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Samples can be prone to ascertainment and attrition biases. The Australian Genetics of Depression Study is a large publicly recruited cohort (n = 20,689) established to increase the understanding of depression and antidepressant treatment response. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not. We observed that older, male participants with higher education were more likely to donate a saliva sample. Self-reported bipolar disorder, ADHD, panic disorder, PTSD, substance use disorder, and social anxiety disorder were associated with lower odds of donating a saliva sample, whereas anorexia was associated with higher odds of donation. Male and younger participants showed higher odds of agreeing to record linkage. Participants with higher neuroticism scores and those with a history of bipolar disorder were also more likely to agree to record linkage whereas participants with a diagnosis of anorexia were less likely to agree. Increased likelihood of consent was associated with increased genetic susceptibility to anorexia and reduced genetic risk for depression, and schizophrenia. Overall, our results show moderate differences among these subsamples. Most current epidemiological studies do not search for attrition biases at the genetic level. The possibility to do so is a strength of samples such as the AGDS. Our results suggest that analyses can be made more robust by identifying attrition biases both on the phenotypic and genetic level, and either contextualising them as a potential limitation or performing sensitivity analyses adjusting for them. [ABSTRACT FROM AUTHOR]

There is significant interest in the possible influence of chronotype on clinical states in young people with emerging mental disorders. We apply a dynamic approach (bivariate latent change score modelling) to examine the possible prospective influence of chronotype on depressive and hypo/manic symptoms in a youth cohort with predominantly depressive, bipolar, and psychotic disorders (N = 118; 14–30-years), who completed a baseline and follow-up assessment of these constructs (mean interval = 1.8-years). Our primary hypotheses were that greater baseline eveningness would predict increases in depressive but not hypo/manic symptoms. We found moderate to strong autoregressive effects for chronotype (β = -0.447 to −0.448, p < 0.001), depressive (β = -0.650, p < 0.001) and hypo/manic symptoms (β = -0.819, p < 0.001). Against our predictions, baseline chronotypes did not predict change in depressive (β = -0.016, p = 0.810) or hypo/manic symptoms (β = 0.077, p = 0.104). Similarly, the change in chronotype did not correlate with the change in depressive symptoms (β = -0.096, p = 0.295) nor did the change in chronotype and the change in hypo/manic symptoms (β = -0.166, p = 0.070). These data suggest that chronotypes may have low utility for predicting future hypo/manic and depressive symptoms in the short term, or that more frequent assessments over longer periods are needed to observe these associations. Future studies should test whether other circadian phenotypes (e.g. sleep-wake variability) are better indicators of illness course. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain and depression are highly comorbid and difficult-to-treat disorders. We previously showed this comorbidity is associated with higher depression severity, lower antidepressant treatment effectiveness and poorer prognosis in the Australian Genetics of Depression Study. Objective: The current study aimed to assess whether a genetic liability to chronic pain is associated with antidepressant effectiveness over and above the effect of genetic factors for depression in a sample of 12,863 Australian Genetics of Depression Study participants. Methods: Polygenic risk scores were calculated using summary statistics from genome-wide association studies of multisite chronic pain and major depression. Cumulative linked regressions were employed to assess the association between polygenic risk scores and antidepressant treatment effectiveness across 10 different medications. Results: Mixed-effects logistic regressions showed that individual genetic propensity for chronic pain, but not major depression, was significantly associated with patient-reported chronic pain (PainPRS OR = 1.17 [1.12, 1.22]; MDPRS OR = 1.01 [0.98, 1.06]). Significant associations were also found between lower antidepressant effectiveness and genetic risk for chronic pain or for major depression. However, a fully adjusted model showed the effect of PainPRS (adjOR = 0.93 [0.90, 0.96]) was independent of MDPRS (adjOR = 0.96 [0.93, 0.99]). Sensitivity analyses were performed to assess the robustness of these results. After adjusting for depression severity measures (i.e. age of onset; number of depressive episodes; interval between age at study participation and at depression onset), the associations between PainPRS and patient-reported chronic pain with lower antidepressant effectiveness remained significant (0.95 [0.92, 0.98] and 0.84 [0.78, 0.90], respectively). Conclusion: These results suggest genetic risk for chronic pain accounted for poorer antidepressant effectiveness, independent of the genetic risk for major depression. Our results, along with independent converging evidence from other studies, point towards a difficult-to-treat depression subtype characterised by comorbid chronic pain. This finding warrants further investigation into the implications for biologically based nosology frameworks in pain medicine and psychiatry. [ABSTRACT FROM AUTHOR]

Background: Predictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of 'at-risk' cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population. Method: Multi-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12–30) presenting to mental health services. Results: Of 2330 individuals assessed longitudinally, 4.3% (n = 100) met criteria for new-onset FT BD and 2.2% (n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression. Conclusions: Identifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories. [ABSTRACT FROM AUTHOR]

Background: Distinctions between major depressive disorder (MDD) and perinatal depression (PND) reflect varying views of PND, from a unique etiological subtype of MDD to an MDD episode that happens to coincide with childbirth. This case–control study investigated genetic differences between PND and MDD outside the perinatal period (non‐perinatal depression or NPD). Methods: We conducted a genome‐wide association study using PND cases (Edinburgh Postnatal Depression Scale score ≥ 13) from the Australian Genetics of Depression Study 2018 data (n = 3804) and screened controls (n = 6134). Results of gene‐set enrichment analysis were compared with those of women with non‐PND. For six psychiatric disorders/traits, genetic correlations with PND were evaluated, and logistic regression analysis reported polygenic score (PGS) association with both PND and NPD. Results: Genes differentially expressed in ovarian tissue were significantly enriched (stdBeta = 0.07, p = 3.3e−04), but were not found to be associated with NPD. The genetic correlation between PND and MDD was 0.93 (SE = 0.07; p = 3.5e−38). Compared with controls, PGS for MDD are higher for PND cases (odds ratio [OR] = 1.8, confidence interval [CI] = [1.7–1.8], p = 9.5e−140) than for NPD cases (OR = 1.6, CI = [1.5–1.7], p = 1.2e−49). Highest risk is for those reporting both antenatal and postnatal depression, irrespective of prior MDD history. Conclusions: PND has a high genetic overlap with MDD, but points of distinction focus on differential expression in ovarian tissue and higher MDD PGS, particularly for women experiencing both antenatal and postpartum PND. [ABSTRACT FROM AUTHOR]

