Brain Imaging Assesses Drug Efficacy in Schizophrenia

UAB’s impressive battery of imaging capabilities, including several 3-Tesla magnets, which offer enhanced image quality and a field of view optimized for functional brain imaging, positron emission tomography (PET), and magnetoencephalography, facilitate psychopathology and treatment response research in schizophrenia, says Adrienne C. Lahti, MD, associate professor, Department of Psychiatry and Behavioral Neurobiology. Lahti directs UAB’s Neuroimaging and Translational Research Laboratory.

A disorder of cognition, perception, and motivation, schizophrenia affects 1% of the population and costs society as much as $62 billion each year. While antipsychotic drugs (APDs) alleviate hallucinations and delusions in some patients, up to 60% of patients exhibit only a partial response or do not respond, says Lahti. Moreover, APDs provide little benefit for the illness’s characteristic cognitive impairments.

PET, magnetic resonance spectroscopy (MRS), and functional magnetic resonance imaging (fMRI) allow scientists to evaluate in vivo brain chemistry and functional response to medications that identify drug effects and disease characteristics. Lahti plans to use such brain imaging to predict schizophrenia patients’ response to initial pharmacologic therapy. Her data indicate that after 1 week of treatment, functional changes in the ventral striatum and hippocampus are highly predictive of patient responses to medication after 6 weeks (Psychiatry Res. 2005;139[1]:19-30).

Lahti postulates a hypoglutamatergic basis for schizophrenia and proposes to improve glutamatergic function by understanding and manipulating interaction between dopamine and glutamate. In further studies she will collaborate with James H. Meador-Woodruff, MD, chair of the Department of Psychiatry and Behavioral Neurobiology, and neurobiologist Rosalinda C. Roberts, PhD, to extend her research to processes in the ventral striatum and hippocampus in postmortem brains of schizophrenic patients characterized according to treatment response.

The cognitive dysfunction of schizophrenia is another of Lahti’s interests. Using MRS with fMRI, she can identify regions of the brain that malfunction during cognition, as well as the physiological or neurochemical basis of the abnormality. “The paired use of fMRI and MRS can be extremely valuable in identifying both the location and nature of changes in the brain,” she says.

Lahti’s studies have established the limbic regions such as the hippocampus and anterior cingulate cortex as key players in antipsychotic action, which starts in the dopaminergic-rich area of the ventral striatum (Neuropsychopharmacology. 2004;29[1]:171-178). Future studies will analyze treatment response in those brain regions, she says.

Lahti intends to pinpoint the neuronal mechanism of treatment response to APDs and characterize the process in nonresponders. “Functional MRI allows examination of neuronal circuitry in the brain, providing information about how specialized brain regions communicate with each other,” she says. Still, Lahti will stay focused on improving treatment. “Research must be geared toward treating patients and improving their lives.”

For more information:
Dr. Adrienne Lahti
1.800.UAB.MIST
mist@uabmc.edu