No | Fig. | Description^{*} | Statistics | Power | |
---|---|---|---|---|---|

EPM test | |||||

aa |
3A
| Open arm # | CRS group (n = 24/timepoint) | Paired median difference= –1.0p = 0.0 | –1.0, –1.0 baseline = 0.88 ± 0.18 restraint = 0.32 ± 0.13 |

ab | Healthy group (n = 8/timepoint) | Paired median difference= –1.0p = 0.246 | –1.0, –1.0 baseline = 1.75 ± 0.62 restraint = 0.38 ± 0.26 | ||

ac | Open arm time | CRS group (n = 24/timepoint) | Paired median difference= –1.5p = 0.15 | –8.0, 0.0 baseline = 5.79 ± 1.43 s restraint = 2.52 ± 1.15 s | |

ad | Healthy group (n = 6/timepoint) | Paired median difference= –3.0p = 0.38 | –24.0, 0.0 baseline = 6.83 ± 3.89 s restraint = 2.63 ± 2.01 s | ||

ae |
3B
| Closed arm # | CRS group (n = 24/timepoint) | Paired Cohen’s d = 0.462p = 0.0282 | –0.0122, 0.856 baseline = 5.63 ± 0.66 restraint = 7.20 ± 0.74 |

af | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.114p = 0.639 | –0.647, 0.51 baseline = 8.00 ± 1.72 restraint = 8.63 ± 2.13 | ||

ag | Closed arm time | CRS group (n = 24/timepoint) | Paired Cohen’s d = 0.212p = 0.47 | –0.415, 0.777 baseline = 220.83 ± 9.06 s restraint = 230.60 ± 7.81 s | |

ah | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.056p = 0.888 | –0.848, 0.851 baseline = 221.75 ± 12.82 s restraint = 224.13 ± 16.89 s | ||

ai |
3C
| Grooming # | CRS group (n = 24/timepoint) | Paired Cohen’s d = –0.921p = 0.001 | –1.41, –0.357 baseline = 4.63 ± 0.64 restraint = 2.28 ± 0.31 |

aj | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.232p = 0.464 | –0.511, 1.17 baseline = 3.00 ± 1.10 restraint = 3.63 ± 0.78 | ||

ak | Grooming time | CRS group (n = 23/timepoint) | Paired Cohen’s d = –0.642p = 0.0016 | –1.09, –0.185 baseline = 24.70 ± 3.93 s restraint = 14.48 ± 3.30 s | |

al | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.326p = 0.411 | –1.11, 0.352 baseline = 24.63 ± 9.89 s restraint = 17.75 ± 3.70 s | ||

am |
3D
| Rearing # | CRS group (n = 23/timepoint) | Paired Cohen’s d = –0.2p = 0.422 | –0.732, 0.327 baseline = 17.79 ± 0.86 restraint = 16.92 ± 1.14 |

an | Healthy group (n = 7/timepoint) | Paired Cohen’s d = 0.533p = 0.19 | –0.852, 1.13 baseline = 16.14 ± 1.52 restraint = 17.38 ± 1.82 | ||

ao | Rearing time | CRS group (n = 24/timepoint) | Paired Cohen’s d = 0.187p = 0.501 | –0.364, 0.73 baseline = 41.38 ± 1.72 s restraint = 44.36 ± 3.36 s | |

ap | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.117p = 0.618 | –0.639, 0.552 baseline = 41.88 ± 5.43 s restraint = 43.38 ± 3.42 s | ||

SPT | |||||

aq | CRS group (n = 25/timepoint) | Paired Cohen’s d = 0.289p = 0.312 | –0.294, 0.889 baseline = 0.63 ± 0.03 restraint = 0.69 ± 0.04 | ||

ar | Healthy group (n = 5/timepoint) | Paired Cohen’s d = –0.191p = 0.807 | –1.52, 0.831 baseline = 0.81 ± 0.03 restraint = 0.78 ± 0.07 | ||

FST | |||||

as |
4A
| Total activity | CRS group (n = 19/timepoint) | Paired Cohen’s d = –0.62p = 0.0414 | –1.19, –0.0902 baseline = 42 ± 2 restraint = 37 ± 1 |

at | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.726p = 0.22 | –1.91, 0.489 baseline = 45 ± 3 restraint = 40 ± 2 | ||

au |
4B
| Swimming | CRS group (n = 19/timepoint) | Paired Cohen’s d = 0.0269p = 0.896 | –0.526, 0.489 baseline = 26 ± 2 restraint = 26 ± 2 |

av | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.0p = 0.969 | –1.54, 1.17 baseline = 30 ± 3 restraint = 30 ± 4 | ||

aw | Climbing | CRS group (n = 19/timepoint) | Paired Cohen’s d = –0.696p = 0.021 | –1.22, –0.202 baseline = 16 ± 2 restraint = 11 ± 1 | |

ax | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.8p = 0.12 | –1.92, 0.327 baseline = 15 ± 2 restraint = 10 ± 2 | ||

