Search

Background: Autism spectrum disorders (ASDs) are complex, pervasive, and heterogeneous neurodevelopmental conditions with varying trajectories, significant male bias and largely unknown etiology. However, an understanding of the biological mechanisms driving pathophysiology is evolving. Immune system aberrations, as identified through cytokine profiles, are believed to have a role in ASD. Altered cytokine levels may facilitate identification of ASD subtypes as well as provide biological markers of response to effective treatments. Research exploring the relationship between cytokine profiles and ASD symptoms is, however, in its infancy. The objective of this study was to explore relationships between cytokine levels and the severity of ASD and other clinical traits. Methods: Multiplex assay techniques were used to measure levels of 27 cytokines in plasma samples from a cohort of 144 children diagnosed with ASD. Results: Overall, results showed a significant negative association between platelet-derived growth factor (PDGF)- BB, and the severity of ASD symptoms. Furthermore, a significant interaction with sex suggested a different immune profile for females compared to males. ASD symptom severity was negatively associated with levels of 4 cytokines, IL-1β, IL-8, MIP-1β, and VEGF, in females, but not in males. Conclusions: Results of the present study suggest that an altered cytokine response or profile is associated with the severity of ASD-related symptoms, with sex a potential modifier of this relationship. Further research in larger populations which recognizes the importance of sex comparisons and longitudinal assessments are now required to extend and further describe the role of the immune system in ASD. [ABSTRACT FROM AUTHOR]

Background: The Somatic and Psychological HEalth REport (SPHERE) is a 34-item self-report questionnaire that assesses symptoms of mental distress and persistent fatigue. As it was developed as a screening instrument for use mainly in primary care-based clinical settings, its validity and psychometric properties have not been studied extensively in population-based samples. Methods: We used non-parametric Item Response Theory to assess scale validity and item properties of the SPHERE-34 scales, collected through four waves of the Brisbane Longitudinal Twin Study (N = 1707, mean age = 12, 51% females; N = 1273, mean age = 14, 50% females; N = 1513, mean age = 16, 54% females, N = 1263, mean age = 18, 56% females). We estimated the heritability of the new scores, their genetic correlation, and their predictive ability in a sub-sample (N = 1993) who completed the Composite International Diagnostic Interview. Results: After excluding items most responsible for noise, sex or wave bias, the SPHERE-34 questionnaire was reduced to 21 items (SPHERE-21), comprising a 14-item scale for anxiety-depression and a 10-item scale for chronic fatigue (3 items overlapping). These new scores showed high internal consistency (alpha > 0.78), moderate three months reliability (ICC = 0.47-0.58) and item scalability (Hi > 0.23), and were positively correlated (phenotypic correlations r = 0.57-0.70; rG = 0.77-1.00). Heritability estimates ranged from 0.27 to 0.51. In addition, both scores were associated with later DSM-IV diagnoses of MDD, social anxiety and alcohol dependence (OR in 1.23-1.47). Finally, a post-hoc comparison showed that several psychometric properties of the SPHERE-21 were similar to those of the Beck Depression Inventory. Conclusions: The scales of SPHERE-21 measure valid and comparable constructs across sex and age groups (from 9 to 28 years). SPHERE-21 scores are heritable, genetically correlated and show good predictive ability of mental health in an Australian-based population sample of young people. [ABSTRACT FROM AUTHOR]

Background: Patients with affective disorders of different ages have been found to present weight changes and different circadian activity patterns. This study assessed the effects of age, Body Mass Index (BMI) and depression severity on the activity-rest cycle in persons with affective disorders using a novel multifactorial 24-h analysis method. Methods: Two hundred and thirty-six participants aged between 14 and 85 years underwent 5 to 22 days of actigraphy monitoring (mean duration = 14 days). BMI was also recorded and symptom severity was assessed with the Hamilton Depression Rating Scale (HDRS). Participants were divided into two groups: healthy controls (n = 68) and participants with a lifetime diagnosis of affective disorders (n = 168). First, the multiple regression method was employed to formulate the circadian activity pattern in term of the factors age, BMI and HDRS. For each group, the functional linear analysis method was applied to assess the relative effects of the factors. Finally, Wald-tests were used to assess the contribution of each factor on the circadian activity pattern. Results: In the affective disorders group, higher BMI was associated with higher activity levels from 3 am until 5.30 am and with lower activity levels from 10 am until 10.30 pm. Older age was associated with less activity across the day, evening, and night - from 11 am until 5.30 am. Higher HDRS scores were associated with higher activity around 1:30 am. In healthy controls, the effects of BMI and age on activity patterns were less pronounced and affected a narrower portion of the 24-h period. Conclusion: These findings suggest that older age and higher BMI are linked to lower daytime activity levels. Higher BMI and worse symptom severity were also associated with nocturnal activity patterns suggestive of sleep disturbances. The influence of age and BMI on 24-h activity profiles appear to be especially pronounced in people with affective disorders. [ABSTRACT FROM AUTHOR]

