Comparative familial aggregation of bipolar disorder in patients with bipolar I and bipolar II disorders.

OBJECTIVE: We sought to quantify the prevalence and differential prevalence of a bipolar disorder among family members of patients with a bipolar I or II disorder. METHODS: The sample comprised 1165 bipolar and 1041 unipolar patients, with the former then sub-typed as having either a bipolar I or II condition. Family history data was obtained via an online self-report tool. RESULTS: Prevalence of a family member having a bipolar disorder (of either sub-type) was distinctive (36.8%). Patients with a bipolar I disorder reported a slightly higher family history (41.2%) compared to patients with a bipolar II disorder (36.3%), and with both significantly higher than the rate of bipolar disorder in family members of unipolar depressed patients (18.5%). CONCLUSIONS: Findings support the view that bipolar disorder is heritable. The comparable rates in the two bipolar sub-types support the positioning of bipolar II disorder as a valid condition with strong genetic underpinnings.

Clinical Characteristics Associated With Treatment-Resistant Bipolar Disorder.

There has been limited consideration and empirical studies on treatment-resistant bipolar disorder (TRBD). This exploratory study was designed to identify factors contributing to TRBD in patients with a bipolar (I or II) disorder. Patients were categorized with "low," "medium," or "high" levels of treatment resistance based on a) the total number of psychiatric medications received and, for a second analysis, b) the number of mood stabilizer medications received. The study identified a number of factors associated with TRBD, such as being female and older and having an older age at illness onset, a higher incidences of family depression, less likelihood of being in paid employment, a higher number of lifetime stressors, medical conditions and comorbid anxiety disorders, a different personality and temperament profile, and more regular use of benzodiazepines. There were few factors associated with TRBD when defined by number of mood stabilizers trialed. Potential explanations for these findings were explored.

Determinants of Treatment-Resistant Depression: The Salience of Benzodiazepines.

Treatment-resistant depression (TRD) lacks consensus regarding its definition, despite being common in clinical practice. This study was designed to identify factors contributing to TRD in patients diagnosed with a major depressive disorder. Patients were grouped into "low," "medium," and "high" treatment-resistant (TR) groups based on the number of medications that had been prescribed for their depression. We identified a number of factors linked to TRD. The high TR group was generally older, had a longer depressive episode duration, a higher number of comorbid medical and anxiety disorders, a lower education, and were less likely to be in full-time employment. They also reported less trait irritability and were more likely to view medication as being a contributor to their current depression. Some differences between non-melancholic and melancholic subsets were evident and point to the benefits in research on TRD analyzing the two diagnostic groups separately. The most striking finding was benzodiazepine use, which was significantly more common in the high TR group and within both the melancholic and non-melancholic subsets. Some potential explanations for this finding are offered.

The impact of being newly diagnosed with a bipolar disorder and the short-term outcome of disorder-specific management.

OBJECTIVES: The aim of the study was to determine the impact of a first-time diagnosis of bipolar disorder in patients previously generally managed as having a unipolar disorder, and to quantify the impact of disorder-specific management strategies for such newly diagnosed patients over the following three months. METHODS: A total of 157 patients receiving a diagnosis of bipolar disorder for the first time by a psychiatrist at a specialist depression clinic completed a research interview and questionnaires, with 106 (68%) also completing 12-week quantitative and qualitative evaluations. Assessing psychiatrists undertook baseline and follow-up assessments recording management changes, reactions to the diagnosis and global changes in functioning over time. RESULTS: The majority of patients had a positive response to receiving a diagnosis of bipolar disorder, and most implemented a number of clinician-suggested bipolar management strategies. Patients showed improvement on five of the six self-report measures over the three-month study period. Multivariate analyses quantified lamotrigine as making the most distinctive contribution to 'improver' status, particularly for the bipolar II disorder subset. CONCLUSIONS: Results are encouraging in identifying a generally positive acceptance of a diagnosis of bipolar disorder, improved outcome following the introduction of diagnostic-specific management components, and a distinctive contribution of lamotrigine to improved three-month outcome.

