Predicting bipolar disorder on the basis of phenomenology: implications for prevention and early intervention.

OBJECTIVE: Bipolar disorder is a multifaceted illness and there is often a substantial delay between the first onset of symptoms and diagnosis. Early detection has the potential to curtail illness progression and disorder-associated burden but it requires a clear understanding of the initial bipolar prodrome. This article summarizes the phenomenology of bipolar disorder with an emphasis on the initial prodrome, the evolution of the illness, and the implications for prevention and early intervention. METHODS: A literature review was undertaken using Medline, Web of Science, and a hand search of relevant literature using keywords (e.g., phenomenology, initial or early symptoms, risk factors, and predictors/prediction). Findings from the literature were reviewed and synthesized and have been put into a clinical context. RESULTS: Bipolar disorder is a recurrent, persistent, and disabling illness that typically develops in adolescence or early adulthood. The literature search yielded 28 articles, in which mood lability, nonspecific, non-mood symptoms, and cyclothymic temperament were the most cited prodromal features. CONCLUSIONS: A small number of key prospective studies have provided evidence in support of an initial bipolar prodrome; however, methodological differences across studies have prohibited its clear delineation. It is, therefore, not currently possible to anticipate those who will develop bipolar disorder solely on the basis of early phenomenology. Accurate characterization of the bipolar disorder prodrome through high-quality, prospective research studies with adequate control groups will ultimately facilitate prompt and accurate diagnosis.

Mixed state discrimination: a DSM problem that won׳t go away?

BACKGROUND: DSM׳s replacement of 'mixed episodes' with 'mixed features' has ironically created a specifier, which potentially lacks specificity because it overlooks two key symptoms: psychomotor agitation and distractibility. Therefore, the present study examined the presence of psychomotor agitation and distractibility across the mood disorder spectrum. METHODS: Two hundred patients were diagnosed and assigned to one of three groups (depression, bipolar spectrum disorder (BDspectrum) and bipolar disorder) based on clinical evaluation by a psychiatrist. On the basis of MDQ scores, the depression group was then further subdivided into two groups: unipolar depression (UP) and mixed depression (UPmix). These four groups were then compared to examine the relative distribution of psychomotor agitation and distractibility. Participants underwent a clinical evaluation by a psychiatrist and completed a series of questionnaires. RESULTS: Increased distraction, racing thoughts, and increased irritability were the most commonly reported manic symptoms amongst the unipolar depression group. Further, UPmix and BDspectrum had significantly higher psychomotor agitation and distractibility than the other two groups. LIMITATIONS: The present study depended on self-report measures and did not include standardised measures of distractibility and psychomotor agitation. Future research needs to examine pure unipolar patients without any manic symptoms to clarify further how different this group would be from those with mixed features. CONCLUSIONS: The present findings suggest that distractibility and psychomotor agitation may represent the core of mixed states, as they are more common in patients with mixed depression and bipolar spectrum disorder than patients diagnosed with unipolar depression and bipolar I disorder. Future research and clinical implications are discussed.

Unlocking the diagnosis of depression in primary care: Which key symptoms are GPs using to determine diagnosis and severity?

OBJECTIVE: Diagnosing depression in primary care settings is challenging. Patients are more likely to present with somatic symptoms, and typically with mild depression. Use of assessment scales is variable. In this context, it is uncertain how general practitioners (GPs) determine the severity of depressive illness in clinical practice. The aim of the current paper was to identify which symptoms are used by GPs when diagnosing depression and when determining severity. METHOD: A total of 1760 GPs participated in the RADAR Program, an educational program focusing on the diagnosis and management of clinical depression. GPs identified a maximum of four patients whom they diagnosed with depression and answered questions regarding their diagnostic decision-making process for each patient. RESULTS: Overall, assessment of depression severity was influenced more by somatic symptoms collectively than emotional symptoms. Suicidal thoughts, risk of self-harm, lack of enjoyment and difficulty with activities were amongst the strongest predictors of a diagnosis of severe depression. CONCLUSIONS: The conclusions are threefold: (1) collectively, somatic symptoms are the most important predictors of determining depression severity in primary care; (2) GPs may equate risk of self-harm with suicidal intent; (3) educational initiatives need to focus on key depressive subtypes derived from emotional, somatic and associated symptoms.

Severity alone should no longer determine therapeutic choice in the management of depression in primary care: findings from a survey of general practitioners.

