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Background: Peripheral inflammation has been associated with major depression, however there is a paucity of studies examining whether inflammatory profiles differ across depressive subtypes. The current study sought to compare peripheral inflammatory markers in patients with melancholic versus non-melancholic depression and with healthy controls., Method: Eighty outpatients with a current major depressive episode (MDE) were assigned as having a melancholic or a non-melancholic depressive subtype based on clinician diagnosis and the Sydney Melancholic Prototypic Index (SMPI). Participants provided peripheral venous blood from which plasma levels of cytokines and other inflammatory markers (C-reactive protein (CRP), neutrophil/lymphocyte ratio, plasma cytokines) were compared across the two patient groups and also to a group of 81 age-matched healthy controls., Results: Patients with melancholic and non-melancholic depression demonstrated increased CRP and decreased interferon-gamma (IFN-γ) levels compared to controls. Using clinician diagnosis of subtype, interleukin-12 (IL-12) and interleukin-10 (IL-10) levels were elevated in melancholic patients versus non-melancholic and control groups, with no differences found for the other measured markers of inflammation., Conclusion: Study findings demonstrate shared inflammatory changes across certain inflammatory markers (CRP and IFN-γ) and increases in IL-12 and IL-10 levels specific to melancholic depression. While generally supportive of previous work, our peripheral inflammation findings in melancholic depression are relatively novel and suggest this subgroup may benefit from anti-inflammatory therapies. Further studies are required to replicate these findings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The first monoamine oxidase inhibitors (MAOIs) used for the treatment of depression in the 1950-60s were credited with treating severe melancholic depression (MeD) successfully and greatly reducing the need for electroconvulsive therapy (ECT). Following the hiatus caused by the then ill-understood cheese reaction, MAOI use was relegated to atypical and treatment-resistant depressions only, based on data from insufficiently probing research studies suggesting their comparatively lesser effectiveness in MeD. The siren attraction of new 'better' drugs with different mechanisms amplified this trend. Following a re-evaluation of the data, we suggest that MAOIs are effective in MeD. Additionally, the broad unitary conceptualisation of major depressive disorder (MDD) in the DSM model diminished the chance of demonstrating distinctive responses to different antidepressant drugs (ADs) such as SSRIs, TCAs, and MAOIs, thereby further reducing the interest in MAOIs. More reliable categorical distinction of MeD, disentangling it from MDD, may be possible if more sensitive measuring instruments (CORE, SMPI) are used. We suggest these issues will benefit from re-appraisement via an inductive reasoning process within a binary (rather than a unitary) model for defining the different depressive disorders, allowing for the use of more reliable diagnostic criteria for MeD in particular. We conclude that MAOIs remain essential for, inter alia , TCA-resistant MeD, and should typically be used prior to ECT; additionally, they have a role in maintaining remission in cases treated with ECT (and ketamine/esketamine). We suggest that MAOIs should be utilized earlier in treatment algorithms and with greater regularity than is presently the case., (Copyright © 1964–2023 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

While effectively the 'first antidepressants', the psychostimulants are rarely prescribed as antidepressant drugs seemingly in light of their judged low effectiveness, side effects, tolerance as well as concerns about dependency and abuse. Recent meta-analyses do find some support for them as being effective antidepressants for those with major depression, but they have not been closely evaluated in terms of their specific nuanced role for treating treatment-resistant (unipolar and bipolar) melancholic depression. The author has so prescribed them for over a decade and offers a case for their benefits for a distinct percentage of those with such conditions and notes their relatively few side effects.

Facial affect is expressed dynamically - a giggle, grimace, or an agitated frown. However, the characterisation of human affect has relied almost exclusively on static images. This approach cannot capture the nuances of human communication or support the naturalistic assessment of affective disorders. Using the latest in machine vision and systems modelling, we studied dynamic facial expressions of people viewing emotionally salient film clips. We found that the apparent complexity of dynamic facial expressions can be captured by a small number of simple spatiotemporal states - composites of distinct facial actions, each expressed with a unique spectral fingerprint. Sequential expression of these states is common across individuals viewing the same film stimuli but varies in those with the melancholic subtype of major depressive disorder. This approach provides a platform for translational research, capturing dynamic facial expressions under naturalistic conditions and enabling new quantitative tools for the study of affective disorders and related mental illnesses., Competing Interests: JJ, MC, MH, GP, MB No competing interests declared, (© 2022, Jeganathan et al.)

