Testing hypotheses about the relationship between cannabis use and psychosis

Aim: To model the impact of rising rates of cannabis use on the incidence and prevalence of psychosis under four hypotheses about the relationship between cannabis use and psychosis. Methods: The study modelled the effects on the prevalence of schizophrenia over the lifespan of cannabis in eight birth cohorts: 1940-1944, 1945-1949, 1950-1954, 1955-1959, 1960-1964, 1965-1969, 1970-1974, 1975-1979. It derived predictions as to the number of cases of schizophrenia that would be observed in these birth cohorts, given the following four hypotheses: (1) that there is a causal relationship between cannabis use and schizophrenia; (2) that cannabis use precipitates schizophrenia in vulnerable persons; (3) that cannabis use exacerbates schizophrenia; and (4) that persons with schizophrenia are more liable to become regular cannabis users. Results: There was a steep rise in the prevalence of cannabis use in Australia over the past 30 years and a corresponding decrease in the age of initiation of cannabis use. There was no evidence of a significant increase in the incidence of schizophrenia over the past 30 years. Data on trends the age of onset of schizophrenia did not show a clear pattern. Cannabis use among persons with schizophrenia has consistently been found to be more common than in the general population. Conclusions: Cannabis use does not appear to be causally related to the incidence of schizophrenia, but its use may precipitate disorders in persons who are vulnerable to developing psychosis and worsen the course of the disorder among those who have already developed it. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Choking deaths: the role of antipsychotic medication

Background An increased risk of choking associated with antipsychotic medication has been repeatedly postulated. Aims To examine this association in a large number of cases of choking deaths. Method Cases of individuals who had died because of choking were linked with a case register recording contacts with public mental health services. The actual and expected rates of psychiatric disorder and the presence of psychotropic medication in post-mortem blood samples were compared. Results The 70 people who had choked to death were over 20 times more likely to have been treated previously for schizophrenia. They were also more likely to have had a prior organic psychiatric syndrome. The risk for those receiving thioridazine or lithium was. respectively, 92 times and 30 times greater than expected. Other antipsychotic and psychotropic drugs were not over-represented. Conclusions The increased risk of death in people with schizophrenia may be a combination of inherent predispositions and the use of specific antipsychotic drugs. The increased risk of choking in those with organic psychiatric syndromes is consistent with the consequences of compromised neurological competence. Declaration of interest None.

Assessing cost-effectiveness - Mental health: introduction to the study and methods

Objective: The Assessing Cost-Effectiveness - Mental Health (ACE-MH) study aims to assess from a health sector perspective, whether there are options for change that could improve the effectiveness and efficiency of Australia's current mental health services by directing available resources toward 'best practice' cost-effective services. Method: The use of standardized evaluation methods addresses the reservations expressed by many economists about the simplistic use of League Tables based on economic studies confounded by differences in methods, context and setting. The cost-effectiveness ratio for each intervention is calculated using economic and epidemiological data. This includes systematic reviews and randomised controlled trials for efficacy, the Australian Surveys of Mental Health and Wellbeing for current practice and a combination of trials and longitudinal studies for adherence. The cost-effectiveness ratios are presented as cost (A$) per disability-adjusted life year (DALY) saved with a 95% uncertainty interval based on Monte Carlo simulation modelling. An assessment of interventions on 'second filter' criteria ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') allows broader concepts of 'benefit' to be taken into account, as well as factors that might influence policy judgements in addition to cost-effectiveness ratios. Conclusions: The main limitation of the study is in the translation of the effect size from trials into a change in the DALY disability weight, which required the use of newly developed methods. While comparisons within disorders are valid, comparisons across disorders should be made with caution. A series of articles is planned to present the results.

