Biomedical subjects

John McGrath

Publications and source records attributed to John McGrath.

At least 19 recordsLinked to original sources

PubMed2006

Clinical and demographic features of treated first-episode psychotic disorders: a Zambian study.

BACKGROUND: There is a relative lack of information about the epidemiology of psychotic disorders in the developing world. The aim of this pragmatic study was to describe the correlates of first-episode psychosis in the central African nation of Zambia. METHOD: Selected clinical and demographic variables were collected on patients with psychotic disorders presenting for the first time at the only psychiatric hospital in Zambia (Chainama Hills College Hospital, Lusaka). RESULTS: During the study period, 160 subjects were admitted to the hospital with the first episode of a psychotic disorder. The male to female sex ratio was 2.5:1, with the median age of first admission for both sexes being 26 years. Half of the subjects had a duration of untreated psychosis one month or less. Recent alcohol and other drug abuse was common in males (56%). Clinical evidence of HIV/AIDs was found in 9% of those admitted. Approximately one-third of the subjects had attended a traditional healer for their psychotic symptoms prior to admission. CONCLUSIONS: Understanding the profile of treated first-episode psychosis in the developing world can help optimize the development of local services. Furthermore, characterizing differences in the epidemiology of psychosis between populations may help generate factors that could influence its cause and course.

Adolescent↗

PubMed2006

Incidence of schizophrenia does not vary with economic status of the country: evidence from a systematic review.

BACKGROUND: A recent systematic review found that the prevalence of schizophrenia was lower in developing nations compared to developed nations. However, there is a lack of information about the association between economic status and the incidence of schizophrenia. The aim of this study was to examine the association between economic status and the underlying incidence of schizophrenia based on a recently published systematic review of the incidence of schizophrenia. METHODS: The analyses were based on 167 discrete incidence rates from 52 studies. Nations were divided into three categories according to per capita gross national product. Based on these categories, we compared the incidence rates for schizophrenia when adjusted for within-study variation. RESULTS: The median (and 10-90% quantiles) incidence rates per 100,000 persons for Least Developed Countries (three studies), Emerging Economies (nine studies), and Developed Countries (42 studies) were 20.0 (0.4-35.0), 11.0 (5.0-26.0) and 16.0 (8.0-48.0) respectively. There was no significant difference in incidence rates between these groups. CONCLUSIONS: While there is a lack of information on the incidence of schizophrenia in the developing world, there is no evidence to suggest that the incidence of schizophrenia varies by economic status. In light of the evidence that the prevalence of schizophrenia is higher in developed countries, more research is warranted focused on the interaction between economic measures, and the incidence, prevalence and course of schizophrenia.

Developed Countries↗

PubMed2006

Risk factors for schizophrenia. Follow-up data from the Northern Finland 1966 Birth Cohort Study.

This paper updates single risk factors identified by the Northern Finland 1966 Birth Cohort Study up to the end of year 2001 or age 34. Impaired performance (e.g., delayed motor or intellectual development) or adverse exposures (e.g., pregnancy and birth complications, central nervous system diseases) are associated with an increased risk for schizophrenia. However, upper social class girls and clever schoolboys also have an increased risk to develop schizophrenia, contrasted to their peers. Individuals who subsequently develop schizophrenia follow a developmental trajectory that partly and subtly differs from that of the general population; this trajectory lacks flexibility and responsiveness compared to control subjects, at least in the early stages. We propose a descriptive, lifespan, multilevel systems model on the development and course of schizophrenia.

Journal Article↗

PubMed2005

Psychotic-like experiences in the general community: the correlates of CIDI psychosis screen items in an Australian sample.

BACKGROUND: Apart from individuals with clinical psychosis, community surveys have shown that many otherwise well individuals endorse items designed to identify psychosis. The aim of this study was to characterize the demographic correlates of individuals who endorse psychosis screening items in a large general community sample. METHOD: The National Survey of Mental Health and Wellbeing interviewed 10641 individuals living in private dwellings in Australia. As part of a diagnostic interview (the CIDI), respondents were asked between three and six items originally designed to screen for potential psychosis. We examined the impact of selected demographic variables on endorsement of these items including sex, age, marital status, migrant status, urban/rural status, employment, education, and socio-economic status. RESULTS: An estimated 11.7% of the Australian population endorsed at least one psychosis-screening item. Significantly higher endorsement was associated with younger age, migrants from non-English-speaking backgrounds, those who had never married or who were divorced/separated or unemployed, those living in urban regions and those from the lowest socio-economic levels. CONCLUSIONS: Many of the correlates of endorsement of psychosis-screen items are also associated with psychosis. Unravelling the factors that contribute to this broader non-clinical phenotype will aid our understanding of psychosis.