Importance: Genetic studies with broad definitions of depression may not capture genetic risk specific to major depressive disorder (MDD), raising questions about how depression should be operationalized in future genetic studies.Objective: To use a large, well-phenotyped single study of MDD to investigate how different definitions of depression used in genetic studies are associated with estimation of MDD and phenotypes of MDD, using polygenic risk scores (PRSs).Design, Setting, and Participants: In this case-control polygenic risk score analysis, patients meeting diagnostic criteria for a diagnosis of MDD were drawn from the Australian Genetics of Depression Study, a cross-sectional, population-based study of depression, and controls and patients with self-reported depression were drawn from QSkin, a population-based cohort study. Data analyzed herein were collected before September 2018, and data analysis was conducted from September 10, 2020, to January 27, 2021.Main Outcome and Measures: Polygenic risk scores generated from genome-wide association studies using different definitions of depression were evaluated for estimation of MDD in and within individuals with MDD for an association with age at onset, adverse childhood experiences, comorbid psychiatric and somatic disorders, and current physical and mental health.Results: Participants included 12 106 (71% female; mean age, 42.3 years; range, 18-88 years) patients meeting criteria for MDD and 12 621 (55% female; mean age, 60.9 years; range, 43-87 years) control participants with no history of psychiatric disorders. The effect size of the PRS was proportional to the discovery sample size, with the largest study having the largest effect size with the odds ratio for MDD (1.75; 95% CI, 1.73-1.77) per SD of PRS and the PRS derived from ICD-10 codes documented in hospitalization records in a population health cohort having the lowest odds ratio (1.14; 95% CI, 1.12-1.16). When accounting for differences in sample size, the PRS from a genome-wide association study of patients meeting diagnostic criteria for MDD and control participants was the best estimator of MDD, but not in those with self-reported depression, and associations with higher odds ratios with childhood adverse experiences and measures of somatic distress.Conclusions and Relevance: These findings suggest that increasing sample sizes, regardless of the depth of phenotyping, may be most informative for estimating risk of depression. The next generation of genome-wide association studies should, like the Australian Genetics of Depression Study, have both large sample sizes and extensive phenotyping to capture genetic risk factors for MDD not identified by other definitions of depression. [ABSTRACT FROM AUTHOR]

Sleep fragmentation and reductions in sleep spindles have been observed in individuals with depression. Sleep spindles are known to play a protective role for sleep, and there are indications that melatonin agents can enhance spindles in healthy people. Whether agomelatine, a melatonin agonist indicated for the treatment of depression, may increase spindle density sufficiently to impact sleep continuity in people with depression remains unknown. This proof‐of‐concept study investigated changes in spindles following agomelatine intake in young adults with depression and assessed how they may relate to potential changes in sleep continuity and depressive symptoms. This study was based on an open‐label design. Fifteen participants between 17 and 28 years of age (mean = 22.2; standard deviation [SD] = 3.4) with a diagnosis of a depressive disorder underwent polysomnography before and after an intervention including a 1 hr psychoeducation session centered on sleep and circadian rhythms, and an 8‐week course of agomelatine (25–50 mg) with a guided sleep phase advance. Fast spindle density significantly increased from pre‐ to post‐intervention. This increase in spindle density significantly correlated with a reduction in wake after sleep onset, and a similar trend was found with increased sleep efficiency. There was no significant correlation between spindle parameters and depressive symptoms. These findings suggest that agomelatine may contribute to enhanced sleep consolidation, possibly in part through the modulation of spindle production. This should be confirmed by larger randomized control trials. [ABSTRACT FROM AUTHOR]

The bidirectional relationship between depression and chronic pain is well-recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study (N = 13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health. Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for 10 different antidepressants. Chronic pain was associated with an increased risk of depression (OR = 1.86 [1.37–2.54]), recent suicide attempt (OR = 1.88 [1.14–3.09]), higher use of tobacco (OR = 1.05 [1.02–1.09]) and misuse of painkillers (e.g., opioids; OR = 1.31 [1.06–1.62]). Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR = 0.75 [0.68–0.83]), escitalopram (OR = 0.75 [0.67–0.85]) and venlafaxine (OR = 0.78 [0.68–0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR = 0.45 [0.30–0.67]), escitalopram (OR = 0.45 [0.27–0.74]) and citalopram (OR = 0.32 [0.15–0.67]) specifically for chronic pain (among other indications) reported lower benefits compared to other participants taking these same medications but not for chronic pain. These findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further examination is warranted in targeted interventional clinical trials, which also include neuroimaging genetics and pharmacogenomics protocols. This work will advance the delineation of disease risk indicators and novel aetiological pathways for therapeutic intervention in comorbid pain and depression as well as other psychiatric comorbidities. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to: (a) examine whether treatment‐seeking young adults with social anxiety disorder (SAD) demonstrate similar degrees of distress, quality of life (QoL) and disability to those with other mental disorders; and (b) investigate the impact of comorbidity, specific comorbid conditions and antidepressants use on distress, QoL and disability in treatment‐seeking young adults with SAD. Methods: A cohort of treatment‐seeking young adults (aged 16‐45) diagnosed with SAD (N = 298) or other mental health disorders (N = 842; including depression, N = 349; bipolar, N = 141; psychosis, N = 173) completed self‐report assessments of distress, QoL and disability. Results: Young adults with SAD showed distress and disability of similar degree to those with most other mental disorders. Specifically, young adults with SAD reported significantly lower QoL than those with major depressive disorder or obsessive‐compulsive disorder. Furthermore, young adults with SAD had the most difficulties in getting along with others and the second highest level of distress in comparison to other psychiatric groups. In comparison to antidepressants use, the presence of comorbidity showed a substantial negative influence on these health outcomes, particularly when presenting with comorbid depression or obsessive‐compulsive disorder. Conclusions: Findings highlight significant impairments in young adults seeking treatment for SAD and the important moderating influence of comorbidity. This emphasizes the urgent need for effective management and treatment for its presentation and comorbidities in mental health services targeting young adults. [ABSTRACT FROM AUTHOR]

