Skip to content

Familial Psychiatric Burden High in Bipolar Disorder but Not Correlated with Treatment Response

Key findings

  • This study was a secondary analysis of two multisite, randomized, six-month trials that enrolled 757 outpatients with bipolar disorder type I or II
  • 85% of patients reported at least one first-degree relative with a severe psychiatric disorder (bipolar disorder, major depressive disorder, psychotic disorder, suicide, drug abuse or alcohol abuse), and 19% reported five or more relatives
  • Familial psychiatric history correlated with several measures of greater disease severity and a putatively more difficult-to-treat disorder as indicated by more medications needed
  • Despite being more challenging to treat, patients with a familial severe psychiatric history did not differ from those without such a history in their response to four frequently used pharmacological treatments

The disease course of people with bipolar disorder (BPD) is known to be affected by the familial psychiatric load (the number of family members with severe psychiatric disorders). In turn, a high familial burden of psychiatric disorders may be associated with lower socioeconomic status and cardiometabolic risk factors, both of which are also known to negatively affect a patient's prognosis.

Researchers Ole Köhler-Forsberg, MD, PhD, from Aarhus University and Aarhus University Hospital, and Andrew A. Nierenberg, MD, director of the Dauten Family Center for Bipolar Innovation in the Department of Psychiatry at Massachusetts General Hospital, and colleagues recently conducted the first study in patients with bipolar disorder that explored the overall burden and impact of psychiatric disorders among first-degree relatives (parents, siblings and children).

They report in the Journal of Affective Disorders that a familial psychiatric history is very common and correlates with disease severity but not treatment response.

Study Methods

The researchers performed a secondary analysis of two multisite, randomized, six-month comparative effectiveness trials that enrolled outpatients with BPD type I or II who were 18–68 years old:

  • Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study (n=482), methodology published in Clinical Trials, compared moderate-dose lithium to quetiapine; either drug could be combined with other medications for bipolar disorder
  • Lithium Treatment Moderate-Dose Use Study (n=283), methodology also published in Clinical Trials, compared low-dose lithium and optimized personalized treatment (OPT) to OPT without lithium; patients could be treated with other psychotropic drugs

Prevalence of Familial Psychiatric History

Of the 765 patients in the two trials, 644 (85%) had at least one first-degree relative with a severe psychiatric disorder (BPD, major depressive disorder, psychotic disorder, suicide, drug abuse or alcohol abuse). 146 patients (19%) reported five or more severe psychiatric disorders among first-degree relatives.

Impact of Familial Psychiatric History on Disease Severity

A greater familial psychiatric burden was correlated with:

  • Longer duration of BPD and a greater number of lifetime manic episodes, psychiatric hospitalizations and suicide attempts among the patients (P≤0.01)
  • A trend toward the need for a greater number of psychotropic medications at every visit (P=0.054)

Impact on Sociodemographic and Cardiometabolic Status

  • Patients with more psychiatric disorders in their families had more children, a lower educational level and a lower household income, potentially reflecting multigenerational effects of psychiatric illness
  • After controlling for age and gender there was no correlation between familial psychiatric burden and cardiometabolic factors (e.g., cholesterol levels, waist circumference) or Framingham cardiovascular risk scores

Impact on Treatment Response

There was no difference between patients with or without familial psychiatric history on the Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) or its depression subscale. On the CGI-BP mania subscale, there was a significantly better response among individuals with familial psychiatric history (P=0.02).

There were no differences between groups in response to any of the four treatment arms.

Takeaway Messages

Familial psychiatric history places a greater burden on patients with bipolar disorder, but intensive treatment can result in response rates comparable to those of patients without such a history. These findings also emphasize the importance of supporting families who experience a heavy load of psychiatric disorders.

Learn more about the Dauten Family Center for Bipolar Treatment Innovation

Explore research in the Department of Psychiatry

Related topics


Zeina Chemali, MD, MPH, director of the Neuropsychiatry Clinics and Training in the Departments of Neurology and Psychiatry, outlines the systemic support necessary for health care workers to recover from the COVID-19 pandemic.


Massachusetts General Hospital researchers have reported the first in vivo human evidence of a role for histone deacetylases in the pathophysiology of bipolar disorder as well as in two of its hallmark clinical features, emotional dysregulation and attention deficits.