Association between serotonin transporter genotype, brain structure and adolescent onset major depressive disorder: a longitudinal prospective study

The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD) between age 13–19 years, in a longitudinal study of 174 adolescents (48% males). Increasing copies of S-alleles were found to predict smaller left hippocampal volume, which in turn was associated with increased risk of experiencing a first onset of MDD. Increasing copies of S-alleles also predicted both smaller left and right medial OFC volumes, although neither left nor right medial OFC volumes were prospectively associated with a first episode of MDD during adolescence. The findings therefore suggest that structural abnormalities in the left hippocampus may be present prior to the onset of depression during adolescence and may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness. 5-HTTLPR genotype may also impact upon other regions of the brain, such as the OFC, but structural differences in these regions in early adolescence may not necessarily alter the risk for onset of depression during later adolescence.

Pharmacological treatment in the early phase of bipolar disorders: what stage are we at?

To review available guidelines, explore treatment strategies currently applied, identify critical issues and propose direction for new developments.

Oxidant/antioxidant imbalance is an inherent feature of depression

BACKGROUND: 50% to 60% of the people who have recovered from the first episode of depression experience a relapse. The immune system of the people suffering from depression is in a permanent state of pathological pro-inflammatory readiness. There are some reports that depressive episodes cause sensitization of immune-inflammatory pathways and that staing of depression (e.g. number of depressive episodes) is correlated with immune-inflammatory markers. The main objective of the study was to delineate whether recurrent major depression (rDD) is characterized by alterations in selected immune-inflammatory biomarkers as compared with first episode of depression (ED-I), i.e. expression of mRNA and enzymatic activity of manganese superoxide dismutase (MnSOD, SOD-2), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS, NOS-2), and cyclooxygenase-2 (COX-2). METHODS: The study was carried out in a group of 131 patients: ED-I group - 42 patients, rDD group - 89 patients. Depression severity was assessed with the 17-item Hamilton Depression Rating Scale (HDRS). The number of depression episodes and the disease duration periods were recorded in each patient. For the patients, HDRS was administered at admission during the symptomatic phase, which would generally be either before or shortly after modification of the previous antidepressant drug regimen. Reassessment of the mental condition was conducted after 8 weeks of the pharmacological treatment also with the use of the HDRS scale. RESULTS: No significant statistical differences were found between the analysed groups as regards the intensity of depressive disorders. No differences in the expression of MnSOD, MPO, COX-2 and i-NOS genes on the level of both mRNA and protein were observed between both groups. No significant interrelation was noticed between the number of depression episodes experienced and the expression of selected genes on the mRNA level and protein level. CONCLUSIONS: There is no significant difference in MnSOD, MPO, COX-2 and i-NOS between patients with recurrent depressive disorders and those in a first episode of depression. These findings suggest that these enzymes are trait markers of depression and are not related to staging of depression.

First aid recommendations for psychosis: using the Delphi method to gain consensus between mental health consumers, carers, and clinicians.

BACKGROUND: Members of the general public often lack the knowledge and skills to intervene effectively to help someone who may be developing a psychotic illness before appropriate professional help is received. METHODS: We used the Delphi method to determine recommendations on first aid for psychosis. An international panel of 157 mental health consumers, carers, and clinicians completed a 146-item questionnaire about how a member of the public could help someone who may be experiencing psychosis. The panel members rated each questionnaire item according to whether they believed the statement should be included in the first aid recommendations. The results were analyzed by comparing consensus rates across the 3 groups. Three rounds of ratings were required to consolidate consensus levels. RESULTS: Eighty-nine items were endorsed by >or=80% of panel members from all 3 groups as essential or important for psychosis first aid. These items were grouped under the following 9 headings: how to know if someone is experiencing psychosis; how to approach someone who may be experiencing psychosis; how to be supportive; how to deal with delusions and hallucinations; how to deal with communication difficulties; whether to encourage the person to seek professional help; what to do if the person does not want help; what to do in a crisis situation when the person has become acutely unwell; what to do if the person becomes aggressive. CONCLUSIONS: These recommendations will improve the provision of first aid to individuals who are developing a psychotic disorder by informing the content of training courses.

