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. Author manuscript; available in PMC: 2014 May 5.
Published in final edited form as: Can J Psychiatry. 2013 Jan;58(1):22–31. doi: 10.1177/070674371305800106

Table 3.

Different Concepts of the Bipolar-I Disorder Prodrome

Correll et al. 2007 15 McNamara et al 2010 19 Bechdolf et al. 2010 18 Pavuluri 2010 86 Leopold et al. 2012 23 Brietzke et al. 2012 85
4 illness stages:

  1. early prodromal phase:

    sub-clinical and non-specific symptoms, attenuated mania symptoms

  2. late prodromal phase:

    bipolar disorder NOS

  3. subsyndromal stage:

    cyclothymia, hypomania

  4. syndromal stage:

    bipolar disorder-I and II

3 approaches:

  1. clinical: (e.g. attenuated symptoms, ADHD, ODD, depression etc.)

  2. endophenotypic

  3. genetic (including familial risk and genotype)

 3 illness stages:

  1. putative risk factors:

    first-degree relative with bipolar disorder, sexual/physical abuse, psychosocial stress, substance use/abuse, stimulant/antidepressant medication exposure, n-3 fatty acid deficiency

  2. prodromal clinical features:

    ADHD, unipolar depression, hypomania, anger/irritability, anxiety

  3. mania/bipolar-I disorder onset

 3 risk groups:

  1. sub-threshold mania group

    presence of an A criterion plus at least two B criteria, duration of 2–4 days

  2. depression plus cyclothymic features group

    depression: depressed mood or loss of interest plus 2 depression criteria, duration ≥1 week cyclothymic features: numerous episodes with sub-threshold mania as in group I and depression, duration of sub-threshold mania 4hrs/day for ≥4 cumulative days lifetime

  3. depression plus genetic risk group

    depression as in group II and first-degree relative with bipolar disorder

 5 marker domains:

  1. family history

  2. ‘prodromal symptom complex’

    including symptoms of mania, comorbid ADHD and/or ODD, and temperamental features

  3. neurobiological markers

  4. endophenotypic marker

  5. temperamental features

 3 risk stages:

  1. risk state

    specific changes in sleep and circadian rhythm plus ≥1 other secondary risk factor

  2. high risk state

    one primary plus ≥1 secondary risk factor

  3. ultra-high risk state >1 primary risk factor

Primary risk factors:

  • family history

  • increasing cyclothymia dynamic

  • (hypo-)mania prodrome


Secondary risk factors:

  • changes in sleep

  • impairment in psychosocial functioning

  • symptoms or diagnosis of ADHD

  • substance use/abuse

  • anxiety

  • current or past mood disorder other than bipolar disorder

 3 risk clusters:

  1. genetic risk

  2. environmental risk

    childhood trauma, sexual/physical abuse, neglect or parental loss

  3. profile of risk biomarkers

ADHD: attention deficit-hyperactivity disorder; nos: not otherwise specified; ODD: oppositional defiant disorder