Schizophrenia Research Forum - A Catalyst for Creative Thinking
Home Profile Membership/Get Newsletter Log In Contact Us
 For Patients & Families
What's New
Recent Updates
SRF Papers
Current Papers
Search All Papers
Search Comments
News
Research News
Conference News
Plain English
Forums
Current Hypotheses
Idea Lab
Online Discussions
Virtual Conferences
Interviews
Resources
What We Know
SchizophreniaGene
Animal Models
Drugs in Trials
Research Tools
Grants
Jobs
Conferences
Journals
Community Calendar
General Information
Community
Member Directory
Researcher Profiles
Institutes and Labs
About the Site
Mission
History
SRF Team
Advisory Board
Support Us
How to Cite
Fan (E)Mail
The Schizophrenia Research Forum web site is sponsored by the Brain and Behavior Research Foundation and was created with funding from the U.S. National Institute of Mental Health.
Research News
back to News Search
Brain Imaging Links Motor, Cognitive Deficits in Schizophrenia

22 October 2006. Children who will later develop schizophrenia are more likely to show subtle movement deficits: for example, learning to walk a little later than their peers. As adults, after the disorder has appeared, they perform worse on tests of certain cognitive domains. A new study suggests that these seemingly disparate deficits can be traced to the same brain systems.

In the study, Peter Jones, Edward Bullmore, and colleagues at the University of Cambridge in the UK, with collaborators at the University of Oulu, Finland, combined prospectively gathered data on infant motor development with executive function tests and structural MRI imaging conducted when the study subjects were adults. Writing in PNAS, they report that normal individuals who stand and walk early will, on average, have better performance on cognitive tests of adult executive function. Furthermore, both early motor development and better adult executive function are associated with more grey and white matter in some of the same frontal cortical and cerebellar regions. However, in people with schizophrenia, these correlations break down: earlier motor development and better adult executive function are not associated with these cortical or cerebellar structural differences. Therefore, according to lead author Khanum Ridler and colleagues, the study suggests disruption of these systems might underlie the childhood developmental abnormalities and adult cognitive abnormalities of schizophrenia.

Aberrant early brain development
It is widely accepted in the schizophrenia research field that schizophrenia is a delayed consequence of aberrant early brain development (Weinberger, 1987; Murray and Lewis, 1987). Longitudinal epidemiological studies have shown that subtle abnormalities in social function and cognition during childhood often precede the emergence of psychotic symptoms in adult patients with schizophrenia. Interestingly, abnormalities of early motor development have also been found to be associated with an increased risk of schizophrenia. In adults, a motoric aspect of schizophrenia called extrapyramidal movement disorder tends to be present at first diagnosis before antipsychotic medications are begun.

To account for these observations, it has been suggested that a single brain system may be responsible for the acquisition of early motor skills as well as for aspects of later cognitive function, and that abnormality of this system increases the risk of schizophrenia (Gottesman and Gould, 2003). In separate work, other researchers have posited that the diverse profile of abnormalities seen in patients with schizophrenia can be explained by a “cognitive dysmetria” model in which there is an improper integration of fronto-cerebellar-thalamic circuits that prioritize, process, coordinate, and trigger responses to information (Andreasen et al., 1998).

Infant motor development, adult executive function, and brain structure data
Ridler and colleagues drew a study sample of 93 non-psychotic adults and 43 adults with schizophrenia from the Northern Finland 1966 Birth Cohort of 10,934 individuals. Non-psychotic volunteers were randomly selected from cohort members living in the city of Oulu who had no history of psychosis on the Finnish Hospital Discharge Register. Similarly, adult cohort members with schizophrenia were identified on the Finnish Hospital Discharge Register and confirmed via chart review. Of these patients, 72 percent were taking antipsychotic medications at the time of this study.

For infant motor development data, the authors surveyed the prospective assessments of age at learning to stand without support and to walk with and without support as recorded during children’s visits to welfare centers and during a special Birth Cohort examination at age 1 year. Of note, the authors state that missing data on age at learning to walk were entered as age at time of missing assessment plus 1 month. They did not mention how prevalent missing data were in this study.

Adult executive function testing and whole-brain MRI scanning were performed between 1999 and 2001, when the study subjects were 33-35 years old. When possible, executive function testing was performed on the same day as the MRI scan; if that was not possible, the test was performed within two weeks of the MRI scan. The executive function test used was the computer-based abstraction, inhibition, and working memory (AIM) task.