Background: Mood and anxiety disorders are leading causes of disability and mortality, due largely to their onset during adolescence and young adulthood and broader impact on functioning. Key factors that are associated with disability and these disorders in young people are social and economic participation (e.g. education, employment), physical health, suicide and self-harm behaviours, and alcohol and substance use. A better understanding of the objective markers (i.e. neurobiological parameters) associated with these factors is important for the development of effective early interventions that reduce the impact of disability and illness persistence. Methods: We systematically reviewed the literature for neurobiological parameters (i.e. neuropsychology, neuroimaging, sleep-wake and circadian biology, neurophysiology and metabolic measures) associated with functional domains in young people (12 to 30 years) with mood and/or anxiety disorders. Results: Of the one hundred and thirty-four studies selected, 7.6% investigated social and economic participation, 2. 1% physical health, 15.3% suicide and self-harm behaviours, 6.9% alcohol and substance use, whereas the majority (68.1%) focussed on clinical syndrome. Conclusions: Despite the predominance of studies that solely examine the clinical syndrome of young people the literature also provides evidence of distinct associations among objective measures (indexing various aspects of brain circuitry) and other functional domains. We suggest that a shift in focus towards characterising the mechanisms that underlie and/or mediate multiple functional domains will optimise personalised interventions and improve illness trajectories. [ABSTRACT FROM AUTHOR]

Background: Late-life depression is associated with high rates of morbidity, premature mortality, disability, functional decline, caregiver burden and increased health care costs. While clinical and public health approaches are focused on prevention or early intervention strategies, the ideal method of intervention remains unclear. No study has set out to evaluate the role of neurobiological agents in preventing depressive symptoms in older populations at risk of depression. Methods/Design: Subjects with previously reported sub-threshold depressive symptoms, aged 60 to 74 years, will be screened to participate in a single-centre, double-blind, randomised controlled trial with three parallel groups involving omega-3 fatty acid supplementation or sertraline hydrochloride, compared with matching placebo. Subjects will be excluded if they have current depression or suicide ideation; are taking antidepressants or any supplement containing omega-3 fatty acid; or have a prior history of stroke or other serious cerebrovascular or cardiovascular disease, neurological disease, significant psychiatric disease (other than depression) or neurodegenerative disease. The trial will consist of a 12 month treatment phase with follow-up at three months and 12 months to assess outcome events. At three months, subjects will undergo structural neuroimaging to assess whether treatment effects on depressive symptoms correlate with brain changes. Additionally, proton spectroscopy techniques will be used to capture brain-imaging markers of the biological effects of the interventions. The trial will be conducted in urban New South Wales, Australia, and will recruit a community-based sample of 450 adults. Using intention-to-treat methods, the primary endpoint is an absence of clinically relevant depression scores at 12 months between the omega-3 fatty acid and sertraline interventions and the placebo condition. Discussion: The current health, social and economic costs of late-life depression make prevention imperative from a public health perspective. This innovative trial aims to address the long-neglected area of prevention of depression in older adults. The interventions are targeted to the pathophysiology of disease, and regardless of the effect size of treatment, the outcomes will offer major scientific advances regarding the neurobiological action of these agents. The main results are expected to be available in 2017. Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12610000032055 (12 January 2010) [ABSTRACT FROM AUTHOR]

