New study quantifies risk and risk factors for progression from a diagnosis of unipolar depression to a diagnosis of schizophrenia in the Danish Central Psychiatric Research Register

2017.06.01 | Annette Bang Rasmussen

Postdoc Kate Musliner, PhD MPH, National Center for Register-based Research, Aarhus University

About the study

Depressive symptoms are prevalent first signs of illness among individuals who eventually develop schizophrenia, and are often the precipitating factor leading individuals in the prodromal phase of schizophrenia to seek psychiatric treatment. Without knowledge of a patient’s future illness course, it is difficult for clinicians to distinguish these individuals from patients who present with depressive symptoms but will not develop schizophrenia.  Our aims in this study were to 1) quantify and characterize the risk of progression to schizophrenia among individuals with a diagnosis of unipolar depression and 2) identify groups of unipolar depression patients at elevated risk of progression.

Using information from Danish Civil and Psychiatric registers, we identified a cohort of 71,932 individuals who received their first diagnosis of unipolar depression (ICD-10 codes F32, F33) in a psychiatric hospital facility in Denmark between 1995 and 2013. We followed these individuals for a maximum of 18.5 years to calculate the cumulative incidence of schizophrenia (ICD-10 F20). We used cox regressions to identify characteristics associated with increased hazard of progression.

The cumulative incidence of schizophrenia over 18.5 years was 5.5% in women and 8.4% in men. Patient characteristics associated with risk for progression included younger age; male sex; greater severity, inpatient or emergency room treatment and psychotic symptoms at index depression diagnosis; past or current alcohol and illicit substance use disorders, anorexia, personality disorders, or a disorder with psychotic features; birthplace outside Denmark; and parental history of schizophrenia or neurotic, stress-related, or somatoform disorders. Risk for receiving a schizophrenia diagnosis was highest in the first year following the index depression diagnosis and decreased steadily over the next 10 years. After 10 years, the risk of progression was low, but remained constant throughout the remainder of the follow-up period. Groups of depression patients with different combinations of risk factors had increasingly elevated risks for progression, with 10-year cumulative incidences ranging from 9% to 62%.

The article “Progression from unipolar depression to schizophrenia” was published in Acta Psychiatrica Scandinavica, 2017 Jan;135(1):42-50.

Facts about the study

• We used information from Danish civil and psychiatric registers to identify a cohort of almost 72,000 individuals who received their first depression diagnosis in a psychiatric hospital in Denmark between 1995 and 2013.
• The 18.5 year cumulative incidence of schizophrenia in this cohort of depression patients was 5.5% in women and 8.4% in men.
• Risk of progression was highest in the first year following the index depression diagnosis, and decreased steadily over the next 10 years.
• The strongest predictors of progression included younger age, male sex, past or current psychotic symptoms, and past or current illicit substance abuse disorders. Individuals with all of these characteristics had a 62% probability of progressing to schizophrenia within 10 years of their index depression diagnosis. 

Further information

Kate Musliner, PhD MPH, National Center for Register-based Research, Aarhus University. Email: klm@econ.au.dk