Sandy Kuiper

Chronobiology of mood disorders

As part of a series of papers examining chronobiology [‘Getting depression clinical guidelines right: time for change?’ Kuiper et al. Acta Psychiatr Scand 2013;128(Suppl. 444):24–30; and ‘Manipulating melatonin in managing mood’ Boyce & Hopwood. ActaPsychiatrScand 2013;128(Suppl. 444):16–23], in this article, we review and synthesise the extant literature pertaining to the chronobiology of depression and provide a preliminary model for understanding the neural systems involved.

Modeling bipolar disorder suicidality

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.

Getting depression clinical practice guidelines right: time for change?

As part of a series of papers [‘Chronobiology of mood disorders’ Malhi & Kuiper. Acta Psychiatr Scand 2013;128(Suppl. 444):2–15; and ‘Its time we managed depression: The emerging role of chronobiology’ Malhi et al. Acta Psychiatr Scand 2013;128(Suppl. 444):1] examining chronobiology in the context of depression, this article examines recent western clinical practice guidelines (CPGs) for the treatment of depression with respect to the recommendations they make, in particular as regards chronobiological treatments, and briefly considers the implications of their methodology and approach.

Why is soft bipolar disorder so hard to define

The observation that bipolar disorder (BD) is gradually expanding is not at all new. The boundaries of bipolarity have been gradually shifting outwards from episodic manic depression for decades, starting with the proposal of bipolar II disorder (BD-II) in the 1970s, steadily annexing more and more phenomenology under the aegis of ‘soft bipolarity’ or the ‘bipolar spectrum’, and culminating in ‘bipolar spectrum disorder’, which can be diagnosed in the absence of elevation (Baldessarini, 2000; Ghaemi et al., 2002). Rather than a single illness, we now have a spectrum model that links major depressive disorder (MDD) to BD, in which a steadily greater bipolar diathesis manifests as increased likelihood of subsyndromal mood instability (bipolar disorder not otherwise specified (BD-NOS) or subthreshold BD), hypomania (BD-II) and ultimately mania (bipolar I disorder; BD-I) (Figure 1). The new bipolar spectrum is a broad church. First, it allows any form of mood instability, including brief hypomanic episodes, cyclothymic or hyperthymic personality, and mood swings within a day, and can even trump personality disorder (Akiskal et al., 2000). Second, it is potentially behind a substantial proportion of depressive illness, where it covers a wide phenomenological field including irritable/dysphoric, anxious, agitated, or atypical symptomatology (Akiskal, 2005), as well as psychosis (Ghaemi et al., 2002), and may therefore drive presentations as distinct as brief depressive episodes with preserved mood reactivity and severe psychotic depression (Ghaemi et al., 2002). It has also been linked to difficult or treatment-resistant depressions via early onset, recurrence, and failure to respond to antidepressants (Ghaemi et al., 2002). Finally, bipolarity has been suggested as a component of nearly every disorder we recognise, from psychosis (Keshavan et al., 2011) to personality disorder (Akiskal et al., 2000), anxiety (Akiskal et al., 2006), attention deficit hyperactivity disorder (ADHD) (Zdanowicz and Myslinski, 2010), eating disorders (Lunde et al., 2009), substance use (Maremmani et al., 2006), autistic spectrum disorder (Ragunath et al., 2011), somatisation (Tavormina, 2011), dissociation (Oedegaard et al., 2008), conversion disorder (Ghosal et al., 2009) and dementia (Ng et al., 2008). It even contributes to whether or not we smoke, drink coffee, or eat chocolate (Maremmani et al., 2011). Perhaps unsurprisingly, in such expansive forms, bipolarity is present in 30–55% of all depressive illness (Akiskal et al., 2000) and in 25% of the community (Angst et al., 2003). More conservative estimates place the lifetime bipolar spectrum prevalence much lower, at approximately 2.5% (Merikangas et al., 2011), but it remains clear that prevalence of bipolar diagnosis in the first world is rising sharply (Moreno et al., 2007). Unfortunately, such broad-spectrum bipolarity seems to be a troubled diagnosis. As we expand the phenotype to include briefer or less severe mood swings, the diagnostic field steadily shifts away from episodic elevation towards affective instability (Goldberg et al., 2008), which is itself interesting insofar as this is presently a DSM (Diagnostic and Statistical Manual of Mental Disorders) criterion for borderline personality disorder (BPD) rather than bipolarity. This also has important diagnostic implications. It is notably unclear who should fall within the new ‘soft bipolar’ group and how we should dissect that out from personality disorder. The research offers little guidance on this front, either explicitly ignoring the possibility that personality disorder might need to be modelled diagnostically (Angst et al., 2003), or suggesting as-yet unvalidated operationalised criteria (such as the presence of two or more concurrent manic symptoms), which do not address the overlap and produce markedly different prevalence estimates in different settings (Merikangas et al., 2011). However, it is of even more concern that the shift towards affective instability may be leading to a softening of the way in which existing DSM-IV diagnoses are applied, such that 30–60% of North American patients who are diagnosed with bipolarity in the community subsequently have that diagnosis retracted on formal research assessment (Zimmerman, 2010). As a result, DSM-IV bipolar disorders are now demonstrably overdiagnosed in patients with disorders that phenomenologically overlap with Why is soft bipolar disorder so hard to define?