Background: Depression is common in older people and is associated with underlying brain change increasing the risk of dementia. Sleep disturbance is frequently reported by those with lifetime depression, however whether circadian misalignment also exists is unclear. We aimed to examine circadian rhythms and sleep associations in older patients with and without lifetime depression. Methods: Thirty-four older people meeting DSM-IV criteria for lifetime major depression (mean age = 63.9 years), and 30 healthy controls (mean age = 65.7 years) were recruited. Participants underwent 2-weeks of actigraphy followed by a 3-night protocol including dim light melatonin onset (DLMO) assessment and overnight polysomnography (PSG) for sleep architecture. DLMO and phase angle of entrainment were computed. Results: Compared to controls, participants with depression had a significantly longer phase angle of entrainment (6.82 h ± 1.45 vs. 5.87 h ± 1.60, p = 0.02, Cohens-d = 0.62). A small to moderate yet non-significant difference in DLMO times, with earlier DLMO (34 ± 27 min) observed in depression (20:36 ± 1:48 vs. 21:10 ± 1:48, p = 0.22, Cohens-d = 0.32). Individuals with depression had longer sleep latency and latency to rapid eye movement sleep than controls (all p < 0.05). Conclusion: Circadian advancement and alterations to the timing of sleep and REM onset are evident in older people with lifetime major depression, despite having only mild residual symptoms. Further research examining the prognostic significance of these changes is warranted as well as chronotherapeutic treatment studies. [ABSTRACT FROM AUTHOR]

Background: Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age. Methods: Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer. Results: CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions. Conclusions: Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind. [ABSTRACT FROM AUTHOR]

In this study, we consecutively recruited treatment-seeking young autistic adults without intellectual impairment aged 16–30 years who presented to a mental health service and evaluated general health (distress, quality of life, and disability), functioning (work loss days and social functioning), and mood symptoms (depression, anxiety, and stress) in those diagnosed with autism spectrum disorder (n = 96). This group was compared to young adults presenting to the same service with primary mental health disorders (depression, n = 343; bipolar, n = 132; psychosis, n = 166; and anxiety, n = 303). This study also investigated the influence of mood symptoms on general health and functioning in the autism spectrum disorder group. Young autistic adults reported significant general health and functioning impairments that were of similar degree to those presenting with primary mental health disorders. Interestingly, the autistic group also reported similarly high levels of mood symptoms to those with primary depressive and anxiety disorders. In the autistic group, depressive symptoms were strongly associated with distress, quality of life, and work loss days, while stress symptoms were strongly associated with disability. This study highlights further research, and mental health services are required specifically targeting young autistic adults to address their significant unmet needs. [ABSTRACT FROM AUTHOR]

Objectives: Neurocognitive assessment and feedback to a young adult inpatient.Methods: Computerised neurocognitive assessment and feedback.Results: A collaborative process of personalised intervention.Conclusions: Personalised feedback in this setting can be employed as a management tool to identify and prioritise care. [ABSTRACT FROM AUTHOR]

The aim of the 25 and Up (25Up) study was to assess a wide range of psychological and behavioral risk factors behind mental illness in a large cohort of Australian twins and their non-twin siblings. Participants had already been studied longitudinally from the age of 12 and most recently in the 19Up study (mean age = 26.1 years, SD = 4.1, range = 20-39). This subsequent wave follows up these twins several years later in life (mean age = 29.7 years, SD = 2.2, range =  22-44). The resulting data set enables additional detailed investigations of genetic pathways underlying psychiatric illnesses in the Brisbane Longitudinal Twin Study (BLTS). Data were collected between 2016 and 2018 from 2540 twins and their non-twin siblings (59% female, including 341 monozygotic complete twin-pairs, 415 dizygotic complete pairs and 1028 non-twin siblings and singletons). Participants were from South-East Queensland, Australia, and the sample was of predominantly European ancestry. The 25Up study collected information on 20 different mental disorders, including depression, anxiety, substance use, psychosis, bipolar and attention-deficit hyper-activity disorder, as well as general demographic information such as occupation, education level, number of children, self-perceived IQ and household environment. In this article, we describe the prevalence, comorbidities and age of onset for all 20 examined disorders. The 25Up study also assessed general and physical health, including physical activity, sleep patterns, eating behaviors, baldness, acne, migraines and allergies, as well as psychosocial items such as suicidality, perceived stress, loneliness, aggression, sleep-wake cycle, sexual identity and preferences, technology and internet use, traumatic life events, gambling and cyberbullying. In addition, 25Up assessed female health traits such as morning sickness, breastfeeding and endometriosis. Furthermore, given that the 25Up study is an extension of previous BLTS studies, 86% of participants have already been genotyped. This rich resource will enable the assessment of epidemiological risk factors, as well as the heritability and genetic correlations of mental conditions. [ABSTRACT FROM AUTHOR]

Objective: Internet-delivered cognitive behavioural therapy for insomnia is efficacious for insomnia, and post hoc analyses suggest mood improvements. We undertook the first clinical trial evaluating the efficacy of Internet-delivered cognitive behavioural therapy for insomnia on depressive symptoms as an adjunct to guideline-based treatment of depressive disorders. Methods: Older men undergoing psychiatrist-coordinated treatment for major depressive disorder or dysthymia and who had significant insomnia symptoms were randomised to either adjunctive Internet-delivered cognitive behavioural therapy for insomnia (Sleep Healthy Using The Internet) or online sleep psychoeducation. The primary outcome was change in depressive symptoms (Centre for Epidemiological Studies Depression scale) from baseline to week 12 (post intervention). Secondary outcomes were insomnia and anxiety symptoms. Results: In all, 87 men were randomised (Internet-delivered cognitive behavioural therapy for insomnia = 45; psychoeducation = 42). The mean observed Centre for Epidemiological Studies Depression scale changes by week 12 were 8.2 (standard deviation = 11.5) and 3.9 (standard deviation = 12.8) for Internet-delivered cognitive behavioural therapy for insomnia and psychoeducation, respectively. The adjunctive effect size of 0.35 in favour of Sleep Healthy Using The Internet programme was not statistically significant (group × time difference in the Mixed effect Model Repeat Measurement analysis difference 4.3; 95% confidence interval = [−1.2, 9.8]; p = 0.15). There was a statistically significant effect on insomnia symptoms (group × time p = 0.02, difference 2.7; 95% confidence interval = [0.2, 5.3]; effect size = 0.62). There were no differences in insomnia or depression at 6 months or differential effects on anxiety at any time point. There were no reported adverse trial-related events in the intervention arm. Conclusion: Adjunctive Internet-delivered cognitive behavioural therapy for insomnia for older men being treated for depression can improve insomnia in the short term, without apparent harm. The short-term depressive symptom effect size in this pilot trial was comparable to other adjunctive interventions and may warrant a larger, definitive trial. [ABSTRACT FROM AUTHOR]

