The duration of undiagnosed bipolar disorder: effect on outcomes and treatment response.

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

Screening for bipolar disorder: does gender distort scores and case-finding estimates?

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

Is the DSM-5 duration criterion valid for the definition of hypomania?

BACKGROUND: DSM-IV and DSM-5 impose a 4 day duration criterion for hypomanic episodes yet several studies have suggested that such an imposition may be invalid. We report a study involving a large sample pursuing the likely salience of the DSM duration criterion. METHODS: We analyzed data on hypomanic symptoms provided by two bipolar screening measures - the Mood Disorders Questionnaire (MDQ) and the Mood Swings Questionnaire (MSQ) in a sample of 501 patients meeting DSM and other symptom criteria for a bipolar II disorder (BP II) and contrasted data for 186 meeting the DSM minimum duration of 4 days and 315 experiencing episodes lasting less than 4 days (i.e. 'standard' vs. 'brief' groups). RESULTS: The brief group reported slightly less severe hypomanic episodes, but the two groups did not differ on a number of illness correlates including age of onset of depressive and of hypomanic episodes, or by rates of depressive and bipolar conditions in first-degree family members. LIMITATIONS: The possibility of false positive BP II diagnoses, especially with brief hypomanic episodes, must be conceded while our examination of clinical symptoms was limited to two measures. CONCLUSIONS: This study is consistent with previous studies suggesting that the DSM duration of 4 or more days for a diagnosis of a hypomanic episode is unnecessary to the clinical definition of a BP II disorder. Its preservation is likely to exclude a substantive number of those with a true BP II condition.

High-risk behaviour in hypomanic states.

BACKGROUND: Risk-taking behaviours during hypomanic states are recognised, however the high-risk nature of some behaviours-including the potential for harm to both the individual and others-has not been detailed in the research literature. The current study examines risk-taking behaviours and their consequences (including their potential for impairment) in those with a bipolar II condition. METHOD: Participants were recruited from the Sydney-based Black Dog Institute Depression Clinic. Diagnostic assignment of bipolar II disorder was based on clinician judgement and formal DSM-IV criteria. Participants completed a series of detailed questions assessing previous risk-taking behaviours during hypomanic states. RESULTS: The sample comprised a total of 93 participants. Risk-taking behaviours during hypomania included spending significant amounts of money, excessive alcohol or drug use, dangerous driving and endangering sexual activities. Key consequences included interpersonal conflict, substantial financial burden and feelings of guilt, shame and remorse. Despite recognition of the risks and consequences associated with hypomanic behaviours, less than one-fifth of participants agreed that hypomania should be treated because of the associated risks. LIMITATIONS: Study limitations included a cross-sectional design, reliance on self-report information, lack of controlling for current mood state, and comprised a tertiary referral sample that may be weighted to more severe cases. Findings may therefore not be generalisable and require replication. CONCLUSIONS: Risk-taking behaviours during hypomania are common, and often linked with serious consequences. Whilst hypomania is often enjoyed and romanticised by patients-leading to ambivalence around treatment of such states-careful consideration of the impact of risk-taking behaviour is necessary, while the study raises the question as to what is 'impairment' in hypomania. Findings should advance clinical management by identifying those high-risk behaviours that would benefit from pre-emptive weighting in developing individual's wellbeing plans for managing the condition.

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.

Does testing for bimodality clarify whether the bipolar disorders are categorically or dimensionally different to unipolar depressive disorders?

BACKGROUND: It has been held that if bipolar disorder is categorically distinct, it should differentiate from unipolar depressive disorders by showing bimodality or a 'zone of rarity' in bipolar symptom scores. Two previous studies have failed to demonstrate bimodality. We undertook a third study. METHODS: A total of 1106 patients attending the Black Dog Institute Depression Clinic completed the Mood Disorders Questionnaire (MDQ), in addition to undergoing clinical assessment by an Institute psychiatrist. RESULTS: The distributions of scores for the total number of hypomanic symptoms endorsed by unipolar and bipolar patients were both skewed, with the bipolar group endorsing a high number of hypomanic symptoms and the unipolar group endorsing few symptoms--and so giving the impression of an 'even' distribution generated by two quite distinctly differing sub-groups. However, formal statistical analyses involving mixed modelling provided no clear evidence that a bimodal distribution provided a better fit to the data than a unimodal one. CONCLUSIONS: Failure to statistically demonstrate a 'point of rarity' did not marry with visual inspection of the plotted data--which clearly suggested two groups putatively capturing those with bipolar and unipolar disorders respectively. The paper considers some limitations to the emphasis on 'bimodality' in differentiating potentially differing conditions.

Temperament and personality in bipolar II disorder.

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

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.

Screening for bipolar disorder: the utility and comparative properties of the MSS and MDQ measures.

BACKGROUND: Our objective was to further determine the diagnostic utility of the Mood Swings Survey (MSS) in distinguishing bipolar and unipolar disorders, and draw comparisons between this measure and the widely-used Mood Disorder Questionnaire (MDQ). METHODS: A total of 247 consecutively recruited patients attending the Black Dog Institute Depression Clinic were administered the Mood Swings Survey (MSS) as part of a computerized Mood Assessment Program (MAP), in addition to undergoing clinical assessment by two independent psychiatrists. The MDQ, along with a structured interview assessing DSM-IV criteria for bipolar disorder, was administered to a sub-sample of patients. RESULTS: The MSS-46 demonstrates comparable sensitivity and specificity to the MDQ (86.5% and 60.0% vs. 78.8% and 71.4%) when using pre-established cut-off scores. MSS diagnoses embedded within the computerized program correctly classified 82.2% of cases when compared to clinician diagnosis. Optimal cut-off scores derived in the current sample were > or = 35 (Se=88.5%, Sp=60.0%) for the MSS-46, and > or = 7 (Se=78.8%, Sp=71.4%) for the MDQ, indicating acceptable stability of cut-off scores in differing samples for both measures. LIMITATIONS: ROC analyses compromised 'true' estimates of MSS sensitivity and specificity as a number of patients who did not affirm the initial screener question were excluded from these analyses. CONCLUSIONS: Further work is required to evaluate the diagnostic utility of the MSS in differing clinical and community samples to determine the stability of its cut-off score and to refine the item set.