The study examines how age, sex and substance use disorder are associated with the risk of committing a criminal offence. The study explicitly examines the risk after the first contact to the psychiatric hospital system and after the diagnosis of schizophrenia for those with no previous criminal record; the association between previous non-violent criminality and later violent criminality is also analysed. The study sample comprised 4619 individuals ever diagnosed with schizophrenia. All solved offences were accessible. Data were analysed using Cox's regression. Schizophrenic men had twice the risk of schizophrenic women of committing both violent and non-violent offences. A registered substance use disorder increased the risk 1.9- to 3.7-fold, depending on the starting point for the analyses, while increasing age on first contact or when diagnosed with schizophrenia diminished the risk. Previous non-violent criminality increased the risk for later violent criminality 2.5- to 2.7-fold, depending on the starting point for the analyses. The results suggest that the psychiatric treatment system can play an active role in preventing criminality among individuals with schizophrenia. The preventive measures should be based on a thorough assessment including criminal history at intake and alertness toward young psychotic men with substance use disorders and especially if they also have a criminal history.

Quality of life (QoL) measures are increasingly recognized as necessary parts of outcome assessments in psychosis. The present paper is a comprehensive study of patients with first-episode psychosis where QoL is measured by the commonly used Lehman Quality of Life Interview (L-QoLI). The aim is to examine if the L-QoLI maintain its original structure when used in a group of patients with first-episode psychosis, and to investigate what determines global subjective QoL with a specific emphasis on premorbid adjustment, duration of untreated psychosis (DUP) and clinical symptoms. The study indicates that the psychometric properties of the L-QoLI do not change significantly when used in first-episode samples. The patients report subjective and objective QoL in the fair to good range, with only a moderate association between the objective and subjective measures. Poor global satisfaction is predicted by being single, abusing drugs, being depressed, having a diagnosis of psychotic affective disorder, having poor premorbid social adjustment and DUP over 10 weeks. The study supports the notion that patients with first-episode psychosis construct QoL in the same way as other groups, and that longer durations of compromised function at this stage produces poor satisfaction with life rather than a downward readjustment of expectations.

The rapid cycling variant of bipolar disorder is defined as the occurrence of four periods of either manic or depressive illness within 12 months. Patients suffering from this variant of bipolar disorder have an unmet need for effective treatment. This review examines two major studies in an attempt to update understanding of the current therapies available to treat rapid cycling patients. The first trial compares lamotrigine versus placebo in 182 patients studied for 6 months. The second is a recently completed, 20-month trial comparing divalproate and lithium in 60 patients. Both trials had a double-blind, randomized parallel-group design. The data from the latter study indicate that there are no large differences in efficacy between lithium and divalproate in the long-term treatment of rapid cycling bipolar disorder. In addition, lamotrigine has the potential to complement the spectrum of lithium and divalproate through its greater efficacy for depressive symptoms.

Multiple lines of evidence including recent imaging studies suggest that schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyperstimulation of striatal dopamine (DA) D2 receptors and understimulation of cortical DA D1 receptors. This DA endophenotype presumably emerges from the background of a more general synaptic dysconnectivity, involving alterations in N-methyl-d-aspartate (NMDA) and glutamatergic (GLU) functions. Equally important is the fact that this DA dysregulation might further impair NMDA transmission. The first generation antipsychotic (FGA) drugs are characterized by high affinity to and generally high occupancy of D2 receptors. The efficacy of FGAs is limited by a high incidence of extrapyramidal side-effects (EPS). Second generation antipsychotic (SGA) drugs display reduced EPS liability and modest but clinically significant enhanced therapeutic efficacy. Compared to FGAs, the improved therapeutic action of SGAs probably derives from a more moderate D2 receptor blockade. We will review the effects of SGAs on other neurotransmitter systems and conclude by highlighting the importance of therapeutic strategies aimed at directly increasing prefrontal DA, D1 receptor transmission or NMDA transmission to enhance the therapeutic effect of moderate D2 receptor antagonism.

The relatively high comorbidity of type 2 diabetes and schizophrenia may suggest a shared biological susceptibility to these twoconditions. Family studies have demonstrated an increased risk of diabetes in unaffected relatives of patients with schizophrenia, consistent with a heritable susceptibility trait. Linkage analyses have identified several loci that are associated with schizophrenia and some of these, notably those on chromosomes 2p22.1-p13.2 and 6g21-824.1 have also been observed in linkage studies in type 2 diabetes. In addition, the dopamine D5 receptor on chromosome 5 and the tyrosine hydroxylase gene on chromosome 11 have both been suggested as candidate genes in schizophrenia and may also be implicated in susceptibility to poor glycaemic control. In addition, an increased rate of type II diabetes has been observed in some patients treated with antipsychotics. Potential neurochemical substrates of this effect include the histamine H1 receptor, the 5-HT2C serotonin receptor or the β3 adrenoreceptor. However, the search for a genetic basis to the association between diabetes and schizophrenia is still in its infancy, and much further work needs to be performed, including the systematic screening of all confirmed susceptibility loci and quantitative trait locus mapping of glycaemic control.

