Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism
Information source: University of Ottawa
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Major Depression
Intervention: Open label pharmacotherapy (Other)
Phase: Phase 4
Sponsored by: University of Ottawa
Official(s) and/or principal investigator(s):
Pierre M Blier, MD, Ph.D, Principal Investigator, Affiliation: University of Ottawa Institute of Mental Health Research
Reduction of volume of the hippocampus has been associated with major depression in many
studies. It has been suggested that antidepressants may protect against hippocampus volume
loss in humans associated with multiple episodes of depression and may also reverse the
reduction of volume caused by the depression. In addition, genetic markers for serotonin are
implicated with depression, and may be an indication of reduced response to antidepressant
This study aims to enroll patients who are defined as having treatment resistant depression
(no remission after at least 2 treatments trials with an antidepressant). They will receive
an MRI scan at the initial visit and either 6 months after sustained remission or 12 months
after they enter the study for non-remitters. They will also be asked to give a blood sample
for genotyping. They will be matched by age and handedness to healthy volunteers with no
personal history of depression who will also receive an MRI scan and genotyping.
The first aim is to compare hippocampal volume of depressed subjects to healthy controls. It
is anticipated that subjects will initially have smaller hippocampal volume but of those who
sustain remission, there will be a small increase in hippocampal volume. It is also
anticipated that specific genetic markers will be related to individuals response to
Official title: Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Sustained Remission from Depression and Hippocampal Atrophy
Secondary outcome: 5-HT1a Genetic Markers
Individuals who are defined as having treatment-resistant major depression (failure of at
least 2 trials of an antidepressant at an adequate dose) and currently meet DSM-IV criteria
for depression qualify for this study. At the initial visit, each subject is given an MRI in
order to perform a volumetric analysis of their hippocampus and a blood sample is taken in
order to determine their genotype for the 5-HT1a(serotonin) promoter. Each patient is then
aggressively treated (open label) for depression with the goal of remission. A second MRI
scan is completed 6 months after sustained remission or 12 months from baseline if remission
is not met or sustained.
The investigators will select healthy volunteer controls with no personal or first relative
history of depression and match with the subjects based on age and handedness. Genotyping
and and MRI scan will be performed on the healthy subjects in order to compare all
Hypothesis: It is anticipated that the hippocampal volume will be smaller than those of
matched controls. It is also anticipated that the Homozygous G(-1019) genotype will be more
prevalent in the patient group than in the healthy subjects.
In addition, it is hypothesized that the investigators should find a small increase in
hippocampal volume after long-term treatment. Also, most non-responders will be of
homozygous G(-1019) 5-HT1a genotype and will have the greatest degree of hippocampal
atrophy. Moreover, it is hypothesized that patients carrying a long allele of 5-HTTLPR
polymorphism for 5-HTT might show a better response to antidepressants in general. Finally,
it is anticipated that the TPH*A variant of the gene coding for tryptophan hydroxylase will
be associated with poorer outcome.
Minimum age: 18 Years.
Maximum age: 65 Years.
- Male or female between ages of 18 to 65 years of age.
- A diagnosis of Major Depression according to the DSM-IV criteria
- Failing to achieve remission while receiving at least two different
antidepressants at adequate dosage for at least 6 weeks.
- Initial score of at least 18 on the HAMD-17 item rating scale
- A diagnosis of substance abuse or dependence in the last 6 months or a lifetime
diagnosis of substance abuse according to the DSM-IV criteria, elicited by inquiry.
- A diagnosis of post-traumatic stress disorder, schizophrenia, schizo-affective
disorder and other psychotic disorders, anorexia nervosa or a history of a manic or
- Major medical illnesses including endocrine and neurological disorders, as well as a
history of significant head trauma
- Exposure to oral or intravenous steroids
- Contraindications to magnetic resonance imaging
- An IQ less than 80
Locations and Contacts
University of Ottawa Institute of Mental Health Research, Ottawa, Ontario K1Z 7K4, Canada
University of Ottawa Institute of Mental Health research homepage
Starting date: February 2005
Last updated: January 18, 2011