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October 27, 2005
The Schizophrenia Spectrum
Read more... Schizophrenia Research Journal Articles
Recent Schizophrenia Research Reviews, By Demian Rose, MD, PhD
"Brain Connectivity and the Schizophrenia Spectrum", a summary review of:
Introduction to the Topic
Given that schizophrenia often evolves out of an early “prodromal” period, where symptoms and social functioning worsen gradually, it is often difficult to discriminate it from SPD in an adolescent or young adult who begins to show evidence of magical thinking or socially isolative behavior. It would therefore be useful to look for tests that may be able to better predict the likelihood that a particular individual will eventually develop a relatively benign – if still socially impairing – condition vs. one that may require frequent hospitalization or assisted living. The study below is one that attempts to use neuro-imaging (“brain scans”) to look for reliable differences in brain anatomy between people with SPD, those with schizophrenia, and those who have neither condition.
Who did the study
Why they did the study
It has previously been shown with neuro-imaging that reproducible differences are seen in the frontal and temporal lobes of brains of people with schizophrenia. Using the newest imaging technique – an offshoot of functional magnetic resonance imaging known as diffusion tensor imaging (DTI), which is able to measure brain connectivity as seen in the white matter fiber bundles of the brain (“nerve highways”) – previous studies have demonstrated that one of the most frequent findings is that two of the white matter fiber bundles connecting the prefrontal and temporal lobes of the brain are abnormal in schizophrenia.
In people with SPD, structural (anatomical) imaging studies have shown reduced volume in brain regions that also show decreased volume in schizophrenia. These changes are in gray matter portions of the brain, were the cell bodies of the nerves lie. What had not yet been investigated at the time of this study was whether people with SPD also had similar changes in white matter, i.e. brain connectivity, to those seen in schizophrenia. The authors focus their attention on two particular white matter fiber bundles, called the uncinate fasciculus (UF) and the cingulum bundle (CB), as both of these connect areas of the brain known to be affected in schizophrenia, and have previously been shown, using DTI, to have abnormal connectivity and structural disorganization.
How they designed the study
Neuronal axons in the brain are wrapped in a fatty tissue layer called a myelin sheath, which gives nerve bundles their characteristic white color, hence the name “white matter. White matter connects different areas of gray matter (where neuronal cell bodies reside). Since axon fiber bundles tend to be organized in a parallel fashion, forming long “cords”, similar to a fiber optics cable, water has a much harder time crossing the “water proof” fatty tissue wrappings of a nerve fiber bundle perpendicular to its axis, and a much easier time flowing along its parallel axis. DTI detects very small differences in water diffusion and is able to calculate the thickness and direction of large white matter tracts in the brain. It is therefore an indirect measure of “connectivity”, the size and organization of the major fiber bundles of the brain.
Most subjects performed a number of written and behavioral tests at the beginning of the study, including measures of SPD symptoms and verbal and visual memory. After the testing period, all subjects were scanned in a magnetic resonance imaging scanner, using a previously standardized DTI technique. This scanning focused particularly on the regions of interest mentioned above, namely the uncinate fasciculus (UF) and the cingulum bundle (CB), two white matter tracts implicated in schizophrenia.
What they found
The authors found that, like in schizophrenia, the UF showed reduced neural organization in SPD as compared to controls, and this disorganization correlated with certain symptoms and cognitive impairments. Unlike in schizophrenia, however, the CB showed overall no significant difference in white matter organization in SPD vs. controls, though there were some suggestions that some of the subjects with SPD had mild disorganization that correlated with mild deficits in cognitive function – it is a common finding in (expensive) imaging studies that there are not enough subjects to be sure that very small differences are “real” or simply due to normal and expected variation between subjects.
Together, these data support a “continuum” model of psychosis, with SPD sufferers having mildly impaired connectivity in the frontal and temporal lobes of the brain (only the UF being affected) and subsequently only mild symptoms, while people with schizophrenia have more impaired connectivity (UF and CB) and more severe symptoms.
The Take Home Message
To take social withdrawal and odd beliefs as an example, there are many children and adolescents who will exhibit culturally “strange” behaviors and thoughts about the world that isolate them from most of their peers, but who will never go on to develop schizophrenia. Since SPD shares so many of its symptoms with schizophrenia, it is a common confound in studies that look at prodromal outcomes. This study suggests that it may be possible to perform a simple imaging test that could have predictive value in determining whether someone exhibiting mild symptoms on the schizophrenia spectrum would benefit from anti-psychotics, an important question given the possible side effects of these medications.
Authored by: Nakamura M. McCarley RW, Kubicki M, Dickey CC, Niznikiewicz MA, Voglmaier MM, Seidman LJ, Maier SE, Westin CF, Kikinis R, Shenton ME.
Posted by Demian Rose at October 27, 2005 04:38 PM
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