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Background: Alcohol Use Disorder (AUD) is a significant contributor to global disease burden. AUD has a relatively early onset during young adulthood (Teesson et al., 2010). However, compared to AUD in adults, we have relatively little understanding of AUD in adolescents and emerging adults., Methods: The RADAR study is a prospective cohort study designed to investigate the emergence of AUD in community-dwelling adolescents and emerging adults across Australia (age range = 18-21 at baseline). At 6 monthly intervals over 2.5 years, participants were interviewed regarding alcohol consumption and alcohol use disorder criteria by clinical psychologists using the SCID-IV-RV. This paper reports the baseline findings of the RADAR cohort., Results: Proportions of lifetime criteria endorsement among regular drinkers varied considerably. Tolerance was the most endorsed criterion (50.3%), followed by Social Problems (10.4%) and Larger/Longer (9.0%). The median age of onset for most individual AUD criteria was 18 years of age. 18.4% of our cohort met DSM-5 AUD diagnosis in their lifetime to date, and 16.8% met ICD-11 dependence. When removing Tolerance from the AUD criteria, DSM-5 AUD lifetime prevalence reduced to 11.0%, and ICD-11 AUD lifetime prevalence fell to 7.1% in our cohort., Conclusions: Variable rates of criteria endorsement likely reflect both true differences in the experience of AUD criteria and methodological challenges in the assessment of AUD in an emerging adult age group. High rates of tolerance to the effects of alcohol, and relatively low rates of drinking larger/longer than intended are discussed considering methodological challenges in assessing these criteria in young adults., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Lifetime depression and depression around the time of an acute coronary syndrome event have been associated with poor cardiac outcomes. Our study sought to examine the persistence of this association, especially given modern cardiac medicine's successes., Methods: For 332 patients admitted for an acute coronary syndrome, a baseline interview assessed major depression status, and psychological measures were administered. At 1 and 12 months post-acute coronary syndrome event, telephone interviews collected rates of hospital readmission and/or death and major depression status, while biomarker information was examined using medical records., Results: The 12-month mortality rate was 2.3% and cardiac readmission rate 21.0%. Depression subsequent to an acute coronary syndrome event resulted in a threefold and 2.5-fold increase in 1-month and 12-month odds of cardiac readmission or death, respectively. No relationship with past depressive episodes was found. Poor sleep was associated with higher trait anxiety and neuroticism scores and with more severe depression., Conclusion: Lifetime depression may increase the risk of depression around the time of an acute coronary syndrome but not influence cardiac outcomes. We suggest that poor sleep quality may be causal or indicate high anxiety/neuroticism, which increases risk to depression and contributes to poor cardiac outcomes rather than depression being the primary causal factor.

Mood disorders may lead to major life consequences. This study builds on our preliminary examination of the impact of an extensive set of consequences and was undertaken in a larger clinical sample. Two hundred and forty four adults diagnosed with either unipolar depressive disorder or a bipolar disorder (type I or II) were administered an online survey of 60 items, listing potential consequences of having a mood disorder. Participants estimated the degree of impact (0-100) of each consequence on their life initially, and in the longer term. Items loading highly on the first 'general' factor of a bi-factor analysis were examined. Most items were affirmed by at least 75% of the sample. Significant group differences emerged on ten items. The bipolar group was 1.44-2.27 times more likely to experience difficulty with debts, education, speeding fines, increased risk of harm and delayed family planning. The unipolar group was 1.11-1.67 times more likely to experience social withdrawal, lowered life satisfaction, decreased overall wellbeing and ambition, and missed opportunities. Only one positive consequence (i.e. increased empathy) was identified. This extensive range of mood disorder consequences was highly endorsed by both BP and UP patients and with substantial immediate and ongoing impacts reported., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: To determine if differing developmental factors show specificity to differing manifestations of borderline personality disorder (BPD)., Methods: A clinical sample of 73 females diagnosed with BPD undertook a psychiatrist interview and completed self-report questionnaires, including the semi-structured Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV) assessing for BPD status. A set of negative and potentially traumatic developmental factors were included in the assessment., Results: Childhood sexual abuse, affirmed by 49% of the sample, showed specificity in being linked with DIPD-defined affective instability. DIPD-defined identity disturbance also showed specificity in being associated only with reporting significant non-sexual developmental trauma. DIPD-defined anger and paranoia/dissociation showed minimal specificity and were associated with most antecedent developmental factors in adulthood., Conclusions: Differing manifestations of BPD are likely to be shaped by specific and non-specific developmental events. Clarification of such links has the potential to shape more specific therapeutic interventions.

