[Skip to Navigation]
Original Investigation
September 21, 2022

Risk for Mood, Anxiety, and Psychotic Disorders in Individuals at High and Low Genetic Liability for Bipolar Disorder and Major Depression

Author Affiliations
  • 1Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond
  • 2Department of Psychiatry, Virginia Commonwealth University, Richmond
  • 3Center for Primary Health Care Research, Lund University, Malmö, Sweden
  • 4Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York
  • 5Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York
JAMA Psychiatry. 2022;79(11):1102-1109. doi:10.1001/jamapsychiatry.2022.2873
Key Points

Question  What is the association between genetic risk factors for major depression (MD) and bipolar disorder (BD) in the Swedish population and risks for a range of psychiatric disorders?

Findings  In this cohort study including 2.7 million Swedish adults, BD and MD shared a genetic vulnerability to mood disorders. However, individuals at high genetic liability to MD and BD had substantial and relatively specific risks for anxiety disorders and psychosis, respectively.

Meaning  This study suggests that from a genetic perspective, BD and MD are neither very closely nor only distally related but have both shared and relatively distinct genetic risks.

Abstract

Importance  The nature of the genetic relationship between major depression and bipolar disorder remains unclear and might be clarified by considering disorders outside of the mood spectrum.

Objective  To better understand the relationship between genetic liabilities for major depression (MD) and bipolar disorder (BD).

Design, Setting, and Participants  A cohort study was conducted with data for individuals born in Sweden to Swedish parents from 1960 to 1990, with follow-up through December 31, 2018. The data included family genetic risk scores for MD and BD and International Classification of Diseases codes for a range of disorders as reported in primary care, specialist, and hospital registries. Data analysis was conducted from April 2022 to July 2022.

Exposures  High and low genetic liability were defined as being in the upper and lower 2 risk deciles. Risk was compared in individuals at high genetic liability to (1) MD only, (2) BD only, and (3) both MD and BD and those at (4) high genetic liability to BD and low genetic liability to MD and (5) high genetic liability to MD and low genetic liability to BD.

Main Outcomes and Measures  Risk for nonpsychotic MD and BD, psychotic MD and BD, anxiety disorders, obsessive-compulsive disorder, schizoaffective disorder (SAD), schizophrenia, and other nonaffective psychosis.

Results  Data were included for 2 736 950 individuals with a mean (SD) age at follow-up of 43.9 (9.1) years. High genetic liability to only BD increased risk for nonpsychotic BD, psychotic BD, and SAD. High genetic liability to only MD augmented risk for nonpsychotic MD, anxiety disorders, and nonpsychotic BD. High genetic liability to both BD and MD had the strongest association with risk for nonpsychotic BD, anxiety disorders, and nonpsychotic MD. High genetic liability to BD and low genetic liability to MD increased risk for psychotic BD, nonpsychotic BD, and SAD with no increased risk for nonpsychotic MD or anxiety disorders. High genetic liability to MD and low genetic liability to BD increased risk for nonpsychotic MD, nonpsychotic BD, and anxiety disorders with no increased risk for psychotic BD.

Conclusions and Relevance  In this study, hypotheses that BD and MD are either genetically distinct or genetically closely interrelated were not supported. Both BD and MD were associated with a genetic vulnerability to mood disorders, but even that liability was partially selective. However, compared with individuals at high liability to MD, those at elevated genetic liability for BD had a substantially increased risk for psychosis. Compared with individuals at elevated genetic liability to BD, those at high genetic risk for MD had a considerably augmented risk for anxiety disorders. Clarifying genetic relationships between psychiatric syndromes can be substantially aided by the consideration of profiles of risk for a range of disorders.

Add or change institution
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    ×