Neural, Genetic, and Peripheral Correlates of SSRI Pharmaco-Response

The aim of this pharmako-MRI study is to investigate neural correlates of variable antidepressant treatment response driven by genetic variation in multiple genes involved in depression.

Thirty Major Depressive Disorder (MDD) patients with a concurrent major depressive episode will undergo three MRI scanning sessions after escitalopram treatment initiation. Furthermore, extensive behavioral assessments and measures of potential peripheral markers such lymphocyte mRNA or pharmacological parameters on platelets or lymphocytes will be performed.

Imaging measures have been suggested to be superior for drug response assessment as compared to psychometric scales, which hardly correlate with biological parameters. Since imaging techniques are too expensive and sophisticated for a broad clinical use, this study will provide pilot data on potential peripheral biomarkers of neural activation being related to drug response.

The aim of this pharmako-MRI study is to investigate neural correlates of variable antidepressant treatment response driven by genetic variation in multiple genes involved in depression.

Thirty Major Depressive Disorder (MDD) patients with a concurrent major depressive episode will undergo three MRI scanning sessions at baseline, 4 hours and 8 weeks after escitalopram treatment initiation. During each MRI session, one structural and 3 fMRI scans each engaging different brain circuitries will be performed. All subjects will undergo extensive behavioral assessment and will be genotyped. Furthermore, potential peripheral markers such lymphocyte mRNA or pharmacological parameters on platelets or lymphocytes will be assessed.

The investigators expect that genetic variants which have been associated with variable response to SSRIs in previous Imaging Genetics studies are modulating neural targets of drug response. Moreover, peripheral markers are expected to correlate with these brain region measurements.

Imaging measures have been suggested to be superior for drug response assessment as compared to psychometric scales, which hardly correlate with biological parameters. Since imaging techniques are too expensive and sophisticated for a broad clinical use, this study will provide pilot data on peripheral biomarkers of neural activation being related to drug response. Furthermore, this study will demonstrate whether and how genotypes impact on the dynamics of neural drug response in vivo.

• Scharinger C, Rabl U, Sitte HH, Pezawas L. Imaging genetics of mood disorders. Neuroimage. 2010 Nov 15;53(3):810-21. Epub 2010 Feb 13.
• Pezawas L, Meyer-Lindenberg A. Imaging genetics: Progressing by leaps and bounds. Neuroimage. 2010 Nov 15;53(3):801-3. No abstract available.
• Rabl U, Scharinger C, Müller M, Pezawas L. Imaging genetics: implications for research on variable antidepressant drug response. Exp Rev Clin Pharmacol 3, 471-489, 2010.

Inclusion Criteria:

• Male or female
• Age 18 -45 years
• Right-handedness
• DSM-IV diagnosis of a major depressive episode (SCID)
• a MADRS score ≥20 and ≤ 30
• ability to be managed as outpatients
• ability to fulfill the criteria to undergo an MRI scan
• Caucasian subjects of European ancestry

Exclusion Criteria:

• previous or concurrent major medical or neurological illness
• clinically significant abnormal values in routine laboratory screening or general physical examination
• DSM-IV diagnosis of substance dependence within the past year, except for caffeine or nicotine or current substance abuse
• DSM-IV diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or an anxiety disorder as a primary diagnosis
• the use of any psychotropic drug within the last two months unresponsiveness of a former major depressive episode to an adequate antidepressive drug dosing of at least 6 weeks duration or any kind of therapy resistance
• a history of severe drug allergy or hypersensitivity or known hypersensitivity to escitalopram
• being acutely suicidal either indicated by a score ≥ 5 on item 10 (suicidal thoughts) on the MADRS or a score ≥ 4 on the HAM-D 21 (suicidal thoughts) or according to the investigator´s opinion
• failures to comply with the study protocol or to follow the instructions of the investigating team
• current pregnancy or breast feeding
• metallic implants or other contraindications to MRI