Psychotic episodes occur in a substantial proportion of patients suffering from major mood disorders (both unipolar and bipolar) at some point in their lives. The nature of these episodes is less well understood than the more common, non-psychotic periods of illness and hence their management is also less sophisticated. This is a concern because the risk of suicide is particularly high in this subtype of mood disorder and comorbidity is far more common. In some cases psychotic symptoms may be signs of a comorbid illness but the relationship of psychotic mood to other forms of psychosis and in particular its interactions with schizophrenia is poorly understood. Therefore, our targeted review draws upon extant research and our combined experience to provide clinical context and a framework for the management of these disorders in real-world practice - taking into consideration both biological and psychological interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To consider how a mental health professional might respond to a newly diagnosed depressed patient who inquires into its potential genetic origins and whether they might pass depression on to their children., Methods: Data are provided on risk and pursuit of genetic pathways., Results: As most studies have focussed on DSM-defined major depression - and which is not an entity - no definitive data are available, while there are some few studies indicating a greater genetic risk in those with melancholic than those with non-melancholic depression., Conclusion: We will not know the genetic contribution to clinical depression unless its key sub-types are evaluated as separate conditions. Findings may assist a clinician's response to an inquiring patient.

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers ( www.psymri.com ). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN., (© 2021. The Author(s).)

Background: Burnout and clinical depression have been variably viewed as synonymous or as distinctly differing entities - but with few distinguishing features provided. Failure to differentiate the two conditions can lead to compromised clinical management. We sought to enhance the differentiation of burnout and clinical depression by assembling a list of candidate differentiating features., Methods: In assembling a set of distinguishing clinical features we compared burnout states against the two principal depressive sub-types (i.e. melancholic and non-melancholic depression) rather than against 'major depression' per se. Our candidate features were assembled from a review of salient literature, our clinical observations and from a sub-sample of subjects who self-identified as having experienced both burnout and depression and who volunteered differentiating features., Results: We judged that burnout shares few features with melancholic depression. While burnout and non-melancholic depression share a set of symptoms, differences were greater than commonalities., Limitations: Our findings were based on clinical observation and exploratory research rather than being empirical, and thus future studies are needed to evaluate the validity of our results., Conclusions: We position burnout and clinical depression as categorically distinct and suggest that application of our nominated parameters should assist clinical differentiation of the two syndromes., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To evaluate the development and implementation of clinical practice guidelines for the management of depression globally., Methods: We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries., Findings: We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence., Conclusion: Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes., ((c) 2020 The authors; licensee World Health Organization.)

Objective: A seminal study quantified an increase in placebo (and drug) response rates in antidepressant trials during the eighties, with subsequent key systematic reviews reporting placebo response rates as either having continued to increase or stabilize in trial subjects with major depression. We therefore undertook an additional study examining a more recent period., Method: We analyze response rate data from 121 studies published over the 2001-2015 period and sourced from a previous meta-analysis of antidepressant drugs., Results: Our analyses indicated trends for decreasing placebo response rates over the whole study period. Analyses of consolidated year blocks quantified a significant linear decrease and a significant cubic pattern in placebo response rates. Visual inspection of the yearly data patterns revealed wide fluctuations as well as distinct and correlated peaks and troughs for both placebo and drug responses., Limitations: The key studies we analyzed differed in a number of ways, including selection of inclusion criteria (especially in relation to analyzing published studies alone or together with unpublished studies) and analytic techniques., Conclusions: The markedly fluctuating placebo response patterns evidence an unstable 'signal' so leading principal studies to generate three mutually contradictory conclusions. We suggest that the increase in rates in the 1980s studies reflected the uptake and impact of 'major depression' being used as the diagnostic criterion, while the striking peaks and troughs observable over our study period argue for varying trial characteristics over time or rater biases in judging depression., Competing Interests: Declaration of Competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose of Review: The nosology and management of antidepressant-associated hypomania (AAH) in the treatment of unipolar depression requires clarification. We sought to review recent studies examining AAH, focusing on risk factors, differing explanatory models, and management strategies., Recent Findings: AAH occurs more frequently in those of female gender, younger age, and with a bipolar disorder (BP) family history. Depressive features (e.g., suicidal ideation, psychotic symptoms) in those with AAH were similar to those with established BPs. Explanatory models for AAH describe it as (i) a transient iatrogenic event, (ii) a specific "bipolar III" disorder, (iii) indicative of "conversion" to BP, (iv) acceleration of BP, and (v) coincidental and unrelated to antidepressant medication. Management recommendations include antidepressant cessation, atypical antipsychotic medications, or switching to a mood stabilizer. Determinants and management of AAH in the treatment of unipolar depression requires considerable clarification, likely to be achieved by close clinical review and refined research studies.