Recent research indicates that borderline personality disorder (BPD) can be diagnostically differentiated from the bipolar disorders. However, no studies have attempted to differentiate participants with sub-threshold bipolar disorder or SubT BP (where hypomanic episodes last less than 4 days) from those with a BPD. In this study, participants were assigned a SubT BP, bipolar II disorder (BP II) or BPD diagnosis based on clinical assessment and DSM-IV criteria. Participants completed self-report measures and undertook a clinical interview which collected socio-demographic information, a mood history, family history, developmental history, treatment information, and assessed cognitive, emotional and behavioural functioning. Both bipolar groups, whether SubT BP or BP II, differed to the BPD group on a number of key variables (i.e. developmental trauma, depression correlates, borderline personality scores, self-harm and suicide attempts), and compared to each other, returned similar scores on nearly all key variables. Borderline risk scores resulted in comparable classification rates of 0.74 (for BPD vs BP II) and 0.82 (for BPD vs sub-threshold BP II). Study findings indicate that both SubT BP and BP II disorder can be differentiated from BPD on a set of refined clinical variables with comparable accuracy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study examined the profile of stressful life experiences in patients with unipolar depression (UP) compared to bipolar disorder (BP), including their subsequent psychological impact and affirmation of post-traumatic stress symptoms. We studied 747 tertiary patients diagnosed with either a UP (n = 413) or BP condition (n = 334) according to a structured research interview and psychiatrist assessment. An online assessment collected additional study variables. Results showed that despite being younger in age, the BP group were more likely to have experienced 8 of the stressful life events, including childhood and adulthood abuse. However, both groups judged the consequential 'impact' of those events similarly. The BP group was significantly more likely than the UP group (45% vs. 36%) to affirm exposure to an extremely stressful event across their lifetime, resulting in 26.3% of the BP and 14.5% of the UP group affirming DSM-IV criteria for lifetime PTSD. The onset of DSM-IV-defined post-traumatic symptoms tended to occur in adulthood for both groups, with trauma often following the onset of the mood disorder. Thus, BP patients displayed greater vulnerability toward traumatic experiences and anxiety disorders, but reported a similar psychological impact in response to each stressor, compared with the UP group., (Copyright © 2017. Published by Elsevier B.V.)

Objective: To detail limitations to the construct of 'major depression', argue for repositioning it as a proxy for 'clinical depression' and then operationalize it and its principal constituent depressive subtypes, while preserving the DSM criteria-based format., Method: We summarize limitations to major depression being viewed as a diagnostic entity. Data from 391 clinically depressed patients were analysed to identify high-prevalence non-specific depressive symptoms to define 'clinical depression' as well as the features showing specificity to a melancholic depressive subtype., Results: We identified a set of high-prevalence and generalized symptoms for defining clinical depression and with many being current criteria for major depression. We also developed a refined set of melancholic features and with their underlying distributions generating two classes that correlated strongly with clinical diagnoses of a melancholic or non-melancholic depression, thus validating its capacity to so differentiate. We append criteria sets for diagnosing clinical depression and its principal diagnostic subtypes (psychotic, melancholic and non-melancholic)., Conclusion: This heuristic study reframes and modifies major depression's criteria set to define a domain of clinical depression with additional criteria and then allowing the delineation of three diagnostic subtypes. If this paradigm shift is accepted and further refined, greater precision in diagnosis, treatment and research would be anticipated., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The CORE measure was designed to assess a central feature of melancholia - signs of psychomotor disturbance (PMD) - and so provide an alternate non-symptom based measure of melancholia or of its probability. This review evaluates development and application studies undertaken over the last 25 years to consider how well it has met its original objectives., Methods: All studies published using the CORE measure as either the only or an adjunctive measure of melancholia were obtained and are considered in this review., Results: Findings suggest high reliability in quantifying CORE scores can be achieved and that it has construct validity as a measure of PMD. A number of application studies assessing socio-demographic factors, cognitive and motor impairment, dexamethasone suppression and thyrotropin-releasing hormone, response to psychotherapy and to electroconvulsive therapy support its validity as a measure of melancholia, while functional brain imaging studies suggest that the measure identifies regions of decreased connectivity., Limitations: Use of the CORE benefits from rater training and for subjects to be assessed at or near nadir of their depressive episode. There have been insufficient studies evaluating genetic factors, and the treatment response of CORE-defined melancholic patients to antidepressant drugs of differing classes., Conclusions: The CORE, either as a proxy or direct measure of melancholia, provides a strategy for assigning depressed subjects a diagnosis or melancholic or non-melancholic depression or for estimating the probability of melancholia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

There is accruing clinical and empirical evidence supporting the efficacy of lamotrigine as a treatment for bipolar II disorder. However, the treatment response experienced by those with 'short duration' hypomania (or 'other specified' bipolar disorder) has been under-researched. We reviewed a clinical sample of 123 patients diagnosed with a bipolar II disorder three months following their initial assessment. A research interview evaluated treatment strategies implemented, depressive and hypomanic episode pattern and functional outcomes. Of patients who had achieved a minimum level of 75 mg of lamotrigine, n = 51 were assigned to the BP II disorder group (i.e., hypomanic episodes lasted four days or longer) and n = 28 to the short duration group (i.e., hypomanic episodes always lasted less than four days). There were no significant differences between the two groups at the three-month follow-up on self-report measures of changes in depressive and hypomanic episode pattern or functioning across six domains (i.e., intimate relationships, family relationships, friendships, work relationships, work performance, overall quality of life), and with the majority of patients reporting some level of improvement. Study limitations include being an observational, uncontrolled design with a relatively small sample size for detecting statistical differences. Nonetheless, lamotrigine appeared to be a suitable medication to be trialled in patients who alternate between depressive episodes and short periods of hypomania, (as for those with DSM-defined hypomanic episodes), and should prompt further investigation., (© The Author(s) 2016.)

