John J. McGrath

A Systematic Review of the Prevalence of Schizophrenia

Background Understanding the prevalence of schizophrenia has important implications for both health service planning and risk factor epidemiology. The aims of this review are to systematically identify and collate studies describing the prevalence of schizophrenia, to summarize the findings of these studies, and to explore selected factors that may influence prevalence estimates. Methods and Findings Studies with original data related to the prevalence of schizophrenia (published 1965–2002) were identified via searching electronic databases, reviewing citations, and writing to authors. These studies were divided into “core” studies, “migrant” studies, and studies based on “other special groups.” Between- and within-study filters were applied in order to identify discrete prevalence estimates. Cumulative plots of prevalence estimates were made and the distributions described when the underlying estimates were sorted according to prevalence type (point, period, lifetime, and lifetime morbid risk). Based on combined prevalence estimates, the influence of selected key variables was examined (sex, urbanicity, migrant status, country economic index, and study quality). A total of 1,721 prevalence estimates from 188 studies were identified. These estimates were drawn from 46 countries, and were based on an estimated 154,140 potentially overlapping prevalent cases. We identified 132 core studies, 15 migrant studies, and 41 studies based on other special groups. The median values per 1,000 persons (10%–90% quantiles) for the distributions for point, period, lifetime, and lifetime morbid risk were 4.6 (1.9–10.0), 3.3 (1.3–8.2), 4.0 (1.6–12.1), and 7.2 (3.1–27.1), respectively. Based on combined prevalence estimates, we found no significant difference (a) between males and females, or (b) between urban, rural, and mixed sites. The prevalence of schizophrenia in migrants was higher compared to native-born individuals: the migrant-to-native-born ratio median (10%–90% quantile) was 1.8 (0.9–6.4). When sites were grouped by economic status, prevalence estimates from “least developed” countries were significantly lower than those from both “emerging” and “developed” sites (p = 0.04). Studies that scored higher on a quality score had significantly higher prevalence estimates (p = 0.02). Conclusions There is a wealth of data about the prevalence of schizophrenia. These gradients, and the variability found in prevalence estimate distributions, can provide direction for future hypothesis-driven research.

Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality

Recent systematic reviews have encouraged the psychiatric research community to reevaluate the contours of schizophrenia epidemiology. This paper provides a concise overview of three related systematic reviews on the incidence, prevalence, and mortality associated with schizophrenia. The reviews shared key methodological features regarding search strategies, analysis of the distribution of the frequency estimates, and exploration of the influence of key variables (sex, migrant status, urbanicity, secular trend, economic status, and latitude). Contrary to previous interpretations, the incidence of schizophrenia shows prominent variation between sites. The median incidence of schizophrenia was 15.2/100,000 persons, and the central 80% of estimates varied over a fivefold range (7.7-43.0/100,000). The rate ratio for males:females was 1.4:1. Prevalence estimates also show prominent variation. The median lifetime morbid risk for schizophrenia was 7.2/1,000 persons. On the basis of the standardized mortality ratio, people with schizophrenia have a two- to threefold increased risk of dying (median standardized mortality ratio = 2.6 for all-cause mortality), and this differential gap in mortality has increased over recent decades. Compared with native-born individuals, migrants have an increased incidence and prevalence of schizophrenia. Exposures related to urbanicity, economic status, and latitude are also associated with various frequency measures. In conclusion, the epidemiology of schizophrenia is characterized by prominent variability and gradients that can help guide future research.

Distribution of the vitamin D receptor and 1α-hydroxylase in human brain

Despite a growing body of evidence that Vitamin D is involved in mammalian brain functioning, there has been a lack of direct evidence about its role in the human brain. This paper reports, for the first time, the distribution of the 1,25-dihydroxyvitamin D3 receptor (VDR), and 1α-hydroxylase (1α-OHase), the enzyme responsible for the formation of the active vitamin in the human brain. The receptor and the enzyme were found in both neurons and glial cells in a regional and layer-specific pattern. The VDR was restricted to the nucleus whilst 1α-OHase was distributed throughout the cytoplasm. The distribution of the VDR in human brain was strikingly similar to that reported in rodents. Many regions contained equivalent amounts of both the VDR and 1α-OHase, however the macrocellular cells within the nucleus basalis of Meynert (NBM) and the Purkinje cells in the cerebellum expressed 1α-OHase in the absence of VDR. The strongest immunohistochemical staining for both the receptor and enzyme was in the hypothalamus and in the large (presumably dopaminergic) neurons within the substantia nigra. The observed distribution of the VDR is consistent with the proposal that Vitamin D operates in a similar fashion to the known neurosteroids. The widespread distribution of 1α-OHase and the VDR suggests that Vitamin D may have autocrine/paracrine properties in the human brain.

