Anhedonia in schizophrenia and major depression: state or trait?

<p>Abstract</p> <p>Background</p> <p>In schizophrenia and major depressive disorder, anhedonia (a loss of capacity to feel pleasure) had differently been considered as a premorbid personological trait or as a main symptom of their clinical picture. The aims of this study were to examine the pathological features of anhedonia in schizophrenic and depressed patients, and to investigate its clinical relations with general psychopathology (negative, positive, and depressive dimensions).</p> <p>Methods</p> <p>A total of 145 patients (80 schizophrenics and 65 depressed subjects) were assessed using the Physical Anhedonia Scale and the Social Anhedonia Scale (PAS and SAS, respectively), the Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS, respectively), the Calgary Depression Scale for Schizophrenics (CDSS), and the Hamilton Depression Rating Scale (HDRS). The statistical analysis was performed in two steps. First, the schizophrenic and depressed samples were dichotomised into 'anhedonic' and 'normal hedonic' subgroups (according to the 'double (PAS/SAS) cut-off') and were compared on the general psychopathology scores using the Mann-Whitney Z test. Subsequently, for the total schizophrenic and depressed samples, Spearman correlations were calculated to examine the relation between anhedonia ratings and the other psychopathological parameters.</p> <p>Results</p> <p>In the schizophrenic sample, anhedonia reached high significant levels only in 45% of patients (n = 36). This 'anhedonic' subgroup was distinguished by high scores in the disorganisation and negative dimensions. Positive correlations of anhedonia with disorganised and negative symptoms were also been detected. In the depressed sample, anhedonia reached high significant levels in only 36.9% of subjects (n = 24). This 'anhedonic' subgroup as distinguished by high scores in the depression severity and negative dimensions. Positive correlations of anhedonia with depressive and negative symptoms were also been detected.</p> <p>Conclusion</p> <p>In the schizophrenic sample, anhedonia seems to be a specific subjective psychopathological experience of the negative and disorganised forms of schizophrenia. In the depressed sample, anhedonia seems to be a specific subjective psychopathological experience of those major depressive disorder forms with a marked clinical depression severity.</p

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders

The p250GAP Gene Is Associated with Risk for Schizophrenia and Schizotypal Personality Traits

BACKGROUND: Hypofunction of the glutamate N-Methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. p250GAP is a brain-enriched NMDA receptor-interacting RhoGAP. p250GAP is involved in spine morphology, and spine morphology has been shown to be altered in the post-mortem brains of patients with schizophrenia. Schizotypal personality disorder has a strong familial relationship with schizophrenia. Several susceptibility genes for schizophrenia have been related to schizotypal traits. METHODS: We first investigated the association of eight linkage disequilibrium-tagging single-nucleotide polymorphisms (SNPs) that cover the p250GAP gene with schizophrenia in a Japanese sample of 431 schizophrenia patients and 572 controls. We then investigated the impact of the risk genetic variant in the p250GAP gene on schizotypal personality traits in 180 healthy subjects using the Schizotypal Personality Questionnaire. RESULTS: We found a significant difference in genotype frequency between the patients and the controls in rs2298599 (χ(2) = 17.6, p = 0.00015). The minor A/A genotype frequency of rs2298599 was higher in the patients (18%) than in the controls (9%) (χ(2) = 15.5, p = 0.000083). Moreover, we found that subjects with the rs2298599 risk A/A genotype, compared with G allele carriers, had higher scores of schizotypal traits (F(1,178) = 4.08, p = 0.045), particularly the interpersonal factor (F(1,178) = 5.85, p = 0.017). DISCUSSION: These results suggest that a genetic variation in the p250GAP gene might increase susceptibility not only for schizophrenia but also for schizotypal personality traits. We concluded that the p250GAP gene might be a new candidate gene for susceptibility to schizophrenia

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

Exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes

Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7×10(-8) per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene

Association of AKT1 gene variants and protein expression in both schizophrenia and bipolar disorder

The AKT1 gene has been associated with the genetic aetiology of schizophrenia. Following the overlap model of bipolar disorder and schizophrenia, we aimed to investigate AKT1 genetic variants and protein expression in both diseases. A total of 679 subjects with European ancestry were included: 384 with schizophrenia, 130 with bipolar disorder and 165 controls. Six single nucleotide polymorphisms (SNPs) were investigated for association with the diseases using single- and multi-locus analyses. AKT1 and AKT2 protein levels were measured in post-mortem brain tissues from ante-mortem diagnosed schizophrenia (n = 30) and bipolar disorder subjects (n = 12) and matched controls. The analysis identified a significant global distortion in schizophrenia (P = 0.0026) and a weak association in bipolar disorder (P = 0.046). A sliding window procedure showed a five-SNP haplotype (TCGAG) to be associated with schizophrenia (P = 1.22 x 10(-4)) and bipolar disorder (P = 0.0041) and a four-SNP haplotype (TCGA) with the combined sample (1.73 x 10(-5)). On the basis of selected genotypes, a significant difference in protein expression emerged between subjects (P < 0.02). In conclusion, our findings, by showing the involvement of the AKT1 gene in both schizophrenia and bipolar disorder, support the role of AKT1 in the genetics of both disorders and add support to the view that there is some genetic overlap between them