There are generic measures available to assess functional impairment associated with clinical conditions, but no measure has been developed to specifically evaluate consequences of differing mood disorders, our current objective. In this study, 208 participants took part in a research interview which aimed to differentiate clinical depression from non-clinical mood states. The 126 participants who met diagnostic criteria for clinical depression (i.e., bipolar disorder, melancholic depression or non-melancholic depression) were asked to judge whether they had experienced any of 24 consequences of their depressive episodes with the measure focusing on occupational, personal and interpersonal functioning. Such consequences were affirmed by 100% of participants diagnosed with bipolar disorder, 84% of those experiencing melancholic depression and 74% of those who had experienced a non-melancholic depressive episode. Results from a three-factor solution were consistent with the expected domains (i.e. work and relationships; self-care and daily functioning; intimate relationships and coping), and had sound goodness of fit properties. Participants with bipolar disorder were more likely to affirm each item compared to participants with unipolar depression, and participants with melancholic depression affirmed each item at a higher rate than participants who had experienced non-melancholic episodes. The new measure (the Consequences of Depression Scale; CODS) could be utilised in research and clinical activities seeking to identify and quantify the personal and economic burden of mood disorders, and provides an additional perspective for evaluating the impact of mood disorders on interpersonal, personal and occupational functioning., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To detail the disconnect between the quantified efficacy of the mood stabilizer lamotrigine in its registration controlled trials and its later judged clinical effectiveness and consider some determinants of disconnects between some efficacy trial findings and 'real-world' clinical effectiveness judgments., Method: Published articles considering lamotrigine as a treatment for the bipolar I or II disorders were selected for review. While randomized controlled trials were weighted, we also consider open trials and effectiveness observations from clinician researchers and demonstrate that lamotrigine has been quite variably judged over time., Results: We suggest that the early trials evaluating lamotrigine for acute bipolar disorder depression focused on a suboptimal clinical target, and in so doing, ensured less lamotrigine efficacy compared with trials of bipolar disorder preventative treatment. Moreover, a number of additional methodological limitations compromised analyses. We also detail variable reporting of actual study results. The initial sharp disconnect (between efficacy and effectiveness judgments) has narrowed as lamotrigine has been evaluated and progressively taken up as a maintenance mood stabilizer., Conclusion: The lamotrigine disconnect story provides a number of salutary lessons that are salient to evaluating the effectiveness and ecological niche of any psychotropic medication. The lamotrigine story presented here argues strongly for the wisdom of encouraging an iterative process between efficacy studies and clinical observation., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Studies suggest that differentiating melancholic from non-melancholic depressive disorders is advanced by use of illness course as well as symptom variables but, in practice, potentially differentiating variables are generally positioned as having equal value. Judging that differentiating features are more likely to vary in their signal intensity, we sought to determine the number of features required to effect differentiation and their hierarchical order., Methods: The 24-item clinician-rated Sydney Melancholia Prototype Index (SMPI-CR) was completed for 364 unipolar depressed patients. The sample was divided into two cohorts according to the recruitment period. An RPART classification tree analysis identified the most discriminating SMPI items in the development sample of 197 patients, and examined the sensitivity and specificity of the diagnostic decisions, then sought to replicate findings in a validation sample of 169 patients., Results: Independent analyses of putative SMPI items identified only seven items as required to discriminate those with clinically-diagnosed melancholic or non-melancholic depression when the conditions were examined separately. An RPART analysis considering differentiation of melancholic and non-melancholic depression in the total samples retained five of those items in the classification tree, three of which were non-symptom items, and with 92% sensitivity and 80% specificity in the development sample. This reduced item set showed 93% sensitivity and 82% specificity in the validation sample., Limitations: Our clinical judgment of melancholic or non-melancholic depression may not correspond with the clinical logic employed by other clinicians., Conclusion: Only five SMPI items were required to derive a succinct and efficient decision tree, comprising high sensitivity and specificity in differentiating melancholic and non-melancholic depression. Current study findings provide an empirical model that could enrich clinicians׳ approach to differentiating melancholic and non-melancholic depression., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The independence or interdependence of grief and major depression has been keenly argued in relation to recent DSM definitions and encouraged the current study., Methods: We report a phenomenological study seeking to identify the experiential and phenomenological differences between depression and grief as judged qualitatively by those who had experienced clinical (n=125) or non-clinical depressive states (n=28)., Results: Analyses involving the whole sample indicated that, in contrast to grief, depression involved feelings of hopelessness and helplessness, being endless and was associated with a lack of control, having an internal self-focus impacting on self-esteem, being more severe and stressful, being marked by physical symptoms and often lacking a justifiable cause. Grief was distinguished from depression by the individual viewing their experience as natural and to be expected, a consequence of a loss, and with an external focus (i.e. the loss of the other). Some identified differences may have reflected the impact of depressive "type" (e.g. melancholia) rather than depression per se, and argue for a two-tiered model differentiating normative depressive and grief states at their base level and then "clinical" depressive and 'pathological' grief states by their associated clinical features., Limitations: Comparative analyses between the clinical and non-clinical groups were limited by the latter sub-set being few in number. The provision of definitions may have shaped subjects׳ nominated differentiating features., Conclusion: The study identified a distinct number of phenomenological and clinical differences between grief and depression and few shared features, but more importantly, argued for the development of a two-tiered model defining both base states and clinical expressions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The apoplast is a distinct extracellular compartment in plant tissues that lies outside the plasma membrane and includes the cell wall. The apoplastic compartment of plant leaves is the site of several important biological processes, including cell wall formation, cellular nutrient and water uptake and export, plant-endophyte interactions and defence responses to pathogens. The infiltration-centrifugation method is well established as a robust technique for the analysis of the soluble apoplast composition of various plant species. The fluid obtained by this method is commonly known as apoplast washing fluid (AWF). The following protocol describes an optimized vacuum infiltration and centrifugation method for AWF extraction from Phaseolus vulgaris (French bean) cv. Tendergreen leaves. The limitations of this method and the optimization of the protocol for other plant species are discussed. Recovered AWF can be used in a wide range of downstream experiments that seek to characterize the composition of the apoplast and how it varies in response to plant species and genotype, plant development and environmental conditions, or to determine how microorganisms grow in apoplast fluid and respond to changes in its composition.

The Hypomanic Personality Scale (HPS) was designed to measure a predispositional personality style to bipolar disorder. Its properties have largely been assessed in non-clinical samples. We undertook a number of analyses to determine if it is likely to be a measure of actual personality style or is confounded by items capturing hypomanic/manic mood symptoms. A total of 112 bipolar and 164 unipolar patients completed the measure. Several principal components analyses were undertaken and associations were examined between HPS items and scores on a measure designed to identify bipolar disorder--the Mood Swings Questionnaire (MSQ). Principal components analyses generated a similar set of four factors in both the unipolar and bipolar sample sub-sets and congruent with previous analyses undertaken in non-clinical samples, suggesting identification of normative dimensions that underpin hypomanic and manic mood states. A number of HPS items correlated highly with the MSQ. Results suggest that HPS is unlikely to simply be a measure of personality style and appears strongly confounded by hypomanic/manic mood symptoms. The measure may therefore--in its current form--be inappropriate for at-risk research seeking to determine the capacity of personality style to predict onset of a bipolar disorder., (Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.)

Introduction: There are commonly long delays between the onset of bipolar disorder (BP), seeking of treatment and acquiring a bipolar disorder diagnosis. Whether a longer duration of undiagnosed bipolar disorder (DUBP) leads to an inferior treatment response is unclear in the literature., Method: We conducted two studies with independent samples of BP patients who had received a first-time diagnosis of BP - first investigating whether DUBP was related to clinical and social outcomes at the time of assessment (n=173) and, second, whether response to mood stabiliser medication was affected by DUBP when assessed three months following assessment and intervention (n=64)., Results: Participants׳ mean DUBP was 18-20 years (from the onset of mood episodes). After controlling for age, a longer DUBP was associated with employment difficulties, whereas a shorter DUBP was associated with a history of engaging in self-harm behaviours, as well as a reduced likelihood of experiencing social costs as consequence of the mood disorder. The majority of study variables were statistically unrelated to DUBP. In a multivariate analysis, age was the only predictor variable to make a significant contribution to the DUBP (33%). Across the 3-month intervention period, participants improved significantly on all but one outcome measure. The participants׳ likelihood to improve, become worse or experience minimal/no change over the study period was not significantly related to the DUBP., Limitations: Self-reporting poses a risk to measurement precision. Being a naturalistic observation, no specific dose of medication was prescribed. The small sample of BP I patients provided insufficient statistical power to undertake meaningful separate analyses of the BP I and BP II participants., Conclusion: Early detection and intervention remains important for helping to reduce morbidity and risks