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Objective: To compare the 2022 NICE guidelines (NG222) and 2020 RANZCP clinical practice guidelines (MDcpg 2020 ) recommendations for the treatment of depression using psychodynamic psychotherapy., Conclusions: Both guidelines recommend psychological interventions first-line. However, only short-term psychodynamic psychotherapy (STPP) is recommended, and in the NG222 it is ranked last for less severe depression and 7th for more severe depression. In contrast, cognitive behavioural therapy and behavioural activation are deemed the more clinically effective and cost-effective psychological therapies. And antidepressants play a significant role - largely in more severe depression.

Background: Despite homogenous clinical presentations between bipolar and unipolar disorders, there are distinct neurobiological differences. Chronicity of illness may be a factor impacting and sustaining certain neural features. The goal of this study was to investigate common and shared neural mechanisms underlying mood disorders, and possible sustained neural changes relating to illness chronicity by investigating a cohort of euthymic patients with bipolar disorder (BD), unipolar depression who had responded to treatment (treatment-sensitive depression, TSD), and a chronically treatment-resistant depressed (TRD) group., Methods: One hundred and seventy-two participants (40 BD, 39 TSD, 40 TRD, and 53 age-gender-matched healthy controls) underwent resting-state fMRI scans. Seed-based and independent component analyses were performed to investigate group differences in resting-state connectivity between the four groups., Results: All three clinical groups had significantly lower connectivity within the frontoparietal network (FPN) relative to controls. TRD and BD were significantly different from TSD (TRD, BD > TSD) but were not significantly different from each other. TRDs were also significantly different from both BD and TSD for salience network connectivity with the posterior cingulate (DMN) and the FPN with frontal pole (DMN). Additionally, the BD group exhibited greater DMN-FPN (sgACC-RDLPFC) connectivity relative to TRD, TSD, and controls, which was correlated with a previous number of depressive episodes, in the BD group only., Conclusions: BD demonstrated shared and differential connectivity features relative to symptomatic TRD and euthymic TSD groups. The increased sgACC-RDLPFC connectivity in BD and its correlation with a number of depressive episodes could be a neural feature associated with illness chronicity., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Perinatal depression (PND) screening recommendations are made by national, state-based and professional organisations; however, there is disagreement regarding screening timing, provider responsible, screening setting, screening tool as well as the follow-up and referral pathways required post-screening. This systematic review aimed to identify, describe and compare PND screening recommendations from member countries of the Organisation for Economic Co-operation and Development (OECD). Publications were identified through systematically searching PubMed, Google and the Guidelines International Network (GIN). Recommendations regarding PND screening endorsement, timing, frequency, responsible provider, tools/assessments and follow-up and referral were extracted. Twenty-one publications, including guidelines, from five countries were included. Most made recommendations in support of PND screening using the Edinburgh Postnatal Depression Scale. Details differed regarding terminology used, as well as frequency of screening, follow-up mechanisms and referral pathways. A broad range of health providers were considered to be responsible for screening. This is the first review to identify and compare PND screening recommendations from OECD member countries; however, only online publications published in English, from five countries were included. Heterogeneity of publication types and inconsistency in definitions rendered quality assessment inappropriate. While most publications generally endorsed PND screening, there are exceptions and the associated details pertaining to the actual conduct of screening vary between and within countries. Developing clear, standardised recommendations based on current evidence is necessary to ensure clarity amongst healthcare providers and a comprehensive approach for the early detection of PND., (© 2022. The Author(s).)

There has been a longstanding debate as to whether the bipolar disorders differ categorically or dimensionally, with some dimensional or spectrum models including unipolar depressive disorders within a bipolar spectrum model. We analysed manic/hypomanic symptom data in samples of clinically diagnosed bipolar I, bipolar II and unipolar patients, employing latent class analyses to determine if separate classes could be identified. Mixture analyses were also undertaken to determine if a unimodal, bimodal or a trimodal pattern was present. For both a refined 15-item set and an extended 30-item set of manic/hypomanic symptoms, our latent class analyses favoured three-class solutions, while mixture analyses identified trimodal distributions of scores. Findings argue for a categorical distinction between unipolar and bipolar disorders, as well as between bipolar I and bipolar II disorders. Future research should aim to consolidate these results in larger samples, particularly given that the size of the unipolar group in this study was a salient limitation., (Copyright © 2021. Published by Elsevier B.V.)