Reforming Australian public sector accounting : an episode of institutional thinking

In recent years in Australia, accounting reforms have been developed which have resulted in the application of commercial systems of accounting to diverse public sector organisations. The reforms, which include the requirement to recognise infrastructure and heritage resources as assets in financial reports, endorse financial notions of accountability and performance that have been traditionally applied within private sector, profit-seeking organisations. Such notions are applied to a range of public sector organisations for the first time, even though the primary missions or objectives of many of these organisations are social, rather than financial in orientation. This critical, interpretative case study, set within the context of not-for-profit public museums, seeks to enhance an understanding of public sector accounting change based on these unique social organisations. The study examines three aspects of the reforms, namely, their development, their promotion and their defence. This examination is undertaken using the ideas contained in Mary Douglas’ (1986) How Institutions Think as the key theoretical construct. The supplementary perspectives of problematisation and epistemic communities are used to assist in applying the primary theoretical construct by explaining how, and by whom, these reforms were advocated and implemented in this specific instance. The study shows how the interpretation and application of the statements comprising the conceptual framework have shaped the development, promotion and defence of detailed standards developed for specific public sector organisations. In doing so, the study addresses two key research questions: (1) How were financial notions of accountability and performance of Australian public sector organisations constructed during the period 1976-2001 and articulated in the CF, once its development began, within this reform period? (2) How were these notions and other concepts of financial reporting outlined in the CF interpreted and applied in the (i) development; (ii) promotion; and (iii) defence of detailed accounting standards for not-for-profit public museums in Australia during the period under investigation? The study demonstrates that the concepts of financial reporting outlined in the conceptual framework were used by a relatively small group of technical experts located in influential positions in accounting regulation and in other fields to justify the application of accrual accounting within diverse public sector organisations. During the period examined, only certain questions were posed and certain issues considered and many problems associated with the implementation of the reforms were not considered. Accordingly, a key finding of the study is that each aspect of the reform period was guided and constrained by institutional thinking. In addition, the study shows how the framework's content can be used to permit equally well-argued, but conflicting, accounting policies to be adopted and defended for the same items, indicating the framework to be of only limited value as a technical tool. This leads to another key finding of the study, namely, that the framework is best understood as a political tool, serving a crucial role in enabling accrual accounting reforms to be developed, promoted and defended within the public sector. Thus, the study seeks to offer an enhanced understanding of the nature and determinants of accounting change, and accordingly, it broadens an understanding of the use of the conceptual framework, as an institution, in developing, promoting and defending changes to accounting practice.

Is phase-specific, community-oriented treatment of early psychosis- an economically viable method of improving outcome?

Objective: The Early Psychosis Prevention and Intervention Centre (EPPIC) provides a comprehensive 'real-world' model of early intervention to young people experiencing an emerging psychotic disorder. A prospective study has already provided evidence of improved clinical outcome at 12 months after entry. The present study examined whether the service was also cost-effective.

Method: A cost-effectiveness analysis compared EPPIC with its immediate precursor service, from the perspective of the government funding agency. Only direct costs were included.

Results: EPPIC proved to be more cost-effective. The weighted average cost per patient for the first 12 months was cheaper (by äD 7110 per patient), while treatment outcomes were superior. The savings were due to the marked reduction in in-patient costs outweighing substantial increases in the costs of community care.

Conclusion: These results, while encouraging in terms of the further development of integrated, phase-specific intervention programmes for early psychosis, are not conclusive, and further research is required.

The impact of age at onset of bipolar I disorder on functioning and clinical presentation

Objectives: Recent studies have proposed the existence of three distinct subgroups of bipolar 1 disorder based on age at onset (AAO). The present study aims to investigate potential clinical and functional differences between these subgroups in an Australian sample.