Background: Switching antidepressant medications is recommended when an initial antidepressant is not effective, when it is unable to be tolerated or when there are significant drug interactions. The aim of this paper is to review the evidence regarding when to switch antidepressants and the optimal approach to switching., Methods: Clinical and academic experts in mood disorders from Australia and New Zealand (Treatment Algorithm Group, TAG) met to discuss the key considerations regarding switching antidepressants in the treatment of depression and formulate recommendations about switching strategies., Results: While switching is recommended, there is limited data to guide on how best to approach switching antidepressants (e.g. whether to switch within class or out of class), and how to define the best time to consider switching. Broadly, switching within class after non-response is recommended for mild-moderate depression and out-of-class for patients with a more severe depression or melancholia., Limitations: There is a limited evidence-base to draw on to make definitive recommendations on switching approaches., Conclusions: Switching antidepressants is an appropriate strategy to use if there is a minimal response to an initial antidepressant. Further research is required to determine the optimal switching approach., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: We consider how to choose an antidepressant (AD) medication for the treatment of clinical depression., Method: A narrative review was undertaken addressing antidepressant 'choice' considering a range of parameters either weighted by patients and clinicians or suggested in the scientific literature. Findings were synthesised and incorporated with clinical experience into a model to assist AD choice., Results: Efficacy studies comparing ADs offer indicative guidance, while precision psychiatry prediction based on genetics, developmental trauma, neuroimaging, behavioural and cognitive biomarkers, currently has limited clinical utility. Our model offers guidance for AD choice by assessing first for the presence of a depressive subtype or symptom cluster and matching choice of AD class accordingly. Failing this, an AD can be chosen based on depression severity. Within-class choice can be determined by reference to personality style, patient preference, medical or psychiatric comorbidities and side-effect profile., Conclusion: Clarification of AD choice would occur if medications are trialled in specific depressive subtypes rather than using the generic diagnosis of major depressive disorder (MDD). Such 'top-down' methods could be enhanced by 'bottom-up' studies to classify individuals according to symptom clusters and biomarkers with AD efficacy tested in these categories. Both methods could be utilised for personalised AD choice., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.)

Objective: To investigate the extent and reasons contributing to discrepancies between those receiving a DSM as against a clinical diagnosis of a bipolar disorder (BP) and/or a borderline personality disorder (BPD)., Method: We interviewed participants previously receiving a BP or BPD diagnosis, studying those who met DSM or clinical criteria for one or both conditions. We compared the numbers of participants allocated to the three diagnostic categories according to rater strategy to calculate concordance rates and determine reasons for discordance., Results: Rates of assignment to BP, BPD and comorbid BP/BPD varied according to the diagnostic strategy. Concordance rates were reduced as BP disorder duration criteria were relaxed, with discordance mainly arising from clinical allocation of a BP disorder for those DSM assigned as unipolar depression. Rates of BPD allocation varied marginally, with discordance mostly arising from so clinically diagnosed receiving a comorbid BP/BPD DSM diagnosis. Finally, DSM overestimated comorbidity compared with clinician diagnoses. Of central importance, not imposing the DSM duration criteria for BP did not increase the prevalence of misdiagnosing BPD, a finding at variance with the literature., Conclusion: Rates and reasons for discordance between clinical and DSM diagnosis are detailed, which should assist clinical decision-making., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 examine the evidence for shared pathophysiological pathways in acute coronary syndrome and major depression and to conceptualise the dynamic interplay of biological systems and signalling pathways that link acute coronary syndrome and depression within a framework of neuro-visceral integration., Methods: Relevant articles were sourced via a search of published literature from MEDLINE, EMBASE and PubMed using a variety of search terms relating to biological connections between acute coronary syndrome and depression. Additional articles from bibliographies of retrieved papers were assessed and included where relevant., Results: Despite considerable research efforts, a clear understanding of the biological processes connecting acute coronary syndrome and depression has not been achieved. Shared abnormalities are evident across the immune, platelet/endothelial and autonomic/stress-response systems. From the available evidence, it seems unlikely that a single explanatory model could account for the complex interactions of biological pathways driving the pathophysiology of these disorders and their comorbidity., Conclusion: A broader conceptual framework of mind-body or neuro-visceral integration that can incorporate the existence of several causative scenarios may be more useful in directing future research and treatment approaches for acute coronary syndrome-associated depression., (© The Royal Australian and New Zealand College of Psychiatrists 2015.)

