Psychiatry - Research Publications

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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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    New developments in the management of major depressive disorder and generalized anxiety disorder: role of quetiapine.
    Baune, BT (Informa UK Limited, 2008-12)
    Quetiapine has demonstrated efficacy in schizophrenia, bipolar disorder and in the treatment of specific symptom clusters such as agitation and sleep problems in mood disorders. In this review, randomized controlled studies demonstrating efficacy, safety and tolerability of quetiapine in major depressive disorder (MDD) and general anxiety disorder (GAD) are evaluated. The results show that quetiapine monotherapy and quetiapine augmentation of antidepressant treatment in MDD and GAD are efficacious for short-term and maintenance treatment at a dose range between 50 and 300 mg/day. Quetiapine appears to have a specific but overall mild side-effect profile, though, some adverse effects such as sedation and somnolence may lead to withdrawal from treatment in some patients. Overall, the available evidence suggests that there is a significant role for quetiapine in the treatment of MDD and GAD.
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    The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population.
    Paul, R ; Henry, L ; Grieve, SM ; Guilmette, TJ ; Niaura, R ; Bryant, R ; Bruce, S ; Williams, LM ; Richard, CC ; Cohen, RA ; Gordon, E (Informa UK Limited, 2008-02)
    BACKGROUND: Previous studies have examined the impact of early life stress (ELS) on the gross morphometry of brain regions, including the corpus callosum. However, studies have not examined the relationship between ELS and the microstructural integrity of the brain. METHODS: In the present study we evaluated this relationship in healthy non-clinical participants using diffusion tensor imaging (DTI) and self-reported history of ELS. RESULTS: Regression analyses revealed significant reductions in fractional anisotropy (FA) within the genu of the corpus callosum among those exposed to the greatest number of early life stressors, suggesting reduced microstructural integrity associated with increased ELS. These effects were most pronounced in the genu of the corpus callosum compared to the body and splenium, and were evident for females rather than males despite no differences in total ELS exposure between the sexes. In addition, a further comparison of those participants who were exposed to no ELS vs. three or more ELS events revealed lower FA in the genu of the corpus callosum among the ELS-exposed group, with trends of FA reduction in the body and the whole corpus callosum. By contrast, there were no relationships between ELS and volumetric analysis of the CC regions. The two group did not differ significantly on measures of current depression, stress or anxiety. CONCLUSION: Our results reveal that greater exposure to ELS is associated with microstructural alterations in the white matter in the absence of significant volumetric changes. Importantly, our results indicate that exposure to ELS is associated with abnormalities on DTI despite the absence of clinically significant psychiatric symptoms. Future studies are needed to determine whether specific types of ELS are more likely to impact brain structure and function.
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    Transitions of care from child and adolescent mental health services to adult mental health services (TRACK study): A study of protocols in greater London
    Singh, SP ; Paul, M ; Ford, T ; Kramer, T ; Weaver, T (BIOMED CENTRAL LTD, 2008-06-23)
    BACKGROUND: Although young people's transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) in England is a significant health issue for service users, commissioners and providers, there is little evidence available to guide service development. The TRACK study aims to identify factors which facilitate or impede effective transition from CAHMS to AMHS. This paper presents findings from a survey of transition protocols in Greater London. METHODS: A questionnaire survey (Jan-April 2005) of Greater London CAMHS to identify transition protocols and collect data on team size, structure, transition protocols, population served and referral rates to AMHS. Identified transition protocols were subjected to content analysis. RESULTS: Forty two of the 65 teams contacted (65%) responded to the survey. Teams varied in type (generic/targeted/in-patient), catchment area (locality-based, wider or national) and transition boundaries with AMHS. Estimated annual average number of cases considered suitable for transfer to AMHS, per CAMHS team (mean 12.3, range 0-70, SD 14.5, n = 37) was greater than the annual average number of cases actually accepted by AMHS (mean 8.3, range 0-50, SD 9.5, n = 33). In April 2005, there were 13 active and 2 draft protocols in Greater London. Protocols were largely similar in stated aims and policies, but differed in key procedural details, such as joint working between CAHMS and AMHS and whether protocols were shared at Trust or locality level. While the centrality of service users' involvement in the transition process was identified, no protocol specified how users should be prepared for transition. A major omission from protocols was procedures to ensure continuity of care for patients not accepted by AMHS. CONCLUSION: At least 13 transition protocols were in operation in Greater London in April 2005. Not all protocols meet all requirements set by government policy. Variation in protocol-sharing organisational units and transition process suggest that practice may vary. There is discontinuity of care provision for some patients who 'graduate' from CAMHS services but are not accepted by adult services.
