Discriminating melancholic and non-melancholic depression by prototypic clinical features.

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.

Keeping mum about dad: "contracts" to protect gamete donor anonymity.

This article considers the legal status of so-called contracts for anonymity between fertility clinics and donors of gametes that were made in the period before legislation authorising disclosure. It notes that while clinics frequently cite the existence of these "contracts" to argue against retrospective legislation authorising disclosure of the donor's identity, they may be nothing more than one-sided statements of informed consent. However, the article notes that even if an agreement between a donor and a clinic is not contractual, it does not follow that a person conceived through assisted reproductive technology has any right of access to the identity of the donor. The writer has not been able to locate examples of written promises by the clinics promising anonymity. There are written promises by the donors not to seek the identity of the recipients. These promises do not bind the resulting offspring nor do they appear to be supported by consideration. The article suggests that the basis for any individual donor to restrain a clinic from revealing their identity may be found in promissory estoppel. Nevertheless, there is no real issue in Australia concerning clinics revealing these details absent legislative authority. The issue is whether parliaments will legislate to authorise the disclosure. The article notes that it would be rare for parliaments to legislate to overturn existing legal contracts but suggests that the contract argument may not be as strong as has been thought.

A diagnostic profile of those who return a false positive assignment on bipolar screening measures.

OBJECTIVES: Our aim was to identify the diagnostic profile of patients classified as 'false positives' on two bipolar screening measures; the Mood Swings Questionnaire (MSQ) and the Mood Disorders Questionnaire (MDQ). METHODS: A total of 1534 patients attending the Black Dog Institute Depression Clinic completed the MSQ-46, and a smaller subset of 852 completed the MDQ. All patients underwent clinical assessment by one or more Institute psychiatrists. RESULTS: Using clinical assignment (i.e. bipolar vs. unipolar) as the criterion measure for assessing the screening measures, the overall agreement rates were 84% for the MSQ-46 and 74% for the MDQ. Patients identified as 'false positives' were most likely to be clinically diagnosed as having a unipolar non-melancholic depression (37% for MSQ-46; 46% for MDQ), or a primary anxiety condition with secondary non-melancholic depression (19% for MSQ-46; 15% for MDQ). In addition, within the unipolar non-melancholic group, 46% of the MSQ-46 assigned false positives and 63% of the MDQ assigned false positives had co-morbid anxiety conditions. CONCLUSIONS: These findings suggest that patients with anxiety conditions account for a significant proportion of false positive diagnoses on bipolar screening tests - a finding that should be conceded in the development and refinement of such screening measures and in clinical assessment of the possibility of a bipolar disorder.

The impact of detecting bipolar disorder in previously diagnosed unipolar patients at a specialist depression clinic.

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.

Inching toward Bethlehem: mapping melancholia.

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.

Synthesis of glucose derivatives modified at the 4-OH as potential chain-terminators of cellulose biosynthesis; herbicidal activity of simple monosaccharide derivatives.

A series of D-glucose derivatives that have been modified at C-4 were synthesised from D-galactose as potential chain terminators of cellulose biosynthesis. Two compounds displayed herbicidal activity in pre-emergence tests and in addition a cell expansion assay at higher concentrations revealed symptomology of a third compound that was indicative of inhibition of cellulose biosynthesis.

Omega-3 deficiency associated with perinatal depression: case control study.

Women are depleted of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during the perinatal period due to fetal diversion. An association has been shown between lowered n-3 PUFAs and depression in general. We therefore hypothesise that women with lower n-3 PUFA levels are at greater risk of depression during pregnancy. Sixteen depressed and 22 non-depressed women were recruited during the third trimester and fasting bloods were taken for plasma fatty acid analysis. High docosahexaenoic acid (DHA), high total n-3 and a low n-6:n-3 ratio were associated with significantly lower odds of depression. After adjustment for parity, age and education level, those with high DHA still had significantly lower odds of being depressed. Those with high total n-3 and a low n-6:n-3 ratio were also at significantly reduced risk of depression, although the magnitude of the difference was reduced. Study results quantified women with lower omega-3 PUFA levels as being six times more likely to be depressed antenatally, compared to women who had higher omega-3 PUFA levels. The prophylactic benefits of supplementation either prenatally or during pregnancy require close study to assess whether omega-3 PUFAs play a role in the prevention of perinatal depression.

