Behavior and Mood Problems in Children of Bipolar Parents

Video  |  Audio (Length:  21 min.)

Boris Birmaher, M.D.
Bibliography

B. Birmaher
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Abstract
Due to the increased public awareness about the existence of bipolar (BP) disorder in youth, parents with either personal or family history of BP are often referring their children for evaluation wondering if their children’s behavior and emotional problems are due to BP disorder. Many of these children, as well as other child referrals to our clinic present with mood lability, irritability, anger, aggressiveness, agitation, explosiveness, temper tantrums, and ADHD-like symptoms without presenting classical BP symptomatology raising the following questions: Are these symptoms of other mood and non-mood disorders (e.g., recurrent unipolar agitated MDD; ADHD)?; prodromal symptoms of BP?; symptoms by which bipolar disorder manifests in early childhood?; or the manifestations of a tendency for mood lability independent of any psychiatric disorder? In order to answer these questions, we are conducting a 5-year longitudinal, high-risk study examining the psychopathological and functional status of children and adolescents (ages 2-18.11 years old) of parents with BP and comparing them with children of non-bipolar, community control parents, with frequency matched on age, ethnicity, and neighborhood. Offspring and their parents are being assessed with standardized instruments at intake and every other year (alternating between face-to-face and phone interviews) to examine the differential incidence of psychopathology, dimensional measures of behavior and emotional regulation (e.g., impulsivity, mood lability, aggression), psychosocial functioning, pubertal status, and family psychiatric history. The information derived from this study will help clarify the various cross-sectional and longitudinal clinical presentations of childhood-onset BPD and shed light on the current controversies regarding the diagnosis of BPD in this age group. Also, this information will help decrease the usual delay between onset of the disorder and the initiation of treatment, guide the clinicians to more specific indications for mood stabilizing agents, provide information for parents with regard to prognosis, and enhance the ability of future family-genetic studies to detect liability genes. In this symposium we will present cross-sectional data collected during the first 1-1/2 years of the study.

Course of Bipolar Disorder in Pregnancy

Video  |  Audio (Length:  12 min.)

Adele C. Viguera, M.D.
Bibliography

A.C. Viguera
Harvard Medical School, Boston, MA, USA

Abstract
Introduction: There is wide agreement that the postpartum period presents unusually high risk for recurrence for bipolar disorder, however, the risks associated with pregnancy itself remain less well-characterized. Some have recently suggested that pregnancy may have an apparent “protective” effect on the course of bipolar disorder (Groff 2001), while other investigators have noted high recurrence risks of around 50% (Blehar 1989, Viguera 2000, Freeman 2001).
Specific Aims: To quantify recurrence risk and time-to first recurrence in pregnant women with bipolar disorder who discontinue mood stabilizer compared to those who maintain mood stabilizer during pregnancy. To identify predictors of recurrence in this study population.
Methods: Pregnant women (N=50) with DSM-IV diagnosis of bipolar disorder were prospectively and systematically followed once a trimester throughout pregnancy. Subjects were recruited from the Massachusetts General Hospital Perinatal and Reproductive Psychiatry Program after consultation on the relative risks of fetal exposure to psychotropics and of recurrences of illness during maintenance treatment and after discontinuation of mood stabilizer. Treatment was not controlled for given the ethical issues involved with a pregnant population. Informed consent was obtained on all subjects and all study procedures were approved by the MGH Institutional review Board. Recurrence was defined as a new episode of mania, hypomania, or major depression based on the SCID mood module during pregnancy (weeks 1-40). Analytic methods included contingency tables (chi-square or Fischer exact p), Kaplan Meier survival analysis, and Cox-proportional hazards modeling.
Results: Subjects who experienced a recurrence in pregnancy did not differ significantly from those women who remained stable by several factors including: age, diagnostic subtype, age of onset, time since last episode prior to conception, or history of full inter-episode recovery, or rate of taper. Subjects who experienced a recurrence were more likely to have discontinued maintenance mood stabilizer, a history of greater number of past episodes, and co-morbid illness. The overall, crude recurrence risk in this sample of pregnant bipolar women was 66%. Crude risk of recurrence during the first 40 weeks following discontinuation of mood stabilizer was 80.56%(29/36) compared to 28.57% (4/14) among women who continued maintenance mood stabilizer (Pearson chi-square 12.13, p=0.00001). Kaplan-Meier survival functions over the 40-week period of risk during pregnancy were compared for women who continued or discontinued mood stabilizer. The distribution of types of episodes at recurrence were as follows: 58% major depression, 16% mania, 13% hypomania, and 13% mixed state.
Discussion: These findings indicate a very high risk of recurrence during pregnancy in women with bipolar disorder who discontinue maintenance mood stabilizer, but a powerful protective effect of remaining on mood stabilizer. The most important predictor of relapse was discontinuation of mood stabilizer even when adjusting for other important predictors such as number of prior episodes. Risk for recurrence was also greatest in women with a history of multiple prior episodes. Rate of taper was not associated with an increased risk for relapse as we have previously reported in a retrospective study of pregnant vs. nonpregnant women with bipolar disorder who discontinued lithium (Viguera 2000). Lack of a statistically significant difference between gradual vs. abrupt discontinuation of mood stabilizer in this study sample may be a result of a small sample size or the fact that subjects were treated with a variety of mood stabilizers other than lithium.