Importance: Biologic systems involved in the regulation of motor activity are intricately linked with other homeostatic systems such as sleep, feeding behavior, energy, and mood. Mobile monitoring technology (eg, actigraphy and ecological momentary assessment devices) allows the assessment of these multiple systems in real time. However, most clinical studies of mental disorders that use mobile devices have not focused on the dynamic associations between these systems.Objectives: To examine the directional associations among motor activity, energy, mood, and sleep using mobile monitoring in a community-identified sample, and to evaluate whether these within-day associations differ between people with a history of bipolar or other mood disorders and controls without mood disorders.Design, Setting, and Participants: This study used a nested case-control design of 242 adults, a subsample of a community-based sample of adults. Probands were recruited by mail from the greater Washington, DC, metropolitan area from January 2005 to June 2013. Enrichment of the sample for mood disorders was provided by volunteers or referrals from the National Institutes of Health Clinical Center or by participants in the National Institute of Mental Health Mood and Anxiety Disorders Program. The inclusion criteria were the ability to speak English, availability to participate, and consent to contact at least 2 living first-degree relatives. Data analysis was performed from June 2013 through July 2018.Main Outcomes and Measures: Motor activity and sleep duration data were obtained from minute-to-minute activity counts from an actigraphy device worn on the nondominant wrist for 2 weeks. Mood and energy levels were assessed by subjective analogue ratings on the ecological momentary assessment (using a personal digital assistant) by participants 4 times per day for 2 weeks.Results: Of the total 242 participants, 92 (38.1%) were men and 150 (61.9%) were women, with a mean (SD) age of 48 (16.9) years. Among the participants, 54 (22.3%) had bipolar disorder (25 with bipolar I; 29 with bipolar II), 91 (37.6%) had major depressive disorder, and 97 (40.1%) were controls with no history of mood disorders. A unidirectional association was found between motor activity and subjective mood level (β = -0.018, P = .04). Bidirectional associations were observed between motor activity (β = 0.176; P = .03) and subjective energy level (β = 0.027; P = .03) as well as between motor activity (β = -0.027; P = .04) and sleep duration (β = -0.154; P = .04). Greater cross-domain reactivity was observed in bipolar disorder across all outcomes, including motor activity, sleep, mood, and energy.Conclusions and Relevance: These findings suggest that interventions focused on motor activity and energy may have greater efficacy than current approaches that target depressed mood; both active and passive tracking of multiple regulatory systems are important in designing therapeutic targets. [ABSTRACT FROM AUTHOR]

Nick Martin is a pioneer in recognizing the need for large sample size to study the complex, heterogeneous and polygenic disorders of common mental disorders. In the predigital era, questionnaires were mailed to thousands of twin pairs around Australia. Always quick to adopt new technology, Nick's studies progressed to phone interviews and then online. Moreover, Nick was early to recognize the value of collecting DNA samples. As genotyping technologies improved over the years, these twin and family cohorts were used for linkage, candidate gene and genome-wide association studies. These cohorts have underpinned many analyses to disentangle the complex web of genetic and lifestyle factors associated with mental health. With characteristic foresight, Nick is chief investigator of our Australian Genetics of Depression Study, which has recruited 16,000 people with self-reported depression (plus DNA samples) over a time frame of a few months - analyses are currently ongoing. The mantra of sample size, sample size, sample size has guided Nick's research over the last 30 years and continues to do so. [ABSTRACT FROM AUTHOR]

Background and aim: This study assessed the association between depressive symptom severity and cognition in middle-to-older aged adults with mild-to-moderate depression and cardiovascular risk factors using an online test battery (CogState) and whether changes in depressive symptoms over 3 months were associated with changes in cognition. Methods: Participants (mean age = 57.8) with cardiovascular risk and mild–to-moderate depressive symptoms completed measures of psychomotor speed, learning, and executive function prior to (n = 445)_and after (n = 334) online depression or attention control interventions. The symptom severity-cognition relationship was examined both cross-sectionally and prospectively. Results: Participants exhibited significantly reduced psychomotor speed and variable impairments on measures of learning and executive functioning relative to normative data. However, there was no association of depression severity with cognition at baseline or of change in depressive symptoms with change in cognitive performance. Limitations: Participants were well-educated, which may have protected against cognitive decline. Attrition may limit generalisability, though is unlikely to explain the lack of association between depression symptoms and cognition. Conclusions: Adults with comorbid mild-to-moderate depressive symptoms and cardiovascular risks performed less well than age-matched normative data on three online cognitive tests; however, we were unable to show any symptom-cognition association cross-sectionally or longitudinally, despite significant improvements in depressive symptoms. This challenges the generalisability of such associations found in more severely unwell clinical samples to those with a broader depressive symptom profile, or suggests that underlying cardiovascular disease may account for the association seen in some clinical studies. This has implications for scaling up selective prevention of cognitive decline. [ABSTRACT FROM AUTHOR]