Effects of microinjections of apomorphine and haloperidol into the inferior colliculus on the latent inhibition of the conditioned emotional response

Electrical or chemical stimulation of the inferior colliculus (IC) induces fear-like behaviors. More recently, consistent evidence has shown that electrical stimulation of the central nucleus of the IC supports Pavlovian conditioning and latent inhibition (Li). LI is characterized by retardation in conditioning and also by an impaired ability to ignore irrelevant stimuli, after a non-reinforced pre-exposure to the conditioned stimulus. LI has been proposed as a behavioral model of cognitive abnormalities seen in schizophrenia. The aim of the present study was to determine whether dopaminergic mechanisms in the IC are involved in LI of the conditioned emotional response (CER). To induce LI, a group of rats was pre-exposed (PE) to six tones in two sessions, while rats that were not pre-exposed (NPE) had two sessions without tone presentations. The conditioning consisted of two tone presentations to the animal, followed immediately by a foot shock. PE and NPE rats received IC microinjections of physiological saline, the dopaminergic agonist apomorphine (9.0 mu g/0.5 mu L/side), or the dopaminergic antagonist haloperidol (0.5 mu g/0.5 mu L/side) before both pre-exposure and conditioning. During the test, the PE rats that received saline or haloperidol had a lower suppression of the licking response compared to NPE rats that received vehicle or haloperidol, indicating that latent inhibition was induced. There was no significant difference in the suppression ratio in rats that received apomorphine injections into the IC, indicating reduced latent inhibition. These results suggest that dopamine-mediated mechanisms of the IC are involved in the development of LI. (C) 2008 Elsevier Inc. All rights reserved.

Acoustic hypersensitivity in adult rats after neonatal ventral hippocampus lesions

Rats with a bilateral neonatal ventral hippocampus lesion (NVHL) are used as models of neurobiological aspects of schizophrenia. In view of their decreased number of GABAergic interneurons, we hypothesized that they would show increased reactivity to acoustic stimuli. We systematically characterized the acoustic reactivity of NVHL rats and sham operated controls. They were behaviourally observed during a loud white noise. A first cohort of 7 months` old rats was studied. Then the observations were reproduced in a second cohort of the same age after characterizing the reactivity of the same rats to dopaminergic drugs. A third cohort of rats was studied at 2, 3, 4, 5 and 6 months. In subsets of lesioned and control rats, inferior colliculus auditory evoked potentials were recorded. A significant proportion of rats (50-62%) showed aberrant audiogenic responses with explosive wild running resembling the initial phase of audiogenic seizures. This was not correlated with their well-known enhanced reactivity to dopaminergic drugs. The proportion of rats showing this strong reaction increased with rats` age. After the cessation of the noise, NVHL rats showed a long freezing period that did neither depend on the size of the lesion nor on the rats` age. The initial negative deflection of the auditory evoked potential was enhanced in the inferior colliculus of only NVHL rats that displayed wild running. Complementary anatomical investigations using X-ray scans in the living animal, and alizarin red staining of brain slices, revealed a thin layer of calcium deposit close to the medial geniculate nuclei in post-NVHL rats, raising the possibility that this may contribute to the hyper-reactivity to sounds seen in these animals. The findings of this study provide complementary information with potential relevance for the hyper-reactivity noted in patients with schizophrenia, and therefore a tool to investigate the underlying biology of this endophenotype. (C) 2009 Elsevier B.V. All rights reserved.

Overshadowing in conditioned taste aversion or in conditioned emotional response after neonatal ventral hippocampal lesions in rats

The neonatal hippocampus lesion thought to model schizophrenia should show the same modifications in behavioural tests as other models, especially pharmacological models. namely decreased latent inhibition, blocking and overshadowing. The present study is set out to evaluate overshadowing in order to complement our previous studies, which had tested latent inhibition. ""Overshadowing"" refers to the decreased conditioning that occurs when the to-be-conditioned stimulus is combined with another stimulus at the conditioning stage. We used the same two Pavlovian conditioning paradigms as in our previous works, namely conditioned taste aversion (CTA) and conditioned emotional response (CER). A sweet taste overshadowed a salty conditioned stimulus, and a tone overshadowed a flashing light. Totally different stimuli were used to counter possible sensory biases. The protocols were validated with two groups of Sprague Dawley rats. The same two protocols were then applied to a cohort of rats whose ventral hippocampus had been destroyed when they were 7 days old. Only rats with extended ventral hippocampus lesions were included. The overall effect of Pavlovian conditioning was attenuated, significantly so in the conditioned emotional response paradigm, but overshadowing appeared not to be modified in either the conditioned emotional response or the conditioned taste aversion paradigm. (C) 2008 Elsevier B.V. All rights reserved.

