Psychiatry - Research Publications

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    ETHICAL ISSUES AND ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)
    JUDD, FK ; BIGGS, BA ; BURROWS, GD (AUSTRALIAN NZ J PSYCHIATRY, 1989-12)
    Acquired Immunodeficiency Syndrome (AIDS) has received much publicity and medical attention. Interest has focused on education, epidemiology, treatment and prevention of the syndrome. This paper raises other issues for consideration, including problems associated with HIV testing, confidentiality, informed consent and the dilemmas facing those involved in the treatment of patients suffering from HIV infection.
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    Genetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks
    Fornito, A ; Zalesky, A ; Bassett, DS ; Meunier, D ; Ellison-Wright, I ; Yuecel, M ; Wood, SJ ; Shaw, K ; O'Connor, J ; Nertney, D ; Mowry, BJ ; Pantelis, C ; Bullmore, ET (SOC NEUROSCIENCE, 2011-03-02)
    The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09-0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization.
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    The relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD - a monozygotic twin study
    Hall, T ; Galletly, C ; Clark, CR ; Veltmeyer, M ; Metzger, LJ ; Gilbertson, MW ; Orr, SP ; Pitman, RK ; McFarlane, A (BMC, 2012-12)
    BACKGROUND: PTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD. METHODS: Our study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins. RESULTS: There were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD. CONCLUSIONS: These findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.
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    Teaching psychiatry in Ethiopia.
    Hanlon, C ; Fekadu, D ; Sullivan, D ; Alem, A ; Prince, M (Cambridge University Press (CUP), 2006-04)
    There is a pressing need to train psychiatrists in low- and middle-income countries. Psychiatrists from high-income countries have an opportunity to share expertise in teaching and assessing trainees, while learning much in the process. Three trainees from a London psychiatric hospital were invited to help organise a revision course for the Department of Psychiatry, Addis Ababa University, and this paper reports their experiences.
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    Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF).
    McMurray, JJV ; Anand, IS ; Diaz, R ; Maggioni, AP ; O'Connor, C ; Pfeffer, MA ; Solomon, SD ; Tendera, M ; van Veldhuisen, DJ ; Albizem, M ; Cheng, S ; Scarlata, D ; Swedberg, K ; Young, JB ; RED-HF Committees Investigators, (Wiley, 2013-03)
    AIMS: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. METHODS AND RESULTS: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. CONCLUSION: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.
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    Anesthetics Rapidly Promote Synaptogenesis during a Critical Period of Brain Development
    De Roo, M ; Klauser, P ; Briner, A ; Nikonenko, I ; Mendez, P ; Dayer, A ; Kiss, JZ ; Muller, D ; Vutskits, L ; Chédotal, A (PUBLIC LIBRARY SCIENCE, 2009-09-16)
    Experience-driven activity plays an essential role in the development of brain circuitry during critical periods of early postnatal life, a process that depends upon a dynamic balance between excitatory and inhibitory signals. Since general anesthetics are powerful pharmacological modulators of neuronal activity, an important question is whether and how these drugs can affect the development of synaptic networks. To address this issue, we examined here the impact of anesthetics on synapse growth and dynamics. We show that exposure of young rodents to anesthetics that either enhance GABAergic inhibition or block NMDA receptors rapidly induce a significant increase in dendritic spine density in the somatosensory cortex and hippocampus. This effect is developmentally regulated; it is transient but lasts for several days and is also reproduced by selective antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal slice cultures reveals that this effect is mediated through an increased rate of protrusions formation, a better stabilization of newly formed spines, and leads to the formation of functional synapses. Altogether, these findings point to anesthesia as an important modulator of spine dynamics in the developing brain and suggest the existence of a homeostatic process regulating spine formation as a function of neural activity. Importantly, they also raise concern about the potential impact of these drugs on human practice, when applied during critical periods of development in infants.
