality of psychosis show an evolution of the schizotypal concept, initially defined as being part of the schizophrenia spectrum and which now appears to be more broadly linked to a concept of unitary psychosis, including the bipolar disorder. CONCLUSION: Dimensions of psychosis seem to be associated with different familial aggregation and risk of psychosis, suggesting that they are underlined by different physiopathological processes. Hence, the dimensional approach can help to disentangle the genetic heterogeneity of the disease

Biomarkers of bipolar disorder: specific or shared with schizophrenia?

International audienceKraepelin's observations of the differences in the course and outcome of dementia praecox and manic depression fundamentally influenced thinking about bipolar disorder (BP) and schizophrenia (SZ) for over a century. In modern times, there is increasing awareness that a greater understanding of the similarities between these two highly prevalent and disabling conditions can teach us as many lessons about the pathophysiology of severe mental disorders as does the pursuit of differentiating factors. We review publications on developmental, genetic, epidemiological, and outcome research that challenges the Kraepelian dichotomy. We highlight the increasing evidence of the overlap in genetic susceptibility. Neuro-developmental studies provide evidence of shared early pathological processes, whilst neurophysiological investigations also suggest that different genes may have a role in the development of both phenotypes. There is also evidence of overlapping neurocognitive phenotypes. It has become increasingly clear that a simple binary classification of these disorders represents an oversimplification. It may be more apposite to think in terms of genetic influences on six continuous symptom dimensions: neurobiological, cognitive, positive, negative, depressive and manic symptoms

No evidence for physical anhedonia as a candidate symptom or an endophenotype in bipolar affective disorder.

International audienceObjectives: Bipolar affective disorder (BPAD) is clinically and genetically heterogeneous and the affected phenotype is poorly defined, hampering studies of its genetic basis. Studies of specific, familial, clinical indicators of BPAD may be useful for identifying heritable forms. Homogeneous forms of the disease may be identified in patients (candidate symptom approach) and some vulnerability markers may be sought in unaffected relatives of patients (intermediate traits or endophenotypes). Physical anhedonia (PA) is considered a possible candidate symptom and endophenotype in schizophrenia, but has never been specifically investigated in BPAD. Methods: Physical anhedonia scores (measured using Chapman's Physical Anhedonia Scale) were compared in 351 euthymic bipolar patients, 130 of their first-degree relatives and 170 healthy controls with no personal or familial history of schizophrenia, mood disorders or suicidal behavior. We investigated intrafamilial resemblance of PA and compared the progressive and clinical characteristics of hedonic and anhedonic bipolar probands. Results: Physical anhedonia was a stable trait in normothymic bipolar patients and significant intrafamilial correlation of PA scores was observed in bipolar families. However, PA scores were similar in unaffected relatives and controls and the clinical characteristics of anhedonic and hedonic patients did not differ significantly. Physical anhedonia was not associated with an increased familial risk for bipolar disorder. Conclusions: Physical anhedonia is a stable, familial dimension in BPAD families. It cannot be considered an endophenotype because unaffected relatives of bipolar patients and healthy controls have similar PA scores. It also cannot be considered a candidate symptom because it does not identify a homogeneous clinical and familial sub-group of bipolar patients. Given the results of previous studies, PA might be a specific candidate symptom (and endophenotype) to schizophrenia. However, the validation of this hypothesis requires replication studies in bipolar disorder and schizophrenia and further investigations in other psychiatric diseases (in particular across the mood disorder spectrum)

Étude pilote des relations entre manifestations psychotiques et environnement de résidence

International audienceCet article aborde les déterminants des troubles psychotiques à travers l’étude des manifestations psychotiques « atténuées » (ou schizotypie quantitative) ; manifestations plus fréquentes que les troubles constitués (telle que la schizophrénie) mais rarement identifiés et pris en charge alors qu’ils impactent la qualité de vie. Si les déterminants individuels de ces troubles « atténués » sont plutôt bien connus, l’impact des déterminants contextuels (caractéristiques sociales, urbanistiques) des lieux de vie sur leur présence ou leur intensité n’a, par contre, pas encore été étudié. Les relations entre contexte de résidence et schizophrénie ont, en revanche, fait l’objet de recherches spécifiques.A partir de données recueillies auprès de 255 adultes résidant dans trois quartiers de la commune de Créteil, cette étude s’intéresse aux relations entre les représentations (dont l’étendue) du quartier de résidence, les caractéristiques (socio-démographiques et urbanistiques) du quartier etles scores de schizotypie

Psychotic Experiences Are Associated With Paternal Age But Not With Delayed Fatherhood in a Large, Multinational, Community Sample

Advanced paternal age has been consistently associated with an increased risk of schizophrenia. It is less known if such an association also exists with subclinical/attenuated forms of psychosis. Additionally, it has been suggested that it is not paternal age per se, but rather delayed fatherhood, as a marker of a genetic liability of psychosis, that is the cause of the association. The aim of the current study was to examine whether paternal age and/or delayed fatherhood (paternity age) predict self-reported positive, negative, and/or depressive dimensions of psychosis in a large sample from the general population. The sample (N = 1465) was composed of control subjects from the 6 countries participating in the European Union Gene-Environment Interaction study. The CAPE, a self-report questionnaire, was used to measure dimensions of subclinical psychosis. Paternal age at the time of respondents' birth and age of paternity were assessed by self-report. We assessed the influence of the variables of interest (paternal age or paternity age) on CAPE scores after adjusting for potential confounders (age, gender, and ethnicity). Paternal age was positively associated with the positive dimension of the CAPE. By contrast, paternity age was not associated with any of the psychosis dimensions assessed by the CAPE. Thus, our results do not support the idea that delayed fatherhood explains the association between age of paternity and psychosis risk. Furthermore, our results provide arguments for the hypothesis of an etiologic continuum of psychosis