Omega-3 fatty acids as a treatment for perinatal depression: randomized double-blind placebo-controlled trial.

OBJECTIVE: Epidemiological, biological marker and treatment studies, as well as neuroscientific theories, indicate a possible link between omega-3 fatty acids and perinatal depression (PND). Hence the aim of the present study was to assess whether omega-3 fatty acid treatment is superior to placebo in the treatment of PND. METHOD: A double-blind randomized placebo-controlled trial was undertaken. Women with major depression during the perinatal period received either fish oil or placebo for six weeks. Changes in depression scores were recorded weekly. RESULTS: A total of 26 subjects were recruited and there was no significant difference in depression scores between those receiving fish oil and those receiving the placebo. CONCLUSIONS: This is formally a negative study, suggesting that there is no benefit for omega-3 fatty acids over placebo in treating PND. The reason could be that the study was underpowered due to recruitment difficulties and therefore we suggest that it may be unwise to interpret this result as conclusive. Omega-3 is a natural product that is a safe and well-tolerated treatment. Further research is therefore needed in this area to establish whether omega-3 fatty acids are an effective treatment for PND.

The role of fatty acids in the development and treatment of mood disorders.

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.

Omega-3 fatty acids and mood disorders.

OBJECTIVE: This article is an overview of epidemiological and treatment studies suggesting that deficits in dietary-based omega-3 polyunsaturated fatty acids may make an etiological contribution to mood disorders and that supplementation with omega-3 fatty acids may provide a therapeutic strategy. METHOD: Relevant published studies are detailed and considered. RESULTS: Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega-3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. CONCLUSIONS: Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach. This review identifies a number of hypotheses and studies for consideration. In particular, the authors argue for studies clarifying the efficacy of omega-3 supplementation for unipolar and bipolar depressive disorders, both as individual and augmentation treatment strategies, and for studies pursuing which omega-3 fatty acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is likely to provide the greatest benefit.

Role of omega-3 fatty acids as a treatment for depression in the perinatal period.

OBJECTIVES: To consider the possible rationale and utility of omega-3 fatty acids as a treatment for depression in the perinatal period. METHOD: A review of published and unpublished research was undertaken, using electronic databases, conferences proceedings and expert informants. RESULTS: Relevant bodies of evidence include an epidemiological link between low fish intake and depression. Laboratory studies show correlations between low omega-3 fatty acid levels and depression, as well as reduced levels of omega-3 in non-depressed women during the perinatal period. Treatment studies using omega-3 in patients with mood disorders further support an omega-3 contribution, as do neuroscientific theories. Research into omega-3 and infant development also highlights potential effects of depletion in the perinatal period and supports infant safety and benefits of supplementation. CONCLUSIONS: There is a relative lack of knowledge about the safety of standard antidepressants in the perinatal period. There is a clear need for more research into alternative treatments, such as omega-3 fatty acids, in the management of depression in the perinatal period.

The big idea: clients' perspectives of change processes in cognitive therapy.

This study reports on analyses carried out by the authors on five 'end of therapy' evaluations conducted with clients who had received a brief course of cognitive therapy for depression. The clients' evaluation was based on Elliott's (1996) Change Interview Schedule. The transcripts were then analysed using grounded theory methods, and arranged into 10 categories and three category clusters. The category clusters included 'the listening therapist', 'the big idea' and 'feeling more comfortable with self'. Clients' reported cognitive and emotional processes fit with Stiles et al.'s (1990) assimilation model.

Practice-based outcomes of dialectical behaviour therapy (DBT) targeting anger and violence, with male forensic patients: a pragmatic and non-contemporaneous comparison.

OBJECTIVE: To examine the effectiveness of an eighteen-month treatment based on dialectical behaviour therapy (DBT) targeting anger and violence, on a group of male forensic patients. METHOD: Eight male forensic patients in a high security hospital who met the criteria for borderline personality disorder measured by the Personality Assessment Inventory underwent 18 months of treatment. They completed three psychometric tests at pre-, mid- and post-treatment and at a six-month follow up. A comparison group (TAU) of nine patients, assessed as having similar personality disorders, received the usual treatment available in the hospital but excluding DBT. They completed the same tests at the same time intervals corresponding to the pre-, mid- and post-testing of the DBT group. In both groups, all instances behaviours related to anger and violence were monitored for three six-month periods, prior to, during and post-treatment. RESULTS: Overall, patients in the DBT group made greater gains than patients in the TAU group in reducing the seriousness of violence-related incidents, and in self report measures of hostility, cognitive anger, disposition to anger, outward expression of anger and anger experience. CONCLUSION: The results suggest a potential for DBT to impact positively and lastingly on violent behaviour and components of anger in male forensic patients when compared with standard treatment. The power of the current study to detect group differences was reduced by small ns, large confidence intervals, and a non-contemporaneous comparison group. Cost-effective strategies are proposed to take forward research on DBT with this population.

