Sustained Medically Unexplained Physical Symptoms in Euthymic Patients With Recurrent Depression: Predictive Value for Recurrence and Associations With Omega 3- And 6 Fatty Acids and 5-HTTLPR?

J Affect Disord. 2012 Feb;136(3):604-11. doi: 10.1016/j.jad.2011.10.024. Epub 2011 Nov 17.


Background: Identification of potentially modifiable risk factors for recurrence in recurrent depression could provide opportunities to improve preventive interventions. In this study we aimed to examine the predictive value of medically unexplained physical symptoms (MUPS) on time to recurrence in recurrent depression. Additionally, to elucidate pathophysiological mechanisms that could explain the relations between MUPS and depression, we investigate the association between a sustained high level of MUPS, and (I) omega (ω)-3 and -6 fatty acid (FA)-status and (II) functional polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR).

Methods: Based on three Physical Symptom Checklist (PCS) scores over 12 months, we defined two groups of remitted recurrently depressed patients: 41 patients with a sustained high number of MUPS and 34 patients with a sustained low number or no MUPS. Patients were followed-up for 3.5 years while recurrence of their depression was monitored. In addition, we analyzed patients' erythrocyte's FA-profiles and triallelically genotyped their 5-HTTLPR.

Results: A sustained high level of MUPS predicted consecutive depression recurrence over 3.5 years (adjusted relative risk 2.8). FA-status and distribution of 5-HTTLPR variant frequencies did not differ between patients with sustained high compared to low/absent MUPS-levels.

Limitations: Our sample was relatively small.

Conclusion: Remitted recurrently depressed patients with sustained MUPS have a considerably increased risk of recurrence. Having sustained MUPS is not associated with either erythrocyte ω-3 or -6 FA-levels or 5-HTTLPR polymorphism. Recognition and reducing MUPS in an early state could prevent a (depressive) relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Depressive Disorder, Major / genetics*
  • Erythrocytes / chemistry
  • Fatty Acids, Omega-3 / genetics
  • Fatty Acids, Omega-6 / analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Prognosis
  • Promoter Regions, Genetic
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Risk Factors
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins