The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study

Aim Estimate the prevalence of cannabis dependence and its contribution to the global burden of disease. Methods Systematic reviews of epidemiological data on cannabis dependence (1990-2008) were conducted in line with PRISMA and meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed protocols, with cross-checking and consistency checks. DisMod-MR, the latest version of generic disease modelling system, redesigned as a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. The disability weight associated with cannabis dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk factor for schizophrenia were also estimated. Results There were an estimated 13.1 million cannabis dependent people globally in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14% (0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2 million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs since 1990 largely due to population growth. Countries with statistically higher age-standardised DALY rates included the United States, Canada, Australia, New Zealand and Western European countries such as the United Kingdom; those with lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 DALYs globally. Conclusion Cannabis dependence is a disorder primarily experienced by young adults, especially in higher income countries. It has not been shown to increase mortality as opioid and other forms of illicit drug dependence do. Our estimates suggest that cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden.

Health states for schizophrenia and bipolar disorder within the Global Burden of Disease 2010 Study

A comprehensive revision of the Global Burden of Disease (GBD) study is expected to be completed in 2012. This study utilizes a broad range of improved methods for assessing burden, including closer attention to empirically derived estimates of disability. The aim of this paper is to describe how GBD health states were derived for schizophrenia and bipolar disorder. These will be used in deriving health state-specific disability estimates. A literature review was first conducted to settle on a parsimonious set of health states for schizophrenia and bipolar disorder. A second review was conducted to investigate the proportion of schizophrenia and bipolar disorder cases experiencing these health states. These were pooled using a quality-effects model to estimate the overall proportion of cases in each state. The two schizophrenia health states were acute (predominantly positive symptoms) and residual (predominantly negative symptoms). The three bipolar disorder health states were depressive, manic, and residual. Based on estimates from six studies, 63% (38%-82%) of schizophrenia cases were in an acute state and 37% (18%-62%) were in a residual state. Another six studies were identified from which 23% (10%-39%) of bipolar disorder cases were in a manic state, 27% (11%-47%) were in a depressive state, and 50% (30%-70%) were in a residual state. This literature review revealed salient gaps in the literature that need to be addressed in future research. The pooled estimates are indicative only and more data are required to generate more definitive estimates. That said, rather than deriving burden estimates that fail to capture the changes in disability within schizophrenia and bipolar disorder, the derived proportions and their wide uncertainty intervals will be used in deriving disability estimates.

Importance of animal models in schizophrenia research

Objective This review aims to summarize the importance of animal models for research on psychiatric illnesses, particularly schizophrenia. Method and Results Several aspects of animal models are addressed, including animal experimentation ethics and theoretical considerations of different aspects of validity of animal models. A more specific discussion is included on two of the most widely used behavioural models, psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, followed by comments on the difficulty of modelling negative symptoms of schizophrenia. Furthermore, we emphasize the impact of new developments in molecular biology and the generation of genetically modified mice, which have generated the concept of behavioural phenotyping. Conclusions Complex psychiatric illnesses, such as schizophrenia, cannot be exactly reproduced in species such as rats and mice. Nevertheless, by providing new information on the role of neurotransmitter systems and genes in behavioural function, animal 'models' can be an important tool in unravelling mechanisms involved in the symptoms and development of such illnesses, alongside approaches such as post-mortem studies, cognitive and psychophysiological studies, imaging and epidemiology.

Lost in space: The place of the architectural milieu in the aetiology and treatment of schizophrenia

Purpose – Psychological and epidemiological literature suggests that the built environment plays both causal and therapeutic roles in schizophrenia, but what are the implications for designers? The purpose of this paper is to focus on the role the built environment plays in psycho‐environmental dynamics, in order that negative effects can be avoided and beneficial effects emphasised in architectural design. Design/methodology/approach – The approach taken is a translational exploration of the dynamics between the built environment and psychotic illness, using primary research from disciplines as diverse as epidemiology, neurology and psychology. Findings – The built environment is conceived as being both an agonist and as an antagonist for the underlying processes that present as psychosis. The built environment is implicated through several means, through the opportunities it provides. These may be physical, narrative, emotional, hedonic or personal. Some opportunities may be negative, and others positive. The built environment is also an important source of unexpected aesthetic stimulation, yet in psychotic illnesses, aesthetic sensibilities characteristically suffer from deterioration. Research limitations/implications – The findings presented are based on research that is largely translated from very different fields of enquiry. Whilst findings are cogent and logical, much of the support is correlational rather than empirical. Social implications – The WHO claims that schizophrenia destroys 24 million lives worldwide, with an exponential effect on human and financial capital. Because evidence implicates the built environment, architectural and urban designers may have a role to play in reducing the human costs wrought by the illness. Originality/value – Never before has architecture been so explicitly implicated as a cause of mental illness. This paper was presented to the Symposium of Mental Health Facility Design, and is essential reading for anyone involved in designing for improved mental health.