associated with untreated BP. However, the variation in DUBP was mostly a function of age and did not substantially affect clinical status at assessment, or lead to an inferior response to mood stabilising medication., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Gender differences in rates of bipolar disorder have been described, with most studies reporting males as over-represented in those diagnosed with a bipolar I disorder and females over-represented in those diagnosed with a bipolar II disorder. This could reflect true differences in prevalence or measurement error emerging from screening or case-finding measures. We examine the possible contribution of the latter by examining one screening measure-the Mood Swings Questionnaire (MSQ)., Methods: We analyse MSQ data from a large sample of age- and gender-matched bipolar I and bipolar II patients (and their composite group). Gender differences were examined in terms of prevalence and severity of MSQ symptoms, MSQ sub-scales scores and total MSQ scores, employing univariate and differential item functioning (DIF) analyses., Results: Both male and female bipolar I patients reported higher total MSQ and higher mysticism MSQ sub-scale scores than their male and female bipolar II counterparts. There were no gender differences when bipolar I, bipolar II and composite bipolar groups were separately examined on both total and sub-scale MSQ scores, suggesting that gender does not impact on MSQ scoring. When item analyses of bipolar I and II groups were undertaken separately, a number of differences emerged, but as few were consistent across bipolar sub-types such differences could reflect chance and failure to control for multiple comparisons. The over-representation of some items in females and some in males may have contributed to the comparable total and sub-scale scores., Limitations: Large sample size and only one measure (i.e. MSQ) examined., Conclusion: As total and sub-scale MSQ scores were uninfluenced by gender we can conclude that this screening test is not confounded by gender and, if representative of other such screening measures, would indicate that any differential prevalence of the bipolar disorders identified in community studies possibly reflects gender differences in their occurrence rather than artefactual consequences of screening measures having a gender bias., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: This paper seeks to determine the relevance and likely salience of cognitive behaviour therapy (CBT) as a treatment for melancholic depression., Methods: The findings of a randomised trial comparing 12-week outcome of 18 patients with melancholic depression receiving antidepressant medication and 11 receiving CBT were evaluated, and qualitative explanations for the outcomes were provided principally by the treating CBT practitioners., Results: In the trial, CBT showed no improvement in depression severity in the first four weeks and then some level of improvement over the subsequent eight weeks. Outcome was superior for those receiving antidepressant medication at 12 weeks and was first demonstrated at four weeks. The benefits of CBT appeared to be in settling anxiety, dealing with cognitive processing of having a melancholic depression and addressing any personality vulnerabilities., Conclusion: While a pilot study, our qualitative reports indicate that CBT may provide a useful role in managing melancholia as an adjunct to antidepressant medication. Future studies examining such a combination treatment model should seek to determine if indicative data provided here argue for a sequencing model of CBT being introduced after medication has addressed core biological underpinnings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Bipolar (BP) disorder has been linked to creativity following investigation of prominent artists and controlled trials of creativity in BP disorder patients. However, it is unclear whether creativity is differentially expressed across the BP I and BP II subtypes., Methods: 219 patients (aged 19-63 years) diagnosed with BP disorder by clinical interview and DSM-IV criteria were asked whether they tended to be more creative during hypo/manic episodes, and answered five questions about personality styles associated with creativity. Qualitative analyses were performed on a smaller subset of 69 BP patients (n=19 BP I, n=50 BP II) who provided written responses of the types of creative activities engaged in when hypo/manic and any perceived advantages or disadvantages of their creative pursuits., Results: 82% of BP patients affirmed being creative when hypo/manic, with comparable results for the BP I and BP II subtypes (84% and 81% respectively). Both BP subtypes engaged mostly in writing, painting, work or business ideas and 'other' forms of art; however BP II patients were more likely to draw and be musical. Both subgroups reported the consequences of feeling good, being productive or quitting their project. BP I patients were more likely to overspend during their creative highs while BP II patients were more likely to experience improved focus and clarity. BP patients affirming creative highs were significantly more likely to report creative personality styles more generally outside of a mood episode., Limitations: BP patients' self-reported creative activities were not retrospectively judged for quality or originality and so may reflect common creative abilities rather than exceptional quality. The impact of depressive episodes on creativity was not assessed. Uneven sample sizes in the BP I and BP II subgroups may have compromised statistical power., Conclusion: Creativity during hypo/manic episodes was extremely common in both BP subtypes. While some nuances in activity type and outcomes were observed, no significant creative phenotype specific to BP I or BP II disorder emerged., (Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.)

