Lower morning levels of cortisol and neuropeptides in blood samples from patients with bipolar disorder

Emrah Yildiz, Gulcin Elboga, Merve Cıkılı Uygun, Rabia Yilmaz, Yavuz Selvi, Hasan Ulusal, Esra Çelik, Musa Sahpolat, Zeynep Zehra Yildiz, Onur Hursitoglu, Abdurrahman Altindag, Mehmet Tarakçıoğlu, Harry Pantazopoulos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Several lines of evidence indicate that circadian rhythm disruption is associated with bipolar disorder (BPD). This strong association, along with evidence from genome wide association studies (GWAS) implicating clock and clock controlled genes with BDP and efficacy of lithium treatment, suggests that BPD circadian rhythm disruption may represent a core etiology feature. Lower morning expression of the neuropeptide somatostatin (SST) has been previously reported in the brain and cerebral spinal fluid of subjects with BPD, coinciding with increased morning severity of anxiety and depression. We aimed to test the hypothesis that levels of neuropeptides involved in circadian rhythm regulation, including somatostatin (SST), neuropeptide-Y (NPY), arginine vasopressin (AVP), vasoactive intestinal peptide (VIP) and cortisol levels, are altered in blood samples collected in the morning from patients BPD. Method: Thirty nine patients diagnosed as BPD according to DSM-5, and 38 healthy controls were enrolled in the study. Blood were collected at 9 AM from all subjects. Serum levels of SST, NPY, AVP, VIP and cortisol were measured. Results: We observed significantly lower levels of SST (p = 0.001), NPY (p = 0.001), VIP (p = 0.001) and cortisol levels (p = 0.001) in the morning in subjects with BPD compared to control subjects. Significant positive effects of Young Mania Rating Scale and lithium treatment with cortisol, SST, and VIP levels were observed. Conclusion: Our study suggests that lower morning levels of SST, NPY, VIP and cortisol may represent biomarkers underlying disrupted biological rhythms and behavioral and sleep disturbances observed in patients with BPD.

Original languageEnglish (US)
Article number100406
JournalJournal of Affective Disorders Reports
StatePublished - Dec 2022
Externally publishedYes


  • Anxiety
  • Anxiety/anxiety disorders
  • Bipolar disorder
  • Circadian rhythm
  • Depression
  • Neuropeptide
  • Sleep disorders

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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