Is a delay in the diagnosis of bipolar disorder inevitable

OBJECTIVE A diagnosis of bipolar disorder (BD) is often preceded by an initial diagnosis of depression, creating a delay in the accurate diagnosis and treatment of BD. Although previous research has focused on predictors of a diagnosis change from depression to BD, the research on this delay in diagnosis is sparse. Therefore, the present study examined the time taken to make a BD diagnosis following an initial diagnosis of major depressive disorder in order to further understand the patient characteristics and psychological factors that may explain this delay. METHOD A total of 382 patients underwent a clinical evaluation by a psychiatrist and completed a series of questionnaires. RESULTS Ninety patients were initially diagnosed with depression with a later diagnosis of BD, with a mean delay in diagnostic conversion of 8.74 years. These patients who were later diagnosed with BD were, on average, diagnosed with depression at a younger age, experienced more manic symptoms, and had a more open personality style and better coping skills. Cox regressions showed that depressed patients with diagnoses that eventually converted to BD had been diagnosed with depression earlier and that this was related to a longer delay to conversion and greater likelihood of dysfunctional attitudes. CONCLUSION The findings from the present study suggested that an earlier diagnosis of depression is related to experiencing a longer delay in conversion to BD. The clinical implications of this are briefly discussed, with a view to reducing the seemingly inevitable delay in the diagnosis of BD.

To BD or not to BD: functional neuroimaging and the boundaries of bipolarity

Bipolar disorders are major mood disorders defined by the presence of discrete episodes of depression and either mania, in bipolar I disorder, or hypomania, in bipolar II disorder. There is little contention that both are serious psychiatric conditions or that they are associated with substantial suffering, disability, risk of suicide and cost to the community. Recently, focus has shifted away from classic manic-depressive illness toward a ‘bipolar spectrum’ model, which allows for much softer presentations to be conceptualized as bipolarity, but the boundaries of this concept remain contentious. In this article, we will consider the contribution of neuroimaging to delineating the bipolar phenotype and differentiating it from similar disorders.

The relationship between bipolar disorders, anxiety, and trauma – implications for clinical practice

Objective: To assess the relationship between bipolar spectrum disorders, anxiety disorders, trauma, and personality function. Method: A cohort of 37 diagnostically challenging bipolar spectrum patients, including both bipolar and personality disordered patients, were assessed using the Structured Combined Interview for DSM-IV to establish diagnosis of bipolarity and anxiety. Diagnoses were then quantitatively related to personality function, using the DSM-5 Level of Personality Function Scale, and to attachment, using the Relationship Questionnaire and Relationship Style Questionnaire. Results: Number of comorbid anxiety disorders was significantly related to both personality and attachment, but not to bipolar status. Patients with more than one anxiety disorder were significantly more likely to have an underlying disturbance of personality. Conclusions: The presence of multiple anxiety disorders in bipolar spectrum patients may indicate heightened risk of an underlying personality disorder. Replication in a larger and more representative sample is needed.