Background: This study aimed to improve the accuracy of bipolar disorder diagnoses by identifying symptoms that help to distinguish mania/hypomania in bipolar disorders from general 'happiness' in those with unipolar depression., Methods: An international sample of 165 bipolar and 29 unipolar depression patients (as diagnosed by their clinician) were recruited. All participants were required to rate a set of 96 symptoms with regards to whether they typified their experiences of manic/hypomanic states (for bipolar patients) or when they were 'happy' (unipolar patients). A machine learning paradigm (prediction rule ensembles; PREs) was used to derive rule ensembles that identified which of the 94 non-psychotic symptoms and their combinations best predicted clinically-allocated diagnoses., Results: The PREs were highly accurate at predicting clinician bipolar and unipolar diagnoses (92% and 91% respectively). A total of 20 items were identified from the analyses, which were all highly discriminating across the two conditions. When compared to a classificatory approach insensitive to the weightings of the items, the ensembles were of comparable accuracy in their discriminatory capacity despite the unbalanced sample. This illustrates the potential for PREs to supersede traditional classificatory approaches., Limitations: There were considerably less unipolar than bipolar patients in the sample, which limited the overall accuracy of the PREs., Conclusions: The consideration of symptoms outlined in this study should assist clinicians in distinguishing between bipolar and unipolar disorders. Future research will seek to further refine and validate these symptoms in a larger and more balanced sample., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice., Methods: An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients., Results: Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines., Conclusion: During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.

Background: Cognitive compromise is a common experience for patients with depression and other mood disorders. Depressed patients sustain deficits in working memory and attentional distortions in emotional processing and negative attention biases, which may contribute to maintaining their depressive state., Methods: The Mood Assessment and Classification (MAC) Committee comprised academic psychiatrists with clinical expertise in the management of mood disorders. The independently convened committee met to discuss contentious aspects of mood disorders diagnosis and assessment with the express aim of informing clinical practice and future research., Results: The Committee specifically identified cognition as an important aspect for clinicians to consider in the context of depression and mood disorders. This article highlights some of the barriers to assessment and proposes tools that have the potential to be implemented in clinical practice., Limitations: The conclusions drawn within this article are based on expert opinion. We have noted the limitations of the literature that informs this opinion., Conclusions: As cognitive ability has been closely linked to patients' ability to achieve functional recovery, it is imperative that clinicians are able to identify patients with cognitive deficits and are equipped with tools to conduct effective cognitive assessments. Examining cognitive factors may generate a deeper understanding of the pathogenesis of depression and mood disorders which can ultimately be used to inform treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose of Review: The key question for melancholia is whether it should have status as a separate disorder and the literature of the last 12-24 months is surveyed largely from that perspective., Recent Findings: A number of interesting findings have appeared across a broad range of issues, but, with the possible exception of some large clinical trials, remain largely unreplicated., Summary: Supporters of melancholia as a distinct entity will find little comfort in the recent literature.

Background: Depression is a common disorder in primary care. Disruptions to the circadian rhythms associated with depression have received little attention yet offer new and exciting approaches to treatment., Objective: This article discusses circadian rhythms and the disruption to them associated with depression, and reviews nonpharmaceutical and pharmaceutical interventions to shift circadian rhythms., Discussion: Features of depression suggestive of a disturbance to circadian rhythms include early morning waking, diurnal mood changes, changes in sleep architecture, changes in timing of the temperature nadir, and peak cortisol levels. Interpersonal social rhythm therapy involves learning to manage interpersonal relationships more effectively and stabilisation of social cues, such as including sleep and wake times, meal times, and timing of social contact. Bright light therapy is used to treat seasonal affective disorders. Agomelatine is an antidepressant that works in a novel way by targeting melatonergic receptors.

Background: While interpersonal sensitivity, as rated by the Interpersonal Sensitivity Measure (IPSM) has previously been found to be an efficient predictor of depression, there has been less interest in the relationship between the IPSM and anxiety disorders. This study examines the performance of the IPSM in discriminating between cases and non-cases of the various anxiety disorders. The contribution of depression and the perception of parental environment, to any relationships found, are also examined., Methods: A cohort of 156 men and women has been assessed at 5-yearly intervals since baseline in 1978, in their last year of teacher training. In this fourth wave of follow-up, subjects completed a series of self-report questionnaires, including the IPSM, and scales measuring neuroticism and trait depression. Perceived parental environment, measured at baseline, was also included. DSM-III-R major depression and anxiety disorders were generated using the Composite International Diagnostic Interview. The IPSM subscales were moderately stable over time. 'Timidity' was associated with agoraphobia and simple phobia, and 'separation anxiety' with agoraphobia, panic disorder and generalised anxiety disorder. 'Separation anxiety' and 'timidity' showed differential gender effects for simple phobia. 'Fragile inner self' and 'separation anxiety' were associated with subjects with a history of repeated episodes of major depression, and the former, with perception of poor parental care., Limitations: The IPSM was not available for inclusion prior to the 1988 wave., Conclusions: While the IPSM subscales were consistently correlated with neuroticism, they displayed differential associations with specific anxiety disorders, episodes of major depression and early parental environment. These findings offer greater understanding of mechanisms concerning the relationship of vulnerability to anxiety disorders and depression.

