Background
A fundamental challenge for understanding neuropsychiatric disease is identifying
sources of individual differences in psychopathology, especially when there is substantial
heterogeneity of symptom expression, such as is found in schizophrenia (SCZ). We hypothesized
that such heterogeneity might arise in part from consistently widespread yet variably
patterned alterations in the connectivity of focal brain regions.
Methods
We used resting state functional connectivity magnetic resonance imaging to identify
variable global dysconnectivity in 23 patients with DSM-IV SCZ relative to 22 age-,
gender-, and parental socioeconomic status-matched control subjects with a novel global
brain connectivity method that is robust to high variability across individuals. We
examined cognitive functioning with a modified Sternberg task and subtests from the
Wechsler Adult Intelligence Scale—Third Edition. We measured symptom severity with
the Scale for Assessment of Positive and Negative Symptoms.
Results
We identified a dorsolateral prefrontal cortex (PFC) region with global and highly
variable dysconnectivity involving within-PFC underconnectivity and non-PFC overconnectivity
in patients. Variability in this “under/over” pattern of dysconnectivity strongly
predicted the severity of cognitive deficits (matrix reasoning IQ, verbal IQ, and
working memory performance) as well as individual differences in every cardinal symptom
domain of SCZ (poverty, reality distortion, and disorganization).
Conclusions
These results suggest that global dysconnectivity underlies dorsolateral PFC involvement
in the neuropathology of SCZ. Furthermore, these results demonstrate the possibility
that specific patterns of dysconnectivity with a given network hub region might explain
individual differences in symptom presentation in SCZ. Critically, such findings might
extend to other neuropathologies with diverse presentation.
Key Words
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Article info
Publication history
Published online: April 18, 2011
Accepted:
February 10,
2011
Received in revised form:
January 25,
2011
Received:
November 9,
2010
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