BACKGROUND: The treatment of depression in primary care remains suboptimal for reasons that are complex and multifactorial. Typically GPs have to make difficult decisions in limited time and therefore, the aim of this study was to examine the management of depression of varying severity and the factors associated with treatment choices. METHOD: Nested within a primary care educational initiative we conducted a survey of 1760 GPs. The GPs each identified four patients with clinical depression whom they had treated recently and then answered questions regarding their diagnosis and management of each patient. RESULTS: Comorbid anxiety, sadness and decreased concentration appeared to direct the management of depression toward psychological therapy, whereas comorbid pain and a patient's overall functioning, such as the ability to do simple everyday activities, directed the initiation of pharmacological treatment. The use of antidepressants with a broader spectrum of actions (acting on multiple neurotransmitters) increased from mild to severe depression, whereas this did not occur with the more selective agents. SSRIs were prescribed more frequently compared with all other antidepressants, irrespective of depression severity. LIMITATIONS: GPs chose the RADAR programme and therefore they were potentially more likely to have an interest in mental health compared to GPs who did not participate. CONCLUSIONS: GPs do not appear to be determining pharmacological treatment based on depression subtype and specificity, but rather on the basis of the total number of symptoms and overall severity. While acknowledging important differences between primary care and specialist practice, it is suggested that guidelines to assist GPs in matching treatment to depression subtype may be of practical assistance in decision-making, and the delivery of more effective treatments.

Modeling bipolar disorder suicidality.

OBJECTIVES: To review the psychosocial, neuropsychological, and neurobiological evidence regarding suicide and bipolar disorder (BD), to enable the development of an integrated model that facilitates understanding, and to provide a useful framework for future research. METHODS: A two-stage literature review was conducted. First, an electronic literature search was performed using key words (e.g., bipolar disorder, suicide risk, and neuroimaging) and standard databases (e.g., MEDLINE). Second, theoretical suicide models were reviewed, and their evidence base and relevance to BD were evaluated in order to determine a guiding theoretical framework for contextualizing suicide in BD. RESULTS: Although accumulating clinical, cognitive, and neurobiological correlates of suicide have been identified in BD, extant research has been largely atheoretical. The Cry of Pain (CoP) and an adapted version of the model, the Schematic Appraisals Model of Suicide (SAMS), provide a useful schema for examining vulnerability to suicide in BD, by taking into account biopsychosocial determinants of suicidality. In combination, these also provide a model within which the neural correlates of suicide can be integrated. CONCLUSIONS: The proposed Bipolar Suicidality Model (BSM) highlights the psychosocial precursors to suicidality in BD, while recognizing the key role of cognitive deficits and underlying functional neurobiological abnormalities. It usefully integrates our knowledge, and provides a novel perspective that is intended to meaningfully inform future research initiatives, and can lead to a better understanding of suicidality in bipolar disorder. Ultimately, it is hoped that it will facilitate the development of targeted interventions that diminish the risk of suicide in bipolar disorder.

Neural antecedents of emotional disorders: a functional magnetic resonance imaging study of subsyndromal emotional symptoms in adolescent girls.

BACKGROUND: Emotional symptoms (ES) emerge forme fruste in adolescence, before manifesting as fully fledged emotional disorders. Studies indicate that subsyndromal ES precede the onset of emotional disorders. We hypothesized that adolescents showing subsyndromal ES will show perturbations in the emotion regulatory frontolimbic network (FLN) during emotion processing. METHODS: Fifty-eight female adolescents underwent functional magnetic resonance imaging while viewing an image-based emotion-processing task. Within this sample, 33 (56.9%) displayed emotional symptoms and 25 (43.1%) did not. Clinical measures, including assessments of mood and anxiety, were administered and participants were allocated to one of two groups based on the presence (ES+) or absence (ES-) of subsyndromal ES. Group comparisons were used to identify differential patterns of neural engagement and their relationship to clinical variables. RESULTS: Groups displayed emotion-specific differences in FLN activity with increased frontal activity in ES+ girls during positive emotion processing and decreased frontal and limbic activity during negative emotion processing. Trait anxiety was the strongest clinical predictor of group membership (ES+ versus ES-) and displayed a significant negative correlation with hippocampal neural activity during negative emotion processing. In addition, between the groups, the hippocampus displayed a pattern of reverse coupling with the amygdala and insula that was also significantly correlated with trait anxiety. CONCLUSIONS: There is divergence in the pattern of FLN neural processing in adolescent female subjects determined by emotional symptoms. Future research is needed to corroborate these findings and to underline their implications longitudinally.

Is coping well a matter of personality? A study of euthymic unipolar and bipolar patients.

BACKGROUND: Euthymic bipolar disorder (BD) patients often demonstrate better clinical outcomes than remitted patients with unipolar illness (UP). Reasons for this are uncertain, however, personality and coping styles are each likely to play a key role. This study examined differences between euthymic BD and UP patients with respect to the inter-relationship between personality, coping style, and clinical outcomes. METHODS: A total of 96 UP and 77 BD euthymic patients were recruited through the CADE Clinic, Royal North Shore Hospital in Sydney, and assessed by a team comprising Psychiatrists and Psychologists. They underwent a structured clinical diagnostic interview, and completed self-report measures of depression, anxiety, stress, personality, coping, social adjustment, self-esteem, dysfunctional attitudes, and fear of negative evaluation. RESULTS: Compared to UP, BD patients reported significantly higher scores on levels of extraversion, adaptive coping, self-esteem, and lower scores on trait anxiety and fear of negative evaluation. Extraversion correlated positively with self-esteem, adaptive coping styles, and negatively with trait anxiety and fear of negative evaluation. Trait anxiety and fear of negative evaluation correlated positively with eachother, and both correlated negatively with self-esteem and adaptive coping styles. Finally, self-esteem correlated positively with adaptive coping styles. LIMITATIONS: The results cannot be generalised to depressive states of BD and UP, as differences in the course of illness and types of depression are likely to impact on coping and clinical outcomes, particularly for BD. CONCLUSIONS: During remission, functioning is perhaps better 'preserved' in BD than in UP, possibly because of the protective role of extraversion which drives healthier coping styles.

Balanced efficacy, safety, and tolerability recommendations for the clinical management of bipolar disorder.

OBJECTIVE: To provide practical and clinically meaningful treatment recommendations that amalgamate clinical experience and research findings for each phase of bipolar disorder. METHODS: A comprehensive search of the literature was undertaken using electronic database search engines (Medline, PubMed, Cochrane reviews) using key words (e.g., bipolar depression, mania, treatment). All relevant randomised controlled trials were examined, along with review papers, meta-analyses, and book chapters known to the authors. In addition, the recommendations from accompanying papers in this supplement have been distilled and captured in the form of summary boxes. The findings, in conjunction with the clinical experience of international researchers and clinicians who are practiced in treating mood disorders, formed the basis of the treatment recommendations within this paper. RESULTS: Balancing clinical experience with evidence informed and lead to the development of practical clinical recommendations that emphasise the importance of safety and tolerability alongside efficacy in the clinical management of bipolar disorder. CONCLUSIONS: The current paper summarises the treatment recommendations relating to each phase of bipolar disorder while providing additional, evidence-based, practical insights. Medication-related side effects and monitoring strategies highlight the importance of safety and tolerability considerations, which, along with efficacy information, should be given equal merit.

The clinical management of bipolar disorder complexity using a stratified model.

OBJECTIVE: To provide practical and clinically meaningful treatment recommendations that amalgamate clinical and research considerations for several common, and as yet understudied, bipolar disorder complex presentations, within the framework of a proposed stratified model. METHODS: A comprehensive search of the literature was undertaken using electronic database search engines (Medline, PubMed, Web of Science) using key words (e.g., bipolar disorder, anxiety, rapid cycling, and subsyndromal). All relevant randomised controlled trials were examined, in addition to review papers, meta-analyses, and book chapters known to the authors. The findings formed the basis of the treatment recommendations within this paper. RESULTS: In light of the many broad presentations of bipolar disorder, a stratified model of bipolar disorder complexity was developed to facilitate consideration of the myriad of complexities that can occur during the longitudinal course of illness and the appropriate selection of treatment. Evidence-based treatment recommendations are provided for the following bipolar disorder presentations: bipolar II disorder, subsyndromal symptoms, mixed states, rapid cycling, comorbid anxiety, comorbid substance abuse, and for the following special populations: young, elderly, and bipolar disorder around the time of pregnancy and birth. In addition, some key strategies for countering treatment non-response and alternative medication recommendations are provided. CONCLUSIONS: Treatment recommendations for the more challenging presentations of bipolar disorder have historically received less attention, despite their prevalence. This review acknowledges the weaknesses in the current evidence base on which treatment recommendations are generally formulated, and additionally emphasises the need for high-quality research in this area. The stratified model provides a means for conceptualizing the complexity of many bipolar disorder presentations and considering their management.