Grothe, Michel J., Scheef, Lukas, Bäuml, Josef, Meng, Chun, Daamen, Marcel, Baumann, Nicole, Zimmer, Claus, Teipel, Stefan, Bartmann, Peter, Boecker, Henning, Wolke, Dieter, Wohlschläger, Afra and Sorg, Christian (2017) Reduced cholinergic basal forebrain integrity links neonatal complications and adult cognitive deficits after premature birth. Biological Psychiatry, 82 (2). pp. 119-126. doi:10.1016/j.biopsych.2016.12.008

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Abstract

Background

Premature-born individuals have an increased risk for long-term neurocognitive impairments. In animal models, the development of the cholinergic basal forebrain (cBF) is selectively vulnerable to adverse effects of perinatal stressors, and impaired cBF integrity results in lasting cognitive deficits. We hypothesized that in premature-born individuals cBF integrity is impaired and mediates adult cognitive impairments associated with prematurity.

Methods

We used MRI-based volumetric assessments of a cytoarchitectonically defined cBF region-of-interest to determine differences in cBF integrity between 99 adults who were born very preterm and/or with very low birth weight (VP/VLBW) and 106 term born controls from the same birth cohort. MRI-derived cBF volumes were studied in relation to neonatal clinical complications after delivery as well as intelligence measures (IQ) in adulthood.

Results

In VP/VLBW adults, cBF volumes were significantly reduced compared to term-born adults (-4.5%, F(1, 202) = 11.82, p = 0.001). Lower cBF volume in VP/VLBW adults was specifically associated with both neonatal complications (rpart(92) = -0.35, p < 0.001) and adult IQ (rpart(88) = 0.33, p = 0.001) even after controlling for global gray matter and white matter volume. In an additional path analytic model, cBF volume significantly mediated the association between neonatal complications and adult cognitive deficits.

Conclusions

Results provide first time evidence in humans that cBF integrity is impaired after premature birth and links neonatal complications with long-term cognitive outcome. Data suggest that cholinergic system abnormalities may play a relevant role for long-term neurocognitive impairments associated with premature delivery.

Item Type:	Journal Article
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Mental Health and Wellbeing Faculty of Science, Engineering and Medicine > Science > Psychology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Cognition disorders , Premature infants, Cholinergic mechanisms, Intelligence tests , Newborn infants
Journal or Publication Title:	Biological Psychiatry
Publisher:	Elsevier
ISSN:	0006-3223
Official Date:	15 July 2017
Dates:	Date Event 15 July 2017 Published 15 December 2016 Available 13 December 2016 Accepted
Volume:	82
Number:	2
Page Range:	pp. 119-126
DOI:	10.1016/j.biopsych.2016.12.008
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	China Scholarship Council (CSC), Germany. Bundesministerium für Bildung und Forschung (BMBF)
Grant number:	File No: 2010604026 (CSC), BMBF 01ER0801, BMBF 01EV0710, BMBF 01ER0803 (BMBF)

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