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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.)

Background: We report on the assessment and outcome of the first 1000 patients referred to a tertiary referral depression clinic established to assess the utility of diagnostic sub-typing on clinical course of illness., Methods: Diagnostic, treatment recommendations, prognostic judgments and 12-week outcome data were examined., Results: Nearly 40% of those with a primary mood disorder were diagnosed with bipolar disorder, of whom three-quarters received such a diagnosis for the first time. Alternative diagnoses or formulations were provided for 68% of the total sample, with the therapeutic paradigm altered for the majority (86%) of patients. Improvement rates were indicative of a higher level of improvement in those diagnosed with bipolar disorder (some 70%) compared to those with unipolar disorders (some 60%). Overall, however, rates of 'full remission' were low, being 2% and up to 12% for bipolar and unipolar patients respectively and perhaps reflecting the tertiary nature of the assessing clinical facility. Baseline clinician predictions were in the order of 60% accuracy in predicting outcome, irrespective of diagnostic grouping., Limitations: Anticipation factors (e.g. attending a specialist tertiary referral service) may have contributed non-specifically to outcome. Use of clinician-derived diagnoses rather than strict DSM-IV criteria limits comparisons to other studies., Conclusions: The high rates of a first-time bipolar diagnosis suggest that detection and diagnosis of this condition continues to be problematic. Low remission rates underline the chronic nature of many mood disorders, and the need for ongoing management given the high risk of relapse. Our findings offer support for the importance of identifying bipolar disorder and distinguishing depressive sub-types in order to shape more targeted treatments, a task that might be advanced by the establishment of more tertiary referral services., (Copyright © 2010 Elsevier B.V. All rights reserved.)

This study aimed to examine the short-term clinical impact of identifying bipolar disorder in patients previously managed as having a unipolar disorder. The study was incorporated within a consecutive sample of 1000 patients attending a specialist depression clinic for diagnostic and management considerations. Of those assessed, 34% were evaluated as having a bipolar disorder, with this condition having been diagnosed for the first time in three-quarters of those patients. We reviewed sample members 12 weeks later and compared the courses of the "newly diagnosed" and "established" bipolar subsets. Some four-fifths of the bipolar patients reported a degree of improvement, whereas there were no clear differences between the two bipolar subsets. The nondifferential outcome of the bipolar (previously and newly diagnosed) subsets could suggest that there were nonspecific benefits of assessment or that the management was optimized for both groups. Future studies examining the impact of diagnosing a bipolar disorder would therefore benefit from the close consideration of the optimal control group or control strategy.

Background: As melancholia has resisted symptom-based definition, this report considers possible explanations and options for moving forward. Clinician-assigned melancholic and non-melancholic groups were initially compared to refine a candidate set of differentiating symptoms alone for examination against a set of non-clinical validators. Analyses then examined the capacity of both the refined symptom and validator sets to discriminate the assigned melancholic and non-melancholic subjects., Methods: Subjects completed measures assessing symptoms and correlates (putative validators) of diagnostic sub-type, and were assessed independently by two psychiatrists., Results: Analyses identified 14 severity-based symptoms as discriminating clinically-diagnosed groups - with melancholic subjects differing significantly from non-melancholic subjects across a number of validators. Such symptom-based discrimination was superior to DSM-IV and Newcastle Index assignment in a study sub-set. While the refined symptom set had an overall accurate classificatory rate of 68%, use of the combined sets of refined symptoms and validators improved classification to 80%., Conclusions: Melancholia definition is improved by the use of correlates in addition to depressive symptoms, suggesting that melancholia may be mapped more precisely by use of multiple co-ordinates or data sources., (Copyright 2009 Elsevier B.V. All rights reserved.)

Purpose of Review: There is increasing evidence from epidemiological, case-control and randomized clinical trials for a link between omega-3 deficiency and the development of mood disorders. This article examines recent evidence for this association., Recent Findings: During the past year our understanding of the effect of omega-3 depletion on the structure and function of the brain has been furthered by research examining human brain tissue and by studies utilizing animal models of depression. Human and animal research has also provided further evidence for omega-3 affecting mood via its anti-inflammatory effects. Previous clinical trials indicated that omega-3 can be effective as an adjunctive treatment for those with treatment-resistant depression. More recent clinical trial data indicate that omega-3 may also be an effective monotherapy for childhood depression and for depressed mood in patients who engage in recurrent self-harm. The recent clinical trial data regarding omega-3 as a treatment for bipolar disorder are inconclusive, however, and clinical trials in postnatal depression are still lacking., Summary: This article reviews the most important recent papers in this burgeoning and interesting research area.