Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response

J Psychiatr Res. 2019 Mar;110:1-8. doi: 10.1016/j.jpsychires.2018.12.006. Epub 2018 Dec 8.


Background: This study, for the first time, compared illness and antidepressant response characteristics of young subjects with major depression (MDD) at low (LRMDD) or high-risk (HRMDD) for developing bipolar disorder with characteristics of young bipolar (BPD) subjects and healthy controls (HC).

Methods: One hundred and six young (15-30 yr), medication-free subjects MDD subjects (HRMDD, N = 51; LRMDD, N = 55) were compared with 32 BPD (Type I: 14; Type II: 18) as well as 49 HC subjects. Baseline illness characteristics and frequency of comorbid conditions were examined using Analysis of Variance and Cochran-Armitage trend test. Additionally, in MDD subjects, the effect of open-label antidepressant treatment for up to 24 months with periodic assessments was compared between HRMDD and LRMDD groups for treatment response, remission and (hypo)mania switch while controlling for attrition.

Results: Significant gradation from LRMDD to HRMDD to BPD groups was found for increasing occurrence of alcohol dependence (p = 0.006), comorbid PTSD (p = 0.006), borderline personality traits (p = 0.001), and occurrence of melancholic features (p < 0.005). Antidepressant treatment response was similar between the two groups except that for the 12-month period HRMDD showed a trend for a lower response. Switch to (hypo)mania was infrequent in both groups though the HRMDD showed a higher occurrence of spikes in (hypo)mania symptoms (>25% increase in YMRS scores)(p = 0.04).

Conclusion: Findings of the study indicate that a substantial proportion of young MDD subjects share BPD illness characteristics. These HRMDD subjects, if treated with antidepressants, need to be monitored for development of BPD.

Trial registration: NCT01811147.

Keywords: Antidepressant treatment; Bipolar disorder; Depression; Hypomania; Mania; Subthreshold symptoms; Young-adults; Youth.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Alcoholism / epidemiology
  • Antidepressive Agents / pharmacology*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / epidemiology
  • Bipolar Disorder / physiopathology*
  • Borderline Personality Disorder / epidemiology
  • Comorbidity
  • Depressive Disorder / epidemiology
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / epidemiology
  • Depressive Disorder, Major / physiopathology*
  • Disease Progression*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Outcome Assessment, Health Care*
  • Risk
  • Young Adult


  • Antidepressive Agents

Associated data