Background While the association between affective disorders and sleep and circadian disturbance is well established, little is known about the neurobiology underpinning these relationships. In this study, we sought to determine the relationship between a marker of circadian rhythm and neuronal integrity (N-Acetyl Aspartate, NAA), oxidative stress (glutathione, GSH) and neuronal-glial dysfunction (Glutamate + Glutamine, Glx). Methods Fifty-three young adults (age range 15-33 years, mean = 21.8, sd = 4.3) with emerging affective disorders were recruited from a specialized tertiary referral service. Participants underwent clinical assessment and actigraphy monitoring, from which sleep midpoint was calculated as a marker of circadian rhythm. Proton magnetic resonance spectroscopy was performed in the anterior cingulate cortex (ACC). The metabolites NAA, GSH and Glx were obtained, and expressed as a ratio to Creatine. Results Neither NAA or GSH were associated with sleep midpoint. However, higher levels of ACC Glx were associated with later sleep midpoints (rho = 0.35, p = 0.013). This relationship appeared to be independent of age and depression severity. Conclusions This study is the first to demonstrate that delayed circadian phase is related to altered glutamatergic processes. It is aligned with animal research linking circadian rhythms with glutamatergic neurotransmission as well as clinical studies showing changes in glutamate with sleep interventions. Further studies may seek to examine the role of glutamate modulators for circadian misalignment. [ABSTRACT FROM AUTHOR]

The article presents research on the effects of delayed sleep onset in depressed young people, with information on the circadian abnormalities in depressed young adults. Topics include risk factors, such as substance use, in delayed sleep phases; the cohort of help-seeking young adults with mental health problems; and the correlation between mental illness and delayed sleep phase.

Background It is an open question as to whether differential developmental trajectories, potentially representing underlying pathophysiological processes, can form the basis of a more useful typology in young persons who present for mental health care. Methods A cohort of 605 young people was recruited from youth mental health services that target the early phases of anxiety, mood or psychotic disorders. Participants were assigned to one of three clinical sub-types (anxious-depression; mania-fatigue; developmental-psychotic) according to putative developmental trajectories. Results The distribution of subtypes was: 51% anxiety-depression, 25% mania-fatigue and 24% developmental-psychotic, with key differences in demographic, clinical, family history and neuropsychological characteristics. When analyses were limited to 286 cases with 'attenuated' or sub-threshold syndromes, the pattern of differences was similar. Multinomial logistic regression demonstrated that compared to the developmental-psychotic subtype, both the mania-fatigue and anxiety-depression subtypes were younger and more depressed at presentation, but less functionally impaired. Other discriminating variables between the developmental-psychotic and mania-fatigue sub-types were that the latter were significantly more likely to have a family history of bipolar disorder but have less likelihood of impaired verbal learning; whilst the anxious-depression group were more anxious, more likely to have a family history of depression, and had a higher premorbid IQ level. Conclusions This cross-sectional evaluation provides preliminary support for differing developmental trajectories in young persons presenting for mental health care. Prospective follow-up is needed to examine the predictive validity of this approach and its relationships to underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Background With a rapidly ageing population and increasing life expectancy, programs directed at improving the mental health and quality of life (QOL) of older persons are extremely important. This issue may be particularly relevant in the aged-care residential sector, where very high rates of depression and poor QOL are evident. This study aims to investigate the fixed and modifiable risk factors of psychological distress and QOL in a cohort of Australians aged 60 and over living in residential and community settings. Methods The study examined the relationship between demographic, health and lifestyle factors and the outcome variables of self-reported QOL and psychological distress (K10 scores) based on data from 626 Australians aged 60 and over from the 45 and Up Study dataset. Univariate and multivariate regression analyses (performed on a subset of 496) examined risk factors related to psychological distress and QOL adjusting for age and residential status. Results Significant psychological distress was experienced by 15% of the residential sample and 7% of the community sample and in multivariate analyses was predicted by older age, more functional limitations, more time spent sleeping and lower levels of social support (accounting for 18.2% of the variance). Poorer QOL was predicted by more functional limitations and greater levels of psychological distress. Together these variables accounted for 35.0% of the variance in QOL ratings. Conclusions While psychological distress was more common in residential settings, programs targeting modifiable risk factors have the potential to improve QOL and reduce psychological distress in older persons living in both residential and community settings. In particular, promoting health and mobility, optimising sleep-wake cycles and increasing social support may reduce levels of psychological distress and improve QOL. [ABSTRACT FROM AUTHOR]

