Mark Agius

Distribution of tract deficits in schizophrenia

BackgroundGray and white matter brain changes have been found in schizophrenia but the anatomical organizing process underlying these changes remains unknown. We aimed to identify gray and white matter volumetric changes in a group of patients with schizophrenia and to quantify the distribution of white matter tract changes using a novel approach which applied three complementary analyses to diffusion imaging data.Methods21 patients with schizophrenia and 21 matched control subjects underwent brain magnetic resonance imaging. Gray and white matter volume differences were investigated using Voxel-based Morphometry (VBM). White matter diffusion changes were located using Tract Based Spatial Statistics (TBSS) and quantified within a standard atlas. Tracts where significant regional differences were located were examined using fiber tractography.ResultsNo significant differences in gray or white matter volumetry were found between the two groups. Using TBSS the schizophrenia group showed significantly lower fractional anisotropy (FA) compared to the controls in regions (false discovery rate <0.05) including the genu, body and splenium of the corpus callosum and the left anterior limb of the internal capsule (ALIC). Using fiber tractography, FA was significantly lower in schizophrenia in the corpus callosum genu (p = 0.003).ConclusionsIn schizophrenia, white matter diffusion deficits are prominent in medial frontal regions. These changes are consistent with the results of previous studies which have detected white matter changes in these areas. The pathology of schizophrenia may preferentially affect the prefrontal-thalamic white matter circuits traversing these regions.

Long-term trajectories of cognitive deficits in schizophrenia: A critical overview

BACKGROUND Cognitive disturbances are widely pronounced in schizophrenia and schizophrenia spectrum disorders. Whilst cognitive deficits are well established in the prodromal phase and are known to deteriorate at the onset of schizophrenia, there is a certain discrepancy of findings regarding the cognitive alterations over the course of the illness. METHODS We bring together the results of the longitudinal studies identified through PubMed which have covered more than 3 years follow-up and to reflect on the potential factors, such as sample characteristics and stage of the illness which may contribute to the various trajectories of cognitive changes. RESULTS A summary of recent findings comprising the changes of the cognitive functioning in schizophrenia patients along the longitudinal course of the illness is provided. The potential approaches for addressing cognition in the course of schizophrenia are discussed. CONCLUSIONS Given the existing controversies on the course of cognitive changes in schizophrenia, differentiated approaches specifically focusing on the peculiarities of the clinical features and changes in specific cognitive domains could shed light on the trajectories of cognitive deficits in schizophrenia and spectrum disorders.

Availability of mental health service providers and suicide rates in Slovenia: a nationwide ecological study.

Aim To investigate the influence of socioeconomic factors, mental health service availability, and prevalence of mental disorders on regional differences in the suicide rate in Slovenia. Methods The effects of different socioeconomic factors, mental health service availability, and mental disorders factors on suicide rates from 2000-2009 were analyzed using a general linear mixed model (GLMM). Pearson correlations were used to explore the direction and magnitude of associations. Results Among socioeconomic factors, unemployment rate ranked as the most powerful predictor of suicide and an increase of one unit in the unemployment rate increased regional suicide rate by 2.21 (β = 2.21, 95% confidence intervals [CI] = 1.87-2.54, P < 0.001). On the other hand, higher marriage/divorce ratio was negatively related to the suicide rate and an increase of one unit in marriage/divorce ratio reduced regional suicide rate by 1.16 (β = -1.16, 95% CI = -2.20 to -0.13, P < 0.031). The most influential mental health service availability parameter was higher psychiatrist availability (4 psychiatrists and more working at outpatient clinics per 100 000 inhabitants), which was negatively correlated with the suicide rate and reduced regional suicide rate by 2.95 (β = -2.95, 95% CI = -4.60 to -1.31, P = 0.002). Another negatively correlated factor was the antidepressant/anxiolytic ratio higher than 0.5, which reduced the regional suicide rate by 2.32 (β = -2.32, 95% CI = -3.75 to -0.89, P = 0.003). Among mental health disorders, only the prevalence of alcohol use disorders was significantly related to the regional suicide rates and an increase of one unit in the prevalence of alcohol use disorders per 1000 inhabitants increased the regional suicide rate by 0.02 (β = 0.02, 95% CI = 0.01- 0.03, P = 0.008). Conclusions Besides unemployment, which was a very strong predictor of suicide rates, unequal availability of mental health services and quality of depressive disorder treatment may contribute to variations in suicide rates in different regions.

