Related Experiment Video
Updated: May 19, 2026

Closed-Loop Neurostimulation for Biomarker-Driven, Personalized Treatment of Major Depressive Disorder
Published on: July 7, 2023
Subthreshold symptoms and time to relapse/recurrence in a community cohort of bipolar disorder outpatients
C De Dios1, E Ezquiaga, J L Agud
1University Hospital La Paz, IDIPAZ, Madrid, Spain. cdios.scsm@salud.madrid.org
Background:
Researchers have previously found that persistent subthreshold symptoms increase the risk and shorten the time until an affective relapse in bipolar disorder (BD) patients. Research has mainly focused on patients from tertiary Care Centers in USA. We tested the hypothesis that even in a different setting, BD outpatients with subsyndromal affective symptoms would re.turn to a subsequent major affective episode significantly faster than completely asymptomatic at baseline. Secondarily, we analysed other variables related to time and risk to relapse.
Methods:
A community cohort of BD outpatients from Madrid (Spain) followed-up in a systematic prospective follow-up protocol for up to five years were evaluated. Patients in clinical euthymia at baseline were included and evaluated quarterly.
Results:
Initially, 225 patients were included in the survival analysis. Of them, according to predefined psychometric criteria, 163 were in euthymia (72.4%) and 62 (27.6%) suffered subsyndromal symptoms. Median follow-up was 157.6 weeks (95% CI, 78.14 to 111); 57.3% of patients experienced at least one affective episode during their follow-up. Median survival time to first affective episode was 109 weeks for patients in euthymia at baseline, versus 35 weeks for those with subsyndromal symptoms (p<0.0001). Psychosocial stress (p=0.003; HR 2.20; 95% CI 1.31-3.68) and the affective mood baseline state, subsyndromal vs. euthymic (p=0.046; HR 1.74; 95%CI 1.009-3.020), were related to time to first affective episode.
Limitations:
Naturalistic study, some of the data collected were necessarily retrospective.
Conclusions:
In Spanish non-tertiary psychiatric outpatients, subsyndromal BD symptoms and psychosocial stress at baseline predict earlier episode relapse/recurrence.
Related Concept Videos
Bipolar Disorder
Psychological and Sociocultural Causes of Schizophrenia
Depressive Disorders: MDD and Dysthymia
Psychosis: Goals of Pharmacotherapy
Classification of Illness
An illness is a response to a disease in which the person's level of functioning is changed compared with a previous level. The general classification of illness includes acute and chronic.
Acute illness is severe and...
Negative and Cognitive Symptoms of Schizophrenia
Negative Symptoms
Negative symptoms of schizophrenia manifest as deficits in normal emotional and behavioral functioning, profoundly impacting daily life. Individuals with schizophrenia often display a flat affect, characterized by a near-total absence of emotional expression,...
