BackgroundBipolar disorder is highly heritable and therefore longitudinal
observation of children of affected parents is important to mapping the
early natural history.AimsTo 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.MethodA 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.ResultsHigh-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.ConclusionsFindings underscore the importance of a developmental approach in
conjunction with an appreciation of familial risk to facilitate earlier
accurate diagnosis in symptomatic youth.
Clinical diagnoses in young offspring from eastern Québec multigenerational families densely affected by schizophrenia or bipolar disorder