Adolescent↗

PubMed2005

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.

Epidemiologic Studies↗

PubMed2005

Queensland Centre for Mental Health Research: the first 17 years.

OBJECTIVE: To reflect on the establishment and evolution of the Queensland Centre for Mental Health Research. METHOD: Narrative historical review. RESULTS: First established as an inpatient research unit in December 1987, the focus of the Centre evolved in concert with the skills of the staff. After the structure was revised in 1996 and 1999, the Centre has evolved into a group with four main research streams--epidemiology, developmental neurobiology, genetics and policy and economics. Although the group maintains a strong focus on serious mental disorders such as schizophrenia, our policy and economic work has a wider perspective. The Queensland Centre for Mental Health Research is based in an historic mental health service, with laboratories in collaborating universities and institutes. Key lessons learnt by the group along the way relate to the importance of focusing on a restricted range of research topics in order to build a critical mass. CONCLUSIONS: Given a facilitating environment, hospital-based research groups can prosper. Over the last 17 years, a cost-efficient, focused and productive research group has evolved that has made contributions to international research.

Academic Medical Centers↗

PubMed2005

Response of cytoskeleton of murine osteoblast cultures to two-step freezing.

Understanding the ultrastructural response of cells to the freezing process is important for designing cryopreservation strategies for cells and tissues. The cellular structures of attached cells are targets of cryopreservation-induced damage. Specific fluorescence staining was used to assess the status of the actin filaments (F-actin) of murine osteoblasts attached to hydroxyapatite discs and plastic coverslips for a two-step freezing process. The F-actin of dead cells was depolymerized and distorted in the freezing process, whereas that of live cells had little change. The results suggest that the cytoskeleton may support the robustness of cells during cryopreservation. The present study helps to investigate the damage mechanism of attached cells during the freezing process.

Actins↗

PubMed2005

Communicating about medications during primary care outpatient visits: the role of electronic medical records.

OBJECTIVES: To assess the role of electronic medical records (EMR) in facilitating the content and process of patient-provider exchanges about medications during outpatient primary care visits. METHODS: Fifty encounters with six physicians using the EMR were videotaped, transcribed and content-analysed by applying conversation analysis and ethnomethodology techniques. The analysis focused on three aspects of medication communication: (1) process of care: practices by patients and physicians to implement medication decisions; (2) themes: medication topics that consistently emerge; and (3) names: ways patients and physicians refer to medications. In-depth analysis of 20 encounters examined the extent to which either or both parties initiated, expanded and concluded medication discussions. RESULTS: On average 21.2 (range: 8-35; SD=7.4) distinct exchanges per encounter were observed. Of those, 33% were related to medication. Of the 350 medication-related exchanges throughout the encounters, 56% were categorised as routine medication discussion such as ordering and/or refilling medications. Mailing issues were the next most common medication-related exchanges (10.6%), followed by partial adherence (8.9%), self-regulation (7.4%), alternative therapy/over-the-counter medication (6.6%), side effects (6%) and formulary issues (4.6%). Patients and providers used three ways to name medications: generic/scientific name (42%); physical description (39.7%) and brand name (18.3%). Forty-one percent of exchanges included initiation by one or both parties but no further discussion of the issue; 42% included initiation and expansion by both parties but not conclusion; only 17% of exchanges contained complete medication exchanges (initiation, expansion and conclusion) by both parties. CONCLUSIONS: EMR facilitated content and process of communication regarding medications during outpatient encounters, especially among patients taking multiple medications and patients who used physical descriptions to identify their medications. EMR use stimulated medication exchanges, leading to further expansion about the topic. However, fewer than one-fifth of exchanges ended with clear conclusions by both parties regarding prescribed medication regimens.

Adult↗

PubMed2004

Maternal vitamin D3 deprivation and the regulation of apoptosis and cell cycle during rat brain development.

Recently, it has been shown that the prenatal vitamin D(3) depletion is associated with altered brain development. Given the antiproliferative and pro-apoptotic properties of vitamin D(3) in various cell types, we examined the effects of maternal vitamin D(3) deprivation on cell proliferation and apoptosis within the rat cortex at several developmental stages. Our results confirm that vitamin D(3) regulates these processes in the developing brain at both cellular and molecular levels. Compared to control animals, the embryos and pups from vitamin D(3) depleted mothers had significantly less apoptotic cells, this finding being most pronounced at birth. Additionally, there were significantly more mitotic cells but this was not associated with any particular developmental period. Targeted gene arrays specific for apoptosis and cell cycle genes confirmed a pattern of transcription deregulation in the deplete group consistent with the known properties of vitamin D(3). While most current vitamin D(3) research is focussed on the pro-apoptotic and prodifferentiating properties of vitamin D(3) as adjuncts for the treatment of cancers, our findings highlight the important role that this hormone plays in normal development via these same properties specifically in the brain.