Multiple approaches have been adopted in an attempt to effectively identify and discriminate melancholic and non-melancholic depressive subtypes. We recently developed the Sydney Melancholia Prototype Index (SMPI) which incorporates antecedent and illness course variables as well as symptoms, with clinician-rated and self-rated SMPI versions, and with the former having been shown to have superior sensitivity and specificity in discriminating melancholic from non-melancholic depression. The aim of this study was to further evaluate the capacity of the SMPI to identify melancholia in comparison to DSM-based and clinician-judged assignments. The sample comprised 214 patients diagnosed with melancholic or non-melancholic depression according to a detailed clinical assessment and by the Mini International Neuropsychiatric Structured Interview (MINI) assessing formal DSM-IV melancholia criteria. DSM-IV assignment to melancholic versus non-melancholic depression was contrasted with clinician-judged allocation, the combination of these two strategies ("concordant diagnoses"), and to the SMPI (CR or clinician-rated and SR or self-report versions), with the likely validity of each approach examined against historical ascriptions for melancholia. DSM-IV criteria assigned the highest percentage of the sample with a melancholic diagnosis (64%), whereas the SMPI-SR assigned the smallest percentage with a melancholic diagnosis (37%). DSM-IV assignment was associated with the fewest number of validating variables, whilst SMPI-CR and independent clinician diagnosis were associated with the greatest number of differentiating variables including negative childhood experiences, past and recent stressors, satisfaction with life and perceived social support. These comparative analyses provide further support for the SMPI-CR in identifying and discriminating melancholic depression from non-melancholic depression. Replication of these findings in other samples with independent raters is recommended., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: DSM-IV criteria for mania/hypomania overlap considerably. We sought to examine the utility of a model differentiating bipolar I and II disorders by weighting the presence or absence of psychosis during manic/hypomanic episodes as opposed to simply weighting symptom severity., Methods: A set of 632 patients with a so-assigned clinical bipolar I or II disorder diagnosis contributed to the principal analyses, and a subset of 210 was included in a comparative analyses of DSM-assigned diagnoses. We also examined the impact of duration of highs on symptom patterns and the extent to which depressive episodes were psychotic or non-psychotic melancholic in type., Results: There were no group differences for bipolar I and II patients (clinical or DSM groups) by age, gender, age of onset or age of formal bipolar diagnosis. Clinically assigned bipolar I patients returned higher severity scores than bipolar II patients on manic/hypomanic symptoms, but such differentiation was limited. Clinically-assigned bipolar I patients were more likely than bipolar II patients to be diagnosed with psychotic depression, and had lower rates of non-melancholic depression. Duration of highs had some impact on the phenomenology of highs, but not on the phenomenology of depression., Limitations: We cannot establish the degree to which clinicians validly differentiated those with bipolar disorder, and accurately judged the lifetime presence of psychotic features and of depressive subtype differentiation., Conclusions: Findings support the utility of an alternative model to DSM-IV in weighting the respective presence or absence of psychotic symptoms during highs in differentiating bipolar I and II disorders., (© 2013 Elsevier B.V. All rights reserved.)

Background: While there have been many studies comparing direct and indirect costs engendered individually and nationally by those with unipolar (UP) and bipolar (BP) disorders, there has been no previous study comparing costs across the bipolar I (BP I) and bipolar II (BP II) disorders., Methods: We examine direct and indirect costs attributable to a mood disorder in a sample of 44 BP I, 102 BP II and 279 UP patients attending a tertiary referral clinic, and with comparable illness durations of some 20 years and comparable treatment durations. We calculated direct and indirect costs incurred for their lifetime of illness based on relevant cost structures, in Australian dollars., Results: The mean lifetime indirect costs for BP I patients was $134,318, as against $76,821 for BP II and $68,347 for UP patients, joining with respective health care costs of $26,353, $17,580 and $27, 237, to generate total costs of $160,671/BP I patient, $94,401/BP II patient and $95,584/UP patient. BP I patients differentiated most distinctly in costs as a consequence of a higher prevalence of government benefits, time off work and longer periods in hospital. UP patients had more stable work histories than both BP sub-sets. BP II patients were less likely to be hospitalised than both the BP I and UP patients., Limitations: Being drawn from a tertiary referral clinic, the study sample is not necessarily representative, with this nuance potentially having influenced cost differences between groups., Conclusions: This is the first cost of illness study directly comparing BP I and BP II patients (and with an additional comparison group of UP patients). Findings indicate that BP I illness generates more direct and indirect costs than BP II illness, while the latter was generally comparable with UP depression in terms of the lifetime cost., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Clinical differentiation of bipolar conditions (and especially bipolar II disorder) from unipolar conditions is not always straightforward. We sought to identify illness antecedents and correlates that may assist their differentiation and complement clinical symptoms., Methods: We undertook detailed comparative analyses of comprehensive data obtained from patients diagnosed with a bipolar or unipolar mood disorder., Results: The sample comprised 138 bipolar (45 bipolar I and 93 bipolar II) and 214 unipolar participants. Univariate analyses identified numerous differentiating variables, while multivariate analyses generated a refined variable list to determine discriminatory capacity. Controlling for all other factors, those with a bipolar (I or II) condition were more likely than the unipolar sub-set to report a family history of bipolar disorder, experiencing bullying at school, to make a suicide/self-harm attempt, and be less likely to be clinically judged as having 'problematic' personality traits. Factors differentiating bipolar II from unipolar sub-sets included the aforementioned variables, as well as higher rates of lifetime heavy drinking and female gender, and briefer depressive episodes in the bipolar II group. Bipolar I and II sub-sets differentiated solely by higher rates of hospitalization in the former group., Limitations: Some study variables (e.g., hospitalization) may merely reflect DSM-IV diagnostic criteria or consequences rather than illness antecedents or correlates. Other self-reported variables (e.g., bullying) are subject to memory biases, and may reflect higher-order variables (e.g., early problematic personality traits)., Conclusions: Study findings provide assistance to determining non-symptom features that may improve discrimination of the bipolar disorders from themselves and from unipolar conditions., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Numerous studies have considered whether bipolar depression is phenomenologically similar or different to unipolar depression. While there have been some relatively consistent individual features identified, no clear clinical phenotype has been defined for bipolar depression., Methods: A self-report and clinician-rated measure of the Sydney Melancholia Prototype Index ('SMPI') was used to assess prototypic features of melancholic and non-melancholic depression in a sample of 901 patients clinically diagnosed with bipolar disorder or unipolar depression. The majority also completed a self-report (SDS) severity of depression measure, and provided current and historical data on depression, anxiety, global functioning and stressor severity., Results: Comparative analyses favoured the SMPI-CR above the SMPI-SR measure in terms of discriminatory strengths. The previously determined SMPI-CR difference score cut-off of 4 or more for differentiating melancholic from non-melancholic depression was replicated in this larger sample. SMPI item and prototypic pattern analyses indicated that bipolar depression corresponded closely to unipolar melancholic depression in terms of clinical pattern features but not in regard to a number of socio-demographic, illness course and correlate variables. 