Title:



Supplementary Online Content

Zhu F, Liu F, Guo W, et al. Disrupted asymmetry of inter- and intra-hemispheric functional connectivity in patients with drug-naive, first-episode schizophrenia and their unaffected siblings.

EBioMedicine.

eMethods 1. Data acquisition and preprocessing.

eTable 1. Baseline demographic and clinical characteristics of the study participants.

eTable 2. PANSS scores of the patient group: baseline and 8 weeks after olanzapine treatment.

eTable 3. Baseline group comparison of the PAS scores using a correlation coefficient threshold of r > 0.25.

eTable 4. Comparison of demographic and clinical characteristics between the good response group and the poor response group.

eTable 5. Baseline comparison of the PAS scores between the good response group and the poor response group.

eFigure 1. Spatial maps of the PAS scores for patients, unaffected siblings and healthy controls.

eFigure 2. Group comparison of the PAS scores using a correlation coefficient threshold of r> 0.2.

eFigure 3. Group comparison of the PAS scores using a correlation coefficient threshold of r> 0.25.

eFigure 4. Baseline group comparison of the PAS scores between the good response group and poor response group.

This supplementary material has been provided by the authors to give readers additional information about their work.

eMethods 1. Data acquisition and preprocessing

MRI images were obtained using a 3T MRI scanner (General Electric, Fairfield, Connecticut, USA). The participants were required to remain motionless and awake with their eyes closed. Soft earplugs and foam pads were used to decrease scanner noise and head motion. Resting-state functional magnetic resonance imaging (fMRI) images were obtained with a gradient-echo echo-planar imaging (EPI) sequence using the following parameters: repetition time/echo time = 2000 ms/30 ms, 30 slices, 64 × 64 matrix, 90° flip angle, 24 cm field of view, 4 mm slice thickness, 0.4 mm gap, and 250 volumes lasting for 500 s.

The DPABI software (1) was used to preprocess the images. After slice timing and head motion correction, participants with over 2 mm maximal translation and 2° maximal rotation were excluded. Several covariates, including Friston-24 head motion parameters acquired via rigid body correction (2), signal from a ventricular region of interest, and signal from a region centered in the white matter, were removed. In addition, mean framewise displacement (FD) was applied to address the residual effects of motion as a covariate in group analyses. The global signal was not removed as it is still a controversial practice in the resting-state fMRI field (3). The data were then normalized to a symmetrical standard template from the VMHC analysis of the REST software (4, 5) and resampled to 3 × 3 × 3 mm3 voxels. Finally, the images were bandpass-filtered (0.01–0.08 Hz) and linearly detrended. Scrubbing (removing time points with FD > 0.2mm) was also used as an aggressive head motion control strategy.

References

1. Yan CG, Wang XD, Zuo XN, Zang YF (2016): DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging. Neuroinformatics. 14:339-351.

2. de Kwaasteniet B, Ruhe E, Caan M, Rive M, Olabarriaga S, Groefsema M, et al. (2013): Relation between structural and functional connectivity in major depressive disorder. Biol Psychiatry. 74:40-47.

3. Hahamy A, Calhoun V, Pearlson G, Harel M, Stern N, Attar F, et al. (2014): Save the global: global signal connectivity as a tool for studying clinical populations with functional magnetic resonance imaging. Brain Connect. 4:395-403.

4. Zuo XN, Kelly C, Di Martino A, Mennes M, Margulies DS, Bangaru S, et al. (2010): Growing together and growing apart: regional and sex differences in the lifespan developmental trajectories of functional homotopy. J Neurosci. 30:15034-15043.

5. Song XW, Dong ZY, Long XY, Li SF, Zuo XN, Zhu CZ, et al. (2011): REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One. 6:e25031.

eTable 1. Baseline demographic and clinical characteristics of the study participants

| |Patients (n = 44) |Siblings (n = 42) |Controls (n=44) |p value |

|Gender (male/female) |28/16 |28/14 |23/21 |0.35 |

|Age (years) |23.45±4.24 |23.57±3.62 |23.55±2.58 |0.99 |

|(range) |(18-37) |(19-33) |(19-29) | |

|Education (years) |11.11±2.46 |12.13±2.24 |11.30±1.67 |0.11 |

|(range) |(6-16) |(9-17) |(9-15) | |

|FD (mm) |0.03±0.03 |0.03±0.01 |0.03±0.02 |0.34 |

|(range) |(0.01-0.14) |(0.01-0.05) |(0.01-0.14) | |

|loss of temporal degrees of freedom |1.16±2.57 |0.90±2.12 |1.48±2.65 |0.56 |

|(range) |(0-10) |(0-9) |(0-9) | |

|Illness duration (months) |22.34±7.01 | | | |

|(range) |(10-36) | | | |

|Dosage of olanzapine (mg/d) |18.30±5.17 | | | |

|(range) |(10-30) | | | |

FD = framewise displacement; Values are expressed as mean±SD.

eTable 2. PANSS scores of the patient group: baseline and 8 weeks after olanzapine treatment

|PANSS |Baseline |week 8 |p value |

|Positive symptoms score |22.48±5.37 |7.50±1.19 | 0.25.

[pic]

ANCOVA results in the PAS scores across groups controlling for the mean FD and age based on a correlation coefficient threshold of r > 0.25. ANCOVA = analysis of covariance; PAS = parameter of asymmetry; FD = framewise displacement

eFigure 4. Baseline group comparison of the PAS scores between the good response group and poor response group.

[pic]

Baseline group comparison of the PAS scores between the good response group and the poor response group based on the threshold of the median RR. PAS = parameter of asymmetry; RR = reduction ratio of the PANSS total scores after 8 weeks of olanzapine treatment

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