Animals↗

PubMed2004

Maintaining and updating semantic context in schizophrenia: an investigation of the effects of multiple remote primes.

Conflicting findings regarding the ability of people with schizophrenia to maintain and update semantic contexts have been due, arguably, to vagaries within the experimental design employed (e.g. whether strongly or remotely associated prime-target pairs have been used, what delay between the prime and the target was employed, and what proportion of related prime-target pairs appeared) or to characteristics of the participant cohort (e.g. medication status, chronicity of illness). The aim of the present study was to examine how people with schizophrenia maintain and update contextual information over an extended temporal window by using multiple primes that were either remotely associated or unrelated to the target. Fourteen participants with schizophrenia and 12 healthy matched controls were compared across two stimulus onset asynchronies (SOAs) (short and long) and two relatedness proportions (RP) (high and low) in a crossed design. Analysis of variance statistics revealed significant two- and three-way interactions between Group and SOA, Group and Condition, SOA and RP, and Group, SOA and RP. The participants with schizophrenia showed evidence of enhanced remote priming at the short SOA and low RP, combined with a reduction in the time course over which context could be maintained. There was some sensitivity to biasing contextual information at the short SOA, although the mechanism over which context served to update information appeared to be different from that in the controls. The participants with schizophrenia showed marked performance decrements at the long SOA (both low and high RP). Indices of remote priming at the short (but not the long) SOA correlated with both clinical ratings of thought disorder and with increasing length of illness. The results support and extend the hypothesis that schizophrenia is associated with concurrent increases in tonic dopamine activity and decreases in phasic dopamine activity.

Adult↗

PubMed2004

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

BACKGROUND: Understanding 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. METHODS: Studies 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. RESULTS: We 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). CONCLUSIONS: There 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.

Cohort Studies↗

PubMed2004

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.

Adult↗

PubMed2004

Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia.

BACKGROUND: While the association between increased maternal age and congenital disorders has long been recognized, the offspring of older fathers are also at increased risk of congenital disorders related to DNA errors during spermatogenesis. Recent studies have drawn attention to an association between increased paternal age and increased risk of schizophrenia. The aim of the current study was to examine both paternal and maternal age as risk factors for the broader category of psychosis. METHOD: We used data from three sources examining psychosis: a population-based cohort study (Denmark), and two case-control studies (Sweden and Australia). RESULTS: When controlling for the effect of maternal age, increased paternal age was significantly associated with increased risk of psychosis in the Danish and Swedish studies. The Australian study found no association between adjusted paternal age and risk of psychosis. When controlling for the effect of paternal age, younger maternal age was associated with an increased risk of psychoses in the Danish study alone. CONCLUSIONS: The offspring of older fathers are at increased risk of developing psychosis. The role of paternally derived mutations and/or psychosocial factors associated with older paternal age warrants further research.

Adolescent↗

PubMed2004

Correlates of victimisation amongst people with psychosis.

BACKGROUND: While much attention has been given to the prediction of violent offending behaviour amongst people with psychotic disorders, less attention has been given to the fact that these same individuals are often the victims of violence. In this paper, we examine victimisation amongst participants in a prevalence study of psychosis, and describe demographic and clinical correlates of victimisation. METHOD The study was based on the Australian National Survey of Mental Health and Wellbeing--Low Prevalence (Psychotic) Disorders. The participants were asked if they had been a victim of violence in the previous year. The association between selected demographic and clinical variables and being a victim of violence was examined using logistic regression. RESULTS: Of the 962 individuals with psychosis, 172 reported being a victim of violence in the past 12 months (17.9 %). The odds of being a victim were increased in those who: (a) were female, (b) were homeless, (c) had a lifetime history of substance abuse, (d) had been arrested in the previous 12 months, (e) had poorer social and occupational function, and (f) had higher scores on the disorganisation summary score. CONCLUSIONS: Clinicians should remain mindful that one out of every six individuals with a psychotic disorder reports being a victim of violence in the previous year. Models of care that address issues related to symptom relief, accommodation, and exposure to high-crime areas may reduce the rates of victimisation amongst those with psychotic disorders.

Adult↗

PubMed2004

Bacterial ghosts--biological particles as delivery systems for antigens, nucleic acids and drugs.

Despite the exponential rate of discovery of new antigens and DNA vaccines resulting from modern molecular biology and proteomics, the lack of effective delivery technology is a major limiting factor in their application. The bacterial ghost system represents a platform technology for antigen, nucleic acid and drug delivery. Bacterial ghosts have significant advantages over other engineered biological delivery particles, owing to their intrinsic cellular and tissue tropic abilities, ease of production and the fact that they can be stored and processed without the need for refrigeration. These particles have found both veterinary and medical applications for the vaccination and treatment of tumors and various infectious diseases.