'Atypical features' were common across bipolar and unipolar disorders, but somewhat more prevalent in bipolar disorder., Limitations: There was no distinction made for the bipolar group between subtypes I and II, with the study simply comparing bipolar with unipolar disorders. The apparent superiority of the clinician-rated in comparison to the SMPI-SR measure may reflect a clinician judgement bias., Conclusions: The SMPI-CR measure indicated that bipolar depression corresponds closely to melancholic depression in terms of its clinical phenotype., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To assess whether psychiatrists in the community operate to a sub-typing model of mood disorders when choosing psychotropic medications., Method: Patients assessed through the Black Dog Institute depression clinic provided information on their previously prescribed and current medications, on how effective they found them and whether they had to be ceased due to side-effects. The prevalence of each medication trialled was analysed according to diagnosis (bipolar I, bipolar II, unipolar melancholic depression or unipolar non-melancholic depression)., Results: Analyses indicate that psychiatrists prescribe medications differentially in line with diagnosis. This effect was found in both previously prescribed and currently prescribed medications, and was most distinct for mood stabiliser and antipsychotic medications. Several medications, in contrast, appeared to have been trialled by the majority of patients, regardless of diagnosis. Analyses of effectiveness and cessation due to side-effects were compromised by small sub-sample sizes., Conclusions: Psychiatrists in the community appear to operate to a sub-typing model of mood disorders, preferentially prescribing many medications according to mood disorder sub-type.

Background: Melancholia is positioned as either a more severe expression of clinical depression or as a separate entity. Support for the latter view emerges from differential causal factors and treatment responsiveness but has not been convincingly demonstrated in terms of differential clinical features. We pursue its prototypic clinical pattern to determine if this advances its delineation., Methods: We developed a 24-item measure (now termed the Sydney Melancholia Prototype Index or SMPI) comprising 12 melancholic and 12 non-melancholic prototypic features (both symptoms and illness correlates). In this evaluative study, 278 patients referred for tertiary level assessment at a specialized mood disorders clinic completed the self-report SMPI as well as a depression severity measure and a comprehensive assessment schedule before clinical interview, while assessing clinicians completed a clinician version of the SMPI items following their interview. The independent variable (diagnostic gold standard) was the clinician's judgment of a melancholic versus non-melancholic depressive episode. Discriminative performance was evaluated by Receiver Operating Characteristics (ROC) analysis of four strategies for operationalising the SMPI self-report and SMPI clinician measures, and with the former strategies compared to ROC analysis of the depression severity measure. The external validity of the optimally discriminating scores on each measure was tested against a range of clinical variables., Result: Comparison of the two self-report measures established that the SMPI provided greater discrimination than the depression severity measure, while comparison of the self-report and clinician-rated SMPI measures established the latter as more discriminating of clinically diagnosed melancholic or non-melancholic depression. ROC analyses favoured self-report SMPI distinction of melancholic from non-melancholic depression being most optimally calculated by a 'difference' score of at least four or more melancholic than non-melancholic items being affirmed (sensitivity of 0.69, specificity of 0.77). For the clinician-rated SMPI measure, ROC analyses confirmed the same optimal difference score of four or more as highly discriminating of melancholic and non-melancholic depression (sensitivity of 0.84, specificity of 0.92). As the difference score had positive predictive values of 0.90 and 0.70 (for the respective clinician-rated and self-report SMPI forms) and respective negative predictive values of 0.88 and 0.70, we conclude that the clinician-rated version had superior discrimination than the self-report version. External validating data quantified the self-rated and clinician-rated Index-assigned non-melancholic patients having a higher prevalence of anxiety disorders, a higher number of current and lifetime stressors, as well as elevated scores on several personality styles that are viewed as predisposing to and shaping such non-melancholic disorders., Limitations: Assigned melancholic and non-melancholic diagnoses were determined by clinician judgement, risking a circularity bias across diagnostic assignment and clinical weighting of melancholic and non-melancholic features. The robustness of the Index requires testing in primary and secondary levels of care settings., Conclusions: The clinician-rated SMPI differentiated melancholic and non-melancholic depressed subjects at a higher level of confidence than the self-report SMPI, and with a highly acceptable level of discrimination. The measure is recommended for further testing of its intrinsic and applied properties., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Over the last three decades, cyclothymia has been positioned in one of two principal ways: formally classified as a mood disorder, and less formally categorized at a "cyclothymic temperament" (CT) level. This review considers its historic evolution and provides five models for conceptualizing independence or interdependence between cyclothymia as a temperament style and as a formal mood disorder. Findings argue for CT to be conceded and appropriately defined. Secondly, it is recommended that cyclothymia's expression as a mood disorder should be positioned within the bipolar II disorder class-albeit perhaps having briefer mood swings and fewer episodes, more rapid cycling, and greater reactivity to environmental factors than is conceptualized currently for bipolar II disorders. By allowing cyclothymia both axis I and axis II status (although necessitating differing terminology), research evaluating any shared biological underpinnings and any predisposition provided by the CT temperament style to a later formalized bipolar II condition would be advanced., (© 2012 Wiley Periodicals, Inc.)

