Please see below a selected listings of our publications and articles of interest. If you are interested in accessing the full article, feel free to contact our research coordinator at


The emergent course of bipolar disorder: Observations over two decades from the Canadian high-risk offspring cohort

Duffy A, Goodday, S.M., Keown-Stoneman, C, Grof, P. American Journal of Psychiatry (2018). 


Objective: The authors sought to describe the emergent course of bipolar disorder in offspring of affected parents subgrouped by parental response to lithium prophylaxis. Methods: Parent bipolar disorder was confirmed by the best-estimate procedure and lithium response by research protocol. High-riskoffspring (N=279) and control subjects (N=87) were blindly assessed, annually on average, with the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version or the Schedule for Affective Disorders and Schizophrenia-Lifetime version. DSM-IV diagnoses were confirmed using the best-estimate procedure in blind consensus reviews. Cumulative incidence and median age at onset were determined for lifetime syndrome- and symptom-level data. Mixed models assessed the association between parent and offspringcourse. A multistate model was used to estimate the clinical trajectory into bipolar disorder. Results: The cumulative incidence of bipolar disorder was 24.5%, and the median age at onset was 20.7 years (range, 12.4 to 30.3). The clinical course of the affected parent was associated with that of the affected child. Depressive episodes predominated during the early bipolar course, especially among offspring of lithium responders. Childhood sleep and anxiety disorders significantly predicted 1.6-fold and 1.8-fold increases in risk of mood disorder, respectively, and depressive and manic symptoms predicted 2.7-fold and 2.3-fold increases in risk, respectively. The best-fit model of emerging bipolar disorder was a progressive sequence from nonspecific childhood antecedents to adolescent depression to index manic or hypomanic episode. Subthreshold sleep symptoms were significantly associated with transition from well to non-mood disorder, and psychotic symptoms in mood episodes were significantly associated with transition from unipolar to bipolar disorder. Conclusions: Bipolar disorder in individuals at familial risk typically unfolds in a progressive clinical sequence. Childhood sleep and anxiety disorders are important predictors, as are clinically significant mood symptoms and psychotic symptoms in depressive episodes.


The Early Natural History of Bipolar Disorder: What We Have Learned From Longitudinal High-Risk Research

Duffy, Anne. Canadian Journal of Psychiatry (2010). 55(8): 477-485. 


Longitudinal high-risk research has provided convergent evidence that major mood and psychotic disorders often develop from nonspecific antecedents in predisposed people over time and development. For example, bipolar disorder (BD) appears to evolve from nonspecific childhood antecedents, including anxiety and sleep problems, followed by adjustment and minor mood disturbances through early adolescence, culminating in major mood episodes in later adolescence and early adulthood. Therefore, the current cross-sectional symptom-based diagnostic approach requires rethinking: it considers neither the familial risk nor the longitudinal clinical course, with the consequence that the early stages of illness are not recognized as belonging to the end-stage disorder. Emerging evidence of identifiable clinical stages in the development of BD has tremendous potential for early identification, development of stage-specific treatments, and advancing our understanding of the pathophysiology associated with illness onset and progression. The clinical staging model also has direct implications for the optimal organization of clinical services for high-risk youth. Specifically, specialty psychiatric programs are needed that break down traditional institutional barriers to provide surveillance and timely comprehensive psychiatric assessment during the entire risk period, from childhood through to early adulthood. In this regard, the development of specialty psychiatric programs aiming to identify youth in the early stages of evolving psychosis are substantially ahead of services for youth in the early stages of evolving major mood disorders.



Goodday, S.M., Preisig, M., Gholamrezaee, M., Grof, P., Duffy, A. (2018). Temperament and self-esteem in the high-risk offspring of bipolar parents: Vulnerability and scar effects. Journal of Affective Disorder.


Duffy, A, Heffer, N, Goodday, S, Weir, W, Patten, S, Malhi, G and Cipriani, A. (2018). Efficacy and tolerability of lithium treatment of acute mania in children with bipolar disorder: A systematic review. A report from the joint ISBD-IGSLi Task Force on Lithium Treatment. Bipolar Disorders.


Duffy, A, Keown-Stoneman, C, Goodday, SM, Saunders, K, Horrocks, J, Grof, P. Weir, A, Hinds, C, Geddes, J. (2018). Daily and weekly mood ratings using a remote capture method in high-risk offspring of bipolar parent: Compliance and symptom monitoring. Bipolar Disorders.


Goodday, S.M., Bentall, R., Jones, R., Weir, A., Duffy, A. (2018). Coping Strategies and self-esteem in the high- risk offspring of bipolar parents. Australia and New Zealand Journal of Psychiatry.


Duffy, A., Malhi, G.S., Carlson, G.A. (2018). The challenge of psychiatric diagnosis: Looking beyond the symptoms   to the company that they keep. Bipolar Disorders.


Duffy, A. (2018). Early Intervention in Bipolar disorders: Where we are now and need to go next. Bipolar Disorders.


Duffy, A and Grof, P. (2018). Lithium treatment in children and adolescents. Pharmacopsychiatry.


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


Duffy, A. (2012). The nature of the association between childhood ADHD and the development of bipolar disorder. American Journal of Psychiatry. 169(12): 1247-55.


Duffy A, Alda M, Hajek T, Grof P. (2009). Early course of bipolar disorder in high-risk offspring: A prospective study. British Journal of Psychiatry. 195(5): 457-8.

Duffy A., Alda M., Kutcher S., Fusee C., Grof P. (1998). Psychiatric symptoms and syndromes among adolescent children of parents with lithium-responsive or lithium-nonresponsive bipolar disorder. American Journal of Psychiatry. 155(3): 431-433.



Lithium in Neuropsychiatry: the Comprehensive Guide.