Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Heterogeneity in 10-Year Course Trajectories of Moderate to Severe Major Depressive Disorder A Danish National Register-Based Study

Katherine L. Musliner, PhD1,2,3; Trine Munk-Olsen, PhD1,2; Thomas M. Laursen, PhD1,2; William W. Eaton, PhD3; Peter P. Zandi, PhD3; Preben B. Mortensen, DrMedSc1,2
[+] Author Affiliations
1National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark
3Department of Mental Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
JAMA Psychiatry. 2016;73(4):346-353. doi:10.1001/jamapsychiatry.2015.3365.
Text Size: A A A
Published online

Importance  Evidence suggests that long-term trajectories of major depressive disorder (MDD) are heterogeneous. The Danish Psychiatric Central Research Register (DPCRR) provides a rare opportunity to examine patterns and correlates of long-term trajectories in a large sample of patients with moderate to severe MDD.

Objective  To characterize patterns and correlates of 10-year course trajectories of MDD in the DPCRR.

Design, Setting, and Participants  A cohort containing 11 640 individuals born in Denmark in 1955 or later with their first recorded MDD diagnosis in the DPCRR between 1995 and 2002 was established. Patients were followed for 10 years from the date of their initial MDD diagnosis. Data were obtained from Danish civil and psychiatric national registers in June 2013 and were analyzed from April 4, 2014, to December 17, 2015. Correlates of trajectory class membership were sex, characteristics of the first recorded MDD episode (ie, age, severity, inpatient treatment, and record of suicide attempt or self-harm), and psychiatric diagnoses in parents (ie, depression, bipolar disorder, schizophrenia-spectrum disorders, substance abuse, and anxiety or somatoform disorders).

Main Outcomes and Measures  The outcome variable was past-year contact at a psychiatric hospital with a main diagnosis of MDD during each of the 10 years following the initial MDD diagnosis. Trajectories were modeled using latent class growth analysis.

Results  The sample included 11 640 individuals (7493 [64.4%] women) aged 18 to 48 years (mean [SD], 31.4 [7.3]) at their first recorded MDD diagnosis. Four trajectory classes were identified: brief contact (77.0%) (characterized by low probability of contact after 2 years); prolonged initial contact (12.8%) (characterized by high decreasing probability of contact during the first 5 years); later reentry (7.1%) (characterized by moderate probability of contact during the second 5 years); and persistent contact (3.1%) (characterized by high or moderate probability of contact throughout). Female sex (odds ratio [OR] range, 1.82-2.22), inpatient treatment (OR range, 1.40-1.50), and severity at first recorded MDD episode (OR range: moderate, 1.61-1.84; severe, 1.93-2.23; and psychotic, 2.73-3.07) were associated with more severe trajectories. Parental anxiety (OR, 1.34 [95% CI, 1.10-1.63]) and depression (OR, 1.63 [95% CI, 1.28-2.09]) were associated with the prolonged initial contact and later reentry classes, respectively. Parental schizophrenia was associated with the persistent contact class (OR range, 2.55-3.04).

Conclusions and Relevance  Most people treated for moderate to severe MDD in Danish psychiatric hospitals do not receive additional MDD treatment after 2 years; however, a minority receive specialty treatment for up to a decade. Observable heterogeneity in the course may be indicative of underlying etiologic differences.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Patterns of 10-Year Course Trajectories of Major Depressive Disorder (MDD)

Class 1 indicates brief contact (77.0%); class 2, prolonged initial contact (12.8%); class 3, later reentry (7.1%); and class 4, persistent contact (3.1%). The model included the following covariates: sex, birth year, rural birthplace, age at initial diagnosis, calendar year at initial diagnosis, inpatient treatment at initial diagnosis, record of suicide attempts or self-harm, initial episode severity (mild [reference], moderate, severe without psychotic features, severe with psychotic features, or severity unspecified), and parental history of psychiatric diagnoses in the Danish Psychiatric Central Research Register (depression, bipolar disorder, psychotic illness, substance abuse, and anxiety or somatoform disorders). Data markers indicate predicted probabilities; error bars, 95% CIs.

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

3 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Accuracy of Clinical Findings in Endemic Areas

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Data Analysis and Statistical Methods