Background: Anhedonia represents a core symptom of major depression and may be a potential marker for melancholia. However, current understanding of this construct in depressive sub-types is limited., Method: Participants were recruited from the Black Dog Institute (Sydney) and Massachusetts General Hospital (Boston). Diagnostic groups were derived on the basis of agreement between clinician and DSM-IV diagnosis from structured interviews. Currently depressed unipolar melancholic, non-melancholic and healthy control participants were administered a probabilistic reward task (PRT) to assess a behavioural correlate of anhedonia-blunted reward-based learning. Self-reported measures of anhedonia, approach and avoidance motivation were completed by the Sydney sample., Results: Relative to healthy controls and non-melancholic participants, melancholic depressed participants had reduced response bias, highlighting blunted reward learning. Moreover, although non-melancholic participants were characterized by a delayed response bias, melancholic depressed participants failed to develop a bias throughout blocks. Response bias showed no associations with self-report measures of hedonic tone in depressed participants. Positive associations were observed between response bias, approach and avoidance motivation in non-melancholic participants only., Limitations: Possible medication, fatigue and anxiety effects were not controlled; small sample sizes; inclusion criteria may have excluded those with severe melancholia and led to underestimation of group differences., Conclusions: Melancholia is characterised by a reduced ability to modulate behaviour as a function of reward, and the motivational salience of rewarding stimuli may differ across depressive sub-types. Results support the view that melancholia is a distinct sub-type. Further exploration of reward system functioning in depressive sub-types is warranted., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Lifetime rates of depression are distinctly higher in women reflecting both real and artefactual influences. Most prevalence studies quantifying a female preponderance have examined severity-based diagnostic groups such as major depression or dysthymia. We examined gender differences across three depressive sub-type conditions using four differing measures to determine whether any gender differences emerge more from severity or symptom prevalence, reflect nuances of the particular measure, or whether depressive sub-type is influential., Methods: A large clinical sample was recruited. Patients completed two severity-weighted depression measures: the Depression in the Medically Ill 10 (DMI-10) and Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR) and two measures weighting symptoms and illness correlates of melancholic and non-melancholic depressive disorders - the Severity of Depressive Symptoms (SDS) and Sydney Melancholia Prototype Index (SMPI). Analyses were undertaken of three diagnostic groups comprising those with unipolar melancholic, unipolar non-melancholic and bipolar depressive conditions., Results: Women in the two unipolar groups scored only marginally (and non-significantly) higher than men on the depression severity measures. Women in the bipolar depression group, did however, score significantly higher than men on depression severity. On measures weighted to assessing melancholic and non-melancholic symptoms, there were relatively few gender differences identified in the melancholic and non-melancholic sub-sets, while more gender differences were quantified in the bipolar sub-set. The symptoms most commonly and consistently differentiating by gender were those assessing appetite/weight change and psychomotor disturbance., Conclusion: Our analyses of several measures and the minimal differentiation of depressive symptoms and symptom severity argues against any female preponderance in unipolar depression being contributed to distinctly by these depression rating measures. Our analyses indicated that gender had minimal if any impact on depression severity estimates. Gender differences in depressive symptoms and severity were more distinctive in bipolar patients, a finding seemingly not previously identified or reported., Limitations: The study had considerable power reflecting large sample sizes and thus risks assigning significant differences where none truly exist, although we repeated analyses after controlling for the type I error rate., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The definition and delineation of melancholia have remained elusive for an extended period. A longstanding signal of psychomotor disturbance has been operationalized via the observer-rated CORE measure and with CORE-assigned melancholic and nonmelancholic compared in several Australian studies. Replication studies in other regions have not previously been reported. This study compares Brazilian patients with melancholic and nonmelancholic depression according to the CORE measure of psychomotor disturbance in terms of clinical characteristics, suicide ideation, stressful life events, quality of life, parental care, and personality styles., Methods: A total of 181 patients with unipolar major depression attending a tertiary care outpatient service in Brazil were evaluated in relation to melancholic status and study variables., Results: The CORE-assigned melancholic patients presented higher symptom severity, greater prevalence of suicide ideation, and Axis I comorbidities than nonmelancholics. Scores of dysfunctional personality styles and dysfunctional parental care measures were also higher among melancholics. Quality-of-life scores were low in both groups., Limitations: The absence of a criterion standard for the diagnosis of melancholia and the use of medication can be potential limitations of the study., Conclusion: Differences suggest that CORE-assigned melancholia defines a distinct group of patients and probably a disorder distinct from nonmelancholic depression not only in quantitative but also in qualitative aspects., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Since its introduction in DSM-III, the validity of dysthymia has been debated. Our objective is to further examine the concept of dysthymia in an outpatient sample, and explore whether its constituents can be meaningfully apportioned., Methods: 318 patients attending the Black Dog Institute Depression Clinic were assessed by the Mini-International Neuropsychiatric Interview, and completed several self-report measures, in addition to a clinical assessment by an Institute psychiatrist. The characteristics of patients with major depressive disorder (MDD), dysthymic disorder and double depression were examined. Latent Class Analysis (LCA) and Latent Profile Analysis (LPA) were then conducted with the aim of detecting distinct classes based on depressive symptomatology and personality domains, respectively. Finally, clinicians' formulations of the study patients were examined., Results: Depression groups mainly differed on parameters of severity. Although LCA and LPA analyses indicated the presence of distinct classes, these only moderately correlated with the MINI-diagnosed groups. Finally, there was evidence for considerable heterogeneity within clinicians' formulations of dysthymia., Limitations: Inadequate sample numbers for various measures limited the power of the LPA and our sample was weighted to patients with a more severe depressive condition which may affect the detection of a distinct 'dysthymic' personality profile., Conclusions: Despite employing a variety of techniques, we were unable to obtain a clear homogeneous picture of dysthymia. Rather, there was evidence for a distinct heterogeneity in clinician-derived diagnoses. These findings allude to the questionable discriminant validity of dysthymia and may encourage future research and discussion on this important topic., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: This paper aims to present an overview of screening and safety considerations for the treatment of clinical depressive disorders and make recommendations for safety monitoring., Method: Data were sourced by a literature search using MEDLINE and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content., Results: Screening and monitoring can detect medical causes of depression. Specific adverse effects associated with antidepressant treatments may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment., Conclusion: The adoption of safety monitoring guidelines when treating clinical depression is likely to improve overall physical health status and treatment outcome. It is important to implement these guidelines in the routine management of clinical depression.