Objective: To review the proposition that antidepressants have a delayed onset of action by employing measurement and analytic strategies that overcome problems confounding interpretation of many efficacy studies., Method: A subset of patients was recruited to the longitudinal component of the Australasian database study, was assessed at baseline, and then completed measures of depression and anxiety when treatment commenced, and every 3 days over the next 4 weeks. The trajectories of defined 4-week outcome responders and non-responders were compared., Results: Both groups showed a similar decrease in depression (and anxiety) over the first 3 days. A clear trend break then occurred, with little further improvement in the non-responders, as against distinct and progressive improvement in the responders. Ongoing early improvement (across days 3-6) was a strong predictor of responder status., Conclusions: The small sample size limits firm interpretation, although distinct interpretive advantages to the study design are evident. Findings are compatible with a number of recent studies arguing against any extensive delayed onset of action for the antidepressant drugs, but argue for caution in interpreting immediate improvement as predicting likely responder status, and more for examining early and sustained improvement as such a marker.

Background: Over the past decade several new classes of antidepressants have become available for the treatment of depression. Their use has become widespread and some have suggested that the older tricyclic antidepressants (TCAs) should no longer be used as first line treatment., Objective: To examine the place of TCAs in the treatment of depression., Discussion: The TCAs still have an important place in the treatment of depression. The newer agents are equally effective as the TCAs for treatment of mild to moderate depression, but there are indicators the TCAs are more efficacious for severe depression. The newer drugs have a different side effect profile and some potentially serious problems such as drug interactions and the serotonin syndrome. TCAs are potentially lethal in overdose, so their use in the suicidal patient must be accompanied by comprehensive clinical care, taking precautions to minimise risk of suicide.

This study aims to use valid measures to a) estimate the prevalence of depressive disorder and b) identify psychosocial factors associated with depression in a sample of socially disadvantaged women with children. One hundred ninety-three women, recruited through a doorknock of public housing estates completed an interview that included the Diagnostic Interview Schedule to identify cases of depression and the Mannheim Interview for Social Support. The women also completed self-report questionnaires assessing psychological morbidity, life events, perceptions of intimate relationships, and personality factors. The 6-month prevalence of major depression was 17% and the lifetime prevalence 29%. Major depression was associated with perceptions of low parental care during childhood and low care from current partner, vulnerable personality style, increased reporting of life events, and an unsatisfactory social support network.

We examine the dexamethasone suppression test as a biological correlate of melancholia as defined by the CORE system, a scale for rating objective signs of psychomotor disturbance. Postdexamethasone cortisol concentrations and rates of nonsuppression were higher in CORE, Newcastle, and DSM-III-R defined melancholic groups. These differences, however, were no longer significant after partialling out the combined effects of age, dexamethasone, and basal cortisol concentrations. There was a significant correlation between the CORE (but not the Newcastle) scale and 8:00 AM postdexamethasone cortisol levels, which persisted after partialling out those same three covariates. Dexamethasone concentrations themselves were lower in CORE- and Newcastle-defined melancholics, though these were no longer significant after covarying for cortisol concentrations. Dexamethasone levels were also significantly inversely correlated with CORE and Newcastle scales. A significant correlation between CORE (but not Newcastle) scores and dexamethasone levels at 4:00 PM persisted after partialling out the effects of age and cortisol. These findings indicate an intriguing relationship between the CORE system as a dimensional construct for rating psychomotor disturbance, and both postdexamethasone cortisol and dexamethasone concentrations.

Objective: We examined the reasons for which doctors refer and patients request referral to our tertiary Mood Disorders Unit (MDU), focussing on congruence and 'fit', and the potential for more efficient use of referral resources., Method: A postal survey of patients (n = 265 or 83% responders) and referrers (n = 156 or 94% responders) sought views regarding referral and service components. Ratings from 156 matched referrer-patient dyads were compared., Results: Overall, referrers and patients were satisfied with the MDU. There was disparity between what referrers sought and what patients thought were the reasons for referral, and different perceptions of the value of interventions and the amount of improvement. Congruent matched referrer-patient judgements of patient outcome were more likely to correspond with objective clinician ratings than discordant ratings. Satisfaction with MDU contact or intervention was not necessarily linked to improvement; better management of chronic depression was also valued. Referrer and patient responses to open-ended questions highlighted beneficial ingredients of referral., Conclusions: There was considerable lack of fit between referrers' and patients' experience of the referral. Better communication between referrer and patients can clarify the purpose of referral and possibly lead to increased compliance with medical regimens.

