Natural History of Bipolar I Disorder

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CAT: The Long-Term Natural History of the Weekly Symptomatic Status of Bipolar I Disoder (2002). Judd et al., Archives of General Psychiatry, 59, 530-537

Lewis L. Judd, MD; Hagop S. Akiskal, MD; Pamela J. Schettler, PhD; Jean Endicott, PhD; Jack Maser, PhD; David A. Solomon, MD; Andrew C. Leon, PhD; John A. Rice, PhD; Martin B. Keller, MD

Arch Gen Psychiatry. 2002;59:530-537.

Background: To our knowledge, this is the first prospective natural history study of weekly symptomatic status of patients with bipolar I disorder (BP-I) during long-term follow-up.

Methods: Analyses are based on ongoing prospective follow-up of 146 patients with Research Diagnostic Criteria BP-I, who entered the National Institute of Mental Health (Bethesda, Md) Collaborative Depression Study from 1978 through 1981. Weekly affective symptom status ratings were analyzed by polarity and severity, ranging from asymptomatic, to subthreshold levels, to full-blown major depression and mania. Percentages of follow-up weeks at each level as well as number of shifts in symptom status and polarity during the entire follow-up period were examined. Finally, 2 new measures of chronicity were evaluated in relation to previously identified predictors of chronicity for BP-I.

Results: Patients with BP-I were symptomatically ill 47.3% of weeks throughout a mean of 12.8 years of follow-up. Depressive symptoms (31.9% of total follow-up weeks) predominated over manic/hypomanic symptoms (8.9% of weeks) or cycling/mixed symptoms (5.9% of weeks). Subsyndromal, minor depressive, and hypomanic symptoms combined were nearly 3 times more frequent than syndromal-level major depressive and manic symptoms (29.9% vs 11.2% of weeks, respectively). Patients with BP-I changed symptom status an average of 6 times per year and polarity more than 3 times per year. Longer intake episodes and those with depression-only or cycling polarity predicted greater chronicity during long-term follow-up, as did comorbid drug-use disorder.

Conclusions: The longitudinal weekly symptomatic course of BP-I is chronic. Overall, the symptomatic structure is primarily depressive rather than manic, and subsyndromal and minor affective symptoms predominate. Symptom severity levels fluctuate, often within the same patient over time. Bipolar I disorder is expressed as a dimensional illness featuring the full range (spectrum) of affective symptom severity and polarity.

METHODS

Subjects

• Subject recruitment: White, BP-1, entering during an affective episode as part of NIMH Collaborative -Treatments?
• Wide age range
• Gender split okay but not balanced
• Education: ?Downward drift
• Wide range of first onset
• Wide range of initial severity
• Only 99 subjects with greater than 10 years follow-up; Minimum was 2 years with "fair" or better recall.
• Why drop-out?: self-selection, suicide, treatment failure/success

Follow-Up

• q6mos x 5 years and then yearly: ?recall bias ("chronological memory prompts?"); also reviewed medical records
• Good ICC's but see paragraph 2 under Follow-Up procedures. Some weeks dropped due to inaccurate recall (3.1%).

STATS/RESULTS

1. Weeks in symptom status, Total Follow-Up weeks (for "fair" or better accuracy)
2. Total, average yearly number of changes in symptom status/polarity
3. Subgroups of BP-1 with covariates (they call them predictors) of chronicity
4. Long-term chronicity: total percentage of follow-up weeks spent with full syndromal MDD/manic, total percentage of follow-up week with any affective symptoms
5. ANOVA, two-tailed, .05, normality met?

See sentence two in results. Changes in symptom status/polarity: different sub-pop's. Lots of people varied, both between poles and within. Within was greater for depression, a majority, than for mania. "Predictors" of chronicity: poor social functioning in 5 years prior to intake, depressive only or cycling-mixed at intake, RDC drug use disorder at intake or f/u.

DISCUSSION/CONCLUSIONS

• included varying levels of symptomatology; BP-1 a "spectrum" disorder?
• Sub threshold was modal; depression>manic spectrum
• BP-1 not as chronic or not as severe as MDD? (percentage of patients with symptoms? Or severity of symptoms through time?) Symptomatic during nearly half of f/u.
• Their definition of chronicity "reliable and meaningful"
• Generalizability: severely ill, tertiary care, white patients
• Not much consideration of mixed states
• "The focus of this article is on characterizing in the aggregate the overall long-term symptomatic status of BP­-1 based on the sample as a whole."

Presented by Matt DeJohn, MD