Aim: To examine the comparative effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) and Cognitive Behaviour Therapy (CBT) as treatments for non-melancholic depression., Method: Participants who met criteria for a current episode of major depressive disorder were randomly assigned to either an 8-week MBCT (n=19) or CBT (n=26) group therapy condition. They were assessed at pre-treatment, 8-week post-group, and 6- and 12-month follow-ups., Results: There were significant improvements in pre- to post-group depression and anxiety scores in both treatment conditions and no significant differences between the two treatment conditions. However, significant differences were found when participants in the two treatment conditions were dichotomized into those with a history of four or more episodes of depression vs those with less than four. In the CBT condition, participants with four or more previous episodes of depression demonstrated greater improvements in depression than those with less than four previous episodes. No such differences were found in the MBCT treatment condition. No significant differences in depression or anxiety were found between the two treatment conditions at 6- and 12-month follow-ups., Limitations: Small sample sizes in each treatment condition, especially at follow-up., Conclusions: MBCT appears to be as effective as CBT in the treatment of current depression. However, CBT participants with four or more previous episodes of depression derived greater benefits at 8-week post-treatment than those with less than four episodes., (Copyright © 2010. Published by Elsevier B.V.)

Objective: Earlier studies demonstrated that those with atypical depression show a differentially superior response to monoamine oxidase inhibitor (MAOI) antidepressants. This study compares ratings of effectiveness for a range of treatments, amongst depressed subjects with and without atypical features., Method: In an on-line survey, individuals experiencing likely clinical depression rated symptoms experienced when depressed, including 'atypical features' and the effectiveness of previous treatments. Mean treatment effectiveness ratings were compared amongst those with 'atypical depression' (n = 338) and 'non-atypical depression' (n = 377)., Results: There were few significant differences between the 'atypical depression' and 'non-atypical depression' groups in effectiveness ratings for drug treatments, and none for psychological treatments. The 'atypical depression' group had significantly lower mean effectiveness ratings for some selective serotonin reuptake inhibitor antidepressants. Few respondents had trialed MAOIs., Conclusion: While MAOIs are rarely prescribed, a range of non-MAOI drug and psychological treatments are of some perceived benefit for depressed patients with atypical features.

Objective: The aim of the present study was to examine the associations between eight personality styles and retrospective self-reported response to a wide range of treatments for depression, including pharmacological, psychological and alternative strategies., Method: An online survey posted on the Black Dog Institute website was completed by 3486 respondents reporting a history of treatment for depression. Inclusion criteria resulted in a sample of 2692 respondents. Participants completed the Temperament and Personality Questionnaire, which assesses eight personality dimensions: anxious worrying, perfectionism, personal reserve, irritability, social avoidance, rejection sensitivity, self-criticism and self-focus., Results: A series of linear regressions quantified that the personality dimensions--as well as age and gender--accounted for very little of the variance in self-reported treatment effectiveness (1-7%). Self-criticism was associated with a poorer response to most treatments, and social avoidance was associated with a poorer response to psychological treatments (e.g. cognitive behaviour therapy) and behavioural strategies (e.g. exercise). Several other weak associations are reported., Conclusion: The association between personality style and retrospective self-reported treatment response was overall weak at most. The association between a personality style of self-criticism and poor treatment response warrants clarification.