A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology

BackgroundUnderstanding variations in the incidence of schizophrenia is a crucial step in unravelling the aetiology of this group of disorders. The aims of this review are to systematically identify studies related to the incidence of schizophrenia, to describe the key features of these studies, and to explore the distribution of rates derived from these studies.MethodsStudies with original data related to the incidence of schizophrenia (published 1965–2001) were identified via searching electronic databases, reviewing citations and writing to authors. These studies were divided into core studies, migrant studies, cohort studies and studies based on Other Special Groups. Between- and within-study filters were applied in order to identify discrete rates. Cumulative plots of these rates were made and these distributions were compared when the underlying rates were sorted according to sex, urbanicity, migrant status and various methodological features.ResultsWe identified 100 core studies, 24 migrant studies, 23 cohort studies and 14 studies based on Other Special Groups. These studies, which were drawn from 33 countries, generated a total of 1,458 rates. Based on discrete core data for persons (55 studies and 170 rates), the distribution of rates was asymmetric and had a median value (10%–90% quantile) of 15.2 (7.7–43.0) per 100,000. The distribution of rates was significantly higher in males compared to females; the male/female rate ratio median (10%–90% quantile) was 1.40 (0.9–2.4). Those studies conducted in urban versus mixed urban-rural catchment areas generated significantly higher rate distributions. The distribution of rates in migrants was significantly higher compared to native-born; the migrant/native-born rate ratio median (10%–90% quantile) was 4.6 (1.0–12.8). Apart from the finding that older studies reported higher rates, other study features were not associated with significantly different rate distributions (e.g. overall quality, methods related to case finding, diagnostic confirmation and criteria, the use of age-standardization and age range).ConclusionsThere is a wealth of data available on the incidence of schizophrenia. The width and skew of the rate distribution, and the significant impact of sex, urbanicity and migrant status on these distributions, indicate substantial variations in the incidence of schizophrenia.

Vitamin D3 and brain development

Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D(3) acts during brain development. We demonstrate that rats born to vitamin D(3)-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D(3) has important ramifications for the developing brain.

Psychotic disorders in urban areas: an overview of the study on low prevalence disorders

Objective: This paper reports on a study designed within the framework of the National Survey of Mental Health and Wellbeing to: estimate the prevalence of psychoses in urban areas of Australia; identify profiles of symptomatology, impairments and disabilities; collect information on services received and needed; and explore quality of life issues in a broadly representative sample of people with psychotic illnesses. Method: The study was conducted over four areas in the Australian Capital Territory, Queensland, Victoria and Western Australia, as a two-phase survey: (i) a census and screening for psychosis of all individuals who made contacts with mental health services during a period of 1 month in 1997; and (ii) interviews with a stratified random sample (n = 980) of the screen-positive individuals (n = 3800) using a standardised instrument. Results: The point prevalence (1 month) of psychotic disorders in the urban population aged 18–64 is in the range of 4–7 per 1000 with a weighted mean of 4.7 per 1000. People with psychotic disorders experience high rates of functional impairments and disability, decreased quality of life, persistent symptoms, substance-use comorbidity and frequent side effects of medication. Although the utilisation of hospital-based and community mental health services, as well as of public and non-governmental helping agencies, is high, the majority live in extreme social isolation and adverse socioeconomic circumstances. Among the many unmet needs, the limited availability of community-based rehabilitation, supported accommodation and employment opportunities is particularly prominent. Conclusions: The so-called ‘low-prevalence’ psychotic disorders represent a major and complex public health problem, associated with heavy personal and social costs. There is a need for a broad programmatic approach, involving various sectors of the community, to tackle the multiple dimensions of clinical disorder, personal functioning and socioeconomic environment that influence the course and outcome of psychosis and ultimately determine the effectiveness of service-based intervention.

Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease

Increasingly vitamin D deficiency is being associated with a number of psychiatric conditions. In particular for disorders with a developmental basis, such as autistic spectrum disorder and schizophrenia the neurobiological plausibility of this association is strengthened by the preclinical data indicating vitamin D deficiency in early life affects neuronal differentiation, axonal connectivity, dopamine ontogeny and brain structure and function. More recently epidemiological associations have been made between low vitamin D and psychiatric disorders not typically associated with abnormalities in brain development such as depression and Alzheimers disease. Once again the preclinical findings revealing that vitamin D can regulate catecholamine levels and protect against specific Alzheimer-like pathology increase the plausibility of this link. In this review we have attempted to integrate this clinical epidemiology with potential vitamin D-mediated basic mechanisms. Throughout the review we have highlighted areas where we think future research should focus.

Hypothesis: Is low prenatal vitamin D a risk-modifying factor for schizophrenia?

The central nervous system is increasingly being recognised as a target organ for vitamin D via its wide-ranging steroid hormonal effects and via the induction of various proteins such as nerve growth factor. This paper proposes that low maternal vitamin D may impact adversely on the developing foetal brain, leaving the affected offspring at increased risk of adult-onset schizophrenia. The hypothesis can parsimoniously explain diverse epidemiological features of schizophrenia, such as the excess of winter births, increased rates of schizophrenia in dark-skinned migrants to cold climates, the increased rate of schizophrenia births in urban versus rural setting, and the association between prenatal famine and schizophrenia. Studies that will allow rejection of the hypothesis are proposed.

People living with psychotic illness in 2010: the second Australian national survey of psychosis.

Objective: The 2010 Survey of High Impact Psychosis (SHIP) is Australia’s second national psychosis survey. This paper provides an overview of its findings, including comparisons with the first psychosis survey and general population data. Methods: The survey covered 1.5 million people aged 18–64 years, approximately 10% of Australians in this age group. A two-phase design was used. In phase 1, screening for psychosis took place in public mental health services and non-government organizations supporting people with mental illness. In phase 2, 1825 of those screen-positive for psychosis were randomly selected and interviewed. Data collected included symptomatology, substance use, functioning, service utilization, medication use, education, employment, housing, and physical health including fasting blood samples. Results: The estimated 1-month treated prevalence of psychotic disorders in public treatment services was 3.1 people per 1000 population; the 12-month treated prevalence was 4.5 people per 1000. The majority (63.0%) of participants met ICD-10 criteria for schizophrenia/schizoaffective disorder. One-half (49.5%) reported attempting suicide in their lifetime and two-thirds (63.2%) were rated as impaired in their ability to socialize. Over half (54.8%) had metabolic syndrome. The proportion currently smoking was 66.1%. Educational achievement was low. Only 21.5% were currently employed. Key changes in the 12 years since the first survey included: a marked drop in psychiatric inpatient admissions; a large increase in the proportion attending community mental health clinics; increased use of rehabilitation services and non-government organizations supporting people with mental illness; a major shift from typical to atypical antipsychotics; and large increases in the proportions with lifetime alcohol or drug abuse/dependence. Conclusion: People with psychotic illness face multiple challenges. An integrated approach to service provision is needed to ensure that their living requirements and needs for social participation are met, in addition to their very considerable mental and physical health needs.

1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons

There is an accumulation of evidence implicating a role for vitamin D(3) in the developing brain. The receptor for this seco-steroid is expressed in both neurons and glial cells, it induces nerve growth factor (NGF) and it is a potent inhibitor of mitosis and promoter of differentiation in numerous cells. We have therefore assessed the direct effect of vitamin D(3) on mitosis, neurite outgrowth, as well as NGF production as a possible mediator of those effects, in developing neurons. Using cultured embryonic hippocampal cells and explants we found the addition of vitamin D(3) significantly decreases the percentage of cultured hippocampal cells undergoing mitosis in conjunction with increases in both neurite outgrowth and NGF production. The role of vitamin D(3) during brain development warrants closer scrutiny.