Background: The present study investigated Default Mode Network (DMN) functional connectivity in subjects with a lifetime history of major depression, comparing those with and without current sleep disturbance. Controls were included to assess DMN abnormalities specific to depression.Methods: A total of 93 adults aged 50 years and over were recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney, Australia. The sample comprised two groups, including 22 controls and 71 participants with a lifetime history of DSM-IV major depression (with depressive episode current or remitted). 52 of those with a lifetime history of depression also met criteria for Mild Cognitive Impairment (MCI). Participants underwent resting-state fMRI along with comprehensive psychiatric, neuropsychological, and medical assessment. Subjective sleep quality was assessed via the Pittsburgh Sleep Quality Index (PSQI). Sleep disturbance was defined as a PSQI score > 5. A total of 68% (n = 48) of cases with a lifetime history of depression met criteria for sleep-disturbance. DMN functional connectivity was assessed via ROI-to-ROI analyses.Results: Relative to controls, those with lifetime major depression demonstrated significantly increased functional connectivity between the ventromedial prefrontal cortex and the temporal pole. Within the depression group (n = 48), those with current sleep disturbance had significantly increased connectivity between the anterior medial prefrontal cortex and both the parahippocampal cortex and the hippocampal formation, relative to those without sleep disturbance (n = 23). These results were present after controlling for MCI diagnosis.Conclusions: Current sleep disturbance together with depression is associated with distinct abnormalities in DMN functioning incorporating regions responsible for self-reflection and declarative memory processes. Impaired sleep is associated with increased connectivity between these regions. Future studies may augment these findings with complementary imaging techniques including cortical thickness and diffusion tensor imaging, as well as high density electroencephalogram recording. [ABSTRACT FROM AUTHOR]

Background: A clinical and research challenge is to identify which depressed youth are at risk of "early transition to bipolar disorders (ET-BD)." This 2-part study (1) examines the clinical utility of previously reported BD at-risk (BAR) criteria in differentiating ET-BD cases from unipolar depression (UP) controls; and (2) estimates the Number Needed to Screen (NNS) for research and general psychiatry settings. Methods: Fifty cases with reliably ascertained, ET-BD I and II cases were matched for gender and birth year with 50 UP controls who did not develop BD over 2 years. We estimated the clinical utility for finding true cases and screening out non-cases for selected risk factors and their NNS. Using a convenience sample (N = 80), we estimated the NNS when adjustments were made to account for data missing from clinical case notes. Results: Sub-threshold mania, cyclothymia, family history of BD, atypical depression symptoms and probable antidepressant-emergent elation, occurred significantly more frequently in ET-BD youth. Each of these "BAR-Depression" criteria demonstrated clinical utility for screening out non-cases. Only cyclothymia demonstrated good utility for case finding in research settings; sub-threshold mania showed moderate utility. In the convenience sample, the NNS for each criterion ranged from ~4 to 7. Conclusions: Cyclothymia showed the optimum profile for case finding, screening and NNS in research settings. However, its presence or absence was only reported in 50% of case notes. Future studies of ET-BD instruments should distinguish which criteria have clinical utility for case finding vs screening. [ABSTRACT FROM AUTHOR]

Importance: Increased activity and energy alongside mood change are identified in the DSM-5 as cardinal symptoms of mania and hypomania. A wide range of existing research suggests that this revision may be valid, but systematic integration of the evidence has not been reported. The term activation is understood as emerging from underlying physiological change and having objective (observable motor activity) and related subjective (energy) levels.Objectives: To systematically review studies of the clinical phenomenon of activation in bipolar disorder, to determine whether activation is statistically abnormal in bipolar disorder and demonstrably distinct from mood, and to identify any significant between- and within-individual differences in the dynamics of activation.Evidence Review: This systematic review of MEDLINE, PsycINFO, EMBASE, CINAHL, and PubMed databases from January 1, 1970, until September 30, 2016, identified 56 of a possible 3284 citations for (1) data-driven analyses of the dimensions and factor structure of mania and bipolar depression and (2) longitudinal studies reporting real-time objective monitoring or momentary assessment of daytime activity in individuals with bipolar disorder compared with other clinical or healthy control samples. Hand search of reference lists, specialty journals, websites, published conference proceedings, and dissertation abstracts and contact with other researchers ensured inclusion of gray literature and additional analyses as well as raw data if appropriate. Quality assessment was perfomed using the National Institutes of Health quality assessment tool.Findings: A total of 56 studies met eligibility criteria for inclusion in the review including 29 analyses of the factor structure of bipolar disorder, 3 of activity data from experimental sampling or ecological momentary assessment, and 20 actigraphy and 4 laboratory-based studies. Synthesizing findings across the studies revealed that the most robust finding was that mean levels of activity are lower during euthymia and depression in patients with bipolar disorder compared with healthy controls and other comparison groups (11 studies). The 7 ecological and laboratory studies show less organized or predictable patterns of behavior and a relative lack of habituation among patients with bipolar disorders compared with others. Factor analytic studies provide fairly consistent evidence that mood and activation represent distinct dimensions of bipolar disorder. Ten studies that examined interindividual and intraindividual patterns of activity suggest that mania may be better characterized by differences in robustness, variability, predictability, or complexity of activation rather than mean levels of activity.Conclusions and Relevance: Within the limitations of the data, this synthesis of available evidence broadly supports the elevation of activation as a criterion A symptom for bipolar disorder in DSM-5. Although the importance of activation in bipolar disorders has been acknowledged for more than a century, this review suggests that this critical construct is understudied and should be the topic of more systematic high-quality research. [ABSTRACT FROM AUTHOR]

Purpose: To examine the associations between depression course, functional disability, and Not in Education or Training (NEET) status in a clinical sample of young adults with mental health problems.Methods: Young adults aged 15-25 years seeking help from four primary mental health services were invited to participate in a prospective cohort study evaluating the course of psychiatric disorders in youth. Demographic and clinical characteristics, including depressive symptomatology and functioning, were evaluated through clinical interview and self-report at baseline and 12 month follow-up.Results: A total of 448 young adults participated (70 % female; M: 20.05 years, SD = 2.85). A significant interaction effect for time and depression course was found, such that those who became depressed reported an increase in functional disability and those whose depression remitted reported a significant reduction in functional disability. Developing depression was not a significant predictor of becoming NEET and vice versa: remitted depression did not make a person more likely to reengage in employment or education.Conclusions: This is the first study to examine the course of depression, functional disability, and NEET rates among help-seeking young adults. This study confirms the importance of symptom reduction for improved functioning; however, functional disability remained greater than that seen in young people in the community and there was no association between a change in depression and a change in NEET status. These results argue that services need to address functional outcomes and reengagement with education and employment in addition to symptom reduction. [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]