Objective: To overview limitations to the concept and construct of major depression., Method: The objectives in initially conceptualizing major depression are examined against its subsequent utility and relevance to clinicians and researchers., Results: It is argued that, as defined, major depression does not differentiate clinical depression well from expressions of non-clinical depression or sadness, that its criteria set do not generate reliable diagnoses, that a diagnosis of major depression means little in and of itself (as it effectively comprises multiple types of depression) and that it fails to inform us about cause, natural history or differential treatment response., Conclusion: Limitations to the concept of major depression would benefit from wider appreciation to advance changes to the clinical diagnosis of depressive sub-types.

Objective: Approximately 50% of patients with depression report symptoms of pain, yet the clinical and biological mechanisms underlying this association remain unclear. Recent neuroimaging studies, however, support the contention that depression, as well as pain distress and rejection distress, share the same neurobiological circuits. In this study, we aimed to examine the hypothesis that perception of increased pain during depression is related to increased rejection sensitivity., Method: The present study analysed data from a study of 186 treatment-resistant depressed patients who met DSM-IV criteria for depression and had completed a self-report questionnaire regarding currently perceived pain and rejection sensitivity., Results: A major increase in the experience of pain during depression was predicted by a major increase in rejection sensitivity during depression., Conclusion: The experience of increased pain during depression is related to increased rejection sensitivity. Research to further elucidate this relationship is required.

Classification of any mental disorder is likely to have clinical utility only if it is based on a valid underlying model. The depressive disorders have long provoked debates as to whether a categorical or a dimensional model is all explanatory. This paper will argue that no single (categorical or dimensional) model is likely to be valid, and that a mix of models is required to classify, diagnose and shape management decisions for the mood disorders. After reviewing limitations to the dimensionally based official classificatory systems (DSM-IV and ICD-10), and noting some of the consequences, a set of alternative strategies is outlined. In essence, identifying syndromal 'fuzzy sets' from phenotypic and aetiological clustering, a model that occurs in the rest of medicine.

Objectives: A patient who had experienced bipolar disorder for over 20 years and who had been euthymic for most of that period while highly compliant with lithium, had falsely low lithium levels reported over two periods, 6 years apart, and was actually lithium toxic on the most recent occasion. At that latter time the spuriously low lithium levels reported on the assay risked dispelling any clinical suspicion of lithium toxicity, although toxicity was later confirmed., Method: Case report., Results: The latter incident identified a serious problem, whereby it is likely that the particular assay risks generating spuriously low values when high serum levels of lithium are present--a so-called 'hook phenomenon' that has been described for some quantitative immunoassays., Conclusions: It is in situations of high potential gravity--when lithium toxicity is present--that lithium quantification is most likely to be compromised and low values generated. Also of grave concern is the fact that there are no regulatory processes in place to communicate this problem to lithium prescribers.

This paper reviews 30 years of longitudinal research, initially undertaken to examine gender differences in rates of major depression and psychosocial risk factors for depression. The research focus has broadened to include the impact of anxiety on depression onset, coping styles for stress and depression, genetic and environmental influences on depression onset, and more recently, a shift towards examining positive mental health. The original cohort consisted of a socially homogenous group of postgraduate teacher trainees and does not attempt to represent the normal variability in an adult population. However, the issues raised by this research provide many insights about real and artefactual factors that contribute to the rate and experience of depression. The study findings are supplemented by data from other studies undertaken by this research team that are pertinent to the topic and add weight to some of the observations from the Teachers' Study.

Background: Low reported rates of depression in Chinese populations could reflect real or artefactual factors, and might be clarified by studying acculturated Chinese in western regions. We therefore sought to determine whether reported rates of depressive disorders differ in resident Chinese and matched non-Chinese controls in a large US community survey., Method: We accessed data from the US National Epidemiological Survey of Alcoholism and Related Conditions, involving 306 Chinese subjects and 306 matched non-Chinese subjects., Results: The Chinese reported significantly lower lifetime and 12-month major depression rates, and a lower lifetime rate of dysthymia. Similar rates were quantified for Chinese born in the US and Chinese born overseas. The Chinese did not differ from controls in terms of recurrence rates of major depression., Limitation: Due to our matching analytic strategy, the reported statistics (e.g. prevalences) apply to our matched samples and should not be taken as estimates for the population., Conclusions: Findings indicate that westernisation does not eliminate differences in depression rates long described in Chinese regions, and favour a model whereby the Chinese have a lower vulnerability to depression onset.

