One Step Closer to Earlier Diagnosis of Bipolar Disorder and Psychoses

Summary: Genetic risk score for bipolar disorder is associated with an increased risk of developing bipolar symptoms. The genetic risk factor for schizophrenia is linked to an increased risk of those with depression developing psychosis.

Source: Aarhus University

In a new study from the Danish psychiatry project iPSYCH, researchers have identified genetic risk factors for developing bipolar disorder and psychoses among people with depression. In the longer term, the results may contribute to ensuring the correct diagnosis is made earlier, so that the patients can receive the correct treatment as quickly as possible.

Bipolar disorder and psychoses such as schizophrenia are serious mental disorders, which often have a great impact on a person’s life and well-being. In a number of cases, bipolar disorder and schizophrenia are first diagnosed several years after the onset of the disorder. This is associated with unfavourable prognosis for the course of the disorders. The sooner the patient gets the correct diagnosis and begins targeted treatment, the better the prognosis. For this reason, researchers are aiming at identifying risk factors that will aid psychiatrists to reach the correct diagnosis as early as possible.

Depression often precedes bipolar disorder and psychoses

Many people who develop bipolar disorder or psychoses initially come into contact with the mental health services due to depression. A research team from iPSYCH therefore set out to examine a dataset consisting of 16,949 people aged 10-35 who had been treated for depression at a psychiatric hospital in Denmark.

“Our goal with the study was to investigate whether genetic factors are associated with an increased risk of developing bipolar disorder or psychosis among patients with depression. This knowledge can potentially be used in clinical practice to identify patients who should be monitored even more closely,” explains the lead author of the research article based on the study, Senior Researcher Katherine Musliner from the National Centre for Register-based Research.

Among the factors the researchers looked into in the study was whether the genetic risk scores for bipolar disorder and schizophrenia – i.e. a person’s individual genetic risk of developing these disorders – could possibly help psychiatrists determine which of their patients with depression was at greatest risk of subsequently developing bipolar disorder or a psychosis.

“One thing we discovered was that the genetic risk score for bipolar disorder is associated with an increased risk of developing bipolar disorder, and that the genetic risk score for schizophrenia is associated with an increased risk of developing a psychosis among patients who have been diagnosed with depression,” says Katherine Musliner, stressing that the effect of the genetic risk scores were relatively small.

Family history weighs heavily

Another member of the research group behind the study, Professor Søren Dinesen Østergaard from the Department of Clinical Medicine and Aarhus University Hospital – Psychiatry, emphasises that caution is needed when interpreting the results.

This shows a brain
Bipolar disorder and psychoses such as schizophrenia are serious mental disorders, which often have a great impact on a person’s life and well-being. Image is in the public domain.

“At present, the genetic risk scores cannot contribute to early diagnosis of bipolar disorder and psychoses in clinical practice, but it cannot be ruled out that this could be the future scenario. On the other hand, our study confirms that having a parent with bipolar disorder or a psychosis is a strong predictor for the development of these particular disorders after depression. This underlines the importance of getting information about mental disorders in the family as part of the assessment of people suffering from depression,” he explains.

The results have been published in the American Journal of Psychiatry.

Background for the results

The study is a register-based study with data from 16,949 people who were treated for depression at a psychiatric hospital in Denmark in the period from 1994 to 2016.

The study was carried out in collaboration between researchers from Aarhus University, the University of Copenhagen, Statens Serum Institut and Johns Hopkins University.

Funding: The study is financed by the Lundbeck Foundation.

About this psychology research article

Aarhus University
Katherine L. Musliner – Aarhus University
Image Source:
The image is in the public domain.

Original Research: Closed access
“Polygenic Risk and Progression to Bipolar or Psychotic Disorders Among Individuals Diagnosed With Unipolar Depression in Early Life” by Katherine L. Musliner, Ph.D., M.P.H., Morten D. Krebs, M.D., Clara Albiñana, M.Sc., Bjarni Vilhjalmsson, Ph.D., M.Sc., Esben Agerbo, Dr.Med.Sc., M.Sc., Peter P. Zandi, Ph.D., M.P.H., David M. Hougaard, Dr.Med.Sc., M.D., Merete Nordentoft, Dr.Med.Sc., M.D., Anders D. Børglum, Ph.D., M.D., Thomas Werge, Ph.D., M.Sc., Preben B. Mortensen, Dr.Med.Sc., M.D., Søren D. Østergaard, Ph.D., M.D. American Journal of Psychiatry.


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The authors investigated the associations between polygenic liability and progression to bipolar disorder or psychotic disorders among individuals diagnosed with unipolar depression in early life.

A cohort comprising 16,949 individuals (69% female, 10–35 years old at the first depression diagnosis) from the iPSYCH Danish case-cohort study (iPSYCH2012) who were diagnosed with depression in Danish psychiatric hospitals from 1994 to 2016 was examined. Polygenic risk scores (PRSs) for major depression, bipolar disorder, and schizophrenia were generated using the most recent results from the Psychiatric Genomics Consortium. Hazard ratios for each disorder-specific PRS were estimated using Cox regressions with adjustment for the other two PRSs. Absolute risk of progression was estimated using the cumulative hazard.

Patients were followed for up to 21 years (median=7 years, interquartile range, 5–10 years). The absolute risks of progression to bipolar disorder and psychotic disorders were 7.3% and 13.8%, respectively. After mutual adjustment for the other PRSs, only the PRS for bipolar disorder predicted progression to bipolar disorder (adjusted hazard ratio for a one-standard-deviation increase in PRS=1.11, 95% CI=1.03, 1.21), and only the PRS for schizophrenia predicted progression to psychotic disorders (adjusted hazard ratio=1.10, 95% CI=1.04, 1.16). After adjusting for PRSs, parental history still strongly predicted progression to bipolar disorder (adjusted hazard ratio=5.02, 95% CI=3.53, 7.14) and psychotic disorders (adjusted hazard ratio=1.63, 95% CI=1.30, 2.06).

PRSs for bipolar disorder and schizophrenia are associated with risk for progression to bipolar disorder or psychotic disorders, respectively, among individuals diagnosed with depression; however, the effects are small compared with parental history, particularly for bipolar disorder.

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