A number of personality styles have been proposed as vulnerability traits to depression. In this paper methodological problems associated with identifying such traits are discussed. These include state effects contaminating personality scales and the issue of depressive heterogeneity. Potential depression-prone personality traits are then discussed, including obsessionality, neuroticism, dependency and cognitive dysfunction. High interpersonal sensitivity as a risk factor to depression is then discussed.

Melancholia is most commonly distinguished from non-melancholic depression by the presence of psychomotor disturbance (PMD) and a set of 'endogeneity' symptoms. We examine the capacity of an operationalized clinician-rated measure of PMD (the CORE system) to predict diagnostic assignment to 'melancholic/endogenous' classes by the DSM-III-R and Newcastle systems. Examining a pre-established CORE cut-off score (> or = 8) against independent diagnostic assignment, PMD was present in 51% of those assigned as melancholic by DSM-III-R, and 85% of those assigned as endogenous by the Newcastle system, quantifying the extent to which it is 'necessary' to the two definitions of 'melancholia'. Additionally, multivariate analyses established that the addition of a refined set of historically suggested endogeneity symptoms added only slightly to overall discrimination of melancholic and non-melancholic depressives. While only few endogeneity symptoms independent of psychomotor disturbance were suggested, their specific relevance varied against system definition of melancholia (appetite/weight loss and terminal insomnia being identified for DSM-III-R; anhedonia for Newcastle; and diurnal variation in mood and energy for both systems). Results allow consideration of the relative importance of two domains (psychomotor disturbance and 'endogeneity' symptoms) to clinical definition of melancholia, and have the potential to assist both classification and pursuit of neurobiological determinants. We interpret findings as suggesting a 'core and mantle' model for conceptualizing the clinical features of melancholia, with psychomotor disturbance as the core and with independent endogeneity symptoms as only a thin mantle.

We describe the development of a clinical algorithm to differentiate melancholic from non-melancholic depression, using refined sets of 'endogeneity' symptoms together with clinician-rated CORE scores assessing psychomotor disturbance. Assignment by the empirically developed algorithm is contrasted with assignment by DSM-III-R and with several other melancholia sub-typing indices. Both the numbers of 'melancholics' assigned by the several systems and their capacity to distinguish 'melancholics' on clinical, demographic and a biological index test (the DST) varied across the systems with the algorithm being as 'successful' as several systems that include inter-episode and treatment response variables. Analyses provide information on the criteria set developed for DSM-IV definition of 'melancholia'.

In recent years new pharmacological agents have become available for the treatment of depression encouraging many to opt for the biochemical theory as the cause of depression. This article looks at the pros and cons and whether there is still a place for non pharmacological interventions in the treatment of depression.

The clinical characteristics and treatment outcome of a series of 107 patients referred to a mood disorders unit with an episode of "treatment resistant" Major Depression are reviewed. Subjects were categorised by diagnosis (into melancholic and non-melancholic subtypes) and by adequacy of previous treatment. At subsequent review (mean period of 37.5 months) these patients were re-assessed both in terms of outcome and which treatments had been considered to be most effective. Forty one percent of the patient group were fully recovered and a further 43% were partially improved. Different treatments were considered effective for melancholic and non-melancholic sub-types.

The concept of "treatment resistant depression" (TRD) has generally been defined in terms of failure to respond to a standard course of somatic therapy with little reference to diagnostic sub-types or relevant psychosocial factors. In this paper we examine problems with the use of the term "treatment resistant depression" and then outline an approach to TRD employed in an Australian mood disorders unit. After discussing the need for a biopsychosocial assessment, multimodal management strategies for melancholic and non-melancholic TRD patients are described.

We hypothesised that psychomotor disturbance is specific to the melancholic subtype of depression and capable of defining melancholia more precisely than symptom-based criteria sets. We studied 413 depressed patients, and examined the utility of a refined, operationally driven set of clinician-rated signs, principally against a set of historically accepted symptoms of endogeneity. We specified items defining psychomotor disturbance generally as well as those weighted either to agitation or to retardation. We demonstrated the system's capacity to differentiate 'melancholic' and 'non-melancholic' depression (and the comparable success of DSM-III-R and Newcastle criteria systems) by reference to several patient, illness and treatment response variables, to an independent measure of psychomotor disturbance (reaction time) and to a biological marker (the dexamethasone suppression test).

