CHEMISTRY OF THE BRAIN: MOLECULES, MOOD, AND MENTAL ILLNESS - Chemistry: Notable Research and Discoveries - page 93

Like the monoamine hypothesis of depression, such a simple hypoth-
esis was appealing but, perhaps predictably, a little too simple to be true.
Further research using a technique known as positron emission tomogra-
phy (PET) showed the relationship between dopamine and schizophrenia
is more complex. PET detects radioactive emissions of certain isotopes;
these isotopes are incorporated into a molecule and injected into a pa-
tient. The machine measures the radioactivity with detectors positioned
around the body. PET lets researchers study the distribution of certain
molecules in living tissue since, unlike autoradiography, the tissue is not
sliced and treated chemically. The amount of radioactivity must be small,
however, to avoid harming the human subjects.
Dopamine does not cross the blood-brain barrier, so researchers
must inject dopaminelike molecules or other ligands, such as many
schizophrenia medications that bind dopamine receptors, in order to
study dopamine transmission in living subjects. PET studies confirm
that schizophrenia medications block D 2 . But these medications do not
work in every patient, and Adam Wolkin of the New York Veterans
Administration Medical Center and his colleagues discovered that do-
pamine receptor binding was similar in patients that respond to the
medication as well as in those who fail to show improvement. The pa-
per “Dopamine Blockade and Clinical Response: Evidence for Two Bio-
logical Subgroups of Schizophrenia,” published in 1989 in the American
Journal of Psychiatry, showed there may be a group of schizophrenia
patients whose disease has a slightly different nature.
Many researchers have come to believe that schizophrenia is a com-
plex disease, possibly with a number of different causes or courses. PET
studies of schizophrenia have found possible contributions of other re-
ceptors, including the dopamine D 1 receptor as well as receptors for
other neurotransmitters such as glutamate. Genetic researchers are
searching for the genes involved in the expression and regulation of
these receptors, any or all of which may be involved in some number
of patients.
Recent improvements in chemical detection may also help re-
searchers investigate this disease. The Duke University scientist Rima
Kaddurah-Daouk and her colleagues are developing techniques to
analyze hundreds of chemicals quickly and efficiently. Although many
chemicals, including dopamine and other neurotransmitters, do not
cross the blood-brain barrier, an accurate measure of a large number of