Upregulation of the immune response may be involved in the pathogenesis of schizophrenia with changes occurring in both peripheral blood and brain tissue. To date, microarray technology has provided ...a limited view of specific inflammatory transcripts in brain perhaps due to sensitivity issues. Here we used SOLiD Next Generation Sequencing to quantify neuroimmune mRNA expression levels in the dorsolateral prefrontal cortex of 20 individuals with schizophrenia and their matched controls. We detected 798 differentially regulated transcripts present in people with schizophrenia compared with controls. Ingenuity pathway analysis identified the inflammatory response as a key change. Using quantitative real-time PCR we confirmed the changes in candidate cytokines and immune modulators, including interleukin (IL)-6, IL-8, IL-1β and SERPINA3. The density of major histocompatibility complex-II-positive cells morphologically resembling microglia was significantly increased in schizophrenia and correlated with IL-1β expression. A group of individuals, most of whom had schizophrenia, were found to have increased inflammatory mRNA expression. In summary, we have demonstrated changes in an inflammatory response pathway that are present in ∼40% of people diagnosed with schizophrenia. This suggests that therapies aimed at immune system attenuation in schizophrenia may be of direct benefit in the brain.
Cortical grey matter volume deficits and neuro-inflammation exist in patients with schizophrenia, although it is not clear whether elevated cytokines contribute to the cortical volume reduction. We ...quantified cortical and regional brain volumes in fixed postmortem brains from people with schizophrenia and matched controls using stereology. Interleukin (IL)-6, IL-1β, IL-8 and SERPINA3 messenger RNAs (mRNAs) were quantified in the contralateral fresh frozen orbitofrontal cortex. We found a small, but significant reduction in cortical grey matter (1.3%; F(1,85)=4.478, P=0.037) and superior frontal gyrus (6.5%; F(1,80)=5.700, P=0.019) volumes in individuals with schizophrenia compared with controls. Significantly reduced cortical grey matter (9.2%; F(1,24)=8.272, P=0.008) and superior frontal gyrus (13.9%; F(1,20)=5.374, P=0.031) volumes were found in cases with schizophrenia and 'high inflammation' status relative to schizophrenia cases with 'low inflammation' status in the prefrontal cortex. The expression of inflammatory mRNAs in the orbitofrontal cortex was significantly correlated with those in dorsolateral prefrontal cortex (all r>0.417, all P<0.022), except for IL-8. Moreover, average daily and lifetime antipsychotic intake negatively correlated with cortical grey matter and superior frontal gyrus volumes (all r<-0.362, all P<0.05). The results suggest that the reduction in cortical grey matter volume in people with schizophrenia is exaggerated in those who have high expression of inflammatory cytokines. Further, antipsychotic medication intake does not appear to ameliorate the reduction in brain volume.
The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in ...striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes. Gene expression of 12 dopamine-related molecules was examined in post-mortem midbrain (28 antipsychotic-treated schizophrenia cases/29 controls) using quantitative PCR. TH and the synaptic dopamine transporter (DAT) proteins were examined in post-mortem midbrain (26 antipsychotic-treated schizophrenia cases per 27 controls) using immunoblotting. TH and aromatic acid decarboxylase (AADC) mRNA and TH protein were unchanged in the midbrain in schizophrenia compared with controls. Dopamine receptor D2 short, vesicular monoamine transporter (VMAT2) and DAT mRNAs were significantly decreased in schizophrenia, with no change in DRD3 mRNA, DRD3nf mRNA and DAT protein between diagnostic groups. However, DAT protein was significantly increased in putatively treatment-resistant cases of schizophrenia compared to putatively treatment-responsive cases. Midbrain monoamine oxidase A (MAOA) mRNA was increased, whereas MAOB and catechol-O-methyl transferase mRNAs were unchanged in schizophrenia. We conclude that, whereas some mRNA changes are consistent with increased dopamine action (decreased DAT mRNA), others suggest reduced dopamine action (increased MAOA mRNA) in the midbrain in schizophrenia. Here, we identify a molecular signature of dopamine dysregulation in the midbrain in schizophrenia that mainly includes gene expression changes of molecules involved in dopamine synthesis and in regulating the time course of dopamine action.