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    The role of the General Practitioner in weight management in primary care - a cross sectional study in General Practice
    Tham, M ; Young, D (BMC, 2008-12-15)
    BACKGROUND: Obesity has become a global pandemic, considered the sixth leading cause of mortality by the WHO. As gatekeepers to the health system, General Practitioners are placed in an ideal position to manage obesity. Yet, very few consultations address weight management. This study aims to explore reasons why patients attending General Practice appointments are not engaging with their General Practitioner (GP) for weight management and their perception of the role of the GP in managing their weight. METHODS: In February 2006, 367 participants aged between 17 and 64 were recruited from three General Practices in Melbourne to complete a waiting room self - administered questionnaire. Questions included basic demographics, the role of the GP in weight management, the likelihood of bringing up weight management with their GP and reasons why they would not, and their nominated ideal person to consult for weight management. Physical measurements to determine weight status were then completed. The statistical methods included means and standard deviations to summarise continuous variables such as weight and height. Sub groups of weight and questionnaire answers were analysed using the chi2 test of significant differences taking p as < 0.05. RESULTS: The population sample had similar obesity co-morbidity rates to the National Heart Foundation data. 74% of patients were not likely to bring up weight management when they visit their GP. Negative reasons were time limitation on both the patient's and doctor's part and the doctor lacking experience. The GP was the least likely person to tell a patient to lose weight after partner, family and friends. Of the 14% that had been told by their GP to lose weight, 90% had cardiovascular obesity related co-morbidities. GPs (15%) were 4th in the list of ideal persons to manage weight after personal trainer CONCLUSION: Patients do not have confidence in their GPs for weight management, preferring other health professionals who may lack evidence based training. Concurrently, GPs target only those with obesity related co-morbidities. Further studies evaluating GPs' opinions about weight management, effective strategies that can be implemented in primary care and the co-ordination of the team approach need to be done.
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    A factor analytic investigation of the Tripartite model of affect in a clinical sample of young Australians
    Buckby, JA ; Cotton, SM ; Cosgrave, EM ; Killackey, EJ ; Yung, AR (BMC, 2008-09-18)
    BACKGROUND: The Mood and Anxiety Symptom Questionnaire (MASQ) was designed to specifically measure the Tripartite model of affect and is proposed to offer a delineation between the core components of anxiety and depression. Factor analytic data from adult clinical samples has shown mixed results; however no studies employing confirmatory factor analysis (CFA) have supported the predicted structure of distinct Depression, Anxiety and General Distress factors. The Tripartite model has not been validated in a clinical sample of older adolescents and young adults. The aim of the present study was to examine the validity of the Tripartite model using scale-level data from the MASQ and correlational and confirmatory factor analysis techniques. METHODS: 137 young people (M = 17.78, SD = 2.63) referred to a specialist mental health service for adolescents and young adults completed the MASQ and diagnostic interview. RESULTS: All MASQ scales were highly inter-correlated, with the lowest correlation between the depression- and anxiety-specific scales (r = .59). This pattern of correlations was observed for all participants rating for an Axis-I disorder but not for participants without a current disorder (r = .18). Confirmatory factor analyses were conducted to evaluate the model fit of a number of solutions. The predicted Tripartite structure was not supported. A 2-factor model demonstrated superior model fit and parsimony compared to 1- or 3-factor models. These broad factors represented Depression and Anxiety and were highly correlated (r = .88). CONCLUSION: The present data lend support to the notion that the Tripartite model does not adequately explain the relationship between anxiety and depression in all clinical populations. Indeed, in the present study this model was found to be inappropriate for a help-seeking community sample of older adolescents and young adults.
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    Vision and quality of life: Development of methods for the VisQoL vision-related utility instrument
    Peacock, S ; Misajon, R ; Iezzi, A ; Richardson, J ; Hawthorne, G ; Keeffe, J (TAYLOR & FRANCIS INC, 2008)
    PURPOSE: To describe the methods and innovations used in constructing the VisQoL, a vision-related utility instrument for the health economic evaluation of eye care and rehabilitation programs. METHODS: The VisQoL disaggregates vision into six items. Utilities were estimated for item worst responses (the worst level for each item, with all other items at their best level) and VisQoL all-worst responses (all items at their worst level) using the time trade-off procedure. Time trade-off questions require people to imagine living a fixed number of years with a particular health condition and then indicate how many of those years of life they would be willing to trade to have perfect health. Where respondents indicated a health state was "worse than death" negative utilities were estimated. Time trade-off questions minimized the "focusing effect," which occurs if respondents discount the fact that all other aspects of health are at their best when answering questions, by using pictorial and verbal aids. RESULTS: Item utilities were combined using a multiplicative model, and VisQoL model utilities placed on a scale where 0.00 and 1.00 represent full health and death, respectively. The VisQoL allows utilities to be calculated for a wide range of vision-related conditions. CONCLUSION: The 6-item VisQoL has excellent psychometric properties and is specifically designed to be sensitive to vision-related quality of life. It is the first instrument to permit the rapid estimation of utility values for use in economic evaluations of vision-related programs.