Many measures of depression severity appear confounded by including depressive sub-typing features. We report the design of a brief (11 item) self-report scale of depression severity (the AUSSI), assessing both mood state and social impairment domains, and designed to be independent of sub-typing features. Mood severity and functional impairment scores demonstrated some independence in a sample of 360 patients. Patients with a 'melancholic' depressive type (categorised by four differing systems) differed from residual 'non-melancholic' depressed patients by having higher impairment scores, but the assigned groups did not differ, in the main, by mood severity scores. Advantages of the measure are summarised.

The prognosis of depression in the elderly was investigated in a mixed-age sample of 242 consecutive referrals, with DSM-III defined unipolar major depressive episode, to a specialist unit for mood disorders. Subjects were followed up at about 1 and 3.8 years. There was no significant difference in outcome between younger (under 40 years), middle aged (40-59 years) and older (60 years or more) depressed patients. For the 61 elderly subjects with depression, prognosis improved with time, with 25% having a lasting recovery at the first and 41% at the second follow-up. Early onset, recurrence, and poor premorbid personality were associated with a worse prognosis. Three (5%) elderly depressives had committed suicide and seven (11%) had died from natural causes by the second follow-up. Despite some methodological limitations, our findings suggest a more optimistic outlook and the need for longer, more assertive treatment for elderly, depressed patients.

The first wave of a longitudinal and prospective community study of minor psychiatric disorder among a cohort of socially disadvantaged women has been completed. The study hopes to extend the social model of depression, as initially proposed by Brown and Harris [1], by examining the mediating effects of personality factors and social support. Findings from previous studies have been largely restricted to associations between variables which may be at least partly attributable to methodological limitations in design and measurement techniques: specifically, the use of inherently biased sampling methods, single interview, retrospective data collection and less standardized diagnostic criteria to determine caseness. This paper discusses design strategies which were adopted to reduce the confounding between variables resulting from these limitations. The effectiveness of these strategies is evaluated in light of some methodological and ethical issues which have arisen during the recruitment of participants and the first wave of data collection.

Specialist treatment centres, such as the Mood Disorders Unit (MDU) at Prince Henry Hospital, Sydney, have developed in response to the high prevalence of mood disorders and their frequent persistence and treatment resistance. The MDU's assessment and treatment of patients from a state-wide catchment area and its teaching and research effectiveness are reviewed. Of 479 patients assessed between 1985 and 1989, there were 304 with primary depressive disorders, of whom 154 were followed up by clinical assessment at 52 weeks and 231 by telephone interview at 3 1/2 years. At intake, 59% were tertiary referral patients and 88% were from outside the local area. Two-thirds were recovered 3 1/2 years later, despite the disorders having been generally severe and protracted. Treatment modality was associated primarily with diagnosis, but also with age and somewhat with the patient's personality and consultant psychiatrists' preferences. No consistent predictors of outcome were discerned. Specialist tertiary referral centres, such as the MDU, contribute significantly to treatment success, especially of difficult cases, and enrich teaching and research.

Four hundred and thirteen depressed patients were rated on eighteen signs of psychomotor disturbance, and the data examined by factor analyses. A three-factor solution was favoured. In addition to 'retardation' and 'agitation' dimensions (whose derived factor scores suggested independence of those two dimensions), a third 'non-interactive' dimension was evident--with derived factor scores correlating significantly with both the retardation and agitation dimensions. Thus, a 'trunk and branch' analogy was suggested for construing psychomotor disturbance, with a truncal 'psychic' component arborising into retardation and agitation 'motoric' expressions. Higher scores on all three factors were significantly linked with features weighted more to the melancholic 'type' of depression.

We report an inter-rater reliability study of the modified 18-item, sign-based CORE index of melancholia, undertaken on 205 ratings of 35 patients by five clinical research psychiatrists. Inter-rater agreement about the presence or absence of individual items was slight to moderate when examined by the kappa coefficient, but moderate to high when examined by the intraclass correlation statistic. For total CORE scores, perhaps the most important application of the index of melancholia, high levels of intraclass correlation coefficients (ranging 0.79 to 0.90 across the varying rater dyads) were established. When a single cut-off score (of 7/8) was used to allocate patients to either a 'melancholic' or 'non-melancholic' class, only moderate agreement was established between raters in such 'class' assignments--a limitation which can be redressed by imposing a 'probable/possible melancholia' band of scores.

Scores of 69 remitted depressed patients were compared to control subjects on the Interpersonal Sensitivity Measure (IPSM). The patients were categorised into melancholic and non-melancholic sub-groups according to DSM-III criteria. Differences between the depressives and controls were detected but were principally the result of high IPSM scores being returned by the non-melancholic depressives. Melancholic depressives did not differ from the controls in their IPSM scores, supporting the proposition that this depressive sub-type is not associated with a vulnerable personality style.