Abstract The New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney (Australia) is an established human brain bank providing tissue to the neuroscience research community ...for investigations on alcohol-related brain damage and major psychiatric illnesses such as schizophrenia. The NSWBTRC relies on wide community engagement to encourage those with and without neuropsychiatric illness to consent to donation through its allied research programs. The subsequent provision of high-quality samples relies on standardized operational protocols, associated clinical data, quality control measures, integrated information systems, robust infrastructure, and governance. These processes are continually augmented to complement the changes in internal and external governance as well as the complexity and diversity of advanced investigation techniques. This report provides an overview of the dynamic process of brain banking and discusses the challenges of meeting the future needs of researchers, including synchronicity with other disease-focus collections.
Neurogenesis continues in the human subventricular zone and to a lesser extent in the hippocampal subgranular zone throughout life. Subventricular zone-derived neuroblasts migrate to the olfactory ...bulb where survivors become integrated as interneurons and are postulated to contribute to odor discrimination. Adult neurogenesis is dysregulated in many neurological, neurovascular and neurodegenerative diseases. Alcohol abuse can result in a neurodegenerative condition called alcohol-related brain damage. Alcohol-related brain damage manifests clinically as cognitive dysfunction and the loss of smell sensation (hyposmia) and pathologically as generalized white matter atrophy and focal neuronal loss. The exact mechanism linking chronic alcohol intoxication with alcohol-related brain damage remains largely unknown but rodent models suggest that decreased neurogenesis is an important component. We investigated this idea by comparing proliferative events in the subventricular zone and olfactory bulb of a well-characterized cohort of 15 chronic alcoholics and 16 age-matched controls. In contrast to the findings in animal models there was no difference in the number of proliferative cell nuclear antigen-positive cells in the subventricular zone of alcoholics (mean±SD=28.7±20.0) and controls (27.6±18.9, p=1.0). There were also no differences in either the total (p=0.89) or proliferative cells (p=0.98) in the granular cell layer of the olfactory bulb. Our findings show that chronic alcohol consumption does not affect cell proliferation in the human SVZ or olfactory bulb. In fact only microglial proliferation could be demonstrated in the latter. Therefore neurogenic deficits are unlikely to contribute to hyposmia in chronic alcoholics.
•Animal studies show that alcohol decreases adult neurogenesis.•This effect has never been investigated in human brain tissue.•We compared cell proliferation in the olfactory system of alcoholics and controls.•In contrast to animal models there were no differences seen in alcoholics.•Alcohol-related brain damage is unlikely to involve perturbed neurogenesis.
One parameter of the operational framework of the Australian Rural Clinical Training & Support Program (RCTS) is rural health research, yet there are no published reports of the research outcomes ...generated by these hallmarks of Australian rural medical education. To assess the contribution of RCTS to rural health research, their MEDLINE-indexed research publications over the last decade was analysed, using a bibliometric method.
MEDLINE-indexed RCTS publications from 2004 to 2013 were retrieved using validated PubMed queries. Two authors independently checked all retrieved RCTS publications for validity. Australian rural health (ARH) publications from RCTS were selectively enumerated and their proportion among all Australian rural health publications in each year was determined. ARH publications were defined as Australian publications that explore issues relevant to the health of the regional, rural or remote Australian population.RCTS publications related to medical education, Indigenous health, rural service areas, National Health Priority Areas (NHPA), and National Rural Health Alliance Priority Areas (NRHAPA) were analysed. Frequency of publication in different journals was also compared.
A total of 280 RCTS publications were retrieved, increasing from 10 in 2004 to 49 in 2013. ARH topics dominated (177 articles; 67%). RCTS rural health publications increased as a proportion of all ARH publications from 3.4% in 2004 to 7.7% in 2013. Other RCTS publications increased from 2 (20% of total) in 2004 to 19 (39% of total) in 2013, and covered topics such as mental health, cancer, diabetes, obesity and asthma. RCTS medical education publications increased from 3 in 2004 to 14 in 2013. In total, 81 articles were retrieved comprising 28.9% of all RCTS publications. Indigenous health (18; 6%), rural populations (37; 13%) and rural health services (83; 29%) were the other important categories relevant to the RCTS funding parameters. RCTS publications also included NHPA (57; 20%) and NRHAPA (61; 22%). The main journals publishing RCTS research in this time period were Rural and Remote Health (16%), Australian Journal of Rural Health (13%) and Australian Family Physician (9%).
This first study to report on the research efforts of RCTS researchers has shown that they are making a valuable contribution to rural health research and increasingly so within the research parameters indicated. These data represent a benchmark of research strengths and highlight research areas that should be strengthened with targeted research to best promote the health of rural Australians.
Introduction: One parameter of the operational framework of the Australian Rural Clinical Training and Support Program (RCTS) is rural health research, yet there are no published reports of the ...research outcomes generated by these hallmarks of Australian rural medical education. To assess the contribution of RCTS to rural health research, their MEDLINE-indexed research publications over the last decade was analysed, using a bibliometric method.