Gene-gene interaction and gene-pathway analysis of genome-wide association for schizophrenia

Schizophrenia (SZ) is a complex disorder with high heritability and variable phenotypes that has limited success in finding causal genes associated with the disease development. Pathway-based analysis is an effective approach in investigating the molecular mechanism of susceptible genes associated with complex diseases. The etiology of complex diseases could be a network of genetic factors and within the genes, interaction may occur. In this work we argue that some genes might be of small effect that by itself are neither sufficient nor necessary to cause the disease however, their effect may induce slight changes to the gene expression or affect the protein function, therefore, analyzing the gene-gene interaction mechanism within the disease pathway would play crucial role in dissecting the genetic architecture of complex diseases, making the pathway-based analysis a complementary approach to GWAS technique. ^ In this study, we implemented three novel linkage disequilibrium based statistics, the linear combination, the quadratic, and the decorrelation test statistics, to investigate the interaction between linked and unlinked genes in two independent case-control GWAS datasets for SZ including participants of European (EA) and African (AA) ancestries. The EA population included 1,173 cases and 1,378 controls with 729,454 genotyped SNPs, while the AA population included 219 cases and 288 controls with 845,814 genotyped SNPs. We identified 17,186 interacting gene-sets at significant level in EA dataset, and 12,691 gene-sets in AA dataset using the gene-gene interaction method. We also identified 18,846 genes in EA dataset and 19,431 genes in AA dataset that were in the disease pathways. However, few genes were reported of significant association to SZ. ^ Our research determined the pathways characteristics for schizophrenia through the gene-gene interaction and gene-pathway based approaches. Our findings suggest insightful inferences of our methods in studying the molecular mechanisms of common complex diseases.^

How does family intervention improve the outcome of people with schizophrenia?

Background: There is strong evidence of the efficacy of family psychosocial interventions for schizophrenia, but evidence of the role played by the attitudes of relatives in the therapeutic process is lacking. Method: To study the effect of a family intervention on family attitudes and to analyse their mediating role in the therapeutic process 50 patients with schizophrenia and their key relatives undergoing a trial on the efficacy of a family psychosocial intervention were studied by means of the Affective Style Coding System, the Scale of Empathy, and the Relational Control Coding System. Specific statistical methods were used to determine the nature of the relationship of the relatives’ attitudes to the outcome of family intervention. Results: Family psychosocial intervention was associated with a reduction in relatives’ guilt induction and dominance and an improvement in empathy. Empathy and lack of dominance were identified as independent mediators of the effect of family psychosocial intervention. The change in empathy and dominance during the first 9 months of the intervention predicted the outcome in the following 15 months. Conclusion: Relatives’ empathy and lack of dominance are mediators of the beneficial effect of family psychosocial intervention on patient’s outcome.

Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study

Objective: Based on clues from epidemiology and animal experiments, low vitamin D during early life has been proposed as a risk factor for schizophrenia. The aim of this study was to explore the association between the use of vitamin D supplements during the first year of life and risk of developing schizophrenia. Method: Subjects were drawn from the Northern Finland 1966 Birth Cohort (n = 9 114). During the first year of life, data were collected about the frequency and dose of vitamin D supplementation. Our primary outcome measures were schizophrenia, psychotic disorders other than schizophrenia, and nonpsychotic disorders as diagnosed by age 31 years. Males and females were examined separately. Results: In males, the use of either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia (Risk ratio (RR) = 0.08, 95% CI 0.01-0.95; RR = 0.12, 95% CI 0.02-0.90, respectively) compared with no supplementation. In males, the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR = 0.23, 95% CI 0.06-0.95) compared to those on lower doses. There were no significant associations between either the frequency or dose of vitamin D supplements and (a) schizophrenia in females, nor with (b) nonpsychotic disorder or psychotic disorders other than schizophrenia in either males or females. Conclusion: Vitamin D supplementation during the first year of life is associated with a reduced risk of schizophrenia in males. Preventing hypovitaminosis D during early life may reduce the incidence of schizophrenia. (C) 2003 Elsevier B.V. All rights reserved.

