IN VIVO BRAIN IMAGING AND DRUG
DEVELOPMENT
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.