Rapid-Cycling and Mixed States in Adolescents and the Elderly:  A Parallelism

Video  |  Audio (Length:  14 min.)

Athanasios Koukopoulos, M.D.
Bibliography

A. Koukopoulos
Centro Lucio Bini, Rome, Italy

Abstract
The clinical pictures of the various phases of Bipolar Disorder appear to change along with the aging process. The classic involutional melancholia, considered an agitated form of depression (i.e., a mixed affective state), is a typical syndrome of involutional age. Furthermore, depressed patients over 50 years old have been reported to present with more agitation than those under 50 (1). We examined 212 cases (152 women) of agitated depression. The age at onset of the first affective episode was 31.9 years for women and 37.6 for men. The age at index episode of agitated depression was 44.9 for women and 44.5 for men. In 70 patients the age at onset of the first episode of agitated depression as first affective episode was 44.5 years.  The rapid cycling course also has an average onset later in life. In 109 patients with RC course, we found that the mean age at onset of the first affective episode was 28.1 years for women and 30.1 for men while the mean age at onset of rapid cyclicity was 38.8 and 41.2 respectively. Ultra-rapid cycling course is reported to be more frequent in older age (2, 3). Mixed affective states are common in children and adolescents (4, 5), as is the rapid cycling course (6). It is of interest that these severe forms of Bipolar Disorder are more prevalent in children/adolescents and, at the same time, in involutional age, possibly reflecting similarities between the developmental and the involutional stages of the brain. There may exist a parallelism, manifesting in disease course and phenomenology, between the central nervous system that has not yet fully matured and the regressive alterations accompanying the aging process.

References

1.  Brown R.P et al. Involutional melancholia revisited. Am J Psychiatry 1984: Jan, 14(1):24-8.

2.  Alarcon RD, Rapid cycling affective disorders: a clinical review. Compr Psychiatry 1985; 26(6):522-540.

3.  Kramlinger KG et al.  Ultrarapid and ultradian cycling in bipolar affective disorder. Br J of Psychiatry 1996; 168:314-323.

4.  Akiskal H et al., Affective disorders in referred children and younger siblings of manic-depressives. Mode of onset and prospective course. Arch Gen Psychiatry 1985; 42(10):996-1003.

5.  Faedda G.L et al., Pediatric Bipolar Disorder: Phenomenology and Course of Illness. J Affect Disord (submitted).

6.  Geller B et al.  Prepubertal and early adolescent bipolarity differentiate from ADHD by symptoms, grandiose delusions, ultra-rapid or ultradian cycling. J Affec Disord 1998; 51(2):81-91.

7.  Koukopoulos A et al.  Agitated Depression, Spontaneous and Induced, in Mixed States, Rapid Cycling and Atypical Bipolar Disorder Eds Marneros A, Goodwin FK Cambridge University Press (in press).

8. Koukopoulos A et al.  Duration and stability of the rapid-cycling course: a long-term personal follow-up of 109 patients. J Affect Disord. 2003 Jan;73(1-2):75-85.

Changing Prescription Patterns for Lithium and Divalproex in the Treatment of Bipolar Disorder in Old Age: Shifting Practice without Evidence

Video  |  Audio (Length:  17 min.)

Kenneth I. Shulman, M.D.
Bibliography

K.I. Shulman
University of Toronto, Faculty of Medicine, Toronto, Canada

Abstract
The high prevalence of neurologic comorbidity and poor outcome associated with late life mania make this a challenging clinical research priority. Drug utilization information was derived from the Ontario Drug Benefit (ODB) Plan which provides comprehensive drug benefits to over 1 million elderly in Ontario. Using large data sets, we were able to distinguish between psychiatric and anticonvulsant use of lithium and divalproex for use in bipolar disorders in individuals 66 years of age and older.  A dramatic shift in prescription patterns has occurred over the last decade. The new use of lithium carbonate has declined significantly while the new use of divalproex has risen dramatically. Moreover, the prevalent use of lithium carbonate and divalproex in the elderly is now converging. These shifts in prescription patterns for elderly bipolars are occurring in the absence of evidence-based data. This should be a cause for concern and a stimulus for systematic prospective clinical trials of anticonvulsant and psychotropic use in old age bipolar disorders.

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