ay |
4C
| Immobility | CRS group (n = 19/timepoint) | Paired Cohen’s d = 0.611p = 0.0438 | 0.0902, 1.19 baseline = 18 ± 2 restraint = 23 ± 1 |

az | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.726p = 0.22 | 0.0902, 1.19 baseline = 15 ± 3 restraint = 20 ± 2 | ||

ba | Latency | CRS group (n = 19/timepoint) | Paired Cohen’s d = –1.34p = 0.0006 | –2.03, –0.578 baseline = 119 ± 9 s restraint = 71 ± 7 s | |

bb | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.0967p = 0.92 | –1.59, 1.21 baseline = 101 ± 32 restraint = 95 ± 16 | ||

rs-fMRI | |||||

bc |
5A,B
| ICA/dual regression | CRS group with all restraint data [baseline: n = 11 from current cohort and n = 22from Seewoo et al. (2019); restraint: n = 15] | Dual regressionp < 0.05 | |

bd | CRS group with restraint data based on FST findings [baseline: n = 11 from currentcohort and n = 22 from Seewoo et al. (2019); restraint: n = 9] | Dual regressionp < 0.05 | |||

be |
5C
| Salience network CRS group (baseline: n = 9 from current cohort; restraint: n = 15) | Unpaired Cohen’s d = –2.33p = 0.0 | –3.2, –1.29 baseline = 36 ± 3 restraint = 19 ± 1 | |

bf | Salience network Healthy group (baseline: n = 5 from current cohort; restraint: n = 8) | Unpaired Cohen’s d = –0.208p = 0.718 | –1.68, 0.93 baseline = 29 ± 5 restraint = 27 ± 4 | ||

bg |
5D
| Interoceptive network CRS group (baseline: n = 9 from current cohort; restraint: n = 15) | Unpaired Cohen’s d = –1.38p = 0.0032 | –2.13, –0.574 baseline = 39 ± 5 restraint = 23 ± 2 | |

bh | Interoceptive network Healthy group (baseline: n = 5 from current cohort; restraint: n = 8) | Unpaired Cohen’s d = –0.539p = 0.374 | –1.47, 0.685 baseline = 27 ± 2 restraint = 22 ± 4 | ||

bi |
6A
| Seed-based analysis | CRS group with all restraint data [baseline: n = 11 from current cohort and n = 22from Seewoo et al. (2019); restraint: n = 15] | Higher-level FEATp < 0.05, z > 2 | |

bj |
6B
| CRS group (baseline: n = 9 from current cohort; restraint: n = 15) | Unpaired Cohen’s d = 1.51p = 0.0018 | 0.712, 2.18 baseline = 0.13 ± 0.02 restraint = 0.29 ± 0.03 | |

bk | Healthy group (baseline: n = 5 from current cohort; restraint: n = 8) | Unpaired Cohen’s d = 0.752p = 0.214 | –0.318, 1.74 baseline = 0.15 ± 0.03 restraint = 0.24 ± 0.05 | ||

Proton magnetic resonance spectroscopy | |||||

bl |
7C
| Gln | CRS group (n = 17/timepoint) | Paired Cohen’s d = –0.538p = 0.027 | –1.19, –0.0217 baseline: 0.53 ± 0.01 restraint: 0.50 ± 0.01 |

bm | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.743p = 0.174 | –0.127, 1.95 baseline = 0.50 ± 0.02 restraint = 0.54 ± 0.02 | ||

bn |
7D
| Glu | CRS group (n = 17/timepoint) | Paired Cohen’s d = –0.711p = 0.0706 | –1.46, 0.134 baseline: 1.41 ± 0.02 restraint: 1.35 ± 0.02 |

bo | Healthy group (n = 6/timepoint) | Paired Cohen’s d = –1.1p = 0.121 | –2.15, –0.122 baseline = 1.48 ± 0.04 restraint = 1.37 ± 0.04 | ||

bp |
7E
| Gln + Glu (Glx) | CRS group (n = 17/timepoint) | Paired Cohen’s d = –0.84p = 0.0186 | –1.49, –0.115 baseline: 1.94 ± 0.02 restraint: 1.85 ± 0.03 |

bq | Healthy group (n = 7/timepoint) | Paired Cohen’s d = –0.41p = 0.529 | –1.83, 1.12 baseline = 1.97 ± 0.04 restraint = 1.92 ± 0.05 | ||

br | GABA | CRS group (n = 16/timepoint) | Paired Cohen’s d = –0.137p = 0.74 | –0.959, 0.632 baseline: 0.35 ± 0.01 restraint: 0.34 ± 0.01 | |

bs | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.558p = 0.378 | –1.82, 0.926 baseline = 0.37 ± 0.02 restraint = 0.34 ± 0.02 | ||

bt | Gln/Glu | CRS group (n = 17/timepoint) | Paired Cohen’s d = –0.171p = 0.552 | –0.767, 0.275 baseline = 0.38 ± 0.01 restraint = 0.37 ± 0.01 | |

bu | Healthy group (n = 6/timepoint) | Paired Cohen’s d = 1.15p = 0.0632 | 0.45, 2.51 baseline = 0.35 ± 0.02 restraint = 0.41 ± 0.02 | ||