Rewarded associative and instrumental conditioning after neonatal ventral hippocampus lesions in rats

Sprague Dawley rats were submitted to bilateral ventral hippocampus lesions 7 days after birth. This corresponds to the Lipska and Weinberger`s procedure for modeling schizophrenia. The aim of the present work was to test the learning capacity of such rats with an associative Pavlovian and an instrumental learning paradigm, both methods using reward outcome (food, sucrose or polycose). The associative paradigm comprised also a second learning test with reversed learning contingencies. The instrumental conditioning comprised an extinction test under outcome devaluation conditions. Neonatally lesioned rats, once adults (over 60 days of age), showed a conditioning deficit in the associative paradigm but not in the instrumental one. Lesioned rats remained able to adapt as readily as controls to the reversed learning contingency and were as sensitive as controls to the devaluation of outcome. Such observations indicate that the active access (instrumental learning) to a reward could have compensated for the deficit observed under the ""passive"" stimulus-reward associative learning condition. This feature is compared to the memory management impairments observed in clinical patients. (c) 2008 Elsevier B.V. All rights reserved.

Portuguese version of the Delirium Rating Scale-Revised-98: reliability and validity

Objective To assess the validity and the reliability of the Portuguese version of the Delirium Rating Scale-Revised-98 (DRS-R-98). Methods The scale was translated into Portuguese and back-translated into English. After assessing its face validity, five diagnostic groups (n = 64; delirium, depression, dementia, schizophrenia and others) were evaluated by two independent researchers blinded to the diagnosis. Diagnosis and severity of delirium as measured by the DRS-R-98 were compared to clinical diagnosis, Mini-Mental State Exam, Confusion Assessment Method, and Clinical Global Impressions scale (CGI). Results Mean and rnedian DRS-R-98 total scores significantly distinguished delirium from the other groups (p < 0.001). Inter-rater reliability (ICC between 0.9 and 1) and internal consistency (alpha = 0.91) were very high. DRS-R-98 severity scores correlated highly with the CGI. Mean DRS-R-98 severity scores during delirium differed significantly (p < 0.01) from the post-treatment values. The area under the curve established by ROC analysis was 0.99 and using the cut-off Value of 20 the scale showed sensitivity and specificity of 92.6% and 94.6%, respectively. Conclusion The Portuguese version of the DRS-R-98 is a valid and reliable measure of delirium that distinguishes delirium from other disorders and is sensitive to change in delirium severity, which may be of great value for longitudinal studies. Copyright (c) 2007 John Wiley & Sons, Ltd.

No association between the deficit syndrome in psychosis and summer birth in a Southern Hemisphere country (Correspondence)

This Article does not have an abstract.

Psychoses of epilepsy: A study comparing the clinical features of patients with focal versus generalized epilepsies

In the literature, psychosis of epilepsy (POE) has been described as one of the most frequent psychiatric comorbidities of epilepsy, occurring particularly in association with temporal lobe epilepsy. However, the presence of such psychiatric disorders among patients with idiopathic generalized epilepsies has also been mentioned. In this study, we evaluated the clinical features of psychotic disorders in a series of patients with temporal lobe epilepsy related to mesial temporal sclerosis (TLE-MTS) and juvenile myoclonic epilepsy with the aim of describing and comparing the clinical patterns of the psychotic symptoms in such frequent and important epilepsy syndromes. POE occurred most frequently in patients with TLE-MTS (P=0.01), but no differences were observed between the groups with respect to the subtypes and core symptoms of psychoses. The clinical implications of POE in both epilepsy syndromes are discussed. (C) 2011 Elsevier Inc. All rights reserved.

Emotional trauma and abuse in patients with psychogenic nonepileptic seizures

A history of childhood trauma and the presence of dissociative phenomena are considered to be the most important risk factors for psychogenic nonepileptic seizure disorder (PNESD). This case-control study investigated 20 patients with PNESD and 20 with temporal lobe epilepsy (TLE) diagnosed by video/EEG monitoring who were matched for gender and age. Patients with both conditions were not included in the study. Groups were evaluated for age at onset and at diagnosis, worst lifetime weekly seizure frequency, trauma history, and presence of dissociative phenomena. Age at onset (P = 0.007) and age at diagnosis (P < 0.001) were significantly higher in the PNESD group than the control group, as were the scores on the Dissociative Experiences Scale (P < 0.001) and Childhood Trauma Questionnaire (P = 0.014). Only the differences in scores on the Childhood Trauma Questionnaire subscales Emotional Neglect (P = 0.013) and Emotional Abuse (P = 0.014) reached statistical significance. Dissociative phenomena and a reported history of childhood trauma are more common in patients with PNESD than in those with TLE. However, only emotional neglect and abuse were associated with PNESD in this study. (C) 2010 Elsevier Inc. All rights reserved.