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    LTP promotes a selective long-term stabilization and clustering of dendritic spines
    De Roo, M ; Klauser, P ; Muller, D ; Sheng, M (PUBLIC LIBRARY SCIENCE, 2008-09)
    Dendritic spines are the main postsynaptic site of excitatory contacts between neurons in the central nervous system. On cortical neurons, spines undergo a continuous turnover regulated by development and sensory activity. However, the functional implications of this synaptic remodeling for network properties remain currently unknown. Using repetitive confocal imaging on hippocampal organotypic cultures, we find that learning-related patterns of activity that induce long-term potentiation act as a selection mechanism for the stabilization and localization of spines. Through a lasting N-methyl-D-aspartate receptor and protein synthesis-dependent increase in protrusion growth and turnover, induction of plasticity promotes a pruning and replacement of nonactivated spines by new ones together with a selective stabilization of activated synapses. Furthermore, most newly formed spines preferentially grow in close proximity to activated synapses and become functional within 24 h, leading to a clustering of functional synapses. Our results indicate that synaptic remodeling associated with induction of long-term potentiation favors the selection of inputs showing spatiotemporal interactions on a given neuron.
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    N-cadherin mediates plasticity-induced long-term spine stabilization
    Mendez, P ; De Roo, M ; Poglia, L ; Klauser, P ; Muller, D (ROCKEFELLER UNIV PRESS, 2010-05-03)
    Excitatory synapses on dendritic spines are dynamic structures whose stability can vary from hours to years. However, the molecular mechanisms regulating spine persistence remain essentially unknown. In this study, we combined repetitive imaging and a gain and loss of function approach to test the role of N-cadherin (NCad) on spine stability. Expression of mutant but not wild-type NCad promotes spine turnover and formation of immature spines and interferes with the stabilization of new spines. Similarly, the long-term stability of preexisting spines is reduced when mutant NCad is expressed but enhanced in spines expressing NCad-EGFP clusters. Activity and long-term potentiation (LTP) induction selectively promote formation of NCad clusters in stimulated spines. Although activity-mediated expression of NCad-EGFP switches synapses to a highly stable state, expression of mutant NCad or short hairpin RNA-mediated knockdown of NCad prevents LTP-induced long-term stabilization of synapses. These results identify NCad as a key molecular component regulating long-term synapse persistence.
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    Depression in the patient with COPD.
    Wilson, I (Informa UK Limited, 2006)
    This paper explores the recent literature surrounding comorbid depression and COPD. The literature reveals a high prevalence of depression in patients with COPD and some evidence that the depression is a result of the disease. The literature highlights the negative impact of depression on quality of life and a possible impact on mortality. Depression also negatively impacts on compliance and smoking cessation. Treatment of depression in COPD, particularly by cognitive behavioral therapy, has positive impact on quality of life. Tricyclic antidepressants have a positive impact on mood and COPD, but side effects limit their use. The advent of the new antidepressants may improve acceptability and outcomes, but the research is yet to be undertaken. Physical rehabilitation may have a positive impact on mood. This paper highlights the difficulty in screening for depression in patients with COPD due to the overlap of symptoms between the two diseases. Despite the difficulties, it is important to recognize and treat depression in patients with COPD because of the significant likelihood of improvement in quality of life.
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    Australian medical students' perceptions of professionalism and ethics in medical television programs.
    Weaver, R ; Wilson, I (Springer Science and Business Media LLC, 2011-07-29)
    BACKGROUND: Medical television programs offer students fictional representations of their chosen career. This study aimed to discover undergraduate medical students' viewing of medical television programs and students' perceptions of professionalism, ethics, realism and role models in the programs. The purpose was to consider implications for teaching strategies. METHODS: A medical television survey was administered to 386 undergraduate medical students across Years 1 to 4 at a university in New South Wales, Australia. The survey collected data on demographics, year of course, viewing of medical television programs, perception of programs' realism, depiction of ethics, professionalism and role models. RESULTS: The shows watched by most students were House, Scrubs, and Grey's Anatomy, and students nominated watching 30 different medical programs in total. There was no statistical association between year of enrolment and perceptions of accuracy. The majority of students reported that friends or family members had asked them for their opinion on an ethical or medical issue presented on a program, and that they discussed ethical and medical matters with their friends. Students had high recall of ethical topics portrayed on the shows, and most believed that medical programs generally portrayed ideals of professionalism well. CONCLUSIONS: Medical programs offer considerable currency and relevance with students and may be useful in teaching strategies that engage students in ethical lessons about practising medicine.