Clinton Kilts, Emory University

School of Medicine, Atlanta, GA

Major barriers exists to new drug

development in psychiatry.  Such barriers include an incomplete

understanding of the pathophysiology of psychiatric disorders, of the adaptive

brain response related to the therapeutic response to a course of treatment of

the brain penetrance, accumulation and elimination of psychoactive medications,

and of the dose- and time-dependent interactions of such medications with

molecular targets in the brain.  In vivo brain imaging techniques such as

positron emission tomography (PET), functional magnetic resonance imaging (MRI),

single photon emission computed tomography (SPECT) and magnetic resonance

spectroscopy (MRS) are emerging as multimodal approaches to understanding these

processes in the living human brain. Pharmacological studies in fMRI (phMRI) or

PET (phPET) are mapping the functional anatomy of drug actions and drug

response.  Longitudinal imaging studies have potential in exploring

mechanisms of action for enhancing the rate of onset of therapeutic

response.  PET and SPECT studies using radiopharmaceuticals are offering

new insights into the molecular sites of action of psychotherapeutic and

addictive drugs.  Such in vivo molecular imaging approaches also aid

clinical drug trials by optimizing therapeutic/adverse outcomes by identifying

doses prior to trial initiation.  MRS studies further aid drug development

by noninvasively assessing brain penetrance and distribution.  Functional

imaging studies also contribute novelly to drug development by identifying the

neural correlates of treatment nonresponse and of specific symptoms. 

Functional brain imaging techniques are acquiring technological capabilities to

support studies ranging from in vivo gene expression to resolving functional

effects at the level of basic computational units.  These techniques hold

increasingly realized promise to inform the relationship of the brain and mind

and, in doing so, to guide the rational development of more efficacious and

better tolerated medications.