Neurological soft signs and prepulse inhibition of the startle reflex in psychosis: A pilot study.

OBJECTIVE: Prepulse inhibition (PPI) of the startle reflex deficit and neurological soft signs (NSS) are two markers of vulnerability to psychosis. This study investigated the possibility of a PPI-NSS relation due to a putative common biological substrate, hypothesizing that patients with higher NSS scores also show higher PPI deficits. Moreover, we examined the possibility of an association of PPI deficits and NSS with negative symptoms. METHODS: Fifteen subjects with psychosis and fifteen healthy controls underwent PPI and NSS evaluations. RESULTS: Patients did not exhibit higher PPI deficits but only higher NSS rates (p < 0.01), as compared with healthy controls. Higher NSS rates were not associated with PPI deficits, and NSS sensory integration signs correlated positively with negative symptoms (p < 0.01). CONCLUSION: Our study supported the hypothesis that NSS are trait markers whereas PPI deficits state markers and that their putative common biological substrate is not sufficient to determinate an association between them. The study hypothesis, however, needs further investigation.

Cannabis use, gender and age of onset of schizophrenia: data from the ÆSOP study.

An earlier age of onset of schizophrenia has been identified as a poor prognostic indicator. The current study examines the interaction effect of gender and cannabis use on age of onset of schizophrenia and schizoaffective disorder. This research forms part of a two-centre epidemiological study of first-episode psychosis and included individuals with a diagnosis of schizophrenia or schizoaffective disorder and an age of onset between age 16 and 45. Kaplan-Meier curves and Cox proportional hazards regression were used to compare the effects of cannabis use and gender on age of first symptom of schizophrenia. Akaike's information criteria were used to find the model with the best fit to the data. Cannabis users had an earlier age of first symptom than non-users. There was an interaction with gender; the gender difference in age of onset was diminished in cannabis smokers compared with non-cannabis smokers. The model including cannabis use interacting with gender was the most parsimonious model, followed by cannabis use alone. The addition of other illegal drug use did not improve the model. Cannabis use is associated with an earlier age of onset of schizophrenia, and the gender difference in age of onset is reduced among cannabis smokers.

The impact of cannabis use on age of onset and clinical characteristics in first-episode psychotic patients. Data from the Psychosis Incident Cohort Outcome Study (PICOS).

Cannabis use is frequent among first-episode psychosis (FEP) patients and has been associated with several clinical features. This study aimed in an FEP sample to determine whether cannabis use is associated with (1) a higher level of positive symptoms, a lower level of depression and a better premorbid adjustment, (2) an earlier age of onset, and a better premorbid IQ. The study was conducted within the framework of the Psychosis Incident Cohort Outcome Study (PICOS), a multisite collaborative research on FEP patients who attended the psychiatric services in Veneto Region, Italy. Standardized instruments were used to collect sociodemographic, clinical, and drug use data. A total of 555 FEP patients met the inclusion criteria, 517 of whom received an ICD-10 diagnosis of psychosis; 397 (55% males; mean age: 32 yrs ± 9.5) were assessed. Out of these, 311 patients agreed to be interviewed on drug and alcohol misuse; 20.3% was positive for drug misuse: cannabis (19.0%), cocaine (3.9%), and hallucinogens (3.9%). Cannabis use was not associated with a higher level of positive symptoms, but correlated with less severe depressive symptoms. No relationship was observed between premorbid adjustment or IQ and cannabis use. FEP patients who used cannabis had an earlier age of onset than abstinent patients, even after adjusting for gender and diagnosis. Our results suggest a possible causal role of cannabis in triggering psychosis in certain vulnerable subjects. Particular attention must be paid to this behaviour, because reducing cannabis use can delay or prevent some cases of psychosis.

Can the role of genetic factors in schizophrenia be enlightened by studies of candidate gene mutant mice behaviour?

Schizophrenia is one of the most severe psychiatric disorders. Despite the knowledge accumulated over years, aetiology and pathophysiology remain uncertain. Research on families and twins suggests that genetic factors are largely responsible for the disease and implies specific genes as risk factors. Genetic epidemiology indicates a complex transmission mode, compatible with a multi-locus model, with single genes accounting for specific traits rather than for the entire phenotype. To better understand every single gene contribution to schizophrenia, the use of intermediate endophenotypes has been proposed. A straight communication between preclinical and clinical researchers could facilitate research on the association between genes and endophenotypes. Many behavioural tasks are available for humans and animals to measure endophenotypes. Here, firstly, we reviewed the most promising mouse behavioural tests modelling human behavioural tasks altered in schizophrenia. Secondly, we systematically reviewed animal models availability for a selection of candidate genes, derived from linkage and association studies. Thirdly, we systematically reviewed the studies which tested mutant mice in the above behavioural tasks. Results indicate a large mutant mice availability for schizophrenia candidate genes but they have been insufficiently tested in behavioural tasks. On the other hand, multivariate and translational approach should be implemented in several behavioural domains.