Aim US authorities have recommended 'black-box' warnings for antidepressants because of the increased risk of suicidality for individuals up to age 25. There is thus a clinical and ethical imperative to provide effective treatment for youth depression with an acceptable risk-benefit balance. Long-chain omega-3 polyunsaturated fatty acids ( PUFAs) play an important role in a range of physiological processes in living organisms. Supplementation with omega-3 PUFAs has been shown to have a range of beneficial effects on both physical and mental health, and results of previous trials suggest that omega-3 PUFAs may be a safe and effective treatment for depression. However, conclusions from these trials have been limited by their relatively small sample sizes. Methods This trial will test the effectiveness of a 12-week parallel group, double-blind, randomized, placebo-controlled trial of 1.4 g day−1 omega-3 PUFAs in help seeking 15- to 25-year-olds ( N = 400) presenting with major depressive disorder. The primary hypothesis is that young people will show greater improvement of depressive symptoms after 12 weeks of treatment with omega-3 PUFAs plus cognitive behavioural case management compared with treatment with placebo plus cognitive behavioural case management. Conclusion Because of using a large sample, results from this study will provide the strongest evidence to date to inform the use of omega-3 PUFAs as first-line therapy in young people presenting with major depressive disorder. The study also heralds an important step towards indicated prevention of persistent depression, which may reduce the burden, stigmatization, disability and economic consequences of this disorder. [ABSTRACT FROM AUTHOR]

Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in ‘frequency of internet use’ was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in ‘frequency of use after 11 pm’, ‘using the internet to contact peers’, and ‘using the internet primarily to access social networking sites’ was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between ‘frequency of internet use’ and ‘frequency of use after 11 pm’ with social phobia (SP). ‘Using the internet to contact peers’ was positively associated with alcohol abuse, whereas ‘using the internet to contact peers’ and ‘using the internet primarily to access social networking sites’ were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology. [ABSTRACT FROM PUBLISHER]

As online mental health support groups become increasingly popular, they require more support from volunteers and trained moderators who help their users through "interventions" (i.e., responding to questions and providing support). We present a system that supports such human interventions using Natural Language Generation (NLG) techniques. The system generates draft responses aimed at reducing moderators' workload, and improving their efficacy. NLG and human interventions were compared through the ratings of 35 psychology interns. The NLG-based system was capable of generating messages that are grammatically correct with clear language. The system needs improvement, however, moderators can already use it as draft responses. [ABSTRACT FROM AUTHOR]

Aims: To examine the rates and clinical characteristics of mild cognitive impairment (MCI) in older people with depressive symptoms and to determine the relative contribution of hippocampal volume and MCI to memory change. Method: One hundred and fifty-two participants with lifetime Major Depression and remitted or mild symptoms and 28 healthy controls underwent psychiatric and neuropsychological assessments. Magnetic resonance imaging was also conducted in a subset of the patients (n = 81) and healthy controls (n = 18). Results: MCI was diagnosed in 75.7% of the patients and was associated with increasing age, medical burden, vascular risk factors, later age of depression onset and smaller hippocampi. Multiple regression showed that both hippocampal volume and MCI diagnosis mediate memory performance in depression. Conclusions: MCI occurs in older adults with a history of depression and is not simply due to symptom severity. Memory change is linked to underlying hippocampal atrophy in this patient group. [ABSTRACT FROM AUTHOR]

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight. [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. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine perceptions of the helpfulness of treatments/interventions for depression held by elderly care recipients, to examine whether these beliefs are related to help-seeking and whether the experience of depression affects beliefs about treatment seeking, and to identify the characteristics of help-seekers. Method: One hundred eighteen aged care recipients were surveyed on their beliefs about the helpfulness of a variety of treatments/interventions for depression, on their actual help-seeking behaviors, and on their experience of depression (current and past). Results: From the sample, 32.4% of the participants screened positive for depression on the Geriatric Depression Scale, and of these, 24.2% reported receiving treatment. Respondents believed the most helpful treatments for depression were increasing physical activity, counseling, and antidepressant medication. Help-seeking from both professional and informal sources appeared to be related to belief in the helpfulness of counseling and antidepressants; in addition, help-seeking from informal sources was also related to belief in the helpfulness of sleeping tablets and reading self-help books. In univariate analyses, lower levels of cognitive impairment and being in the two lower age tertiles predicted a greater likelihood of help-seeking from professional sources, and female sex and being in the lower two age tertiles predicted greater likelihood of help-seeking from informal sources. In multivariate analyses, only lower levels of cognitive impairment remained a significant predictor of help-seeking from professional sources, whereas both lower age and female sex continued to predict a greater likelihood of help-seeking from informal sources. Conclusion: Beliefs in the helpfulness of certain treatments were related to the use of both professional and informal sources of help, indicating the possibility that campaigns or educational programs aimed at changing beliefs about treatments may be useful in older adults. [ABSTRACT FROM AUTHOR]

With estimates of dementia expected to rise over the coming decades, there is interest in understanding the factors associated with promoting neuroprotection and limiting neurodegeneration. In this study, we examined the change in the volume of the hippocampus over a 2-month period in 34 older people “at risk” of cognitive decline (mean age = 66.8 years, 38% male). Factors that were examined included cognitive reserve, neuropsychological functioning, depression as well as a lifestyle (cognitive training) intervention. The results showed that over a 2-month period, increases in hippocampal size were associated with having higher premorbid intellect, greater occupational attainment, superior memory, and higher levels of functioning. Conversely, depression and disability were associated with decreases in hippocampal volume. Cognitive training was not associated with changes in hippocampal volume. These findings suggest that factors associated with cognitive reserve, cognition and depression may play an integral pathophysiological role in determining hippocampal volumes in “at-risk” older adults. [ABSTRACT FROM PUBLISHER]