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    Modulation of Brain Resting-State Networks by Sad Mood Induction
    Harrison, BJ ; Pujol, J ; Ortiz, H ; Fornito, A ; Pantelis, C ; Yucel, M ; Robertson, E (PUBLIC LIBRARY SCIENCE, 2008-03-19)
    BACKGROUND: There is growing interest in the nature of slow variations of the blood oxygen level-dependent (BOLD) signal observed in functional MRI resting-state studies. In humans, these slow BOLD variations are thought to reflect an underlying or intrinsic form of brain functional connectivity in discrete neuroanatomical systems. While these 'resting-state networks' may be relatively enduring phenomena, other evidence suggest that dynamic changes in their functional connectivity may also emerge depending on the brain state of subjects during scanning. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined healthy subjects (n = 24) with a mood induction paradigm during two continuous fMRI recordings to assess the effects of a change in self-generated mood state (neutral to sad) on the functional connectivity of these resting-state networks (n = 24). Using independent component analysis, we identified five networks that were common to both experimental states, each showing dominant signal fluctuations in the very low frequency domain (approximately 0.04 Hz). Between the two states, we observed apparent increases and decreases in the overall functional connectivity of these networks. Primary findings included increased connectivity strength of a paralimbic network involving the dorsal anterior cingulate and anterior insula cortices with subjects' increasing sadness and decreased functional connectivity of the 'default mode network'. CONCLUSIONS/SIGNIFICANCE: These findings support recent studies that suggest the functional connectivity of certain resting-state networks may, in part, reflect a dynamic image of the current brain state. In our study, this was linked to changes in subjective mood.
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    Development of mental health first aid guidelines for suicidal ideation and behaviour: A Delphi study
    Kelly, CM ; Jorm, AF ; Kitchener, BA ; Langlands, RL (BMC, 2008-03-18)
    BACKGROUND: Suicide is a statistically rare event, but devastating to those left behind and one of the worst possible outcomes associated with mental illness. Although a friend, family member or co-worker may be the first person to notice that a person is highly distressed, few have the knowledge and skills required to assist. Simple guidelines may help such a person to encourage a suicidal individual to seek professional help or decide against suicide. METHODS: This research was conducted using the Delphi methodology, a method of reaching consensus in a panel of experts. Experts recruited to the panels included 22 professionals, 10 people who had been suicidal in the past and 6 carers of people who had been suicidal in the past. Statements about how to assist someone who is thinking about suicide were sourced through a systematic search of both professional and lay literature. The guidelines were written using the items most consistently endorsed by all three panels. RESULTS: Of 114 statements presented to the panels, 30 were accepted. These statements were used to develop the guidelines appended to this paper. CONCLUSION: There are a number of actions which are considered to be useful for members of the public when they encounter someone who is experiencing suicidal thoughts or engaging in suicidal behaviour. These guidelines will be useful in revision of curricula of mental health first aid and suicide intervention training programs. They can also be used by members of the public who want immediate information about how to assist a suicidal person.
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    First aid guidelines for psychosis in Asian countries: A Delphi consensus study
    Jorm, AF ; Minas, H ; Langlands, RL ; Kelly, CM (BioMed Central, 2008-02-21)
    BACKGROUND: Guidelines for how a member of the public should give first aid to a person who is becoming psychotic have been developed for English-speaking countries. However, these guidelines may not be appropriate for use in other cultures. A study was therefore carried out to examine whether it was possible to achieve consensus on guidelines that could apply in a range of Asian countries. METHODS: A Delphi consensus study was carried out with a panel of 28 Asian mental health clinicians drawn from Cambodia, China, Hong Kong, Indonesia, Japan, Malaysia, Mongolia, South Korea, Sri Lanka, Taiwan, Thailand and Vietnam. The panel was given a 211 item questionnaire about possible first aid actions and asked to rate whether they thought these should be included in guidelines. Panel members were invited to propose additional items. RESULTS: After three Delphi rounds, there were 128 items that were rated as "essential" or "important" by 80% or more of the panel members. These items covered: recognition of psychosis, encouraging and assisting the person to seek help, how to interact with the person, responding to acute psychosis, responding to aggression, and what to do if the person refuses to get professional help. CONCLUSION: Despite the diversity of the countries involved, there was consensus on a core set of first aid items that were considered as suitable for assisting a psychotic person. Future work is needed to develop guidelines for specific countries.