We assessed improvement patterns and predictors of outcome over a 1-year period, in a sample of depressed patients receiving treatment from a specialized mood disorders unit. Patients with melancholia had a differential improvement pattern from the nonmelancholics in the first 20 weeks, but case rates and severity levels were comparable at 20 weeks and at 1 year. Only three variables (older age at first episode, less severe depression and extraversion) were predictors of improvement in both groups. Improvement was predicted by less psychomotor disturbance, absence of personality disorder, and higher social functioning in the melancholic patients. A reported absence of timidity and shyness in childhood, a briefer duration of depression, and receipt of individual psychotherapy predicted a better outcome in the nonmelancholic patients. Although significant predictors were few overall, the suggested differential relevance for most of the isolated predictors argues for outcome studies that examine melancholic and nonmelancholic depressive disorders separately.

Although it is now more than 30 years since Leohard originally proposed the distinction between bipolar and monopolar (unipolar) forms of affective disorder, there have been relatively few studies which have investigated clinical features which may differentiate the depressed phase of bipolar disorder from unipolar depression. In this study we examined the value of a new scale for rating depressive mental state signs (the 'core' score system), and a large series of symptoms and risk factors, in distinguishing between 27 age and sex-matched pairs of bipolar and unipolar patients diagnosed as melancholic on several diagnostic criteria. In general, we found a marked similarity between the groups on clinical features of the depressive episode when allowance was made for multiple tests. Bipolar patients, however, had shorter episodes of depression and were less likely to demonstrate 'slowed movements' than unipolar subjects. There were also consistent trends on other items for psychomotor retardation to be less common and agitation to be more likely in the bipolar patients. At the least, these findings suggest that the widely-held belief that bipolar depressed patients typically have psychomotor retardation is not as clear-cut as has been previously described.

Previous studies have demonstrated that abnormalities of personality can contribute to a poor prognosis following a depressive episode. In this study the relevance of a specific personality trait, interpersonal sensitivity, to poor outcome was examined. One hundred and eleven depressives completed the Interpersonal Sensitivity Measure (IPSM) twenty weeks after a baseline assessment. High scores on the IPSM were associated with a poor outcome at one year following the baseline assessment, judged according to whether they had remitted clinically or not and by the degree of change in depression severity measured using the Hamilton and Zung Depression Rating Scales. The relevance of this personality trait to the course and treatment of depression is discussed.

There appear to be few published studies that have examined the levels of agreement between ratings of features of depression as assessed by clinicians and by corroborative witnesses. We therefore report a study of 141 depressed patients assessed by a clinical psychiatrist at a semi-structured interview, reviewing family and historical data as well as depressive symptoms, and rated on a series of designated mental state signs. A family member completed questionnaire data assessing the same features. Moderate agreement was obtained only for several historical items (e.g., previous depressive episode, response to ECT). Agreement was minimal or non-existent on numerous clinical symptoms and signs of depression. A number of sources of disagreement are considered, and it is suggested that discordance may have emerged principally from the contrasting domains and training experiences of the clinicians and the corroborative witnesses.

We examined six systems or scales designed to distinguish melancholia from residual nonmelancholic depressive disorders in a sample of 305 patients. A count of the number of significant psychosocial risk factors showed that a clinical diagnosis was the most differentiating (19 significant risk factors), followed by the Newcastle index (13), DSM-III (10), and the CORE system (10)--the last essentially assessing psychomotor change; Research Diagnostic Criteria (RDC) (7) and an endogeneity symptom scale (2) were the least differentiating. A subsample of "composite melancholics" was derived, comprising 138 who met "melancholia" criteria for DSM-III, RDC, and CORE, and they were contrasted with residual depressives. The composite melancholics were older, had had a briefer depressive episode, and differed significantly on 12 risk factors, essentially being less likely to report deprivational experiences such as deficient parenting and dysfunctional marital relationships. We suggest that such a risk factor strategy is of potential use in refining the clinical definition of melancholia.

Background: There have only been a few studies of the role of carbamazepine in the management of treatment-resistant depression., Method: The response to carbamazepine of 16 melancholic patients, who had been depressed for an extended period despite a number of standard treatments, was studied retrospectively., Results: Seven patients (44%) had a moderate or marked improvement. The responders included both psychotic and nonpsychotic depressives, and patients with concurrent organic brain disease. There was, however, a high rate of complications, with 5 of these 7 responders (71%) having to discontinue carbamazepine because of adverse effects. This high rate of complications may have reflected the older age of our sample., Conclusion: These findings suggest the efficacy of carbamazepine in melancholic patients who have not responded to conventional treatments, but indicate that the high rate of significant side effects may limit its long-term usefulness.