Is there consensus across international evidence-based guidelines for the psychotropic drug management of bipolar disorder during the perinatal period?

BACKGROUND: Clinicians treating a patient with bipolar disorder who is pregnant or breastfeeding may seek advice from bipolar management guidelines that provide recommendations for perinatal treatment. We examine the consistency of such recommendations across several evidence-based guidelines. METHODS: A literature search in the National Guideline Clearinghouse, the Cochrane Database of Systematic Reviews, PsycInfo and PubMed was undertaken using the search terms "bipolar disorder" and "guidelines," which generated 11 sets of evidence-based guidelines published by professional organizations during the 2005-2015 period. Information relevant to management during the perinatal period was reviewed by two independent reviewers, with key themes qualitatively analysed. RESULTS: There was a moderate level of agreement across guidelines regarding the potential teratogenic effects of lithium, sodium valproate and carbamazepine, with most highlighting caution in using these medications during the perinatal period. There was less agreement regarding the safety risks associated with lamotrigine, antipsychotics, and antidepressants, and little agreement regarding the risks and recommendations of medications during breastfeeding. LIMITATIONS: Some differences in recommendations are likely due to varying publication dates, with recent guidelines having more up-to-date evidence available to use when formulating recommendations. Further, due to ethical issues surrounding pregnancy and infant research, the evidence used to formulate perinatal recommendations is largely based on retrospective reports and/or case studies. It is therefore unrealistic to expect such recommendations to be entirely consistent and based on rigorous evidence. CONCLUSIONS: While there was some consistency across guidelines on key recommendations, there were also substantial inconsistencies, with the latter risking compromising clinical management.

Is 'subthreshold' bipolar II disorder more difficult to differentiate from borderline personality disorder than formal bipolar II disorder?

Recent research indicates that borderline personality disorder (BPD) can be diagnostically differentiated from the bipolar disorders. However, no studies have attempted to differentiate participants with sub-threshold bipolar disorder or SubT BP (where hypomanic episodes last less than 4 days) from those with a BPD. In this study, participants were assigned a SubT BP, bipolar II disorder (BP II) or BPD diagnosis based on clinical assessment and DSM-IV criteria. Participants completed self-report measures and undertook a clinical interview which collected socio-demographic information, a mood history, family history, developmental history, treatment information, and assessed cognitive, emotional and behavioural functioning. Both bipolar groups, whether SubT BP or BP II, differed to the BPD group on a number of key variables (i.e. developmental trauma, depression correlates, borderline personality scores, self-harm and suicide attempts), and compared to each other, returned similar scores on nearly all key variables. Borderline risk scores resulted in comparable classification rates of 0.74 (for BPD vs BP II) and 0.82 (for BPD vs sub-threshold BP II). Study findings indicate that both SubT BP and BP II disorder can be differentiated from BPD on a set of refined clinical variables with comparable accuracy.

Vitamin D and depression.

OBJECTIVE: To examine whether vitamin D deficiency or insufficiency is associated with depression and whether vitamin D supplementation is an effective treatment for depression. METHOD: Empirical papers published in recent years were identified using three search engines and online databases - PubMed, Google Scholar and Cochrane Database. Specific search terms used were 'vitamin D', 'depression' and 'treatment' and articles were selected that examined the association between vitamin D deficiency/insufficiency and depression, vitamin D supplementation and Vitamin D as a treatment for depression. Our review weighted more recent studies (from 2011), although also considered earlier publications. RESULTS: Empirical studies appear to provide increasing evidence for an association between vitamin D insufficiency and depression, and for vitamin D supplementation and augmentation in those with clinical depression who are vitamin D deficient. Methodological limitations associated with many of the studies are detailed. LIMITATIONS: Articles were restricted to those in the English language while publication bias may have weighted studies with positive findings. CONCLUSIONS: There remains a need for empirical studies to move beyond cross-sectional designs to undertake more randomised controlled longitudinal trials so as to clarify the role of vitamin D in the pathogenesis of depression and its management, as well as to establish whether currently suggested associations are clinically significant and distinctive.