To establish the impact of antipsychotic medication on the incidence of diabetes, we have analysed data from the prospective French Cohort study of mortality in schizophrenia. This generated a large database of 3470 patients with schizophrenia initially enrolled in 1993 for which data collection on comorbidity has been collected systematically every three years since. The primary objective of the study was to evaluate the mortality rate in the study cohort. From this database, the prevalence and incidence of diabetes can be studied. In 1993, nine patients in 10 were prescribed conventional antipsychotics and the remainder amisulpride and clozapine. Since the introduction of risperidone and olanzapine, atypical antipsychotics are now used in one-third of patients. Multiple antipsychotic medications are used in many patients, with the exception of those receiving clozapine. At inclusion, 2.2% of patients in the study cohort had a diagnosis of diabetes. Morbidity rates were higher in females than in males (3.4% and 1.6%, respectively) and it was only in females that the standard morbidity ratio with respect to the general population was significantly elevated (2.2; 95% confidence intervals: 1.6 and 2.9). The prevalence of diabetes in the study cohort rose over the course of the study. Multivariate regression analysis was performed in order to identify potential determinants of diabetes. For pre-existing diabetes, four factors were identified: age at first hospitalisation, age, obesity and duration of schizophrenia. The same factors with the exception of length of illness were identified for the incident cases. There was no evidence for an interaction between the class and type of antipsychotic medication and risk of treatment emergent diabetes. However, the use of multiple antipsychotic treatments makes the individualisation of specific risks associated with any other antipsychotic drug impossible.

Systematic reviews in mental health have become useful tools for health professionals in view of the massive amount and heterogeneous nature of biomedical information available today. In order to determine the risk of bias in the studies evaluated and to avoid bias in generalizing conclusions from the reviews it is therefore important to use a very strict methodology in systematic reviews. One bias which may affect the generalization of results is publication bias, which is determined by the nature and direction of the study results. To control or minimize this type of bias, the authors of systematic reviews undertake comprehensive searches of medical databases and expand on the findings, often undertaking searches of grey literature (material which is not formally published). This paper attempts to show the consequences (and risk) of generalizing the implications of grey literature in the control of publication bias, as was proposed in a recent systematic work. By repeating the analyses for the same outcome from three different systematic reviews that included both published and grey literature our results showed that confusion between grey literature and publication bias may affect the results of a concrete meta-analysis.

Relapse is one of the key factors in the long-term outcome of schizophrenia. The consequences of relapse are diverse and often unpredictable, and the time to recovery and degree of recovery worsen with each successive relapse. There is now overwhelming evidence that advances in antipsychotic drug treatment have led to significant reductions in the rate of relapse. This review charts the developments that have taken place in antipsychotic therapy from the introduction of depot formulations, through atypical agents, to the development of the first long-acting atypical antipsychotic. Depot formulations of conventional antipsychotics were developed in the 1960s and led to fewer relapses and episodes of hospitalization, compared with oral equivalents. Meta-analysis has confirmed that patients receiving depot antipsychotics experience significantly greater global improvement than those receiving the respective oral agents. Conventional antipsychotics are, however, associated with a range of potentially serious adverse events. The atypical antipsychotics were introduced in the 1990s and have significant advantages over conventional agents with regard to positive and negative symptoms. There is also evidence that atypical agents can reduce the risk of relapse. Importantly, atypical antipsychotics have an improved safety profile compared with older agents, particularly with regard to extrapyramidal symptoms. One disadvantage of atypical agents has been that they are only available in an oral form. The recent development of a long-acting injectable formulation of risperidone means that a new treatment option is available to physicians.

There are few controlled studies evaluating the treatment of bipolar mixed states. Evidence suggests that mixed states may be more responsive to some anticonvulsants than to lithium. Olanzapine alone or in combination with divalproate or lithium has been adequately evaluated in randomized clinical trials involving mixed-state patients, whereas risperidone and quetiapine have not. There is also some evidence demonstrating the efficacy of ziprasidone and aripiprazole. The risk of switching to depression is high in mixed states. Conventional antipsychotics, such as haloperidol, may be less efficacious at protecting against a switch to depression than atypical antipsychotics, divalproate or lithium. When choosing drugs for the treatment of mania, and especially for the treatment of mixed states, their efficacy against manic and depressive symptoms, and their safety in terms of the risk of switching to depression should be taken into account.