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Objective Relapse and acute exacerbation are common in schizophrenia and may impact treatment response and outcome. Evidence is conflicting in respect to superiority of long-acting injectable antipsychotic therapies versus oral antipsychotics in relapse prevention. This randomized controlled study assessed the efficacy of paliperidone palmitate versus oral antipsychotics for relapse prevention. Method Eligible patients with a recent diagnosis of schizophrenia (within 1–5 years) were randomized 1:1 to paliperidone palmitate (n = 376) or oral antipsychotic monotherapy (n = 388) and entered a 2-week initial acute oral treatment phase. Patients who met predefined response criteria were eligible to enter the 24-month rater-blinded core treatment phase. Patients were evaluated for relapse, symptoms, functioning, quality of life, treatment satisfaction, and tolerability. Results In the core treatment phase, time to relapse was significantly longer in the paliperidone palmitate (n = 352) compared with the oral antipsychotics arm (n = 363): 85% of patients were relapse-free at 469 versus 249 days ( P = 0.019). Significantly fewer patients receiving paliperidone palmitate met the relapse criteria (52 [14.8%] versus 76 [20.9%, oral antipsychotics]; P = 0.032), representing a 29.4% relative risk reduction. For paliperidone palmitate, a significantly greater improvement in Positive and Negative Syndrome Scale total score on Day 8 ( P = 0.021) and a trend at endpoint ( P = 0.075) were observed. Functioning improvements were comparable between treatment arms. No new safety signals were identified. Conclusion The observed time to relapse superiority of paliperidone palmitate over oral antipsychotics provides further evidence for the value of long-acting injectable antipsychotic therapies in the treatment of schizophrenia, including during the early stages of illness.

Late-onset schizophrenia (LOS) is a controversial diagnosis, mainly characterized by more positive symptoms and less deterioration. LOS could be considered as either an extreme of typical schizophrenia (but for old age patients, and short duration of the disorder), or an independent group of patients with a specific diagnosis, with no clear evidence in favor or against any of these hypotheses. The aim of the present study is to characterize the memory cognitive profile of LOS patients without related organic factors (N=25), compared to early-onset schizophrenic patients (EOS, N=44), matched for the duration of the disorder, and healthy controls (HC, N=23), matched for the age of patients. Lifetime clinical symptoms and functioning were collected using the DIGS and the PANSS, and components of memory capacity were assessed with the Forward and Backward Digit Span Tasks, Rey Complex Figure and Verbal Fluency Tests. LOS patients were performing significantly better than EOS patients on the digit span task, Rey's complex figure at T1 score and phonemic verbal fluency. However, LOS had significantly lower performances than healthy controls on the digit span task and on both verbal fluency tests. This study provides evidence that LOS had intermediate outcome compared to EOS and controls. LOS can therefore be in line with a dimensional clinical approach of schizophrenia, whereby it presents few memory deficits and few disorganization and negative symptoms with mostly positive symptoms and possibly etiopathogenic specificities. Further studies including more specific memory assessment tests and larger samples are needed to confirm the present finding.

Functional remission is an important treatment goal in schizophrenia, as independent living and reintegration of patients into the community and the workplace is the ultimate goal of any treatment. Nevertheless, assessing functional remission in schizophrenia is problematic, as it is a multifactorial and complex entity reflecting various aspects such as symptoms severity, personal skills and socio-cultural expectancies. The purpose of this study was to create and validate a novel scale for the evaluation of functional remission in schizophrenia. Unlike previous scales, the scale was built on the basis of patients with few schizophrenia symptoms. The "Functional Remission of General Schizophrenia" (FROGS) scale was developed using the expert consensus method following a MEDLINE and standard database search. Out of the 61 initially proposed, 19 items were selected as gathering the core aspects of functional remission in schizophrenia detected in the literature. The FROGS was then evaluated in 432 patients with DSM-IV criteria of schizophrenia, all of them meeting the symptomatic remission criteria of Andreasen et al. [Andreasen, N.C., Carpenter, W.T., Kane, J.M., Lasser, R.A., Marder, S.R., Weinberger, D.R., 2005. Remission in schizophrenia: proposed criteria and rationale for consensus. Am. J. Psychiatry 162 441-449]. Total score was highly reliable. Exploratory factor analysis after oblique rotation revealed that a three-factor solution was the most meaningful. On the basis of item content these three factors were labelled 'Social Functioning,' 'Daily Life' and 'Treatment.' The FROGS total score can be used to measure a general construct for the evaluation of functional remission in schizophrenia.. Further work is required to measure the acceptability, predictive validity, sensitivity to change, and stability of the factor structure of the FROGS.