Examining for any impact of climate change on the association between seasonality and hospitalization for mania.

BACKGROUND: Studies have established higher rates of hospitalization for mania in spring and summer and posit various explanatory climatic variables. As the earth's climate is changing, we pursue whether this is reflected in the yearly seasonal variation in hospitalizations for mania. This would be indicated by the presence of secular changes in both the hospitalization seasonal pattern and climatic variables, and associations between both variable sets. METHODS: Data were obtained for 21,882 individuals hospitalized to psychiatric hospitals in the Australian state of New South Wales (NSW) over a 14-year period (2000-2014) with ICD-diagnosed mania - and with NSW population figures and salient climatic variables collected for the same period. Regression analyses were conducted to examine the predictive value of climate variables on hospital admissions. RESULTS: Data quantified a peak for manic admissions in spring of the southern hemisphere, in the months of October and November. There was a significant linear increase in manic admissions (0.5%/year) over the 14-year time period, with significant variation across years. In terms of climatic variables, there was a significant linear trend over the interval for solar radiation, although the trend indicated a decrease rather than an increase. Seasonal variation in admissions was most closely associated with two climate variables - evaporation in the current month and temperature in the previous month. LIMITATIONS: Hospitalization rates do not necessarily provide an accurate estimate of the onset of manic episodes and findings may be limited to the southern hemisphere, or New South Wales. CONCLUSIONS: While overall findings do not support the hypothesis that climate change is leading to a higher seasonal impact for manic hospital admissions in the southern hemisphere, analyses identified two climate/weather variables - evaporation and temperature - that may account for the yearly spring excess.

Seasonal variations in rates of hospitalisation for mania and hypomania in psychiatric hospitals in NSW.

BACKGROUND: A number of studies have established that manic patients have higher rates of hospitalization in spring. There appears to be no data evaluating whether there is any seasonal variation in hospitalization for those with hypomania. METHODS: Data were obtained for 27,255 individuals hospitalized in NSW psychiatric hospitals over a 14-year period (2000-2014) for ICD-10 diagnosed mania or hypomania. Graphical analyzes examined rates of hospitalisation for hypomania and mania separately, using monthly and seasonal averages. RESULTS: Admission rates were higher for mania compared to hypomania and there was a similar pattern across seasons - with admissions being at their lowest in autumn, increasing in winter, and at their highest for spring. Monthly percentage scores were similar for mania and hypomania and indicated lower admission rates in the first six months of the year (January-June), with a sudden increase in July, and followed by a more gradual increase until December. LIMITATIONS: Hospitalization rates do not necessarily provide an accurate estimate of the onset of hypo/manic episodes, while the validity of those assigned a diagnosis of hypomania could not be established, allowing the possibility that many may have had manic episodes. CONCLUSIONS: Findings indicate that hypomania shows a similar seasonal pattern to mania.

Anxious, irritable and hostile depression re-appraised.

BACKGROUND: While classification of the depression disorders currently favors a dimensional model, this study considered the empirical support for a spectrum model linking personality with phenotypic depressive features, specifically examining patients with 'irritable', 'hostile' and 'anxious' depression. METHODS: Pearson correlations were performed for Temperament and Personality (T&P) scales and state depressive patterns (irritable, hostile and anxious) for patients clinically diagnosed with unipolar melancholic and non-melancholic depressive conditions. RESULTS: Irritable depression was most strongly associated with T&P irritability and anxious depression with T&P anxious-worrying - although these associations lacked specificity and were also correlated with other T&P scales. Hostile depression was most strongly correlated with T&P irritability suggesting that hostile and irritable depression are synonymous patterns. There were no clear indications for more distinct associations for the non-melancholic, compared to the melancholic, subset. LIMITATIONS: Study findings are limited in that measures of state depressive patterns were relatively minimalistic and assignment to melancholic and non-melancholic conditions was measured by clinician judgment and may be subjective in nature. CONCLUSIONS: Findings offer little support in the positioning of anxious and irritable/hostile depression as meaningfully differing patterns, nor for the spectrum model being more specific to the non-melancholic depressive conditions. There would appear to be little utility in preserving these depressive patterns as diagnostic constructs.

