Brain Imaging of Quetiapine Response in Anxious Depression

The purpose of this study is to find out what parts of the brain have increased or decreased connectivity when people are depressed and how Seroquel extended release (XR) changes this connectivity in depressed patients. The genetic samples collected are to look at variation in a gene (serotonin transporter gene), which affects the functioning of the chemical serotonin in the brain.

This study will measure the activity and connectivity in different parts of the brain, while the patients are seeing some pictures, using Magnetic Resonance Imaging (MRI) scan. For this study three MRI scans will be conducted. One before the patient begins on any medication, one during the study after 3 weeks of treatment and one after six more weeks of treatment with seroquel.

Eligibility Criteria:
Inclusion Criteria:

* Provision of written informed consent
* A diagnosis of Major Depressive Episode by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV)
* Females or Males aged 18 - 60 years
* Female subjects of childbearing potential must be using a reliable method of contraception and have a negative serum human chorionic gonadotropin (HCG) test at enrollment
* Able to understand and comply with the requirements of the study
* 17-item Hamilton Depression Rating Scale (HDRS) score \> 15
* Hamilton Anxiety Scale (HAM-A) score \> 15
* Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire
* Able to be managed as outpatients for initial assessment and during treatment as ascertained by the following:

  * Symptoms not worsening by more than 10 points on the HDRS during the course of the study.
  * No danger to self or others.

Exclusion Criteria:

* Pregnancy or lactation
* Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, atypical psychosis, mental retardation, or organic mental (including organic mood) disorder
* Subjects who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
* Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator
* Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
* Use of any of the following cytochrome P450 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
* Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
* Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
* Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within four weeks prior to enrollment
* Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
* Unstable or inadequately treated medical illness (angina pectoris, hypertension) as judged by the investigator
* Involvement in the planning and conduct of the study
* Previous enrollment or randomization of treatment in the present study.
* Participation in another drug trial within four weeks prior enrollment into this study or longer in accordance with local requirements
* A subject with Diabetes Mellitus; people who develop hyperglycemia will be removed from the study
* An absolute neutrophil count (ANC) of 1.5 x 109 per liter
* Use of psychotropics in the past two weeks. If on fluoxetine in the past, then should not have been on this medication for four weeks.
* History of lack of response to Quetiapine extended release.
* Acutely suicidal or homicidal or requiring inpatient treatment.
* Metallic implants.