Associations of presenting symptoms and subsequent adverse clinical outcomes in people with unipolar depression: a prospective natural language processing (NLP), transdiagnostic, network analysis of electronic health record (EHR) data

OBJECTIVE: To investigate the associations of symptoms of mania and depression with clinical outcomes in people with unipolar depression. DESIGN: A natural language processing electronic health record study. We used network analysis to determine symptom network structure and multivariable Cox regression to investigate associations with clinical outcomes. SETTING: The South London and Maudsley Clinical Record Interactive Search database. PARTICIPANTS: All patients presenting with unipolar depression between 1 April 2006 and 31 March 2018. EXPOSURE: (1) Symptoms of mania: Elation; Grandiosity; Flight of ideas; Irritability; Pressured speech. (2) Symptoms of depression: Disturbed mood; Anhedonia; Guilt; Hopelessness; Helplessness; Worthlessness; Tearfulness; Low energy; Reduced appetite; Weight loss. (3) Symptoms of mania or depression (overlapping symptoms): Poor concentration; Insomnia; Disturbed sleep; Agitation; Mood instability. MAIN OUTCOMES: (1) Bipolar or psychotic disorder diagnosis. (2) Psychiatric hospital admission. RESULTS: Out of 19 707 patients, at least 1 depression, overlapping or mania symptom was present in 18 998 (96.4%), 15 954 (81.0%) and 4671 (23.7%) patients, respectively. 2772 (14.1%) patients subsequently developed bipolar or psychotic disorder during the follow-up period. The presence of at least one mania (HR 2.00, 95% CI 1.85 to 2.16), overlapping symptom (HR 1.71, 95% CI 1.52 to 1.92) or symptom of depression (HR 1.31, 95% CI 1.07 to 1.61) were associated with significantly increased risk of onset of a bipolar or psychotic disorder. Mania (HR 1.95, 95% CI 1.77 to 2.15) and overlapping symptoms (HR 1.76, 95% CI 1.52 to 2.04) were associated with greater risk for psychiatric hospital admission than symptoms of depression (HR 1.41, 95% CI 1.06 to 1.88). CONCLUSIONS: The presence of mania or overlapping symptoms in people with unipolar depression is associated with worse clinical outcomes. Symptom-based approaches to defining clinical phenotype may facilitate a more personalised treatment approach and better predict subsequent clinical outcomes than psychiatric diagnosis alone.