To The Editor: The studies aimed at helping us to understand schizophrenia, reviewed by Robert Freedman, M.D. (1) in the March 2007 issue of the Journal, are intriguing. But doesn’t much of the work still seem to focus on one or a few features, while missing the essence? For example, do studies focusing on positive symptoms help to explain negative symptoms, which seem integral to schizophrenia and which severely limit functioning? Testable hypotheses are good, but do we know enough about the complex brain mechanisms that are malfunctioning in schizophrenia to attempt to study or explain them? Possibly not.
For example, schizophrenia is a uniquely human illness (despite useful animal models). A unique aspect of human mental function is our ability to form an internal mental image of the world, replete with images, memories, thoughts, and emotions, to manipulate it, and to imagine how different actions on our part might lead to different goals or results. This ability has led to much of the advancement of civilization. The human brain operates on two levels at the same time: one in contact with reality, the other focused on internally generated “mental images” (when dreaming, internal images are “unopposed”). Whether this “dual processing” is related to the lateralization of the brain (i.e., two brains working somewhat independently) or to the enlargement of the frontal lobes (both relatively unique features of the human brain) or both is unclear.
In schizophrenia, the relationships between internally derived perceptions and outside reality are out of balance; internally derived perceptions are excessively strong (and seem to be external). This conceptualization can explain both positive and negative symptoms. Positive symptoms are because of internally derived perceptions being stronger than usual. Negative symptoms are more attributable to the “weakness” of focus on external reality. Schizophrenia patients are less concerned with how they look, smell, and interact with others, with accomplishments in the real world, and with whether others understand them. They are more concerned with internally derived perceptions.
If the complex mechanism that creates mental images malfunctions, can one measure it? Is the size of the frontal lobe, or blood flow, or levels of dopamine, or an evoked potential, going to tell us much about the relative strength of the mental images? Probably not, since the creation and manipulation of mental images probably involve much of the brain and innumerable neurotransmitters, receptors, and connections. It may be that our complex technologies, although impressive, are still unlikely to clarify the malfunction that causes schizophrenia.
1.Freedman R: Neuronal dysfunction and schizophrenia symptoms. Am J Psychiatry 2007; 164:385–390
The author reports no competing interests.
This letter (doi: 10.1176/appi.ajp.2007.07040656) was accepted for publication in May 2007.