Time is of the essence: A selective review of the fall and rise of brief therapy research.

For compelling reasons of equity and the advance of public health, brief psychotherapy has become the dominant format in both practice and research. One consequence of this is the apparent decline of a distinct stream of brief therapy research. However, much of the agenda formerly identified with that research stream is of increasing importance to the field. Time is indeed of the essence in current psychotherapy research. For example, factors conducive to the time efficiency of brief psychodynamic therapy have been described recently. The important question 'How much therapy is enough?' has been addressed by studies inspired by the dose-response analysis of Howard and colleagues. The value of ultra-brief interventions has been examined. These issues are considered in a selective review, drawing in particular on the work of the Sheffield/Leeds psychotherapy of depression research group. This research treats the number of treatment sessions as an independent variable, thereby providing a causal analysis of the dose-response relationship over a range from two to 16 sessions, illuminated by a comparative analysis of change processes in treatments of different durations. Its results enable some specification of the extent and nature of incremental benefit derived from additional sessions in the psychotherapy of depression.

Appraisal of published reviews of research on psychotherapy and counseling with adults 1990-1998.

Reviews and meta-analyses of research on adult psychotherapy and counseling with adults published in English from 1990 to 1998 (N = 255) were rated according to the criteria advanced by A. D. Oxman and G. H. Guyatt (1988). A majority of the reviews fell substantially short of these basic standards; on average, review articles met only half of the 8 criteria, and only 20% met 7 or more of the criteria. Common deficiencies included failure to describe comprehensive search methods used to locate studies; failure to explain inclusion and exclusion criteria for studies; and failure to provide reliable, unbiased assessments of the studies reviewed. The reviews showed no tendency to improve over the period studied.

Outcomes of patients completing and not completing cognitive therapy for depression.

OBJECTIVES: The aims of this study were to use symptom intensity measures collected at each session (1) to describe the outcomes of clients who received cognitive therapy (CT) for depression in a clinically representative sample, and (2) to compare the outcomes of clients who completed the agreed number of sessions with those who did not. DESIGN AND METHOD: Clients (N = 58) contracted to attend between 12 and 20 sessions of CT completed the Beck Depression Inventory (BDI) immediately prior to each therapy session. The BDI and other measures were collected at intake and, for those who completed therapy, at a post-therapy assessment. RESULTS: Completers' BDI scores improved significantly from intake to post-treatment and significantly more from intake to their final session than did those of non-completers. However, when non-completers' final session scores were matched with scores of randomly selected completers at the corresponding session, the difference in improvement was not significant. A significantly higher proportion of clients who completed the agreed number of sessions achieved reliable and clinically significant change (71.4%, 25/35), compared with just 13% (3/23) of clients who did not. CONCLUSIONS: (1) CT for depression can be effective in a clinically representative population. (2) Attrition from clinical trials may bias estimates of treatment effectiveness.

Convergent validity of the Agnew Relationship Measure and the Working Alliance Inventory.

The convergent validity of the Agnew Relationship Measure (ARM) and the Working Alliance Inventory (WAI) was assessed in samples drawn from 2 comparative clinical trials of time-limited psychotherapies for depression. In 1 sample, clients (n = 18) and therapists (n = 4) completed self-report versions of both measures after every session (n = 198). In the other sample, clients (n = 39) and therapists (n = 6) completed the ARM, and observers subsequently rated selected audiotaped sessions (n = 78) using the WAI. In both samples, the ARM's core alliance scales (Bond, Partnership, and Confidence) were correlated with the WAI's scales (Bond, Tasks, and Goals) strongly when assessed within client and therapist perspectives and, with some qualifications, moderately when assessed between client, therapist, and observer perspectives, supporting the assumption that the ARM and the WAI measure some of the same core constructs.