Methods: Participants (n = 239) were enrolled in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal, observational, cross-sectional study. Assessment measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ-5D). Participants were also asked about their age at the first major affective episode.

Results: Three AAO groups were compared: early (AAO < 20, mean = 15.5 ± 2.72; 44.4% of the participants); intermediate (AAO 20–39, mean = 26.1 ± 4.8; 48.14% of the participants) and late (AAO > 40, mean = 50.6 ± 9.04; 7.4% of the participants). Higher rates of depression, suicidal ideation and binge drinking were reported by the early AAO group. This group also reported poorer quality of life in a number of areas. The early AAO group had a predominant depressive initial polarity and the intermediate group had a manic predominance.

Conclusion: Early AAO is associated with an adverse outcome.

Coping with defeat : acute glucocorticoid and forebrain responses to social defeat vary with defeat episode behaviour

Individuals vary in the way in which they cope with stressful situations. It has been suggested that ‘active’ coping behaviour, characterised by aggression and territorial control, is more effective in moderating the stress associated with social defeat than ‘passive’ coping behaviour, as characterised by immobility, decreased reactivity, and low aggression. We used the rodent ‘resident/intruder’ paradigm to determine whether individual differences in coping behaviour modulate the acute adrenocortical response to social defeat. During the 10 min conflict episode, behaviours displayed by the intruder were recorded and subsequently scored. Intruders that engaged in large numbers of fights and/or frequently used physical structures to block the resident's approach (a behaviour referred to as ‘guarding’), displayed smaller corticosterone responses to defeat than other intruders. Corticosterone responses to defeat were unrelated to a measure of coping style preferences (defensive burying test) obtained prior to the defeat encounter. We further chose to investigate the neurobiological basis of this observation by comparing the patterns of defeat-induced neuronal activation in the forebrains of intruders that displayed high versus low numbers of defensive behaviours during the defeat episode. The results of this analysis indicated that ‘low fight’ and ‘low guard’ intruders, i.e. those that achieved a fight or a guard score below the 20th percentile, had significantly higher numbers of Fos-positive neurons in forebrain regions such as the medial prefrontal cortex and the amygdala than did control animals exposed to an empty resident's cage. In summary, the present data suggest that ‘active’ coping behaviour is associated with both a smaller adrenocortical response and a lower level of ‘neural activation’ following social defeat. This outcome differs from that of earlier studies, a difference that we suggest is due to the fact that the present study is the first to assess coping on the basis of behaviour actually displayed during the conflict interaction.

Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids.

Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre-post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the conclusions that can be drawn from what we believe to be a first-of-its-kind study. Additional studies with larger samples are therefore needed to evaluate the generalizability of these findings.

First aid for depression: a Delphi consensus study with consumers, carers and clinicians.

BACKGROUND: It is unclear how members of the public can best support individuals who are developing a depressive episode before appropriate professional help is received. METHODS: To assess expert consensus, we used the Delphi Method. An expert panel consisting of 167 mental health consumers, carers and clinicians was recruited from developed English-speaking countries. A 99-item questionnaire about how to help someone with depression was developed from a variety of resources. The panel members rated each item according to whether they believed the statement should be included in the first aid recommendations. The results were analysed by comparing consensus rates across the three groups. Three rounds were required to consolidate consensus levels. RESULTS: Sixty-four items were endorsed by > or =80% of panel members from all three groups as essential or important. These items were grouped under the following headings: recognising and acknowledging depression; approaching someone who may be depressed; how to be supportive; what is not helpful for a person who may have depression; whether to encourage the person to seek professional help; whether to encourage the person to use self-help strategies; what to do if the person does not want help. LIMITATIONS: These recommendations may not be applicable outside developed English-speaking countries. CONCLUSIONS: By informing the content of training courses, these recommendations will improve the provision of first aid to individuals who are developing a depressive episode and facilitate the uptake of appropriate professional help.