Background: After 30 years of consensus-derived diagnostic categories in mental health, it is time to head in new directions. Those categories placed great emphasis on enhanced reliability and the capacity to identify them via standardized checklists. Although this enhanced epidemiology and health services planning, it failed to link broad diagnostic groupings to underlying pathophysiology or specific treatment response. Discussion: It is time to adopt new goals that prioritize the validation of clinical entities and foster alternative strategies to support those goals. The value of new dimensions (notably clinical staging), that are both clinically relevant and directly related to emerging developmental and neurobiological research, is proposed. A strong emphasis on 'reverse translation' (that is, working back from the clinic to the laboratory) underpins these novel approaches. However, it relies on using diagnostic groupings that already have strong evidence of links to specific risk factors or patterns of treatment response. Summary: The strategies described abandon the historical divides between clinical neurology, psychiatry and psychology and adopt the promotion of pathways to illness models. [ABSTRACT FROM AUTHOR]

Background: This mixed-methods study was designed to explore young Australian men's attitudes and behaviour in relation to mental health and technology use to inform the development of online mental health services for young men. Methods: National online survey of 486 males (aged 16 to 24) and 17 focus groups involving 118 males (aged 16 to 24). Results: Young men are heavy users of technology, particularly when it comes to entertainment and connecting with friends, but they are also using technology for finding information and support. The focus group data suggested that young men would be less likely to seek professional help for themselves, citing a preference for self-help and action-oriented strategies instead. Most survey participants reported that they have sought help for a problem online and were satisfied with the help they received. Focus group participants identified potential strategies for how technology could be used to overcome the barriers to help-seeking for young men. Conclusions: The key challenge for online mental health services is to design interventions specifically for young men that are action-based, focus on shifting behaviour and stigma, and are not simply about increasing mental health knowledge. Furthermore, such interventions should be user-driven, informed by young men's views and everyday technology practices, and leverage the influence of peers. [ABSTRACT FROM AUTHOR]

Background: Clinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing. Discussion: The development of specific behavioral or pharmacological strategies that target these basic regulatory systems is driving renewed clinical interest. Here, we explore the extent to which objective tests of sleep-wake cycles and circadian function - namely, those that measure timing or synchrony of circadian-dependent physiology as well as daytime activity and nighttime sleep patterns - can be used to identify a sub-class of patients with major depression who have disturbed circadian profiles. Summary: Once this unique pathophysiology is characterized, a highly personalized treatment plan can be proposed and monitored. New treatments will now be designed and old treatments re-evaluated on the basis of their effects on objective measures of sleep-wake cycles, circadian rhythms and related metabolic systems. [ABSTRACT FROM AUTHOR]

Background: It is important to understand the complex inter-relationship between depression and physical illness in order to plan and provide quality health care services for older persons and reduce suffering and early mortality. This study assessed the awareness and knowledge of age-care staff of the link between physical morbidity and depression. Methods: One hundred and nineteen staff from both residential (high and low care) and community aged care facilities were surveyed on their awareness and knowledge of the relationship between physical morbidity and symptoms of depression. Predictors of levels of knowledge were assessed using multiple regression analysis. Results: Awareness of the link between physical morbidity and symptoms of depression was generally high. However, while nearly eighty percent of respondents said they had had training in mental health, they were only able to answer an average of six out of ten of the knowledge questions correctly. Predictors of knowledge were: higher age, higher educational status and working in a high care facility. Conclusions: Responses to the survey questions demonstrated gaps in knowledge about the relationship between depression and physical health. The need for regular ongoing training to improve knowledge and awareness of this relationship is indicated. Treatment of physical health issues which is essential in reducing the risk for depression in older persons in aged care environments could be optimized by improved staff training. [ABSTRACT FROM AUTHOR]