Methods: MEDLINE-indexed RCTS publications from 2004 to 2013 were retrieved using validated PubMed queries. Two authors independently checked all retrieved RCTS publications for validity. Australian rural health (ARH) publications from RCTS were selectively enumerated and their proportion among all Australian rural health publications in each year was determined. ARH publications were defined as Australian publications that explore issues relevant to the health of the regional, rural or remote Australian population. RCTS publications related to medical education, Indigenous health, rural service areas, National Health Priority Areas (NHPA), and National Rural Health Alliance Priority Areas (NRHAPA) were analysed. Frequency of publication in different journals was also compared.
Results: A total of 280 RCTS publications were retrieved, increasing from 10 in 2004 to 49 in 2013. ARH topics dominated (177 articles; 67%). RCTS rural health publications increased as a proportion of all ARH publications from 3.4% in 2004 to 7.7% in 2013. Other RCTS publications increased from 2 (20% of total) in 2004 to 19 (39% of total) in 2013, and covered topics such as mental health, cancer, diabetes, obesity and asthma. RCTS medical education publications increased from 3 in 2004 to 14 in 2013. In total, 81 articles were retrieved comprising 28.9% of all RCTS publications. Indigenous health (18; 6%), rural populations (37; 13%) and rural health services (83; 29%) were the other important categories relevant to the RCTS funding parameters. RCTS publications also included NHPA (57; 20%) and NRHAPA (61; 22%). The main journals publishing RCTS research in this time period were 'Rural and Remote Health' (16%), 'Australian Journal of Rural Health' (13%) and 'Australian Family Physician' (9%).
Conclusions: This first study to report on the research efforts of RCTS researchers has shown that they are making a valuable contribution to rural health research and increasingly so within the research parameters indicated. These data represent a benchmark of research strengths and highlight research areas that should be strengthened with targeted research to best promote the health of rural Australians.
Introduction: The Rural Clinical Training and Support (RCTS) program is an Australian Government initiative to address the shortage of medical practitioners within rural and remote Australia. There ...is a large amount of published information about the RCTS program and rural medical student cohorts who have undertaken short- and long-term rotations. However, very little is known about the academic and professional staff involved in the program, a knowledge gap that may impact workforce and succession planning. To address this, the Federation of Rural Australian Medical Educators (FRAME) initiated the pilot 2014 RCTS Snapshot survey to obtain data on the current RCTS workforce.
Methods: All professional, academic and clinical academic staff (fixed-term and continuing, regardless of fraction) employed through the RCTS program were invited to complete a short, web-based survey. The survey was conducted from March to June 2014. The quantitative variables in the survey included demographics (age and gender), rural background and exposure, employment history in rural/regional areas and at rural clinical schools (RCS), experience and expertise, reasons for working at RCS, and future employment intentions. The last three questions also were of a qualitative open-ended format to allow respondents to provide additional details regarding their reasons for working at RCSs and their future intentions.
Results: The estimated total RCTS workforce was 970. A total of 413 responses were received and 316 (40.9%) complete responses analysed. The majority of respondents were female (71%), the 40-60-year age group was predominant (28%), and professional staff constituted the majority (62%). The below 40-year age group had more professionals than academics (21% vs 12%) and more than 62% of academics were aged above 50 years. Notably, there were no academics aged less than 30 years. The percentage of professional staff with a rural background was higher (62%) than that of academics with a rural background (42%). However, more than 70% of academics had previous exposure to a rural area as an adult and 32% had an exposure as a part of university or the TAFE (technical and further education) system. More than half (62%) of RCTS academics were aged more than 50 years and thus approaching retirement age. The implementation of a FRAME-sponsored leadership and succession program was considered by most staff (84%) as one strategy that could be used to prevent a future shortage of academics. Lifestyle reasons for working at an RCS were common to both academic (54%) and professional (63%) staff. A passion for rural health and building capacity within the rural health workforce were other central themes to emerge from the qualitative data. Uncertainty around contract renewal and future funding were dominant themes to emerge from respondents regarding their future employment intentions within the RCTS program.
Conclusions: This study has provided valuable insights into the professional and academic staff's views and aspirations about the RCTS program. These data on the current RCTS workforce provide a benchmark to which future surveys of the workforce can be compared to monitor trends in turnover or predict future shortages due to cohort ageing.