The Patient-Reported Experience Measure for Improving qUality of care in Mental health (PREMIUM) project in France: study protocol for the development and implementation strategy

Sara Fernandes,1 Guillaume Fond,1 Xavier Zendjidjian,1 Pierre Michel,1 Karine Baumstarck,1 Christophe Lancon,1 Fabrice Berna,2 Franck Schurhoff,2 Bruno Aouizerate,2 Chantal Henry,2 Bruno Etain,2 Ludovic Samalin,2 Marion Leboyer,2 Pierre-Michel Llorca,2 Magali Coldefy,3 Pascal Auquier,1 Laurent&nbsp;Boyer1 On behalf of the French PREMIUM Group 1Aix-Marseille University, School of Medicine, CEReSS &ndash; Health Service Research and Quality of Life Center &ndash; EA 3279 Research Unit, Marseille, France; 2FondaMental Foundation, Cr&eacute;teil, France; 3Institute for Research and Information in Health Economics (IRDES), Paris, France Background: Measuring the quality and performance of health care is a major challenge in improving the efficiency of a health system. Patient experience is one important measure of the quality of health care, and the use of patient-reported experience measures (PREMs) is recommended. The aims of this project are 1) to develop item banks of PREMs that assess the quality of health care for adult patients with psychiatric disorders (schizophrenia, bipolar disorder, and depression) and to validate computerized adaptive testing (CAT) to support the routine use of PREMs; and 2) to analyze the implementation and acceptability of the CAT among patients, professionals, and health authorities.Methods: This multicenter and cross-sectional study is based on a mixed method approach, integrating qualitative and quantitative methodologies in two main phases: 1) item bank and CAT development based on a standardized procedure, including conceptual work and definition of the domain mapping, item selection, calibration of the item bank and CAT simulations to elaborate the administration algorithm, and CAT validation; and 2) a qualitative study exploring the implementation and acceptability of the CAT among patients, professionals, and health authorities.Discussion: The development of a set of PREMs on quality of care in mental health that overcomes the limitations of previous works (ie, allowing national comparisons regardless of the characteristics of patients and care and based on modern testing using item banks and CAT) could help health care professionals and health system policymakers to identify strategies to improve the quality and efficiency of mental health care.Trial registration: NCT02491866. Keywords: patient-reported experience measures, quality of care, item bank, computerized adaptive testing, psychiatr

Differential effects of childhood trauma and cannabis use disorders in ă patients suffering from schizophrenia

International audienceBackground: Childhood trauma (CT) and cannabis use are both ă environmental and modifier risk factors for schizophrenia. However, ă little is known about how they interact in schizophrenia. We examined ă the main effect of each of these two environmental factors on the ă clinical expression of the disease using a large set of variables, and ă we tested whether and how cannabis and CT interact to influence the ă course and the presentation of the illness. ă Methods: A sample of 366 patients who met the DSM-IV-TR criteria for ă schizophrenia was recruited through the FACE-SCZ (Fondamental Advanced ă Centre of Expertise - Schizophrenia) network. Patients completed a large ă standardized clinical evaluation including Structured Clinical Interview ă for DSM Disorders-I (SCID-I), Positive and Negative Symptoms Scale ă (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), Global ă Assessment of Functioning (GAF), Short-Quality of Life-18 (S-QoL-18), ă and Medication Adherence Rating Scale (MARS). We assessed CT with the ă Childhood Trauma Questionnaire and cannabis status with SCID-I. ă Results: CT significantly predicted the number of hospitalizations, GAF, ă and S-QoL-18 scores, as well as the PANSS total, positive, excitement, ă and emotional distress scores. Cannabis use disorders significantly ă predicted age of onset, and MARS. There was no significant interaction ă between CT and cannabis use disorders. However, we found evidence of a ă correlation between these two risk factors. ă Conclusions: CT and cannabis both have differential deleterious effects ă on clinical and functional outcomes in patients with schizophrenia. Our ă results highlight the need to systematically assess the presence of ă these risk factors and adopt suitable therapeutic interventions. (C) ă 2016 Elsevier B.V. All rights reserved