It is time we managed depression: the emerging role of chronobiology

Remarkably, a complete understanding of depression remains beyond us. In clinical practice, clinicians and patients use the term widely to describe a whole host of experiences. Depressive illness spans the whole spectrum, from normalcy to psychosis, overlaps with virtually every psychiatric illness and can occur in the context of a myriad of medical illnesses. No age group is spared, and, apart from conferring obvious morbidity and mortality on the individual affected, it burdens families and societies as a whole and incurs enormous costs. Its seriousness is underpinned by its links to deliberate self-harm and suicide, and yet its pathophysiology remains an enigma. Models that have amalgamated psychological, social and biological factors have each managed to shed light on aspects or facets of the illness. Some have also provided a basis for treatments, but few have truly advanced our understanding of the illness or made recognisable progress towards a cure. The monoamine hypothesis of depression has dominated the development of medications for over half a century, but the efficacy of newer agents has failed to discernibly surpass that of the earliest antidepressants (tricyclics and monoamine oxidase inhibitors). A more benign side effect profile of newer agents has led to much broader prescription of these agents, but at the same time diminished their ability to differentiate from the effects of placebo. The recent thrust towards evidence-based medicine, together with the priority assigned to randomised controlled trial data, has skewed the management of depression as ordained in clinical practice guidelines. The papers in this supplement collectively address these concerns, initially providing insights into the chronobiology of depression (1), in which the links between the neural systems mediating depression are examined with a view to providing a preliminary model that can be further tested and refined. Therapeutic targets within the system, and potential agents that can modulate circadian function, specifically by melatonin, are then outlined in a paper that focuses on therapeutic interventions (2). Finally, the way in which our knowledge from chronobiology is synthesised and presented in clinical practice guidelines is examined in the final paper (3), which tries to address the pitfalls in bridging the gap between the evidence base and clinical practice and understand how failure to adopt novel models of depression may limit the impact and uptake of guidelines. Jointly, these three papers attempt to provide new perspectives on depression, ranging from pathophysiology and treatment through to the way in which our knowledge is translated into clinical practice.

Psychiatric tertiary referral and clinical decision making.

It is little news to any of us that psychiatry is a difficult exercise. Core diagnoses around which we built our practice, such as major depression and generalised anxiety, have turned out to have ‘questionable’ and ‘unacceptable’ reliability when formally assessed by the very organisation that proposed them (Regier et al., 2013). Our best efforts at painstaking diagnosis are often unstable over time, as illness evolves and psychosocial circumstances and phenomenology shift the face of the presentation (Ruggero et al., 2010). Even more concerning, landmark studies such as CATIE and STAR*D demonstrate the limitations of current treatment, and highlight the concern that appropriate and diligent treatment simply does not produce remission in large groups of patients (Insel and Wang, 2009; Lieberman et al., 2005). Given these constraints, it is inevitable that we will both become stuck and make mistakes, not as a function of inattentiveness or incompetence, but rather, as an unavoidable consequence of the nature of our profession. Further, this is substantially more common than we think. Diagnostic error occurs in approximately 15% of general medicine cases (Berner and Graber, 2008), and is likely more frequent in psychiatry, particularly in contested areas such as bipolarity, where approximately half of patients are misdiagnosed at some point (Smith and Ghaemi, 2010; Zimmerman, 2010). Options for addressing our own fallibility are, of course, well described, and nearly every treatment guideline suggests we consider a second opinion or a tertiary referral in the face of treatment resistance (Malhi and Adams, 2009). However, while we all overtly endorse this, in the case of tertiary referral, this principle may be more honoured in the breach than in the observance. At the two major academic centres in Sydney that offer tertiary outpatient mood disorder assessment, most referrals come from GPs (Table 1). Fewer than 100 patients are referred by a psychiatrist annually, a number likely less than the number of psychiatrists in our shared catchment areas. There are numerous possible reasons for this apparent gap between the likely frequency of diagnostic difficulty and the engagement of tertiary expertise. It is possible, for example, that it is simply a parochial issue, or that it is due to factors unrelated to clinical decision making, such as awareness, or service capacity. The large proportion of GP referrals suggests a structural gap may also be present, with direct tertiary referrals filling some of the gulf between the public sector’s focus on severe mental illness and the private sector’s financial constraints. However, the relative underuse of tertiary expertise by psychiatrists may also reflect a broader failure to clarify the nature of tertiary assessment, and we therefore aim to use this paper to reflect on the way in which tertiary assessment intersects with psychiatric decision making.

