Major depressive disorder
MDD
Research on how low mood, loss of interest, and other symptoms combine and relate to everyday functioning.
Research question
Among people with the same total symptom score, do individual symptom patterns improve predictions of later changes in everyday functioning?
Findings
Symptoms and everyday functioning
NICE guidance on adult depression considers symptom frequency and intensity, duration, and effects on personal and social functioning when describing severity.
Varied symptom profiles
A reanalysis of data at the start of the first STAR*D treatment step found 1,030 symptom profiles among 3,703 outpatients with depression in the US multisite study.
Genome-wide associations across 29 countries
A pooled study of 688,808 depression cases and 4,364,225 controls from 29 countries identified 635 genomic loci associated with depression. Some cohorts used self-reported cases that fell short of formal criteria for major depressive disorder.
Relapse after remission in STAR*D
Among STAR*D outpatients who entered a 12-month observational follow-up after one of the first three treatment steps, relapse was less frequent among those in remission at follow-up entry than among those who had not reached remission.
Recurrent depression and hippocampal volume
ENIGMA pooled MRI data from 1,728 people with major depressive disorder and 7,199 controls. Mean hippocampal volume was smaller in the recurrent depression group than in controls. The difference for the first-episode group was statistically inconclusive.
Preventing onset in adults with subthreshold symptoms
An individual participant data meta-analysis pooled 30 randomized trials with 7,201 adults who had subthreshold depressive symptoms and had no major depression at baseline. Across 19 trials with data within 12 months, the incidence rate ratio for major depression was 0.67 (95% CI 0.51–0.88) for psychological interventions versus control. The 24-month estimate from six trials was uncertain.
Depression screening accuracy by reference interview
An analysis of individual data from 44,503 participants in 100 studies found pooled PHQ-9 sensitivity and specificity of 0.85 each at a threshold of 10 or higher in studies using a semistructured diagnostic interview. Specificity was similar across interview types. Sensitivity was higher against semistructured interviews than against fully structured interviews or the MINI.
Short-term comparative trial in treatment-resistant depression
ELEKT-D randomized 403 patients with treatment-resistant major depression without psychotic features. Among 365 participants who started the assigned intervention, 3-week self-reported symptom response was 55.4% with ketamine and 41.2% with electroconvulsive therapy, meeting the prespecified noninferiority criterion. This was a short-term, open-label comparison with 38 withdrawals before treatment began.
Limitations
The STAR*D reanalysis coded each symptom as present or absent in an outpatient sample. The number of profiles can vary with the sample and the coding rule.
Original sources
Depression in adults: treatment and management (NG222)
National Institute for Health and Care Excellence
Depression is not a consistent syndrome: An investigation of unique symptom patterns in the STAR*D study
Eiko I. Fried, Randolph M. Nesse
Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies
PGC Major Depressive Disorder Working Group
Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report
A. John Rush et al.
Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group
Lianne Schmaal et al.
Psychological interventions to prevent the onset of major depression in adults: a systematic review and individual participant data meta-analysis
Claudia Buntrock et al.
Accuracy of the Patient Health Questionnaire-9 for screening to detect major depression: updated systematic review and individual participant data meta-analysis
Zelalem F. Negeri et al.
Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression
Amit Anand et al.