Background: Those working with elderly care recipients require a good working knowledge of depression and appropriate help giving responses. While it is important for age-care staff to recognize depression in care recipients it is also critical that they know the appropriate course of action to assist a care recipient who may be depressed. This study aims to determine the knowledge of age-care staff of appropriate help giving responses, their confidence in knowing what kind of assistance to provide and their actual likelihood of providing help to potentially depressed care recipients and to examine if these measures improve following an intervention training program. Methods: One hundred and two age-care staff were surveyed on their confidence in helping age-care recipients and on their knowledge of appropriate ways to provide assistance. Staff then participated in a two hour depression awareness raising intervention. The survey was repeated immediately following the training and again six months later. Results: Staff confidence in knowing how to provide assistance increased significantly subsequent to training and remained significantly improved at the six month follow up. In addition, a significantly higher proportion of staff reported helping care recipients at the six month follow up. Conclusions: This study highlights the potential of a brief staff training program to provide a cost effective means to improve staff self-confidence and increase the likelihood of staff providing assistance to depressed care recipients. [ABSTRACT FROM AUTHOR]

Background: Reducing suicidal behaviour is a major public health goal. Expanding access to care has been identified as a key strategy. In Australia, a national network of primary-care based services (headspace) has been established for young people with mental ill-health. This study determines the socio-demographic, psychopathological and illness-stage correlates of suicidal ideation in young persons attending headspace services. Methods: Suicidal ideation was recorded using the specific suicide item of the Hamilton Depression Rating Scale (HDRS) in a cohort of subjects aged 12-30 years (N = 494) attending headspace services. Results: Of the 494 young persons assessed, 32% (158/494) had a positive response to any level of the HDRS suicide item, consisting of 16% (77/494) reporting that life was not worth living and a further 16% (81/494) reported thoughts of death or suicidal ideation. Young women (19%; 94/494) were more likely to report any positive response as compared with young men (13%; 64/494) [?2(2,494) = 13.6, p < .01]. Those with 'attenuated syndromes' reported positive responses at rates comparable to those with more established disorders (35% vs. 34%; ?2(1,347) = 0.0, p = 0.87). However, more serious levels of suicidal ideation were more common in those with depressive disorders or later stages of illness. In multivariate analyses, the major predictors of the degree of suicidal ideation were increasing levels of clinician-rated depressive symptoms (beta = 0.595, p < .001), general psychopathology (beta = 0.198, p < .01), and self-reported distress (beta = 0.172, p < .05). Conclusions: Feelings that life is not worth living, thoughts of death or suicidal ideation are common in young people seeking mental health care. These at-risk cognitions are evident before many of these individuals develop severe or persistent mental disorders. Thoughts of death or suicidal ideation may well need to be a primary intervention target in these young people. [ABSTRACT FROM AUTHOR]

Background: The anterior insula cortex is considered to be both the structural and functional link between experience, affect, and behaviour. Magnetic resonance imaging (MRI) studies have shown changes in anterior insula gray matter volume (GMV) in psychosis, bipolar, depression and anxiety disorders in older patients, but few studies have investigated insula GMV changes in young people. This study examined the relationship between anterior insula GMV, clinical symptom severity and neuropsychological performance in a heterogeneous cohort of young people presenting for mental health care. Methods: Participants with a primary diagnosis of depression (n = 43), bipolar disorder (n = 38), psychosis (n = 32), anxiety disorder (n = 12) or healthy controls (n = 39) underwent structural MRI scanning, and volumetric segmentation of the bilateral anterior insula cortex was performed using the FreeSurfer application. Statistical analysis examined the linear and quadratic correlations between anterior insula GMV and participants' performance in a battery of clinical and neuropsychological assessments.Results: Compared to healthy participants, patients had significantly reduced GMV in the left anterior insula (t = 2.05, p = .042) which correlated with reduced performance on a neuropsychological task of attentional set-shifting (ρ = .32, p = .016). Changes in right anterior insula GMV was correlated with increased symptom severity (r = .29, p = .006) and more positive symptoms (r = .32, p = .002).Conclusions: By using the novel approach of examining a heterogeneous cohort of young depression, anxiety, bipolar and psychosis patients together, this study has demonstrated that insula GMV changes are associated with neurocognitive deficits and clinical symptoms in such young patients. [ABSTRACT FROM AUTHOR]