An evaluation of the DSM-5 rules defining mania and hypomania with identical symptom criteria.

BACKGROUND: DSM-IV and DSM-5 provide identical symptom criteria and cut-off scores in defining mania and hypomania, a model seemingly counter-intuitive for classificatory differentiation. We designed a study to examine the impact of such DSM criteria and propose alternative models. METHODS: Prevalence and severity of hypo/manic symptoms as measured by the Mood Swings Questionnaire (MSQ) were compared in age and gender-matched bipolar I and II patients. Use of the MSQ allowed both DSM and additional items to be evaluated in terms of their capacity to differentiate the two bipolar conditions. RESULTS: In comparison to bipolar II participants, the bipolar I participants reported higher prevalence scores on six MSQ symptoms, severity scores on twelve MSQ symptoms and total MSQ scores. While bipolar I and II participants reported similar prevalence rates of DSM-5 symptoms, bipolar I participants returned higher prevalence rates on five (non-DSM) MSQ items. LIMITATIONS: Bipolar sub-type was not formally assessed by a structured diagnostic interview. The degree to which assigned MSQ items corresponded with DSM items might not necessarily have high equivalence. The study would have been enriched by evaluating a number of other symptom constructs. CONCLUSIONS: Findings suggest several optional approaches to differentiating mania and hypomania. The model we favor is one with a core set of features integral to mania and hypomania that is complemented by certain differentiating features. Psychotic features and over-valued ideas might provide the domain for such differentiation.

The status of screening measures for bipolar disorder.

PURPOSE OF REVIEW: Screening measures for bipolar disorder are positioned as playing an important role in improving diagnostic accuracy. This review considers the principal screening measures developed over the past decade. RECENT FINDINGS: Although the development and evaluation of bipolar screening measures were distinct between 2000 and 2010, there has been a decrease in research and evaluation in recent years. This article considers the main impetus for the development of screening measures for bipolar disorder and provides a description and critique of the principal measures used in both clinical and community settings. SUMMARY: Screening measures have an important role in identifying bipolar disorder but are best positioned as a first-stage strategy rather than as definitive diagnostic measures. Although several have been developed and well validated in clinical settings, there is a distinct need for extension studies exploring their classificatory properties in community settings as well as clinical impact studies to determine their 'real world' utility.

Clinical characteristics and temperament influences on 'happy' euphoric and 'snappy' irritable bipolar hypo/manic mood states.

BACKGROUND: While mood elevation and euphoria are the most commonly described phenotypic descriptors of hypo/mania, irritability and anger may dominate. This study was designed to pursue possible determinants of such differing states. METHODS: Patients with bipolar I or II disorder were assigned to an 'irritable/snappy' or 'euphoric/happy' sub-set on the basis of their dominant hypo/manic symptoms. Group differences were examined across clinical, personality, lifestyle and illness impact measures. RESULTS: The two sub-sets did not differ on age of depression onset, family history of mood disorders, or depression severity and impairment. The snappy sub-set reported higher levels of irritability in depressed phases and were more likely to have a comorbid anxiety disorder. Their hypo/manic episodes were shorter and they were more likely to be hospitalized at such times. On a temperament measure they scored as more irritable and self-focussed and as less cooperative and effective - indicative of higher levels of disordered personality functioning. LIMITATIONS: Some comparison analyses were undertaken on a reduced sample size, giving rise to power issues. Our bipolar I and II diagnoses deviated to some extent from DSM-5 criteria in not imposing duration criteria for hypo/manic episodes. CONCLUSIONS: Findings support a spectrum model for the bipolar disorders linking temperament to bipolar symptomatic state and which may have treatment implications.