Recently, it has been suggested that the clinical staging approach be considered a serious alternative framework for conceptualising mood related psychopathology. The fundamental difference between clinical staging and the now dominant categorical diagnostic framework is that the entire illness trajectory becomes relevant, as opposed to simply the end-stage. The concept of disease trajectory has significant implications for animal models of psy-chopathology, and particularly for animal models of depression. This article will introduce and discuss the impli-cations of the clinical staging approach for those undertaking research using animal models of mood disturbance. [ABSTRACT FROM AUTHOR]

Considering the marked changes in sleep and circadian rhythms across the lifespan, age may contribute to the heterogeneity in sleep-wake profiles linked to mood disorders. This study aimed to investigate the contributions of age and depression severity to sleep-wake disturbances. The Hamilton Depression Rating Scale (HDRS) was administered to assess current symptoms severity in 238 persons with a history of a mood disorder between 12 and 90 years of age (y.o.). Actigraphy was recorded over five to 22 days. Regression analyses and analyses of variance [age (12–19 y.o., 20–39 y.o., 40–59 y.o., and ≥60 y.o.) by depression severity (HDRS< and ≥8)] were conducted. The 12–19 y.o. and 20–39 y.o. groups had a delayed sleep schedule and acrophase compared to all other groups. The ≥60 y.o. group had a lower rhythmicity and amplitude (p≤.006) than the 12–19 y.o. group (p≤.046). Participants with a HDRS≥8 spent longer time in bed, had later sleep offset times and had lower circadian rhythmicity than those with a HDRS<8 (p≤.036). Younger age and higher HDRS score correlated with later sleep onset and offset times, longer time in bed, higher WASO, lower sleep efficiency and later acrophase (p≤.023). Age was a significant predictor of delayed sleep and activity schedules (p≤.001). The profile of sleep-wake cycle disturbances associated with mood disorders changes with age, with prominent sleep phase delay during youth and reduced circadian strength in older persons. Conversely, disruptions in sleep consolidation seem more stable across age. [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: We have recently shown that the event-related potential biomarkers, mismatch negativity (MMN) and P3a, are similarly impaired in young patients with schizophrenia- and affective-spectrum psychoses as well as those with bipolar disorder. A data driven approach may help to further elucidate novel patterns of MMN/P3a amplitudes that characterise distinct subgroups in patients with emerging psychiatric disorders. Methods: Eighty seven outpatients (16 to 30 years) were assessed: 19 diagnosed with a depressive disorder; 26 with a bipolar disorder; and 42 with a psychotic disorder. The MMN/P3a complex was elicited using a two-tone passive auditory oddball paradigm with duration deviant tones. Hierarchical cluster analysis utilising frontal, central and temporal neurophysiological variables was conducted. Results: Three clusters were determined: the 'globally impaired' cluster (n = 53) displayed reduced frontal and temporal MMN as well as reduced central P3a amplitudes; the 'largest frontal MMN' cluster (n = 17) were distinguished by increased frontal MMN amplitudes and the 'largest temporal MMN' cluster (n = 17) was characterised by increases in temporal MMN only. Notably, 55% of those in the globally impaired cluster were diagnosed with schizophrenia-spectrum disorder, whereas the three patient subgroups were equally represented in the remaining two clusters. The three cluster-groups did not differ in their current symptomatology; however, the globally impaired cluster was the most neuropsychologically impaired, compared with controls. Conclusions: These findings suggest that in emerging psychiatric disorders there are distinct MMN/P3a profiles of patient subgroups independent of current symptomatology. Schizophrenia-spectrum patients tended to show the most global impairments in this neurophysiological complex. Two other subgroups of patients were found to have neurophysiological profiles suggestive of quite different neurobiological (and hence, treatment) implications. [ABSTRACT FROM AUTHOR]

Objective: The authors evaluated management of illness, including access to specialist mental health care, among people identified by general practitioners as clinically depressed. Methods: Australian primary care practitioners recruited in 2009 completed case reports and collected self-report assessments from five to seven consecutively presenting patients whom they identified as having clinical depression. Results: Among 735 patients with clinical depression, 55% met criteria for major depressive syndrome, 86% reported clinically significant sleep disturbance, and 47% had been depressed for more than 12 months. Most (77%) were prescribed antidepressants, and 30% were prescribed anxiolytics or hypnotics. Patients under shared care with specialist mental health care providers (42%) had more severe, chronic, and recurrent conditions but no demographic advantages. Conclusions: Depressed patients of general practitioners often had chronic, recurrent, and moderately to severely disabling conditions, but fewer than half received specialist care. Access to specialist care, however, appeared to be based on clinical need, with little inequity in sociodemographic characteristics observed. [ABSTRACT FROM AUTHOR]

Aim: Although the use of illness-staging models in clinical medicine has proved particularly useful, the concept has not been widely applied in mental health. Here, we apply a clinical staging framework to a population of help-seeking young people presenting with social anxiety. The goal was to provide a detailed description of common clinical stage of those presenting for treatment of social anxiety, and to delineate the associations between symptom type, severity and clinical stage. Methods: The results of a structured clinical interview along with background clinical information formed the basis for consensus-derived decisions regarding clinical stage. Subjects also completed self-report measures to assess anxiety and depressive symptoms. Comparisons were conducted largely between those subjects who were considered to have reached a critical clinical threshold for discrete or progressive disorders (i.e. those staged at two and beyond) and those with 'attenuated syndromes' (stage 1b - 69% of subjects). Results: One hundred forty-three subjects (63% male, mean age = 22.1 years) were clinically assessed prior to entry into active treatment programmes. Subjects assigned to stage two or above reported more psychological distress, higher depression scores and more alcohol use. However, these subjects did not report more severe anxiety symptoms. A higher incidence of substance misuse was a significant feature of those in later clinical stages. Conclusions: The study suggests that those who present with social anxiety are characterized by a broad range of symptom severity, with a small, though significant proportion representing individuals whose mental health problems have already progressed to a stage characterized by greater co-morbidity and risk of chronicity. Our data specifically suggest that depressive symptoms and substance abuse/dependence may differentiate those in earlier and later clinical stages. [ABSTRACT FROM AUTHOR]