The State of the Art of the DSM-5 “with Mixed Features” Specifier

The new DSM-5 “with mixed features” specifier (MFS) has renewed the interest of the scientific community in mixed states, leading not only to new clinical studies but also to new criticisms of the current nosology. Consequently, in our paper we have reviewed the latest literature, trying to understand the reactions of psychiatrists to the new nosology and its epidemiological, prognostic, and clinical consequences. It seems that the most widespread major criticism is the exclusion from the DSM-5 MFS of overlapping symptoms (such as psychomotor agitation, irritability, and distractibility), with a consequent reduction in diagnostic power. On the other hand, undoubtedly the new DSM-5 classification has helped to identify more patients suffering from a mixed state by broadening the narrow DSM-IV-TR criteria. As for the clinical presentation, the epidemiological data, and the therapeutic outcomes, the latest literature does not point out a univocal point of view and further research is needed to fully assess the implications of the new DSM-5 MFS. It is our view that a diagnostic category should be preferred to a specifier and mixed states should be better considered as a spectrum of states, according to what was stated many years ago by Kraepelin.

The global economic crisis: effects on mental health and what can be done

The character Gordon Gecko in the film ‘Wall Street’ lived by the mantra ‘Greed is Good’. The events that unfolded towards the end of 2008 exposed in dramatic fashion the downside to greed and led to the worst global economic crisis since the Great Depression of the 1930s. Economic contagion in the US spread rapidly as many countries experienced failures in key businesses, declines in consumer wealth and increased financial debts. While the economic and political implications have been studied in detail, the impact on health – especially that of mental health – has received much less attention. This essay aims to achieve a critical analysis of causality (or lack thereof) between an economic crisis and mental health, using a combination of statistical review, psychological theories and common logic. This will hopefully impact on our understanding of the causes of mental health problems in times of economic insecurity and assist in developing strategies to ameliorate them. While an economic downturn is quantifiable, it is not an easy task with mental health. For the purposes of this essay we propose a view of five principal components of mental health, which have been accepted by many Western philosophers and summarized by Peter Warr from the University of Sheffield. These five interacting components of mental health are affective wellbeing, competence, autonomy, aspiration and integrated functioning. However, we recognize that there are other ways of conceptualizing the component of mental health. The crux of this essay is an analysis of causation between the economic downturn and these components of mental health. The downturn is likely to exert its impact through a series of interlinked factors, but studies highlight that job-related problems, particularly unemployment, are the key determinant risk factors for mental-health-related difficulties. Clearly, unemployment is a major concern in times of an economic crisis. Prospective studies unsurprisingly show that unemployment has a causal influence on depression. Common sense dictates that depression will reduce the chance of re-employment and reintegration into an already strained economy and eventually the chronically unemployed suffer increased debts. Longitudinal data show that financial difficulties lead to increased major depression, with housing payment problems and consumer debt leading to poorer mental health. In short, the quintessential ‘vicious cycle’. In relation to the components of mental health, longitudinal studies indicate significant deterioration in affective wellbeing after job loss, with individuals scoring lowly on separate indices of affective wellbeing such as being content and having anxiety and depression. Competence is expected to decline following unemployment because of loss of skills which might be applied in future jobs. The constraints of unemployment might be thought also to cause reduction in autonomy, with studies showing that belief in selfdirection and locus of control decrease. Those keeping their jobs are not immune to the effects of the crisis. Anxiety about job insecurity complicates existing depression and acts as a chronic stressor with cumulative effects over time. On the basis of the five components of mental health, job insecurity most likely affects the aspects of autonomy and aspiration. The autonomy of the individual to determine and control his workload is threatened by the contraction of the workforce as this usually implies that the DECLARATIONS

P01-188 - Mixed affective states; a study within a community mental health team with treatment recommendations