The interaction of age and depression was investigated by comparing differences between elderly (greater than or equal to 60 years old) and younger consecutive in- and out-patient referrals to a tertiary referral mood disorders unit. Older patients with unipolar major depressive episode were more likely to be psychotic and agitated regardless of depressive subtype and less likely to have personality inadequacies or a family history of affective disorder. In this sample, elderly depressives' rating of diagnosis, severity, endogeneity and social impairment were similar, irrespective of age of first onset of depression, but a positive family history and personality abnormalities were less likely in late-onset depressives.

One hundred and forty non-depressed primiparous women in a stable relationship completed two personality measures (the EPI and the IPSM) antenatally, and were then assessed for depression at several times post-natally. The risk of depression at six months was increased up to tenfold by high interpersonal sensitivity and threefold by high neuroticism. When previously depressed women were excluded from analyses, high interpersonal sensitivity and, to a lesser extent, high neuroticism were still associated with an increased risk of being depressed. Interpersonal sensitivity, as measured, is suggested as a refined personality risk factor to both the onset and recurrence of depression.

To examine the necessary and sufficient status of delusions and hallucinations as clinical features of psychotic (delusional) depression, we studied a consecutive sample of 137 patients meeting DSM-III, RDC and our clinical criteria for endogenous depression/melancholia, of whom 35 had delusions and/or hallucinations, and represented our putative 'psychotic depressives' (PDs). The PDs were contrasted with the remaining 'endogenous depressives' (the EDs), and an age- and sex-matched subsample of the latter, the MEDs. Univariate and multivariate analyses of clinical features established that, in addition to the presence of delusions and/or hallucinations, the PDs could be distinguished in particular by severe psychomotor disturbance, as well as by sustained and unvarying depressive content, the absence of any diurnal mood variation and by constipation. Latent class analyses suggested that overt psychotic features (such as delusions and hallucinations) were sufficient but not necessary for a subject to be assigned to the 'psychotic' latent class, and a subsequent chart review suggested that, in some PDs actual psychotic features may not be able to be elicited because of severe psychomotor change, suggesting that clinical reliance on eliciting delusions or hallucinations may result in a number of 'masked psychotic depressives' escaping valid diagnosis.

We review research literature on psychotic (delusional) depression, including demographic, illness pattern, clinical, biological marker and treatment issues. Secondly, we report a study of a consecutive sample of 137 patients meeting criteria for DSM-III melancholia, RDC definite endogenous depression and our "clinical" criteria for endogenous depression, of whom there were 35 "psychotic depressives" (PDs). The PDs were contrasted with the remaining 76 depressives (EDs) and with an age and sex-matched subset (MEDs). The PDs were distinctly older than the EDs at assessment and at initial onset of any affective disorder. Compared to the MEDs, they tended to have longer illnesses, were more likely to be hospitalised (and to have longer stays), to receive (in the past and for the current episode) combination antipsychotic/antidepressant medication and/or ECT, and to have a poorer course over the following year. They were no more likely to have a bipolar pattern, a family history of depressive disorder, schizophrenia or alcoholism, or vegetative depressive features. Developmental psychosocial stressors and antecedent life event stressors were not over-represented. Most of the PDs had delusions, one-fifth reported hallucinations and psychomotor disturbance was marked. Other differential clinical findings were sustained mood disturbance, constipation, and the absence of a diurnal variation in mood and energy.

To study putative differences in central neurotransmitter function in depressive subtypes, growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and prolactin responses to the alpha 2-noradrenergic receptor agonist clonidine (1.3 micrograms/kg i.v.) were examined in 26 subjects with major depression, 13 of whom had melancholia. The responses of 10 of these endogenous/melancholic subjects were compared with those of 10 controls who were matched to the patients on age, sex, and menopausal status. In 15 of the depressed subjects, prolactin and cortisol responses to the putative serotonergic agonist fenfluramine were also examined to test for associations between these challenges. There were no significant differences in any of the responses between melancholic and nonmelancholic depressive subgroups after controlling for age and sex. With the exception of a greater reduction in ACTH in the endogenous/melancholic subjects, there were also no significant differences in hormonal responses between these patients and controls. There was, however, a significantly greater reduction in systolic blood pressure in the control subjects. There were no significant correlations between the responses to clonidine and fenfluramine. The findings suggest that clonidine at a dosage of 1.3 micrograms/kg is neither able to differentiate reliably between depressive subtypes nor to differentiate reliably between depressed and control subjects.

