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The developmental trajectory of bipolar disorder

  • Anne Duffy (a1), Julie Horrocks (a2), Sarah Doucette (a3), Charles Keown-Stoneman (a2), Shannon McCloskey (a4) and Paul Grof (a5)...
Abstract
Background

Bipolar disorder is highly heritable and therefore longitudinal observation of children of affected parents is important to mapping the early natural history.

Aims

To model the developmental trajectory of bipolar disorder based on the latest findings from an ongoing prospective study of the offspring of parents with well-characterised bipolar disorder.

Method

A total of 229 offspring from families in which 1 parent had confirmed bipolar disorder and 86 control offspring were prospectively studied for up to 16 years. High-risk offspring were divided into subgroups based on the parental long-term response to lithium. Offspring were clinically assessed and DSM-IV diagnoses determined on masked consensus review using best estimate procedure. Adjusted survival analysis and generalised estimating equations were used to calculate differences in lifetime psychopathology. Multistate models were used to examine the progression through proposed clinical stages.

Results

High-risk offspring had an increased lifetime risk of a broad spectrum of disorders including bipolar disorder (hazard ratio (HR) = 20.89; P = 0.04), major depressive disorder (HR = 17.16; P = 0.004), anxiety (HR = 2.20; P = 0.03), sleep (HR = 28.21; P = 0.02) and substance use disorders (HR = 2.60; P = 0.05) compared with controls. However, only offspring from lithium non-responsive parents developed psychotic disorders. Childhood anxiety disorder predicted an increased risk of major mood disorder and evidence supported a progressive transition through clinical stages, from non-specific psychopathology to depressive and then manic or psychotic episodes.

Conclusions

Findings underscore the importance of a developmental approach in conjunction with an appreciation of familial risk to facilitate earlier accurate diagnosis in symptomatic youth.

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Copyright
Corresponding author
Professor Anne Duffy, Mathison Centre for Mental Health Research, 4th Floor TRW Building, Room 4D68, Calgary, Alberta T2N 4Z6, Canada. Email: acduffy@ucalgary.ca
Footnotes
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This work was supported by an operating grant (MOP 102761) from the Canadian Institutes of Health Research (CIHR).

Declaration of interest

None.

Footnotes
References
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The developmental trajectory of bipolar disorder

  • Anne Duffy (a1), Julie Horrocks (a2), Sarah Doucette (a3), Charles Keown-Stoneman (a2), Shannon McCloskey (a4) and Paul Grof (a5)...
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The developmental trajectory of bipolar disorder

Marie-Pierre Chenard-Poirier, Senior resident in psychiatry
13 June 2014

The article by Duffy et al. (1) in the February issue tests evidence for a clinical staging model of bipolar disorder for the offspring of lithium responsive parents and the offspring of lithium non-responsive parents. In their analyses, Duffy et al were unable to show a statistically significant difference for the risk of any psychiatric disorder between both subgroups of offspring. Yet they still go on to conclude that the offspring of lithium non-responder parents manifest neurodevelopmental disorders in childhood and psychotic disorders in young adulthood.A second problem is that the neurodevelopmental disorder category includedcluster A traits, which do not readily fit with the others (attention-deficit hyperactivity disorder or learning disorders).A third problem is that schizoaffective disorder was included among the bipolar spectrum disorders in the analyses, a decision that requires further justification.A fourth problem is that, as described in a previous article (2), a diagnosis of bipolar affective disorder NOS was given to participants who presented with manic symptoms meeting threshold DSM-IV diagnostic criteriabut not minimal duration criteria. It is possible that this was the reasonfor a statistically significant difference in the cumulative incidence of bipolar spectrum disorders between the groups of offspring of well parentsand those of parents with a bipolar disorder. Finally, 23% of their participants in the group of offspring of a parent with bipolar disorder-1 were recruited within families, making it unclear how many participants had a parent who did not have the disorder.

Marie-Pierre Chenard-Poirier, senior resident in psychiatry, McGill

Joel Paris, professor of psychiatry, McGill

Duffy, A., Horrocks, J., Keown-Stoneman, C., McCloskey, S., & Grof, P. (2014). The developmental trajectory of bipolar disorder, BritishJournal of Psychiatry, 204: 122-128.

Duffy, A., Alda, M., Crawford, L., Milin, R., & Grof, P. (2007). They early manifestations of bipolar disorder: a longitudinal prospective study of the offspring of bipolar parents, Bipolar Disorders, 9: 828-838.

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Conflict of interest: None declared

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Assessing and Staging Bipolar Disorder

Mark Agius, Clare Research Associate, Clare College Cambridge,
04 March 2014

We congratulate Duffy et al on their paper 'The developmental trajectory of bipolar disorder' [1] . We have long argued that bipolar disorder is often underdiagnosed in community mental health teams, and that the reason for this is often failure to assess the longitudinal trajectory of patients suffering from recurrent depression [2] [3]. We have attempted to remedy this by developing a series of twenty-nine questions to be used in the history taking of all patients with depression and recurrent depression in order to demonstrate the developmental trajectory of the illness [4].These questions are presently being field tested in Bedford and at the University of Perugia. We have also demonstrated that when the systematic assessment of the trajectory of bipolar disorder is carried out in a community mental health team, the number of bipolar patients among the patients assessed by the team increases, but there remain a number of patients who do have unipolar depression [5]; in other words, the assessment of the trajectory of mood disorder patients enables the discrimination between bipolar and unipolar depression.We would comment that Duffy et al raise an important point in suggesting that a history of use of lithium by relatives of the patients changes the trajectory of bipolar disorder, however, in our experience it is very difficult to collect this information from patients , who often do not know details of their relative's illness. Furthermore, Duffy et al are right in suggesting that it is possible to suggest a staging of bipolar disorder similar to McGorry's staging of schizophrenia, but the Schizophrenia staging is underpinned by Pantelis'neuroimaging of the different stages of schizophrenia. To propose a staging model of Bipolar Disorder , we require similar neuroimaging results describing the differences between the individual stages.

References 1.Anne Duffy, Julie Horrocks, Sarah Doucette, Charles Keown-Stoneman,Shannon McCloskey, Paul Grof The developmental trajectory of bipolar disorder BJP February 2014 204:122-1282.Jonathan Rogers, Mark Agius Bipolar and unipolar depression . Psychiatria Danubina, 2012; Vol. 24, Suppl. 1, pp 100-1053.Jonathan Rogers, Mark Agius, Rashid Zaman. Diagnosis of mental illness in primary and secondary care with a focus on bipolar disorder. Psychiatria Danubina, 2012; Vol. 24, Suppl. 1, pp 86-90 4.Mark Agius, Helen Murphy Proving that a patient has bipolar disorder Cutting Edge Psychiatry in Practice 2013;1:174-1805. Eva Nora Bongards, Rashid Zaman, Mark Agius. Can we prevent under-diagnosis and misdiagnosis of bipolar affective disorder? Repeat audits to assess the epidemiological change in the Caseload of a Community Mental Health Team when Bipolar Disorder is accurately assessed and diagnosed. Psychiatria Danubina, 2013; Vol. 25, Suppl. 2, pp 129-134
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Conflict of interest: None declared

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