[corrected] Selected structural and functional neuroimaging correlates of psychomotor slowing were examined [corrected] in older persons with depression. Clinical, neuropsychological, magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT) data were obtained for 32 persons with depression (mean age=55.5) and 17 controls (mean age = 55.4). Psychomotor slowing was measured by simple (SRT) and choice (CRT) reaction times. White matter lesions (WMLs) were visually rated and caudate nucleus regional cerebral blood flow (rCBF) was obtained through the co-registration of MRI and SPECT data. Two SPECT scans were performed (corresponding to the SRT and CRT tasks) and a percentage change score in rCBF (%rCBF) due to the increasing complexity of the second task was calculated. Persons with depression and controls did not differ with respect to %rCBF or frequency of WMLs. In persons with depression, reduced %rCBF was associated with slower CRT. For all subjects, WMLs predicted 14% of the variance in %rCBF. Although CRT was predicted by a combination of older age, WMLs and %rCBF, the diagnosis of depression still predicted a further 25% of the variance. Reduced %rCBF is associated with demonstrable psychomotor slowing and presence of WMLs. While psychomotor slowing is determined in part by subcortical changes, other cortical and illness-dependent factors are likely to be relevant.

Objective: The aim of this study was to determine whether short-term outcome for those referred with a depressive disorder could be predicted from baseline clinical assessment and identify factors contributing to outcome in a clinic operating to a subtyping diagnostic and aetiologically weighted management model., Method: This pilot study involved a consecutive series of 85 patients referred to the Depression Clinic at the Black Dog Institute., Results: Globally assessed baseline prediction was associated with short-term outcome. Comparably high rates of improvement were evident in those with bipolar, melancholic and non-melancholic subtypes, and somewhat lower in those diagnosed with a 'secondary depression'. Qualitative and quantitative analyses established that outcome was most clearly associated with referral source, degree of take up of recommendations and implementation of psychotropic drug strategies., Conclusions: Study results encourage more definitive and comparative study designs to be derived.

Objective: To obtain views of an Australian sample of individuals who had experienced a clinical depressive episode and examine the judged effectiveness of a wide range of professionally recommended, self-help and less orthodox antidepressant strategies., Method: A survey was posted on the Black Dog Institute website until a large sample had been derived. Inclusion criteria resulted in a sample of 2692 respondents., Results: Effectiveness and benefit-burden scores (adjusting for not fully testing a strategy) were quantified for 31 strategies that had been trialled by at least 100 respondents. Many self-help strategies rated as strongly as professionally recommended strategies, with exercise being rated extremely highly. Intra-class comparisons of ratings identified some differentiation of antidepressant drugs but similar results for differing psychotherapies, while alternative drug strategies tended to return lower ratings than most formal antidepressant drugs., Conclusions: Study results, together with results from mental health literacy studies, advance our understanding about consumers' views about the frequency of trialling quite differing strategies and offer some information about their judged effectiveness.

Background: As division between unipolar and bipolar disorders can be problematic, we sought to develop a self-report questionnaire of mood 'highs' that would both distinguish true Bipolar Disorder from any elevated mood states in unipolar depression and sharpen the distinction between Bipolar I and II conditions., Method: A 46-item questionnaire was developed and completed by 157 out-patients presenting with a major depressive episode, and clinically diagnosed as having either Bipolar I (BP-I), Bipolar II (BP-II) or Unipolar (UP) depression, although DSM-IV duration criteria for BP-I and BP-II were not imposed., Results: Factor analyses identified four key constructs to mood 'highs', while additional analyses refined the questionnaire to 27 items. The refined measure was highly accurate in distinguishing composite Bipolar (BP-I and BP-II) from UP subjects (AUC = 0.93, sensitivity = 81%; specificity = 98%, positive predictive value = 0.95). Questionnaire scores were similar for BP-I and BP-II subjects, raising the possibility that the core mood state differs little in severity across the two expressions, and that their distinction allows an alternative model that weights the presence or absence of psychotic features., Conclusions: Our study advances understanding of boundary distinctions between bipolar and unipolar mood disorders, and between BP-I and BP-II conditions, and allows consideration of a model distinguishing BP-I from BP-II by the presence of psychotic features only. The described model is the mirror image of a hierarchical structural model for conceptualizing psychotic and melancholic depression, allowing an 'isomer model' for linking the mood swing states.