INTRODUCTION Agitated Depression and Bipolar mixed states combine depressive and manic symptoms, reflecting severe forms of affective disorders with an increased suicide risk. These states have not been defined with adequate consensus and hence present a diagnostic and therapeutic challenge. In this study, we argue that both states are part of the bipolar spectrum rather than a distinct affective syndrome or a mixed anxiety-depression state. METHODS The current literature has been reviewed and suggestions are made for a unified definition of this entity, which would be valuable in recognising this dangerous state. We have then studied 17 cases of mixed states identified from a database held by a UK community mental health team. We have studied the treatments offered and estimated the time these treatments have taken to end the mixed state and so reduce the risk of suicide. RESULTS Not surprisingly, there are no clear recommendations for treatment of these mixed states. We found that The best results were achieved with a three pronged regimen including increasing/adding mood stabilisers; and/or increasing/adding antipsychotics; as well as decreasing antidepressants. Resolution was achieved in two and a half weeks. DISCUSSION From this work we have deduced several general principles, which are here reviewed and hence we have been able to suggest possible treatment strategies. CONCLUSION Because of the close link between affective mixed states and suicidality, it is of great importance that patients be brought out of the mixed affective state as soon as possible, hence we believe that our findings are of importance in managing these patients. However we recommend further study on a larger sample in order to confirm our findings.

Reduced Blood Alcohol Concentration in Suicide Victims in Response to a New National Alcohol Policy in Slovenia

Background: Addiction is a major social and health problem. Studies on suicide and alcohol at the individual and aggregated level have confirmed a link between alcohol and suicide. Aim: To assess the impact of the new national alcohol policy in Slovenia on the blood alcohol concentration (BAC) in BAC-positive suicide victims before, during and after the implementation of the new national alcohol policy in 2003. Method: Blood samples were collected by forensic pathologists during medicolegal autopsies of suicide victims in order to establish their BAC levels at the time of death. BAC was measured using two routine independent headspace gas chromatography methods (HSS-GC-FID) and expressed in grams per kilogram. Results: During the period before the implementation of the act which limited the availability of alcohol in Slovenia, the BACs of BAC-positive suicide victims were higher than those tested in the period after the implementation of the act. Conclusion: Despite certain limitations, this study demonstrates that legislation measures restricting alcohol availability may be an effective measure of BAC reduction in BAC-positive suicide victims.

Long-term hospitalizations for schizophrenia in the Czech Republic 1998-2012.

Deinstitutionalization has not been pursued in the post-communist Europe until recently. The population of psychiatric patients institutionalized in the regional mental hospitals is, however, largely understudied. The aim of this study is to assess discharges of long-term inpatients with schizophrenia from Czech psychiatric hospitals and to analyse re-hospitalizations within this group. The nationwide register of all-cause inpatient hospitalizations was merged with the nationwide register of all-cause deaths on an individual level basis. Descriptive statistics, survival analysis and logistic regression were performed. 3601 patients with schizophrenia previously hospitalized for more than a year were discharged from Czech mental hospitals between 1998 and 2012. This included 260 patients hospitalized for >20years. Nearly one fifth (n=707) of the long-term patients died during the hospitalization; and discharges of 19.36% (n=697) were only administrative in their nature. Out of 2197 truly discharged patients, 14.88% (n=327) were re-hospitalized within 2weeks after the discharge. The highest odds of rehospitalization were associated with being discharged against medical advice (OR 5.27, CI: 3.77-7.35, p<0.001). These data are important for the ongoing mental health care reforms in the Czech Republic and other countries in the Central and Eastern Europe.

Reality monitoring impairment in schizophrenia reflects specific prefrontal cortex dysfunction

Reality monitoring impairment is often reported in schizophrenia but the neural basis of this deficit is poorly understood. Difficulties with reality monitoring could be attributable to the same pattern of neural dysfunction as other cognitive deficits that characterize schizophrenia, or might instead represent a separable and dissociable impairment. This question was addressed through direct comparison of behavioral performance and neural activity associated with reality monitoring and working memory in patients with schizophrenia and matched healthy controls. Participants performed a word-pair reality monitoring task and a Sternberg working memory task while undergoing fMRI scanning. Distinct behavioral deficits were observed in the patients during performance of each task, which were associated with separable task- and region-specific dysfunction in the medial anterior prefrontal cortex for reality monitoring and dorsolateral prefrontal cortex for working memory. The results suggest that reality monitoring impairment is a distinct neurocognitive deficit in schizophrenia. The findings are consistent with the presence of a range of dissociable cognitive deficits in schizophrenia which may be associated with variable functional and structural dysconnectivity in underlying processing networks.

Assessing and staging bipolar disorder

We congratulate Duffy et al on their paper.[1][1] We have long argued that bipolar disorder is often underdiagnosed by community mental health teams, and that the reason for this is often failure to assess the longitudinal trajectory of patients with recurrent depression.[2][2],[3][3] We have