There is wide evidence for a decreased risk of rheumatoid arthritis in patients with schizophrenia. Nevertheless, very few studies have looked at the risk of schizophrenia in a group of patients with rheumatoid arthritis. We prospectively investigated, with the SCL-90R, 220 consecutive outpatients with rheumatoid arthritis and 196 consecutive outpatients with various medical conditions, half of them suffering from psoriatic arthritis (a medical condition close to rheumatoid arthritis). The SCL-90R appears to be a valuable tool to distinguish patients with schizophrenia from the outpatients of our sample, the former having more ‘‘paranoid ideation’’ (p=0.004) and more ‘‘psychoticism’’ (p

The gene which codes for dopamine receptor D2 (DRD2) is considered as one of the most relevant candidate genes in schizophrenia. Previous genetic studies focusing on this gene gave conflicting results, potentially because of the differences in methodology (linkage versus association studies), and the different loci analyzed (the DRD2 gene having many polymorphisms). We used a progressive strategy with three different approaches (case/control, haplotype relative risk and transmission disequilibrium test) and investigated two genetic polymorphisms (TaqI B1/B2 and TaqI A1/A2, spanning the coding region of the DRD2 gene) in 50 patients with DSM-IV diagnoses of schizophrenia, in their 100 parents and in 50 healthy, matched controls. Firstly, we found a significant excess of the two alleles (B2 and A2) in the schizophrenic group compared to unaffected controls. Secondly, we found an excess of transmission from the parents to their affected children, using the haplotype relative risk design applied to the B2A2 haplotype. Finally, the transmission disequilibrium test showed evidence for linkage between B2A2 haplotype and schizophrenia. The significant excess of the B2A2 haplotype in schizophrenic patients is specifically observed in a subsample of patients with a disease onset occurring after 20 years of age. As the haplotype contains nearly the entire DRD2 gene, we found convergent evidence in our sample for a significant role of the DRD2 gene in the risk for schizophrenia. This haplotype may be more specifically involved in the disorder's onset at a later age in some patients, or, alternatively, may be implicated as a modifying factor acting on age of onset.

Recent prospective findings have shown that cannabis use by young people could be a risk factor for psychotic symptoms in adulthood, but the long-term impact of cannabis abuse on the clinical features of declared schizophrenia remains to be explored. We assessed the independent influence of cannabis abuse on the clinical symptoms of schizophrenia, after controlling for frequently co-occurring addictive disorders. Patients with schizophrenia, and with (N=66), or without (N=139) cannabis abuse, were compared for lifetime positive and negative symptoms, taking into account presence of any other addictive disorders. The incidence of the abuse of drugs other than cannabis was nearly five times greater amongst patients with both schizophrenia and cannabis abuse. When the analyses were limited to subjects with no other abuse, less avolution and fewer apathy symptoms were still detected in patients with schizophrenia and cannabis abuse than in those with no abuse (p=0.0001). In contrast, between-group differences for positive symptoms were abolished when multiple substance abuses were taken into account. The strong association between cannabis abuse and fewer negative symptoms in schizophrenia was thus replicated in this sample, but once co-morbid addictive disorders had been controlled no influence of cannabis abuse on hallucinations was detected. Distinguishing the effects of co-occurring addictive disorder(s) in patients with schizophrenia and cannabis dependence may thus be important when attempting to analyse the impact of cannabis abuse.

The gene coding for the D2 dopamine receptor ( DRD2 ) is considered as one of the most relevant candidate genes in schizophrenia. Previous genetic studies focusing on this gene yielded conflicting results, for example because of differences in methodology (linkage versus association studies) and variability in the loci analyzed (the DRD2 gene having many polymorphic sites). We used a progressive strategy with two different approaches (case-control and transmission disequilibrium test) and investigated six genetic polymorphisms spanning the DRD2 gene in 103 patients with DSM-IV criteria of schizophrenia, their 206 parents and 83 matched healthy control subjects. We found a significant excess of the A2 allele in subject with schizophrenia compared to unaffected controls. An excess of transmission of the A2 allele (and haplotypes containing this marker) from the parents to the affected children was also observed. Interestingly, the TaqI A1/A2 polymorphism, located 9.5 kb downstream from the DRD2 gene, maps in a novel gene, untitled “X-kinase”, and leads to a 713 Glu→Lys substitution in exon 8. As the analysis of the other markers within the DRD2 gene does not improve the strength of the association, our data are in favor of a specific role of the 3′ chromosomic region of the DRD2 gene in the vulnerability to schizophrenia.