Background: There is limited research examining temperament and personality in bipolar II disorder. We sought to determine any over-represented temperament and personality features in bipolar II disorder compared to other affective groups., Method: Scores on a self-report measure of temperament and personality were examined in a sample of 443 participants diagnosed with unipolar, bipolar I and bipolar II disorder., Results: After controlling for age, gender, age of depression onset and current depression severity, those with bipolar II disorder were characterized by higher irritability, anxious worrying, self-criticism and interpersonal sensitivity scores, and with lower social avoidance scores compared to unipolar participants. No differences were found between bipolar sub-types on any temperament and personality sub-scales. Limitations included the lack of a control group, a relatively small sample of bipolar I participants, and with the cross-sectional design disallowing conclusions regarding premorbid personality traits as opposed to illness 'scarring' effects., Conclusions: Further research should seek to clarify whether certain temperament and personality styles are over-represented in bipolar II disorder. Any over-represented characteristics may assist with diagnostic differentiation from phenomenologically similar conditions and lead to more appropriate clinical management., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The capacity of visual working memory (WM) is substantially limited and only a fraction of what we see is maintained as a temporary trace. The process of binding visual features has been proposed as an adaptive means of minimising information demands on WM. However the neural mechanisms underlying this process, and its modulation by task and load effects, are not well understood., Objective: To investigate the neural correlates of feature binding and its modulation by WM load during the sequential phases of encoding, maintenance and retrieval., Methods and Findings: 18 young healthy participants performed a visuospatial WM task with independent factors of load and feature conjunction (object identity and position) in an event-related functional MRI study. During stimulus encoding, load-invariant conjunction-related activity was observed in left prefrontal cortex and left hippocampus. During maintenance, greater activity for task demands of feature conjunction versus single features, and for increased load was observed in left-sided regions of the superior occipital cortex, precuneus and superior frontal cortex. Where these effects were expressed in overlapping cortical regions, their combined effect was additive. During retrieval, however, an interaction of load and feature conjunction was observed. This modulation of feature conjunction activity under increased load was expressed through greater deactivation in medial structures identified as part of the default mode network., Conclusions and Significance: The relationship between memory load and feature binding qualitatively differed through each phase of the WM task. Of particular interest was the interaction of these factors observed within regions of the default mode network during retrieval which we interpret as suggesting that at low loads, binding processes may be 'automatic' but at higher loads it becomes a resource-intensive process leading to disengagement of activity in this network. These findings provide new insights into how feature binding operates within the capacity-limited WM system.

Aim: To investigate dynamic changes in functional brain activity in mild cognitive impairment (MCI) in response to a graded working memory (WM) challenge with increasing memory load., Methods: In an event-related functional magnetic resonance imaging (fMRI) study, 35 MCI and 22 cognitively normal subjects performed a visuospatial associative WM task with 3 load levels. Potential performance differences were controlled for by individually calibrating the number of items presented at each load., Results: An interaction between group and WM load was observed during stimulus encoding. At lower loads, greater activity in the right anterior cingulate and right precuneus was observed in MCI subjects. As the load increased to higher levels, reduced activation in these regions and greater deactivation in the posterior cingulate-medial precuneus were observed in MCI compared to control subjects. Stronger expression of load-related patterns of activation and deactivation in MCI subjects was associated with greater clinical severity and a more abnormal pattern of performance variability., Conclusion: Patterns of overactivation, underactivation and deactivation during successful encoding in MCI subjects were dependent on WM load. This type of graded cognitive challenge may operate like a 'memory stress test' in MCI and may be a useful biomarker of disease at the pre-dementia stage., (Copyright © 2011 S. Karger AG, Basel.)