Background: Establishing an evidence-based method of improving knowledge and attitudes concerning depression has been identified as a priority in Chinese medical education. The purpose of this study was to determine whether a self-directed learning strategy as a part of student-centred education improved knowledge of and attitudes towards depression among Chinese medical students. Methods: A controlled trial in which 205 medical students were allocated to one of two groups: didactic teaching (DT) group or a combined didactic teaching and self-directed learning (DT/SDL) group. The DT/SDL group continued having a series of learning activities after both groups had a lecture on depression together. Student's knowledge and attitudes were assessed immediately after the activities, one month and six months later. Results: The intervention (DT/SDL) group showed substantially greater improvements in recognition of depression as a major health issue and identifying helpful treatments than the DT group. Only the DT/SDL group demonstrated any improvement in attitudes. This improvement was sustained over six months. Conclusions: Self-directed learning is an effective education strategy in improving medical students' knowledge of and attitudes towards depression. [ABSTRACT FROM AUTHOR]

Background: Depression, cardiovascular disease (CVD) risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or webbased interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised controlled trial are to determine the effects of an evidence-based internet intervention program for depression on depressive mood symptoms, cognitive function and treatment adherence in patients at risk of CVD. Methods/Design: This study is an internet-based, double-blind, parallel group randomised controlled trial. The trial will compare the effectiveness of online cognitive behavioural therapy with an online attention control placebo. The trial will consist of a 12-week intervention phase with a 40-week follow-up. It will be conducted in urban and rural New South Wales, Australia and will recruit a community-based sample of adults aged 45 to 75 years. Recruitment, intervention, cognitive testing and follow-up data collection will all be internet-based and automated. The primary outcome is a change in severity of depressive symptoms from baseline to three-months. Secondary outcomes are changes in cognitive function and adherence to treatment for CVD from baseline to three, six and 12-months. Discussion: Prior studies of depression amongst patients with CVD have targeted those with previous vascular events and major depression. The potential for intervening earlier in these disease states appears to have significant potential and has yet to be tested. Scalable psychological programs using web-based interventions could deliver care to large numbers in a cost effective way if efficacy were proved. This study will determine the effects of a web-based intervention on depressive symptoms and adherence to treatment among patients at risk of CVD. In addition it will also precisely and reliably define the effects of the intervention upon aspects of cognitive function that are likely to be affected early in at risk individuals, using sensitive and responsive measures. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000085077 [ABSTRACT FROM AUTHOR]

Background: Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection. Methods: We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides. Results: Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclindependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle. Conclusion: These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis. [ABSTRACT FROM AUTHOR]

Background: Insomnia is a significant risk factor for depression onset, can result in more disabling depressive illness, and is a common residual symptom following treatment cessation that can increase the risk of relapse. Internet-based cognitive behavioural therapy for insomnia has demonstrated efficacy and acceptability to men who are less likely than women to seek help in standard care. We aim to evaluate whether internet delivered cognitive behavioural therapy for insomnia as an adjunct to a standard depression therapeutic plan can lead to improved mood outcomes., Methods/design: Male participants aged 50 years or more, meeting Diagnostic and Statistical Manual of Mental Disorders criteria for current Major Depressive Episode and/or Dysthymia and self-reported insomnia symptoms, will be screened to participate in a single-centre double-blind randomised controlled trial with two parallel groups involving adjunctive internet-delivered cognitive behavioural therapy for insomnia and an internet-based control program. The trial will consist of a nine-week insomnia intervention period with a six-month follow-up period. During the insomnia intervention period participants will have their depression management coordinated by a psychiatrist using standard guideline-based depression treatments. The study will be conducted in urban New South Wales, Australia, where 80 participants from primary and secondary care and direct from the local community will be recruited. The primary outcome is change in the severity of depressive symptoms from baseline to week 12., Discussion: This study will provide evidence on whether a widely accessible, evidence-based, internet-delivered cognitive behavioural therapy for insomnia intervention can lead to greater improvements than standard treatment for depression alone, in a group who traditionally do not readily access psychotherapy. The study is designed to establish effect size, feasibility and processes associated with implementing e-health solutions alongside standard clinical care, to warrant undertaking a larger more definitive clinical trial., Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12612000985886 .

