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

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

 Duffy, Anne. Can J Psychiatry 55 (2010). 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.

Maintenance treatment of adolescent bipolar disorder: open study of the effectiveness and tolerability of quetiapine

Duffy et al. BMC psychiatry 9.1 (2009); 4.


Background: The purpose of the study was to determine the effectiveness and tolerability of quetiapine as a maintenance treatment preventing against relapse or recurrence of acute mood episodes in adolescent patients diagnosed with bipolar disorder. Methods Consenting patients meeting DSM-IV lifetime criteria for a bipolar disorder and clinically appropriate for maintenance treatment were enrolled in a 48-week open prospective study. After being acutely stabilized (CGI-S ≤ 3 for 4 consecutive weeks), patients were started or continued on quetiapine and other medications were weaned off over an 8-week period. Quetiapine monotherapy was continued for 40-weeks and other mood stabilizers or antidepressants were added if clinically indicated. A neurocognitive test battery assessing the most reliable findings in adult patients was administered at fixed time points throughout the study to patients and matched controls. Results: Of the 21 enrolled patients, 18 completed the 48-week study. Thirteen patients were able to be maintained without relapse or recurrence in good quality remission on quetiapine monotherapy, while 5 patients required additional medication to treat impairing residual depressive and/or anxiety symptoms. According to symptom ratings and global functioning scores, the quality of remission for all patients was very good. Neurocognitive test performance over treatment was equivalent to that of a matched control group of never ill adolescents. Quetiapine was generally well tolerated with no serious adverse effects. Conclusions: This study suggests that a proportion of adolescent patients diagnosed with bipolar disorder can be successfully maintained on quetiapine monotherapy. The good quality of clinical remission and preserved neurocognitive functioning underscores the importance of early diagnosis and effective stabilization.

Clinical Trials Registry: D1441L00024

The developmental trajectory of bipolar disorder

Duffy et al. The British Journal of Psychiatry 204.2 (2014): 122-128.


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. Methods: 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.

Investigating Children at High Risk for Bipolar and Psychotic Disorders: Findings and Implications

Grof, Paul. Can J Psychiatry 55 (2010). 475-476.

Introduction: Bipolar disorders (BDs) and psychotic disorders were initially conceived as disorders of adulthood, with an occasional onset in adolescence. However, those concepts are gradually changing, and, based on recent studies of children of parents with BD and psychotic disorders, these aged constructs require intense rethinking. A series of longitudinal studies paints a new, different picture: the true beginnings of these disorders were either different or have changed.

In nearly all departments of psychiatry, adult and childadolescent psychiatry represent 2 separate universes that did not enable continuous studies. However, in recent years, several adult and child specialists have joined forces to investigate the populations of young people at high risk for BDs and psychotic disorders and came up with identical basic findings regarding the early clinical course.

This issue of The Canadian Journal of Psychiatiy offers 2 excellent reviews of this fruitful approach by its major proponents, Dr Anne Duffy and Dr Patrick D McGorry, Dr Barnaby Nelson, Dr Sherilyn Goldstone, and Dr Alison R Yung. They present their findings, and review the relevant literature and convergent conclusions. They report replicated evidence that, in predisposed people over time, major mood and psychotic disorders develop from nonspecific harbingers.

Childhood anxiety: An early predictor of mood disorders in offspring of bipolar parents

Duffy et al. Journal of affective disorders, 150.2 (2013), 363-369.


Background: Anxiety disorders are common among the offspring of parents with bipolar disorder (BD). This study investigated the nature of the association between anxiety disorders and mood disorders in a prospectively studied high-risk cohort. Methods: High-risk offspring were identified from families in which one parent had confirmed BD based on SADS-L interviews and best estimate diagnostic procedures. All agreeable offspring aged 8–25 years were enrolled in a longitudinal study involving repeated KSADS-PL format clinical assessments. Control (C) offspring from families in which neither parent met lifetime criteria for a psychiatric disorder were similarly assessed. All DSM-IV diagnoses in the offspring were confirmed on blind consensus review. Cumulative incidence and adjusted Cox Proportional Hazards models were used to calculate the risk of anxiety disorders and the predictive association with mood disorders. Results: The cumulative incidence of anxiety disorders was higher (23.40% vs. 10.42%; HR=2.136; p=.0382) and occurred earlier (9.79 vs. 14.84 years; p=.0125) in high-risk compared to C offspring. In high-risk offspring generalized anxiety disorders (GAD) followed by social phobia were the most incident anxiety subtypes; while high emotionality (HR 1.111; p=.0096) and shyness (HR 1.144; p=.0053) increased the risk of anxiety disorders. Anxiety disorders increased the adjusted risk of mood disorders (HR 2.166; p=.0004), on average 8.49 years later (SD 5.97). Limitations: The cumulative incidence of BD is relatively low, as the cohort is still in the period of risk. Conclusions Findings highlight the need for longitudinal surveillance of symptomatic high-risk children and suggest anxiety disorders are an important early intervention target.


Lithium in Neuropsychiatry: the Comprehensive Guide.

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