Animal weight and whole-brain volume | |||||

bv |
8A
| Spearman’s rank correlation rho because baseline weights were not normally distributed [n = 33 fromcurrent cohort, n = 41 from Seewoo et al. (2019) and our unpublished data] | S = 28632p = 7.909e-08r = 0.58 | Mean whole-brain volume to weight ratio = 6.64 ± 0.16 mm^{3}/g | |

Hippocampal volume | |||||

bw |
8B
| CRS group (n = 18/timepoint) | Paired Cohen’s d = –0.811p = 0.0032 | –1.33, –0.318 baseline: 5.88 ± 0.01 restraint: 5.85 ± 0.01 | |

bx | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.409p = 0.327 | –1.64, 0.467 baseline = 5.87 ± 0.01 restraint = 5.85 ± 0.02 | ||

Correlations | |||||

by |
9A
| Latency and salience network functional connectivity (not normal; Spearman’s rank correlationrho; n = 35) | R = 0.180S = 5853.7p = 0.3004p _{adj} = 0.4440 | ||

bz |
9B
| Latency and interoceptive network functional connectivity (not normal; Spearman’s rank correlationrho; n = 35) | R = 0.312S = 4909.9p = 0.0678p_{adj} = 0.3627 | ||

ca |
9C
| Salience and interoceptive network functional connectivity (not normal; Spearman’s rank correlationrho; n = 37) | R = 0.595S = 3414p = 0.0001p_{adj} = 0.0017 | ||

cb |
9D
| Latency and cingulate cortex functional connectivity (not normal; Spearman’s rank correlationrho; n = 35) | R = –0.484S = 10597p = 0.0032p_{adj} = 0.0320 | ||

cc |
9E
| Cingulate cortex and salience network functional connectivity (not normal; Spearman’s rankcorrelation rho; n = 37) | R = –0.560S = 13158p = 0.0004p_{adj} = 0.0044 | ||

cd |
9F
| Cingulate cortex and interoceptive network functional connectivity (not normal; Spearman’srank correlation rho; n = 37) | R = –0.402S = 11828p = 0.0142p_{adj} = 0.1137 | ||

ce |
9G
| Latency and Glx/tCr (latency not normal; Spearman’s rank correlation rho; n = 51) | R = 0.180S = 18116p = 0.2055p_{adj} = 0.4440 | ||

cf |
9H
| Latency and hippocampal volume (latency not normal; Spearman’s rank correlation rho; n = 52) | R = 0.262S = 17285p = 0.0605p_{adj} = 0.3627 | ||

cg |
9I
| Postrestraint latency and baseline hippocampal volume of CRS group (normal; Pearson’s product-moment correlation; n = 23) | R = 0.311t_{(21)} = 1.50p = 0.1480p_{adj} = 0.4440 | –0.116, 0.641 | |

ch |
9J
| Hippocampal volume and salience network functional connectivity (salience network functionalconnectivity not normal; Spearman’s rank correlation rho; n = 36) | R = 0.341S = 5124p = 0.0427p_{adj} = 0.2990 | ||

ci |
9K
| Hippocampal volume and interoceptive network functional connectivity (interoceptive networkfunctional connectivity not normal; Spearman’s rank correlation rho; n = 36) | R = 0.299S = 5444p = 0.0764p_{adj} = 0.3627 | ||

cj |
9L
| Hippocampal volume and cingulate cortex functional connectivity (cingulate cortex functionalconnectivity not normal; Spearman’s rank correlation rho; n = 36) | R = –0.431S = 11122p = 0.0091p_{adj} = 0.0822 |

Each analysis includes a letter indicator linking the test in the table to the analysis in the text. The link to the corresponding figure, if any, is indicated under Fig. The estimation statistics, critical value, degrees of freedom, and exact

*p*values are listed for each test under statistics, and the CIs of the tests and mean ± SE are under power.↵* Number of animals are different between groups and among tests because (1) one animal fell off the open arm during baseline EPM testing and baseline and postrestraint EPM data from this animal was excluded from the analyses; (2) FST trials during which the animals managed to escape more than once or were floating horizontally for the duration of the test (with most of their body being completely dry at the end) were excluded from the analyses; (3) sessions during which the CRLB of a metabolite of interest was greater than 20% in the

^{1}H-MRS data were excluded from the analyses; (4) not all animals were imaged at baseline and following restraint because of limited access to the MRI instrument and time taken to scan each animal (∼1.5 h per animal); and (5) animals with variable physiology (e.g., rapidly increasing/decreasing breathing rates) during rs-fMRI scans were excluded from the analyses.