Finding correlations
Ridler and colleagues first looked at the infant motor development data and confirmed earlier findings that the mean age at learning to stand and to walk was significantly delayed in patients with schizophrenia. Whereas those in the non-psychotic group had a mean age of learning to stand of 10.8 months, patients with schizophrenia had a mean age of learning to stand of 11.7 months (P <.002). The results were similar for age of walking with support (9.2 months vs. 10.3 months; P <.0001) and without support (11.9 months vs. 12.5 months; P <.009). As in previous studies, adult executive function was also compromised in patients with schizophrenia at a highly significant level (P <.001). Linking these two assessments, the authors found that precocious infant motor development was positively correlated with better adult executive function in non-psychotic adults. No significant correlation, however, was found between infant motor development and adult executive function in the patients with schizophrenia.

When examining the full-brain MRI scans of the non-psychotic subjects using computational morphometry, the investigators found that earlier infant motor development was significantly positively associated with a greater grey matter density in three areas: the bilateral and medial premotor cortex and the bilateral rostral prefrontal cortex; the left caudate nucleus (head and body) and left thalamus; and the medial cerebellum. Earlier infant motor development was also significantly positively associated with greater white matter volume and density in the frontal lobes, the left parietal lobe, and immediately adjacent to the left caudate nucleus and thalamus. No regions of grey or white matter density or volume were found to be associated with infant motor development in patients with schizophrenia, however.

The investigators also found associations between adult executive function scores and brain structure in non-psychotic subjects which did not carry over to patients with schizophrenia. Again using computational morphometry, Ridler and colleagues found a significant positive association between higher executive function scores and increased grey matter density in four regions: the bilateral medial premotor cortex and left rostral prefrontal cortex; the right inferior and middle frontal gyri; the bilateral medial cerebellum; and the right posterolateral cerebellum. None of these regions was associated with executive function in patients with schizophrenia.

The authors note that there is only partial overlap in the brain regions associated with infant motor development and in those associated with adult executive function. They write, “50 percent of the voxels in prefrontal/premotor cortex associated with adult executive function were also associated with infant motor development; likewise, 48 percent of the voxels in medial cerebellum associated with executive function were also associated with infant motor development.” They go on to suggest that it is “likely that adult executive systems emerge developmentally by integration of additional (prefrontal and lateral cerebellar) regions, with a ‘core’ or prototypic, frontal premotor-medial cerebellar circuit that has previously matured in support of early motor skills.”

In relating their findings to patients with schizophrenia, the researchers suggest that a possible early developmental failure in connectivity in the premotor cortex could lead to disruption in the fronto-cortico-cerebellar system that is critical for adult executive function. They write, “Disruption of this…system is a plausible endophenotype that may underlie both developmental and adult cognitive dysmetria in schizophrenia.”—Jillian Lokere.

Reference:
Ridler K, Veijola JM, Tanskanen P, Miettunen J, Chitnis X, Suckling J, Murray GK, Haapea M, Jones PB, Isohanni MK, Bullmore ET. Fronto-cerebellar systems are associated with infant motor and adult executive functions in healthy adults but not in schizophrenia. Proc Natl Acad Sci. 2006 Oct 6; [Epub ahead of print]. Abstract

 
Comments on News and Primary Papers
Comment by:  Daniel Weinberger, SRF Advisor
Submitted 26 October 2006 Posted 26 October 2006
  I recommend the Primary Papers

This paper by Ridler and colleagues is an interesting novel twist on other evidence that developmental milestones, even in traditionally hard wired motor functions, are slightly delayed in samples of individuals who later manifest schizophrenia. There are two important additional results that emerge from their analysis: first, that early developmental motor milestones predict MRI measures of brain volume and executive function during adulthood in normal individuals; and second, that these predictive relationships are not found in their schizophrenia sample.

The link between early motor and adult cognitive development is not surprising, as child development studies have highlighted the predictive implications of precocious motor development for cognitive development. The link to volumetric measures on MRI is intriguing and novel, though as in all MRI volumetry studies, the tissue compartments that contribute to variance in the MRI measures are uncertain. I doubt that MRI volume measures are sensitive assessments of variation in synaptic abundance or other elements related...  Read more


View all comments by Daniel Weinberger

Comment by:  Patricia Estani
Submitted 2 November 2006 Posted 2 November 2006
  I recommend the Primary Papers
Submit a Comment on this News Article
Make a comment on this news article. 

If you already are a member, please login.
Not sure if you are a member? Search our member database.

*First Name  
*Last Name  
Affiliation  
Country or Territory  
*Login Email Address  
*Confirm Email Address  
*Password  
*Confirm Password  
Remember my Login and Password?  
Get SRF newsletter with recent commentary?  
 
Enter the code as it is shown below:
This code helps prevent automated registrations.

I recommend the Primary Papers

Please note: A member needs to be both registered and logged in to submit a comment.

Comment:

(If coauthors exist for this comment, please enter their names and email addresses at the end of the comment.)

References:


SRF News
SRF Comments
Text Size
Reset Text Size
Email this pageEmail this page

Share/Bookmark
Copyright © 2005- 2014 Schizophrenia Research Forum Privacy Policy Disclaimer Disclosure Copyright