Normalization of GRK2 protein and mRNA measures in patients with depression predict response to antidepressants

• Published in: The international journal of neuropsychopharmacology Vol. 13; no. 1; pp. 83 - 91
• Main Authors: Matuzany-Ruban, Angela, Golan, Moran, Miroshnik, Nataly, Schreiber, Gabriel, Avissar, Sofia
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.02.2010; Oxford University Press
• Subjects: Adult; Antidepressants; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Biomarkers, Pharmacological - blood; Citalopram - pharmacology; Citalopram - therapeutic use; Cyclohexanols - pharmacology; Cyclohexanols - therapeutic use; Depressive Disorder, Major - blood; Depressive Disorder, Major - drug therapy; Female; G-Protein-Coupled Receptor Kinase 2 - blood; Gene Expression Regulation - drug effects; Humans; Kinases; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Male; Mental depression; Middle Aged; Pathophysiology; Proteins; RNA, Messenger - blood; Treatment Outcome; Venlafaxine Hydrochloride; Antidepressant; GRK2; receptor desensitization; post-receptor signal transduction; mood disorders
• ISSN: 1461-1457; 1469-5111; 1469-5111
• DOI: 10.1017/S1461145709000364

G-protein-coupled receptor kinases (GRKs) interfere in receptor–G-protein coupling leading to desensitization of G-protein-mediated receptor signalling. G-protein-coupled receptor signalling and its desensitization were previously implicated in the pathophysiology, diagnosis and treatment of mood disorders. The present study aimed to evaluate alterations in GRK2 protein and mRNA levels in mononuclear leukocytes (MNL) of untreated patients with major depression and the effects and time-course of antidepressant treatments on these alterations. Repeated GRK2 protein and mRNA measurements were carried in MNL of 24 patients with major depression. Each patient was examined while untreated and after 1, 2, 3 and 4 wk of antidepressant treatment; 24 healthy subjects were also studied. GRK2 protein and mRNA levels were evaluated through immunoblot analyses using monoclonal antibodies against GRK2 and reverse transcriptase–polymerase chain reaction, respectively. GRK2 protein and mRNA levels in MNL of untreated patients with major depression were significantly lower than the measures characterizing healthy subjects. The decreased GRK2 protein and mRNA levels were alleviated by antidepressant treatment. Normalization of GRK2 measures preceded, and, thus, could predict clinical improvement by 1–2 wk. These findings support the implication of GRK2 in the pathophysiology of major depression and in the mechanism underlying antidepressant-induced receptor down-regulation and therapeutic effects. GRK2 measurements in patients with depression may potentially serve for biochemical diagnostic purposes and for monitoring and predicting response to antidepressants.