Psychotherapy training wheels

As an incoming psychotherapy educator in Northern Sydney, I read with great interest the recent correspondence between Jureidini (2012) and Harari (2013) on the place of psychodynamic thought, both in psychiatry in general, and more specifically in a busy psychiatric emergency setting. Ultimately, both seem to be making very similar statements about the importance of psychodynamic principles in general practice, and very sensibly invoking the old pillars of empathy, reflection and broader formulation as the containers within which general psychiatric practice becomes meaningful. In this regard, Jureidini’s (2012) invocation of minimalism is an interesting choice. Minimalism is of course an artistic movement that revolves around removal of the unnecessary and paring back to only the essential components, and it (like psychotherapy) is not without controversy. For minimalism to work, there must be a degree of conceptual familiarity (and ideally historical context) on the part of the viewer – a painting consisting solely of a black canvas square may simultaneously be a bold statement in artistic self-definition to the cognoscenti, and a meaningless waste of canvas to the less artistically inclined. Similarly, if you are psychodynamically fluent, even a brief interaction can be elegant and meaningful, be it the starting point for a more detailed exploration, as in Harari’s article (2013), or a thoughtful limited intervention within a practically constrained frame, as Jureidini originally described. However, without the psychodynamic thought that informs that interaction, the brief emergency psychiatry admission becomes a confusing blank canvas that addresses safety and (perhaps) diagnosis, but leaves meaning and narrative in the hands of the patient. In this context, it is worth pausing to note that Jureidini’s (2012) story starts with a baffled trainee, and to consider where such minimalism fits into psychiatric training. We practice in an era where medication is a dominant force, and where there are reasonably clear indications that, over decades, the pendulum has swung from over-reliance on psychodynamic theory (Paris, 2005) to over-reliance on medication (Rosenbluth et al., 2012). Training reflects this, such that it is now possible to complete the training provided by the Royal Australian and New Zealand College of Psychiatrists (RANZCP) without much attention to psychodynamic thought – although the formal training structure can certainly support excellence in this regard, the nature of implementation on the ground is variable. Generalist training requires the delivery of only 150 h of psychotherapy (70 in basic training, 80 in advanced training), which is approximately 1.5% of training time over a period of 5 years. Further, the practicalities of case examination mean that we assess the trainee’s ability to tell a story about therapy rather than actually conduct it. Additionally, psychodynamic theory could hardly be said to be a major focus of written examination, and the psychotherapies are relegated to a handful of entries in the new competency-based system. Advanced training in the psychotherapies, although excellent, attracts only a minority of trainees. Psychological treatment (of any modality) is often implemented patchily in the public sector, and although some registrars will be lucky enough to land in a centre of excellence or be exposed to an inspiring practitioner, most training experience is in the medical model, with psychology as something that happens somewhere else and is done by someone else. Psychiatrists for whom psychodynamic experience was mandatory are moving towards retirement, and with that we risk the knowledge base that informs such interventions draining gradually from the system. The net result is that the vast majority of practical experience in RANZCP training is exactly the sort of psychodynamic minimalism described by Jureidini (2012). It may be an understandable clinical compromise in a complex environment, but when we consider it as a dominant training experience, it is appropriate to ask whether it is adequate or comprehensive. There is a de facto statement inherent in framing psychological thought up as something to fit in between service requirements, rather than an integrated part of practice for every patient, and although both Jureidini and Harari (2013) are clearly practising elegantly and striving to avoid this pitfall, the balance between psychological experience and biomedical experience in training is certainly questionable. To formulate in a sophisticated way or implement a brief