Objective: The new Black Dog Institute Depression Clinic adopts a novel clinical service model that argues for the importance of clinically defining separate mood disorders in order to apply specific management strategies. This paper describes clinic nuances and the impact on diagnosis and management for the first 100 patients assessed., Method: Patients are assessed via a computerized structured self-report program, a semistructured interview undertaken by a psychiatrist and a colloquium involving several practitioners where diagnostic decisions are formulated. A detailed report with treatment recommendations, incorporating psychiatric and psychological perspectives, is sent to the referring clinician. Such data are examined in this report., Results: We offered a differing diagnostic and treatment paradigm for nearly 90% of those diagnosed with a primary mood disorder. Difficulties encountered by referring practitioners are highlighted and the need for an alternative diagnostic and management model is discussed., Conclusions: A subtyping diagnostic management model has the capacity to advance treatment outcome, but requires validation. Our future research will assess the comparative utility of the subtyping model in clinical and research arenas.

Background: We sought to develop a refined measure of eight personality traits or constructs observed in those who develop depression. We report the psychometric properties of the derived Temperament and Personality (T and P) questionnaire, as well as a pilot study examining its capacity to differentiate over-represented personality traits in those with depression., Method: The factor structure of the T&P measure was examined in a general practice sample of 529 subjects. We imposed a range of factorial solutions to determine how higher-order molar constructs arborized to eight lower-order constructs. Scale scores generated at each derived tier were contrasted for 52 out-patients with major depression and control subjects from the general practice sample to pursue over-represented personality constructs, and to clarify if an optimal number of constructs could be identified., Results: In the factor analysis, some 90% of the items loaded on their a priori construct. The questionnaire showed high internal consistency, test-retest reliability and minimal sensitivity to mood state effects. Analyses rejected the hypothesis that risk to depression might be generally affected by individuals merely scoring high on all 'normal' personality styles, whether higher-order or lower-order traits., Conclusions: Findings suggest that, while identified constructs linked well with the widely accepted theoretical model of personality (the Five Factor Model) at one tier, such a fixed model may be too inflexible. We therefore detail potential advantages to using a multi-tiered model of personality traits in application studies.

The authors report on the psychometric characteristics and clinical efficacy of two versions of a recently developed screening measure of depression (the DMI-18 and DMI-10) in the cardiac population. Patients with acute coronary syndrome or heart failure (N = 322) completed the DMI measures, psychosocial questionnaires, and a semistructured clinical interview during the hospital stay. The DMI-18 and DMI-10 measures have adequate psychometric properties, demonstrating high sensitivity and specificity when evaluated against clinical judgment based on a semistructured interview. The DMI-18 and DMI-10 are appropriate for use as screening instruments in cardiac patients.

Objective: To assess the rates and perceived effectiveness of actions used to cope with depression and the factors influencing these in an outpatient sample seeking help for depression., Method: One hundred and seventy-six patients (74 male, 102 female) aged 16-82 years (M = 42, SD = 14.4 years) with a major depressive episode (DSM-IV criteria) were assessed using a number of measures that covered sociodemographics, history of psychiatric illness, actions taken to alleviate depression and their perceived effectiveness. Logistic regression analyses assessed age, gender and illness characteristics associated with the use and perceived effectiveness of strategies adopted to manage depression., Results: Medical interventions were used and perceived to be effective in alleviating depressive symptoms by most of the sample, as were self-help and complementary therapies. Sociodemographic and illness-related characteristics had a significant influence, with younger age and having experienced an episode of anxiety disorder found to be the strongest predictors for the use of coping strategies. Being female was the strongest predictor for their effectiveness., Conclusion: A range of actions for depression, including medical and complementary interventions, were used and found to be helpful in a sample that had sought professional help for depression. Gender, age, depression and anxiety factors were all found to predict the use and perceived effectiveness of these strategies.

Background: A relationship between the serotonin transporter gene, adverse events and onset of major depression has been reported., Aims: To replicate a gene x environment interaction in a cohort with longitudinal data for life events, experience of depression, parental bonding and neuroticism., Method: At the 25-year follow-up, genomic DNA was obtained from 127 cohort members (mean age 48 years) to determine the genotype of the serotonin transporter gene-linked promoter region (5-HTTLPR). Associations were investigated between the 5-HTTLPR genotype, positive and adverse life events and the gene x environment interaction, and also between the 5-HTTLPR genotype and risk factors for depression., Results: No relationship was found between 5-HTTLPR genotype and either risk factors for depression or positive life events. Adverse life events had a significantly greater impact on the onset of depression for individuals with the s/s genotype., Conclusions: The 5-HTTLPR genotype is a significant predictor of onset of major depression following multiple adverse events. This is one of the more robust findings concerning specific biological risk factors for depression.