Strategies for genetic model specification in the screening of genome-wide meta-analysis signals for further replication

Background Meta-analysis is increasingly being employed as a screening procedure in large-scale association studies to select promising variants for follow-up studies. However, standard methods for meta-analysis require the assumption of an underlying genetic model, which is typically unknown a priori. This drawback can introduce model misspecifications, causing power to be suboptimal, or the evaluation of multiple genetic models, which augments the number of false-positive associations, ultimately leading to waste of resources with fruitless replication studies. We used simulated meta-analyses of large genetic association studies to investigate naive strategies of genetic model specification to optimize screenings of genome-wide meta-analysis signals for further replication. Methods Different methods, meta-analytical models and strategies were compared in terms of power and type-I error. Simulations were carried out for a binary trait in a wide range of true genetic models, genome-wide thresholds, minor allele frequencies (MAFs), odds ratios and between-study heterogeneity (tau(2)). Results Among the investigated strategies, a simple Bonferroni-corrected approach that fits both multiplicative and recessive models was found to be optimal in most examined scenarios, reducing the likelihood of false discoveries and enhancing power in scenarios with small MAFs either in the presence or in absence of heterogeneity. Nonetheless, this strategy is sensitive to tau(2) whenever the susceptibility allele is common (MAF epsilon 30%), resulting in an increased number of false-positive associations compared with an analysis that considers only the multiplicative model. Conclusion Invoking a simple Bonferroni adjustment and testing for both multiplicative and recessive models is fast and an optimal strategy in large meta-analysis-based screenings. However, care must be taken when examined variants are common, where specification of a multiplicative model alone may be preferable.

The family attitude scale: Reliability and validity of a new scale for measuring the emotional climate of families

Research on outcomes from psychiatric disorders has highlighted the importance of expressed emotion (EE), but its cost-effective measurement remains a challenge. This article describes development of the Family Attitude Scale (FAS), a 30-item instrument that can be completed by any informant. Its psychometric characteristics are reported in parents of undergraduate students and in 70 families with a schizophrenic member. The total FAS had high internal consistency in all samples, and reports of angry behaviour in FAS items showed acceptable inter-rater agreement. The FAS was associated with the reported anger, anger expression and anxiety of respondents. Substantial associations between the parents' FAS and the anger and anger expression of students was also observed. Parents of schizophrenic patients had higher FAS scores than parents of students, and the FAS was higher if disorder duration was longer or patient functioning was poorer. Hostility, high criticism and low warmth on the Camberwell Family Interview (CFI) were associated with a more negative FAS. The highest FAS in the family was a good predictor of a highly critical environment on the CFI. The FAS is a reliable and valid indicator of relationship stress and expressed anger that has wide applicability. (C) 1997 Elsevier Science Ireland Ltd.

Volume reduction of the corpus callosum and its relationship with deficits in interhemispheric transfer of information in recent-onset psychosis

The present study aimed to investigate the presence of corpus callosum (CC) volume deficits in a population-based recent-onset psychosis (ROP) sample, and whether CC volume relates to interhemispheric communication deficits. For this purpose, we used voxel-based morphometry comparisons of magnetic resonance imaging data between ROP (n = 122) and healthy control (n = 94) subjects. Subgroups (38 ROP and 39 controls) were investigated for correlations between CC volumes and performance on the Crossed Finger Localization Test (CFLT). Significant CC volume reductions in ROP subjects versus controls emerged after excluding substance misuse and non-right-handedness. CC reductions retained significance in the schizophrenia subgroup but not in affective psychoses subjects. There were significant positive correlations between CC volumes and CFLT scores in ROP subjects, specifically in subtasks involving interhemispheric communication. From these results, we can conclude that CC volume reductions are present in association with ROP. The relationship between such deficits and CFLT performance suggests that interhemispheric communication impairments are directly linked to CC abnormalities in ROP. (C) 2010 Elsevier Ireland Ltd. All rights reserved.