Variations in the incidence of schizophrenia: Data versus dogma

The schizophrenia research community has shared a belief that the incidence of schizophrenia shows little variation. This belief is related to the dogma that schizophrenia affects all individuals equally, regardless of sex, race, or nationality. However, there is now robust evidence that the incidence of schizophrenia is characterized by substantial variability. There is prominent variation in the incidence of schizophrenia between sites. The incidence of schizophrenia is significantly higher in males than in females (male:female ratio = 1.4). Migrants and those living in urban areas have a higher incidence of schizophrenia. The incidence of schizophrenia has fluctuations across time. In addition, the prevalence of schizophrenia is also characterized by prominent variation. The realization that schizophrenia is characterized by rich and informative gradients will serve as a catalyst for future research.

International epidemiology of prostate cancer : geographical distribution and secular trends

This review outlines current international patterns in prostate cancer incidence and mortality rates and survival, including recent trends and a discussion of the possible impact of prostate-specific antigen (PSA) testing on the observed data. Internationally, prostate cancer is the second most common cancer diagnosed among men (behind lung cancer), and is the sixth most common cause of cancer death among men. Prostate cancer is particularly prevalent in developed countries such as the United States and the Scandinavian countries, with about a six-fold difference between high-incidence and low-incidence countries. Interpretation of trends in incidence and survival are complicated by the increasing impact of PSA testing, particularly in more developed countries. As Western influences become more pronounced in less developed countries, prostate cancer incidence rates in those countries are tending to increase, even though the prevalence of PSA testing is relatively low. Larger proportions of younger men are being diagnosed with prostate cancer and living longer following diagnosis of prostate cancer, which has many implications for health systems. Decreasing mortality rates are becoming widespread among more developed countries, although it is not clear whether this is due to earlier diagnosis (PSA testing), improved treatment, or some combination of these or other factors.

Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood

Background Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence. The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood. Methods and Findings A sample of singleton children (n = 33,437) was drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 8 mo, 4 y, and 7 y (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test). The main analyses examined the relationship between neurocognitive measures and paternal or maternal age when adjusted for potential confounding factors. Advanced paternal age showed significant associations with poorer scores on all of the neurocognitive measures apart from the Bayley Motor score. The findings were broadly consistent in direction and effect size at all three ages. In contrast, advanced maternal age was generally associated with better scores on these same measures. Conclusions The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood. In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny.

Maternal age and paternal age are associated with distinct childhood behavioural outcomes in a general population birth cohort

Abstract Background Recent studies show that advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism, bipolar disorder and schizophrenia. A body of evidence also suggests that individuals who develop schizophrenia show subtle deviations in a range of behavioural domains during their childhood. The aim of the study was to examine the relationship between paternal and maternal ages and selected behavioural measures in children using a large birth cohort. Method Participants were singleton children (n = 21,753) drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 7 years. The main analyses examined the relationship between parental age and behavioural measures when adjusted for a range of potentially confounding variables, including age of the other parent, maternal race, socio-economic measures, sex, gestation length, maternal marital status, parental mental illness, and child's age-at-testing. Results Advanced paternal age was associated with a significantly increased risk of adverse ‘externalizing’ behaviours at age seven years. For every five year increase in paternal age, the odds of higher ‘externalizing’ behaviours was increased by 12% (OR = 1.12; 95% CI = 1.03, 1.21, p < 0.0001). The relationship persisted after adjusting for potential confounding factors. ‘Internalizing’ behavioural outcome was not associated with advanced paternal age. In contrast, advanced maternal age was significantly protective against adverse ‘externalizing’ behavioural outcomes, but associated with an increased risk of adverse ‘internalizing’ behavioural outcomes. Discussion The offspring of older fathers show a distinctly different pattern of behaviours compared to the offspring of older mothers. The diverse socio-cultural and biologically-mediated factors that underpin these findings remain to be clarified. In light of secular trends related to delayed parenthood, the mechanisms underlying these findings warrant closer scrutiny.