Background: Clinical staging of mental disorders proposes that individuals can be assessed at various sub-syndromal and later developed phases of illness. As an adjunctive rating, it may complement traditional diagnostic silo-based approaches. In this study, we sought to determine the relationships between clinical stage and neuropsychological profile in young persons presenting to youth-focused mental health services., Methods: Neuropsychological testing of 194 help-seeking young people (mean age 22.6 years, 52% female) and 50 healthy controls. Clinical staging rated 94 persons as having an 'attenuated syndrome' (stage 1b) and 100 with a discrete or persistent disorder (stage 2/3)., Results: The discrete disorder group (stage 2/3) showed the most impaired neuropsychological profile, with the earlier stage (1b) group showing an intermediate profile, compared to controls. Greatest impairments were seen in verbal memory and executive functioning. To address potential confounds created by 'diagnosis', profiles for those with a mood syndrome or disorder but not psychosis were also examined and the neuropsychological impairments for the stage 2/3 group remained., Conclusions: The degree of neuropsychological impairment in young persons with mental disorders appears to discriminate those with attenuated syndromes from those with a discrete disorder, independent of diagnostic status and current symptoms. Our findings suggest that neuropsychological assessment is a critical aspect of clinical evaluation of young patients at the early stages of a major psychiatric illness.

Background: More severe and persistent forms of affective disorders are accompanied by grey matter loss in key frontal and temporal structures. It is unclear whether such changes precede the onset of illness, occur early in the course or develop gradually with persistence or recurrence of illness. A total of 47 young people presenting with admixtures of depressive and psychotic symptoms were recruited from specialist early intervention services along with 33 age matched healthy control subjects. All participants underwent magnetic resonance imaging and patients were rated clinically as to current stage of illness. Twenty-three patients were identified as being at an early 'attenuated syndrome' stage, while the remaining were rated as having already reached the 'discrete disorder' or 'persistent or recurrent illness' stage. Contrasts were carried out between controls subjects and patients cohorts with attenuated syndromes and discrete disorders, separately., Results: The patients that were identified as having a discrete or persisting disorder demonstrated decreased grey matter volumes within distributed frontal brain regions when contrasted to both the control subjects as well as those patients in the attenuated syndrome stage. Overall, patients who were diagnosed as more advanced in terms of the clinical stage of their illness, exhibited the greatest grey matter volume loss of all groups., Conclusions: This study suggests that, in terms of frontal grey matter changes, a major transition point may occur in the course of affective illness between early attenuated syndromes and later discrete illness stages.

Background: Subjective memory complaints (SMC) are common but their significance is still unclear. It has been suggested they are a precursor of mild cognitive impairment (MCI) or dementia and an early indicator of cognitive decline. Vascular risk factors have an important role in the development of dementia and possibly MCI. We therefore aimed to test the hypothesis that vascular risk factors were associated with SMC, independent of psychological distress, in a middle-aged community-dwelling population., Methods: A cross-sectional analysis of baseline data from the 45 and Up Study was performed. This is a cohort study of people living in New South Wales (Australia), and we explored the sample of 45, 532 participants aged between 45 and 64 years. SMC were defined as 'fair' or 'poor' on a self-reported five-point Likert scale of memory function. Vascular risk factors of obesity, diabetes, hypertension, hypercholesterolemia and smoking were identified by self-report. Psychological distress was measured by the Kessler Psychological Distress Scale. We tested the model generated from a randomly selected exploratory sample (n = 22, 766) with a confirmatory sample of equal size., Results: 5, 479/45, 532 (12%) of respondents reported SMC. Using multivariate logistic regression, only two vascular risk factors: smoking (OR 1.18; 95% CI = 1.03 - 1.35) and hypercholesterolaemia (OR 1.19; 95% CI = 1.04 - 1.36) showed a small independent association with SMC. In contrast psychological distress was strongly associated with SMC. Those with the highest levels of psychological distress were 7.00 (95% CI = 5.41 - 9.07) times more likely to have SMC than the non-distressed. The confirmatory sample also demonstrated the strong association of SMC with psychological distress rather than vascular risk factors., Conclusions: In a large sample of middle-aged people without any history of major affective illness or stroke, psychological distress was strongly, and vascular risk factors only weakly, associated with SMC, although we cannot discount psychological distress acting as a mediator in any association between vascular risk factors and SMC. Given this, clinicians should be vigilant regarding the presence of an affective illness when assessing middle-aged patients presenting with memory problems.