Objective: Depression and heart disease are major causes of early ill-health retirement. The effect of comorbid depression on the award of ill-health retirement in those with heart disease is unclear, however, and may differ by gender. Given the deleterious effects of ill-health retirement, identifying at-risk groups is important for guiding targeted interventions.Method: We retrospectively analysed baseline data of 20,655 participants from the 45 and Up Study (New South Wales, Australia), who had fully retired between the ages of 45 and 64. We examined the associations of depression and heart disease with ill-health retirement and then adjusted for the presence of common confounders. We then restricted the sample to the 1165 individuals with heart disease prior to retirement, to determine the impact of comorbid depression on IHR and analysed whether there was a differential impact by gender.Results: In the complete sample, 3836 out of 20,655 (18.6%) of the participants retired early due to ill health. Prior heart disease and depression were both independently and strongly associated with ill-health retirement. Those who retired due to ill health were also more likely to be men, less educated, report greater physical disability and were younger at retirement. Among the 1165 for whom heart disease predated any form of retirement, 40% retired due to ill health. Comorbid depression prior to ill-health retirement was strongly associated with an increased risk of this IHR in women (odds ratio = 2.85; 95% confidence interval = 1.20–6.77, p = 0.01), but not in men (interaction term, p = 0.045).Conclusions: Ill-health retirement is common in those with heart disease. Women appear to be particularly susceptible to the effects of comorbid depression. Given the policy emphasis on reducing the number of people leaving the workforce early, women with early heart disease may represent a particular group in whom interventions designed to detect and treat comorbid depression should be targeted. [ABSTRACT FROM PUBLISHER]

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]

The article offers information on the potential advances in the treatment of major depression. It discusses the antidepressant treatment strategies that target the circadian system and highlights the effects of agomelatine as a melatonin-receptor agonist with chronobiotic, antidepressant and anxiolytic effects. It notes that major depression is the leading cause of premature death with long-term antidepressant therapy as an essential component of treatment for individuals with severe depression.

Aims: The study aims to compare social functioning in young people considered to be at risk of psychosis with those meeting criteria for first episode psychosis (FEP) and controls, and to determine the association between social functioning and positive and negative symptoms, depressive symptoms, and social anxiety. Methods: This study examined social functioning in 20 individuals at risk of psychosis, 20 FEP patients and 20 healthy controls. Social functioning was measured using the Social Functioning Scale and World Health Organization Disability Assessment Scale. Psychiatric variables were also measured using the Comprehensive Assessment of At-Risk Mental States, the Brief Psychiatric Rating Scale, the Brief Social Phobia Scale, and the Depression Anxiety and Stress Scale. Results: At-risk individuals had comparable social deficits to the FEP group, and both patient groups had significantly poorer social functioning than controls. Importantly, social functioning was most strongly associated with depressive and social anxiety symptoms and to a lesser extent with positive symptoms. However, negative symptoms did not appear to relate to social functioning. Conclusion: Social functioning impairments precede the onset of full-threshold psychosis and may therefore be a significant marker for the illness. Additionally, associated psychiatric symptoms such as depression and social anxiety may provide an avenue for early interventions of social functioning deficits in psychosis. [ABSTRACT FROM AUTHOR]

Early stages of affective or psychotic disorders may be accompanied by neuropsychological changes that help to predict risk of developing more severe disorders. A comprehensive set of neuropsychological measures was collected in 109 help-seeking young people (16 to 30 years; 54 females), recently diagnosed with an affective or psychotic disorder and presenting with current depression. Hierarchical cluster analysis determined three clusters: one deemed to have a “poor memory” profile (n = 40); another with a “poor mental flexibility” profile (n = 38) and a third with widespread difficulties plus “impaired attention and memory” (n = 31). In general, the three clusters were comparable in demographic, functional and clinical factors suggesting some unique role for neurocognitive impairments. A discriminant function analysis confirmed that the clusters were best characterized by performance in “attentional” versus “learning/memory” measures. Furthermore, profiles of independent neuropsychological variables validated the original solution for two of the clusters, distinguishing all cluster-groups on an attentional measure. The findings of this study suggest that despite presenting with very similar levels of current depressive symptomatology, young help-seeking individuals in the early stages of illness have underlying neuropsychological heterogeneity. Distinct neuropsychological profiling may help to predict later psychiatric outcomes and enhance individually-tailored early intervention strategies. (JINS, 2011, 17, 267–276) [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]

Aim: Early stages of severe mood disorders may be accompanied by neurocognitive changes. Specifically, deficits in verbal memory have been linked to depression in young people. This study examined whether young adults with unipolar compared with bipolar depression showed similar neurocognitive deficits. Methods: A total of 57 young adults (16–32 years) were assessed in this study. Twenty with unipolar and 20 with bipolar depression, all currently depressed, were compared with 17 healthy controls. Neuropsychological assessment included psychomotor speed, attention for routine mental operations, attentional switching, executive control and verbal learning and memory. Results: Both unipolar and bipolar subjects showed significant impairments in verbal memory and attentional switching compared with controls. Both mood disorder groups showed no impairments in psychomotor speed, attention for routine mental operations and executive control. Effects size calculations show that the unipolar and bipolar groups do not differ from each other across a range of neurocognitive measures. Conclusion: Neurocognitive deficits in young adults with current depressive syndromes appear to differ from those typically seen in older patients. In early adulthood, both unipolar and bipolar depression may be distinguished by poor verbal memory, despite intact speed of processing, attention and executive functions. This study suggests that there is utility in neuropsychological testing for young adults in the early stages of severe mood disorders. In order to prevent neurobiological changes inherent to the disease, pharmacological and non-pharmacological interventions that target verbal memory deficits may be optimally delivered early in the disease course. [ABSTRACT FROM AUTHOR]

The article presents a study on a cluster trial in Australia to measure the effectiveness of Internet-based cognitive behaviour therapy (CBT) and improve psychological care. The study was conducted from January 2004 to January 2007 and allocated practices for interventions, which included enhanced general practice (GP) care plus MoodGYM, an Internet-based Australian intervention. The study concluded that primary care patients with depression may derive benefits from an Internet-based CBT program with enhanced psychological care from GPs.