Abnormal functional activation and connectivity in the working memory network in early-onset schizophrenia.
OBJECTIVE
Disruption within the working memory (WM) neural network is considered an integral feature of schizophrenia. The WM network, and the dorsolateral prefrontal cortex (DLPFC) in particular, undergo significant remodeling in late adolescence. Potential interactions between developmental changes in the WM network and disease-related processes for schizophrenia remain unclear. The aim of this study was to determine whether DLPFC activation and functional connectivity are impaired during WM in patients with early-onset schizophrenia (EOS; age of onset <18 years).


METHODS
We used functional magnetic resonance imaging and psychophysiological interaction analysis to respectively measure blood oxygenation level-dependent signal and to derive functional connectivity estimates in response to the two-back WM task from 25 youths with EOS and 20 matched healthy adolescents.


RESULTS
Compared with healthy adolescents, patients with EOS showed reduced engagement of the DLPFC, the anterior cingulate cortex (ACC), and frontal operculum, and had reduced DLPFC connectivity within the WM network. Patients with EOS showed abnormal reduction in the coupling of the DLPFC with the ACC, the inferior parietal lobule, and the middle occipital gyrus. In contrast to healthy adolescents, patients with EOS expressed age-related decrease in the activity of the DLPFC and an increase in its connectivity with the ACC.


CONCLUSIONS
Patients with EOS show dysfunctional engagement and reduced integration within the WM neural network. The pattern of abnormal age-related correlations in DLPFC activity and connectivity suggests that schizophrenia-related processes have an impact on brain regions that show significant late developmental changes.
Institute of Psychiatry, King's College London and Child and Adolescent Mental Health Services, Maudsley Hospital, UK.
Marinos
M
Kyriakopoulos
Danai
D
Dima
Jonathan P
JP
Roiser
Richard
R
Corrigall
Gareth J
GJ
Barker
Sophia
S
Frangou
D000293:Adolescent; D017668:Age of Onset; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012016:Reference Values; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology
D010100:Oxygen