The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery.
BACKGROUND
Cytokines are implicated in the pathophysiology of major depressive disorder (MDD). However, the pattern of alterations in cytokine levels is still unclear. The current study investigated the plasma levels of a range of cytokines in a follow-up design, with the aim of determining their involvement in depression.


METHODS
Fifty medication-free MDD patients with a depressive episode and 34 healthy controls were included at baseline; the patients were followed up after 12 weeks. Before initiating treatment, the patients were diagnosed and assessed for depressive symptoms and blood for cytokine analysis was obtained. The same clinical assessments and cytokine measurements were performed after 12 weeks of "treatment as usual."


RESULTS
The cytokines interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-5, IL-6, IL-7, IL-8, IL-10, granulocyte colony-stimulating factor (G-CSF), and interferon gamma (IFNγ) were significantly elevated (p=0.01-0.047) in depressed patients at baseline compared to healthy controls. After 12 weeks of treatment, the plasma levels of seven of these nine cytokines (IL-1Ra, IL-6, IL-7, IL-8, IL-10, G-CSF, and IFNγ had decreased significantly compared to baseline and did not differ from those in the healthy controls. The depressive symptoms were simultaneously significantly reduced. In addition, the reduction to normal cytokines levels occurred only in those who met the recovery criteria.


CONCLUSIONS
A more general pattern of elevated cytokine levels is described herein relative to what has been described previously shown in MDD. Furthermore, recovery from depression was associated with reduction to normal levels of the majority of the measured cytokines. These results strongly support the notion that a complex network of cytokines is involved in the pathophysiology of MDD.
Ringerike Psychiatric Center, Vestre Viken Hospital Trust, Norway. Electronic address: johan.dahl@vestreviken.no.
Johan
J
Dahl
Faculty of Health Sciences, Buskerud University College, Norway.
Heidi
H
Ormstad
Department of Medical Biochemistry, Oslo University Hospital, Norway.
Hans Christian D
HC
Aass
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychosomatic Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Ulrik Fredrik
UF
Malt
Department of Clinical Sciences, Section for Psychiatry, Lund University, Lund, Sweden.
Lil Träskman
LT
Bendz
Center for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
Leiv
L
Sandvik
Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, Grand Rapids, USA; Van Andel Research Institute, Center for Translational Medicine, Grand Rapids, MI, USA.
Lena
L
Brundin
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Ole A
OA
Andreassen
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000534:rehabilitation*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function / Q000502:physiology*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D015854:Up-Regulation
D000928:Antidepressive Agents; D016207:Cytokines; D018836:Inflammation Mediators
Anti-inflammatory cytokines; Cytokine pattern; Follow-up; Major depressive disorder; Proinflammatory cytokines; Recovery; Th1 cytokines; Th2 cytokines