Development of Magnetic Resonance Imaging Techniques for Studying Mood and Anxiety Disorders

This study is intended to help develop new MRI imaging techniques for studying mood and anxiety disorders. Researchers believe that depression and anxiety disorders may cause structural and functional changes in the brain. This study will optimize the way MRI scans are collected to look at brain structure and examine how the brain behaves while subjects perform particular tasks.

Healthy normal subjects between 18 and 50 years of age who have never had a major psychiatric disorder and who have no first-degree relatives with mood disorders may be eligible for this study. Candidates are screened by phone with questions about their psychiatric and medical history, current emotional state and sleep pattern, and family history of psychiatric disorders. Candidates who pass the preliminary screening then undergo additional screening interviews and laboratory tests.

Participants undergo magnetic resonance imaging (MRI) and neuropsychological testing, as follows:

" MRI scans: Subjects are asked to participate in an MRI study on one of several scanners to measure blood flow in the brain, concentrations of certain chemicals in the brain, or magnetic properties of the brain. MRI uses a strong magnet and radio waves to obtain pictures of the brain. The subject lies still on a narrow bed with a metal coil close to the head. For this study, subjects may be asked to wear a special coil on the neck to help measure blood flow. They may be asked to watch a screen presenting images or to do a task in which they respond to pictures or sounds and may be asked to return for additional scans.

" Neuropsychological testing: Subjects may undergo tests of cognitive performance. Often, people with mood disorders have subtle changes in performance on these tests that allow researchers to pinpoint where brain abnormalities occur. Before the tests can be used in patients, they must be validated by using healthy subjects. These tests are presented either orally, in written form, or on a computer.

A major component of understanding the pathogenesis of mood and anxiety disorders is expected to involve elucidation of abnormalities of brain structure and function associated with these conditions. Historically, post-mortem histopathological and neurochemical assessments constituted the primary methods for investigating abnormalities of brain structure and function in psychiatric disorders. However, the significance of the results from such studies has been limited by the relatively poor availability of specimens from subjects with mood and anxiety disorders who had been unmedicated and clinically well-characterized antemortem. By allowing for in vivo human studies, medical imaging technologies afford efficient, accurate, and non-invasive alternatives for characterizing brain structure and function. The recent, rapid development of magnetic resonance imaging (MRI) technology, in particular, has provided powerful tools for assessing a wide range of cerebral physiological and morphological characteristics. To optimally exploit the potential of rapidly evolving MRI capabilities and hardware in investigations of mood and anxiety disorders, new techniques and applications must be tested and developed. The technical development protocol proposed herein will assess new imaging techniques and hardware, and will develop novel cognitive tasks for application in the study of mood and anxiety disorders.

The primary objective of this protocol is the development of MRI experiments for characterizing the physiological correlates of mood and anxiety disorders. In addition, the pilot projects encompassed within this protocol involve the optimization of existing MRI pulse sequences, the application of new pulse sequences for structural and functional MR imaging, and the development of new functional MRI (fMRI) tasks that can elucidate neural function within the cognitive-behavioral domains affected in mood and anxiety disorders. This protocol will also allow testing of newly developed imaging hardware that can increase the spatial resolution, contrast, and sensitivity of MR images. Such hardware includes the implementation of new radio frequency (RF) coils and patient monitoring equipment. Development of these techniques and applications will directly enhance the sensitivity and specificity of MRI studies of mood and anxiety disorders.

• Depressive Disorder, Major
• Bipolar Disorder
• Panic Disorder
• Stress Disorders, Post-Traumatic

• Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, Raichle ME. Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997 Apr 24;386(6627):824-7.
• Drevets WC, Ongur D, Price JL. Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders. Mol Psychiatry. 1998 May;3(3):220-6, 190-1. Review.
• Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol. 2001 Apr;11(2):240-9. Review.

• INCLUSION CRITERIA:

Healthy Control:

• Male and female subjects between 18 and 65 years of age
• Subjects must be able to give written informed consent prior to participation in this study.
• Subjects who do not currently meet and have never met criteria for any major psychiatric disorder, and who have no known first degree relatives with mood disorders.
• For cognitive experiments utilizing language stimuli only native English speakers will be enrolled.

Major Depressive Disorder:

• Male and female subjects between 18 and 50 years of age.
• Subjects have been found eligible for other ETPB research protocols according to 01-M-0254.
• Subjects must fulfill DSM-IV criteria for Major Depression based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P).
• Subjects must be able to give written informed consent prior to participation in this study.
• For cognitive experiments utilizing language stimuli, only native English speakers will be enrolled.

EXCLUSION CRITERIA:

Healthy Control:

• Subjects with major medical or neurological disorders expected to influence cerebral blood flow or morphology, or taking any medication that is likely to influence the imaging parameters-of-interest within 3 weeks of scanning. A list of common drugs allowed and not allowed during the study appear in Appendix A.
• Women who are pregnant or breastfeeding. Subjects will undergo pregnancy testing no more than 24 hours prior to scanning.
• Subjects with contraindication to MRI scanning such as aneurysm clips, implanted neural stimulator, implanted cardiac pacemaker or auto-defibrillator, cochlear implant, or ocular foreign body.
• A history of drug or alcohol abuse within 1 year or a lifetime history of drug or alcohol dependence (DSM-IV criteria).

Major Depressive Disorder:

• Presence of Axis 1 psychiatric diagnosis other than Major Depression or an Axis 2 disorder
• Subjects with major medical or neurological disorders expected to influence cognitive function or are taking any drugs likely to affect mood or cognitive function within 2 weeks of study participation. Depressed subjects will not be tapered/withdrawn from medications under this study.
• A history of drug or alcohol abuse within 1 year or a lifetime history of drug or alcohol dependence (DSM-IV criteria).