The online version of this article (https://doi.org/10.1186/s12993-018-0134-y) contains supplementary material, which is available to authorized users.
22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental syndrome associated with deficits in cognitive and emotional processing. This syndrome represents one of the highest risk factors for the development of schizophrenia. Previous studies of functional connectivity (FC) in 22q11DS report aberrant connectivity patterns in large-scale networks that are associated with the development of psychotic symptoms.
In this study, we performed a functional connectivity analysis using the CONN toolbox to test for differential connectivity patterns between 54 individuals with 22q11DS and 30 healthy controls, between the ages of 17–25 years old. We mapped resting-state fMRI data onto 68 atlas-based regions of interest (ROIs) generated by the Desikan-Killany atlas in FreeSurfer, resulting in 2278 ROI-to-ROI connections for which we determined total linear temporal associations between each. Within the group with 22q11DS only, we further tested the association between prodromal symptoms of psychosis and FC.
We observed that relative to controls, individuals with 22q11DS displayed increased FC in lobar networks involving the frontal–frontal, frontal–parietal, and frontal–occipital ROIs. In contrast, FC between ROIs in the parietal–temporal and occipital lobes was reduced in the 22q11DS group relative to healthy controls. Moreover, positive psychotic symptoms were positively associated with increased functional connections between the left precuneus and right superior frontal gyrus, as well as reduced functional connectivity between the bilateral pericalcarine. Positive symptoms were negatively associated with increased functional connectivity between the right pericalcarine and right postcentral gyrus.
Our results suggest that functional organization may be altered in 22q11DS, leading to disruption in connectivity between frontal and other lobar substructures, and potentially increasing risk for prodromal psychosis.
Additional file 1. Additional material.
Shprintzen RJ, Goldberg RB, Lewin ML, Sidoti EJ, Berkman MD, Argamaso RV, Young D. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J. 1978;15:56–62. PubMed
Schneider M, Debbane M, Bassett AS, Chow EW, Fung WL, van den Bree M, Owen M, Murphy KC, Niarchou M, Kates WR, Antshel KM, Fremont W, McDonald-McGinn DM, Gur RE, Zackai EH, Vorstman J, Duijff SN, Klaassen PW, Swillen A, Gothelf D, Green T, Weizman A, Van Amelsvoort T, Evers L, Boot E, Shashi V, Hooper SR, Bearden CE, Jalbrzikowski M, Armando M, Vicari S, Murphy DG, Ousley O, Campbell LE, Simon TJ, Eliez S. International consortium on brain and behavior in 22q11.2 deletion syndrome. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International consortium on brain and behavior in 22q11.2 deletion syndrome. Am J Psychiatry. 2014;171:627–39. CrossRefPubMedPubMedCentral
Friston KJ, Frith CD. Schizophrenia: a disconnection syndrome? Clin Neurosci. 1995;3:89–97. PubMed
Manoliu A, Riedl V, Zherdin A, Muhlau M, Schwerthoffer D, Scherr M, Peters H, Zimmer C, Forstl H, Bauml J, Wohlschlager AM, Sorg C. Aberrant dependence of default mode/central executive network interactions on anterior insular salience network activity in schizophrenia. Schizophr Bull. 2014;40:428–37. CrossRefPubMed
Mattiaccio LM, Coman IL, Schreiner MJ, Antshel KM, Fremont WP, Bearden CE, Kates WR. Atypical functional connectivity in resting-state networks of individuals with 22q11. 2 deletion syndrome: associations with neurocognitive and psychiatric functioning. J Neurodev Disord. 2016;8(1):2. CrossRefPubMedPubMedCentral
Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Cannon T, Ventura J, McFarlane W, Perkins DO, Pearlson GD, Woods SW. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull. 2003;29:703–15. CrossRefPubMed
First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute; 2002.
Fedorov A, Beichel R, Kalpathy-Cramer J, Finet J, Fillion-Robin J-C, Pujol S, Bauer C, Jennings D, Fennessy FM, Sonka M, Buatti J, Aylward SR, Miller JV, Pieper S, Kikinis R. 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson Imaging. 2012;30:1323–41. CrossRefPubMedPubMedCentral
Friston KJ, Penny WD, Ashburner JK, Stefan J, Nichols TE. Statistical parametric mapping: the analysis of functional brain images. London: Academic Press; 2006.
Mazaika P, Hoeft F, Glover GH, Reiss AL. Methods and software for fMRI analysis for clinical subjects. Human Brain Mapp. 2009;47:S58.
Kikinis Z, Cho KI, Coman IL, Radoeva PD, Bouix S, Tang Y, Eckbo R, Makris N, Kwon JS, Kubicki M, Antshel KM, Fremont W, Shenton ME, Kates WR. Abnormalities in brain white matter in adolescents with 22q11.2 deletion syndrome and psychotic symptoms. Brain Imaging Behav. 2016. https://doi.org/10.1007/s11682-016-9602-x.
Alonso-Solis A, Corripio I, de Castro-Manglano P, Duran-Sindreu S, Garcia-Garcia M, Proal E, Nunez-Marin F, Soutullo C, Alvarez E, Gomez-Amson B, Kelly C, Castellanos FX. Altered default network resting state functional connectivity in patients with a first episode of psychosis. Schizophr Res. 2012;139:13–8. CrossRefPubMedPubMedCentral
- Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional connectivity analysis
Leah M. Mattiaccio
Ioana L. Coman
Carlie A. Thompson
Wanda P. Fremont
Kevin M. Antshel
Wendy R. Kates
- BioMed Central
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