The Rural Clinical Training and Support (RCTS) program is an Australian Government initiative to address the shortage of medical practitioners within rural and remote Australia. There is a large ...amount of published information about the RCTS program and rural medical student cohorts who have undertaken short- and long-term rotations. However, very little is known about the academic and professional staff involved in the program, a knowledge gap that may impact workforce and succession planning. To address this, the Federation of Rural Australian Medical Educators (FRAME) initiated the pilot 2014 RCTS Snapshot survey to obtain data on the current RCTS workforce.
All professional, academic and clinical academic staff (fixed-term and continuing, regardless of fraction) employed through the RCTS program were invited to complete a short, web-based survey. The survey was conducted from March to June 2014. The quantitative variables in the survey included demographics (age and gender), rural background and exposure, employment history in rural/regional areas and at rural clinical schools (RCS), experience and expertise, reasons for working at RCS, and future employment intentions. The last three questions also were of a qualitative open-ended format to allow respondents to provide additional details regarding their reasons for working at RCSs and their future intentions.
The estimated total RCTS workforce was 970. A total of 413 responses were received and 316 (40.9%) complete responses analysed. The majority of respondents were female (71%), the 40-60-year age group was predominant (28%), and professional staff constituted the majority (62%). The below 40-year age group had more professionals than academics (21% vs 12%) and more than 62% of academics were aged above 50 years. Notably, there were no academics aged less than 30 years. The percentage of professional staff with a rural background was higher (62%) than that of academics with a rural background (42%). However, more than 70% of academics had previous exposure to a rural area as an adult and 32% had an exposure as a part of university or the TAFE (technical and further education) system. More than half (62%) of RCTS academics were aged more than 50 years and thus approaching retirement age. The implementation of a FRAME-sponsored leadership and succession program was considered by most staff (84%) as one strategy that could be used to prevent a future shortage of academics. Lifestyle reasons for working at an RCS were common to both academic (54%) and professional (63%) staff. A passion for rural health and building capacity within the rural health workforce were other central themes to emerge from the qualitative data. Uncertainty around contract renewal and future funding were dominant themes to emerge from respondents regarding their future employment intentions within the RCTS program.
This study has provided valuable insights into the professional and academic staff's views and aspirations about the RCTS program. These data on the current RCTS workforce provide a benchmark to which future surveys of the workforce can be compared to monitor trends in turnover or predict future shortages due to cohort ageing.
Introduction: One parameter of the operational framework of the Australian Rural Clinical Training and Support Program (RCTS) is rural health research, yet there are no published reports of the ...research outcomes generated by these hallmarks of Australian rural medical education. To assess the contribution of RCTS to rural health research, their MEDLINE-indexed research publications over the last decade was analysed, using a bibliometric method.
Methods: MEDLINE-indexed RCTS publications from 2004 to 2013 were retrieved using validated PubMed queries. Two authors independently checked all retrieved RCTS publications for validity. Australian rural health (ARH) publications from RCTS were selectively enumerated and their proportion among all Australian rural health publications in each year was determined. ARH publications were defined as Australian publications that explore issues relevant to the health of the regional, rural or remote Australian population. RCTS publications related to medical education, Indigenous health, rural service areas, National Health Priority Areas (NHPA), and National Rural Health Alliance Priority Areas (NRHAPA) were analysed. Frequency of publication in different journals was also compared.
Results: A total of 280 RCTS publications were retrieved, increasing from 10 in 2004 to 49 in 2013. ARH topics dominated (177 articles; 67%). RCTS rural health publications increased as a proportion of all ARH publications from 3.4% in 2004 to 7.7% in 2013. Other RCTS publications increased from 2 (20% of total) in 2004 to 19 (39% of total) in 2013, and covered topics such as mental health, cancer, diabetes, obesity and asthma. RCTS medical education publications increased from 3 in 2004 to 14 in 2013. In total, 81 articles were retrieved comprising 28.9% of all RCTS publications. Indigenous health (18; 6%), rural populations (37; 13%) and rural health services (83; 29%) were the other important categories relevant to the RCTS funding parameters. RCTS publications also included NHPA (57; 20%) and NRHAPA (61; 22%). The main journals publishing RCTS research in this time period were 'Rural and Remote Health' (16%), 'Australian Journal of Rural Health' (13%) and 'Australian Family Physician' (9%).
Conclusions: This first study to report on the research efforts of RCTS researchers has shown that they are making a valuable contribution to rural health research and increasingly so within the research parameters indicated. These data represent a benchmark of research strengths and highlight research areas that should be strengthened with targeted research to best promote the health of rural Australians.
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