Background: Establishing an evidence-based method of improving knowledge and attitudes concerning depression has been identified as a priority in Chinese medical education. The purpose of this study was to determine whether a self-directed learning strategy as a part of student-centred education improved knowledge of and attitudes towards depression among Chinese medical students., Methods: A controlled trial in which 205 medical students were allocated to one of two groups: didactic teaching (DT) group or a combined didactic teaching and self-directed learning (DT/SDL) group. The DT/SDL group continued having a series of learning activities after both groups had a lecture on depression together. Student's knowledge and attitudes were assessed immediately after the activities, one month and six months later., Results: The intervention (DT/SDL) group showed substantially greater improvements in recognition of depression as a major health issue and identifying helpful treatments than the DT group. Only the DT/SDL group demonstrated any improvement in attitudes. This improvement was sustained over six months., Conclusions: Self-directed learning is an effective education strategy in improving medical students' knowledge of and attitudes towards depression.

Background: Generalised anxiety disorder (GAD) is a high prevalence, chronic psychiatric disorder which commonly presents early in the lifespan. Internet e-health applications have been found to be successful in reducing symptoms of anxiety and stress for post traumatic stress disorder (PTSD), panic disorder, social phobia and depression. However, to date, there is little evidence for the effectiveness of e-health applications in adult GAD. There are no studies which have directly compared e-health applications with recognised evidence-based medication. This study aims to determine the effectiveness of a web-based program for treating GAD relative to sertraline and attention placebo., Methods/design: 120 community-dwelling participants, aged 18-30 years with a clinical diagnosis of GAD will be recruited from the Australian Electoral Roll. They will be randomly allocated to one of three conditions: (i) an online treatment program for GAD, E-couch (ii) pharmacological treatment with a selective serotonin re-uptake inhibitor (SSRI), sertraline (a fixed-flexible dose of 25-100 mg/day) or (iii) an attention control placebo, HealthWatch. The treatment program will be completed over a 10 week period with a 12 month follow-up., Discussion: As of February 2010, there were no registered trials evaluating the effectiveness of an e-health application for GAD for young adults. Similarly to date, this will be the first trial to compare an e-health intervention with a pharmacological treatment., Trial Registration: Current Controlled Trials ISRCTN76298775.

Background: Although major depression (MD) is associated with high levels of disability, the relationships between cognitive dysfunction and self-rated disability are poorly understood. This study examined the relationships between self-rated disability in persons with MD and both self-rated and objectively-measured cognitive functioning., Methods: Twenty-one persons with MD and 21 control participants underwent neuropsychological assessment and z-scores representing deviations from control performance were calculated and averaged across the domains of psychomotor speed, initial learning, memory retention and executive function. Self-ratings of cognitive deficits (SRCDs) were reported on a 6-point scale for overall rating of cognitive change, speed of thinking, concentration, and short-term memory. Disability scores for self-rated physical, mental-health and functional (ie. days out of role) disability were computed from the Brief-Disability Questionnaire and the SF-12 'mental component' subscale., Results: Persons with MD had a mean age of 53.9 years (SD = 11.0, 76% female) and had moderate to high depression severity (mean HDRS 21.7, sd = 4.4). As expected, depression severity was a strong predictor of physical (r = 0.7, p < 0.01), mental-health (r = 0.7, p < 0.01) and functional (r = 0.8, p < 0.001) disability on the Brief Disability Questionnaire. Additionally, for physical disability, both overall SRCDs and objectively-measured psychomotor speed continued to be independent significant predictors after controlling for depression severity, uniquely accounting for 13% and 16% of variance respectively. For functional disability scores, objectively-measured memory impairment and overall SRCDs were no longer significant predictors after controlling for depression severity., Conclusion: While depression severity is associated with disability, the contributions of both self-rated and objectively-measured cognitive deficits are substantial and contribute uniquely and differentially to various forms of disability. Efforts directed at reducing cognitive deficits in depression may have the potential to reduce disability.