Family studies bipolar disorders

Muller DJ, de Luca V, Sicard T, King N, Strauss J, Kennedy JL. Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder family-based association study. Br J Psychiatry 2006 189 317-23. 

Results of family and twin studies suggest a genetic basis for bipolar disorder.4 The lifetime risk of bipolar disorder in relatives of a bipolar patient is 40% to 70% for a monozygotic twin and 5% to 10% for another first-degree relative. 

Both genetic and nongenetic factors play roles in the transmission of mood disorders. The familial nature of mood disorders is well established. Studies over the past 20 years have consistently documented higher rates of mood disorder in the relatives of individuals with major depression and bipolar disorder than in relatives of healthy controls [6,7], The familial aggregation of mood disorders is the outcome of both genetic and environmental factors. 

Bocchetta, A., Piccardi, M.P., Palmas, M.A., Chillotti, C., Oi, A., and Del Zompo, M. (1999) Family-based association study between bipolar disorder and DRD2, DRD4, DAT, and SERT in Sardinia. Am Med Genet 88 522-526. 

Mania. Mania and hypomania can also occur in children and adolescents on SSRIs, and, again, it is not known if there is an added developmental risk (Ven-kataraman et al., 1992). In a fluoxetine treatment study for depression, 3 (of 48) patients developed manic symptoms, even after excluding patients with psychotic depression, bipolar symptoms, or a family history of bipolar disorder (Emslie et al., 1997). In a paroxetine treatment study for depression, 5 adolescents (of 93) were removed for emotional lability and 1 for eupho-ria/expansive mood (Keller et al., 2001). 

The relative absence of systematic studies of bipolar patients under age 18 forces clinicians to extrapolate data from adult studies. There are four major types of studies that provide information on subjects with bipolar disorder double-blind, placebo-controlled studies of patients with acute mania prospective open-label studies of patients with bipolar disorder (which includes mania, hypomania, manic symptoms, or bipolar NOS, people at risk for mania because of their family history, and those with a history of mania who are not currently manic) case series and anecdotal reports. 

Strober, M., Morrell, W., Burroughs, J., Lampert, C., Danforth, H., and Freeman, R. (1988) A family study of bipolar I disorder in adolescence./ Affect Disord 15 255—268. 

One family study indicated that the schizoaffective-manic type tended to aggregate with classic bipolar disorder, while the schizoaffective-depressive type seemed to be more closely related to schizophrenia ( 37). 

On average, symptom severity diminishes by 50% every 5 years between the ages of 10 and 25 years (55, 56). Hyperactivity declines more quickly than impulsivity or inattentiveness. However, symptoms of the condition persist into adulthood in many cases. The strongest predictors of symptomatic persistence are psychiatric co-morbidity, particularly with conduct or bipolar disorder and a family history of ADHD or substance abuse ( 57). A prospective study followed up a cohort of patients older than 16 years old with persistent ADHD symptoms and an age-matched control group and found an 11-fold increase in ongoing ADHD symptoms, a nine-fold increase in antisocial personality disorder, and a four-fold increase in substance abuse ( 58). 

There is a modest link to mood disorders, but it is weak in magnitude and somewhat inconsistent. For example, some studies suggest that BPD often exists in families with other members who have bipolar disorder (220). 

Cho HJ, Meira-Lima I, Cordeiro Q, Michelon L, Sham P, et al. 2005. Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder A systematic review and meta-analysis. Mol Psychiatry 10 771-781. 

Perlis RH, Purcell S, Fagerness J, Kirby A, Petryshen TL, et al. 2008. Family-based association study of lithium-related and other candidate genes in bipolar disorder. Arch Gen Psychiatry 65 53-61. 

Family studies support a high risk-factor association for first-degree relatives with bipolar disorder. Additionally, other conditions are highly represented in relatives of bipolar individuals, including bipolar II, major depression, cyclothymia, schizoaffective disorder, and suicide. 

Ni X, Trakalo JM, Mundo E, Lee L et al (2002) Family-based association study of the sero-tonin-2A receptor gene (5-HT2A) and bipolar disorder. Neuromolecular Med 2 251-259... 

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