Animals↗

PubMed2004

Schizophrenia, vitamin D, and brain development.

Schizophrenia research is invigorated at present by the recent discovery of several plausible candidate susceptibility genes identified from genetic linkage and gene expression studies of brains from persons with schizophrenia. It is a current challenge to reconcile this gathering evidence for specific candidate susceptibility genes with the "neurodevelopmental hypothesis," which posits that schizophrenia arises from gene-environment interactions that disrupt brain development. We make the case here that schizophrenia may result not from numerous genes of small effect, but a few genes of transcriptional regulation acting during brain development. In particular we propose that low vitamin D during brain development interacts with susceptibility genes to alter the trajectory of brain development, probably by epigenetic regulation that alters gene expression throughout adult life. Vitamin D is an attractive "environmental" candidate because it appears to explain several key epidemiological features of schizophrenia. Vitamin D is an attractive "genetic" candidate because its nuclear hormone receptor regulates gene expression and nervous system development. The polygenic quality of schizophrenia, with linkage to many genes of small effect, maybe brought together via this "vitamin D hypothesis." We also discuss the possibility of a broader set of environmental and genetic factors interacting via the nuclear hormone receptors to affect the development of the brain leading to schizophrenia.

Animals↗

PubMed2004

Making medical research clinically friendly: a communication-based conceptual framework.

CONTEXT: It often takes a long time before the results of medical research are actually used by health care practitioners in day-to-day clinical settings. This problem, referred to as "the evidence-to-practice gap", has significant implications for patient health care. Practitioners have difficulty keeping up with the latest information in part because it is reported in hundreds of journals that may not be easily accessed and understood. APPROACH: This essay conceptualizes the evidence-to-practice gap as a communication problem and suggests how academic research can be translated into messages that are easier for practitioners to access, comprehend and incorporate into their medical practice. A "translation framework" shows the importance of targeting messages to specific audiences and provides a communication-based conceptual approach for summarizing research for clinicians. PRACTICAL IMPLICATIONS: Targeting the results of academic research to practitioners will decrease the time it takes for patients to benefit from the latest medical evidence. Translation guidelines can help health researchers write more effectively for both academic and practitioner audiences. Since the evidence-to-practice gap is a systemic problem that begins with how we train our health researchers, educators should consider addressing this topic in the health professions classroom. The framework presented here can serve as the basis for an instructional unit on interpreting and reporting research findings. Finally, information technology can play a much larger role in the communication process because of the enormous advantages of quick access and data organization that computers and the Internet provide. Practitioner-targeted research summaries could be made available on government or not-for-profit sponsored websites as well as by journals themselves. Funding opportunities exist for research that focuses on how technology can help improve health care, and so the time is right for health researchers to investigate ways of making their studies more accessible and quickly usable via web-based distribution. The potential of medical science should not be limited by an information delivery system that we have the knowledge, expertise and resources to improve.

Biomedical Research↗

PubMed2004

Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Clinicians frequently use lithium to augment antipsychotic medication in schizophrenia. Therefore, we undertook a systematic review and meta-analysis of the use of lithium in the treatment of schizophrenia. DATA SOURCES AND STUDY SELECTION: Randomized controlled trials examining lithium (as a sole or an adjunctive compound) in participants with schizophrenia or related disorders were searched in the register of the Cochrane Schizophrenia Group. No language restrictions were applied. The Boolean phrase [lithium* or lithicarb or eskalith or lithobid or lithane or cibalith-s or quilonum or hypnorex] was used to locate articles. The search strategy initially identified 90 references. The authors of the included studies were contacted to obtain original patient data. The data were combined in a meta-analysis. The main outcome parameters were the number of patients with a clinically significant response and the number of patients leaving the studies early. RESULTS: The meta-analysis includes 20 studies (N = 611). The evidence shows that lithium as a sole agent is ineffective in the treatment of schizophrenia. Eleven trials examined the augmentation of antipsychotics with lithium. More patients who received lithium augmentation than those who received antipsychotics alone were classified as responders. However, the superiority was not consistent across different response thresholds, and when patients with prominent affective symptoms were excluded from the analysis, the advantage of lithium augmentation was not significant (p =.07). Significantly more patients taking lithium left the trials early, suggesting a lower acceptability of lithium augmentation compared with that of taking antipsychotics alone. CONCLUSION: Despite some evidence in favor of lithium augmentation, the overall results are inconclusive. A large trial of lithium augmentation of antipsychotic medications will be required in order to detect a benefit of small effect size in patients with schizophrenia who lack affective symptoms.

Affective Symptoms↗