The relevance of three different interpersonal risk factors to post-natal depression was examined. One hundred and forty-nine non-depressed women completed the Parental Bonding Instrument (PBI), the Intimate Bond Measure (IBM) and the Interpersonal Sensitivity Measure (IPSM) antenatally. Post-natal depression was identified using the Edinburgh Post-natal Depression Scale (EPDS) at 1, 3 and 6 months post partum. Significantly increased risks for post-natal depression were found for the women whose spouses provided low care or were overcontrolling and for women with high interpersonal sensitivity. Low maternal care and paternal overprotection were additional predictors when multiple regression analyses were used. Importantly, the different risk factors had their impact at different times post partum. The implication of these findings is discussed.

The strongest statistical support for the binary view of depression has been provided by factor (principal components) analytic studies which delineate a bipolar factor with features interpreted as reflecting "endogenous depression" and "neurotic depression" at opposing poles. We review the seminal studies to suggest instead that the bipolar factor has generally polarised depression and anxiety, and that no such entity or symptom complex of "neurotic depression" has been isolated. Instead "neurotic depression" has been defined principally by features of anxiety and personality style. We argue that the suggested entity is, in fact, a pseudo-entity, being no more than a residual group of non-depressive features without any significant intrinsic depressive characteristics. We support our interpretation by showing comparable solutions in published studies of depressives alone, contrasted with separate analyses of anxious and depressed patients. We also report two studies in which the "neurotic depressive" pole is made to appear and disappear by the inclusion and exclusion of anxiety items. As factor analytic studies have defined the "residual" pole so variably, we argue that some features held to distinguish neurotic depression are of no utility and that such a diagnosis is meaningless. We suggest that the clinician should not proceed (after excluding endogenous depression) to conclude that the default option is necessarily an entity "neurotic depression" and that instead a heterogeneous group of options (e.g. anxiety, personality disorder) require review. If the "neurotic depressive" type of the multivariate analytic studies is a pseudo-entity, then a modified unitary view of depression may be valid.

Seventy-five patients with remitted depression were categorized as having melancholic-endogenous or non-melancholic-nonendogenous depression according to DSM-III criteria, Research Diagnostic Criteria, and the Newcastle endogeneity scale. The patients' scores on four personality scales--the Eysenck Personality Inventory, the Interpersonal Dependency Inventory, locus of control, and the Interpersonal Sensitivity Measure--were then compared. Patients with nonmelancholic-nonendogenous depression were generally rated as having more vulnerable personality styles, but the differences were dependent on the particular diagnostic system used. A principal components analysis isolated three underlying personality constructs--dependency, introversion, and timidity. Patients with nonmelancholic-nonendogenous depression scored as significantly more dependent.

In order to study putative differences in central neurotransmitter function in depressive subtypes, serum cortisol and prolactin responses to the putative serotonin agonist fenfluramine were examined in 30 subjects with major depression. Patients with endogenous depression (melancholia) as defined by each of ICD-9, DSM-III, RDC and Newcastle scale demonstrated a reduced prolactin response to 60 mg oral fenfluramine when compared with non-endogenous subjects. This was independent of either prolactin or cortisol baseline levels, and indicates that there are differences in brain neurotransmitter function in the endogenous and non-endogenous subtypes of depression. Basal prolactin levels were reduced in bipolar compared with unipolar subjects, and delusional compared with non-delusional patients, although there were no differences in the prolactin responses to fenfluramine between these subgroups. Basal cortisol levels and cortisol response to fenfluramine did not distinguish between any of the subtypes.

The possibility that separation of a categorical depressive disease ('melancholia') from remaining depressive disorders can be improved by assessment of mental state signs was examined in patients treated by representative Sydney psychiatrists and patients referred to a specialised mood disorders unit. A set of signs, principally assessing retardation, was derived within the two samples by principal-components and latent-class analyses. Scores were significantly correlated with clinical, DSM-III, and RDC diagnoses, and appeared independent of severity, suggesting that melancholia can be defined phenomenologically. Scores were also associated with several 'validating' factors. Comparative analyses of a refined list of melancholia symptoms suggested that ratings of defined signs are likely to have greater capacity than symptom ratings to differentiate melancholia from residual depressive disorders.

Associations between perceptions of dysfunctional current intimate relationships and subtypes of depressive disorders were quantified in a sample of 136 patients, using the Intimate Bond Measure (IBM). Deficient care was two to three times more likely to be reported by patients with non-melancholic disorders than by matched subjects, but was no more likely to be reported by patients with melancholic disorders, suggesting a risk factor selective for depressive type. Patients who reported markedly deficient care in childhood were more likely to report very poor current intimate relationships. For the remaining patients, however, no evidence of continuity between a dysfunctional parental relationship and a current dysfunctional intimate relationship was found.