EPM test |
aa |
3A
| Open arm # | CRS group (n = 24/timepoint) | Paired median difference= –1.0 p = 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= –1.0 p = 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= –1.5 p = 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= –3.0 p = 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 = 0.462 p = 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 = 0.114 p = 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 = 0.212 p = 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 = 0.056 p = 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 = –0.921 p = 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 = 0.232 p = 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 = –0.642 p = 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 = –0.326 p = 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 = –0.2 p = 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 = 0.533 p = 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 = 0.187 p = 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 = 0.117 p = 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 = 0.289 p = 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 = –0.191 p = 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 = –0.62 p = 0.0414 | –1.19, –0.0902 baseline = 42 ± 2 restraint = 37 ± 1 |
at | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.726 p = 0.22 | –1.91, 0.489 baseline = 45 ± 3 restraint = 40 ± 2 |
au |
4B
| Swimming | CRS group (n = 19/timepoint) | Paired Cohen’s d = 0.0269 p = 0.896 | –0.526, 0.489 baseline = 26 ± 2 restraint = 26 ± 2 |
av | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.0 p = 0.969 | –1.54, 1.17 baseline = 30 ± 3 restraint = 30 ± 4 |
aw | Climbing | CRS group (n = 19/timepoint) | Paired Cohen’s d = –0.696 p = 0.021 | –1.22, –0.202 baseline = 16 ± 2 restraint = 11 ± 1 |
ax | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.8 p = 0.12 | –1.92, 0.327 baseline = 15 ± 2 restraint = 10 ± 2 |
ay |
4C
| Immobility | CRS group (n = 19/timepoint) | Paired Cohen’s d = 0.611 p = 0.0438 | 0.0902, 1.19 baseline = 18 ± 2 restraint = 23 ± 1 |
az | Healthy group (n = 8/timepoint) | Paired Cohen’s d = 0.726 p = 0.22 | 0.0902, 1.19 baseline = 15 ± 3 restraint = 20 ± 2 |
ba | Latency | CRS group (n = 19/timepoint) | Paired Cohen’s d = –1.34 p = 0.0006 | –2.03, –0.578 baseline = 119 ± 9 s restraint = 71 ± 7 s |
bb | Healthy group (n = 8/timepoint) | Paired Cohen’s d = –0.0967 p = 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 regression p < 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 regression p < 0.05 | |
be |
5C
| Salience network CRS group (baseline: n = 9 from current cohort; restraint: n = 15) | Unpaired Cohen’s d = –2.33 p = 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 = –0.208 p = 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 = –1.38 p = 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 = –0.539 p = 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 FEAT p < 0.05, z > 2 | |
bj |
6B
| CRS group (baseline: n = 9 from current cohort; restraint: n = 15) | Unpaired Cohen’s d = 1.51 p = 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 = 0.752 p = 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 = –0.538 p = 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 = 0.743 p = 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 = –0.711 p = 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 = –1.1 p = 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 = –0.84 p = 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 = –0.41 p = 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 = –0.137 p = 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 = –0.558 p = 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 = –0.171 p = 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 = 1.15 p = 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 = 28632 p = 7.909e-08 r = 0.58 | Mean whole-brain volume to weight ratio = 6.64 ± 0.16 mm3/g |
Hippocampal volume |
bw |
8B
| CRS group (n = 18/timepoint) | Paired Cohen’s d = –0.811 p = 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 = –0.409 p = 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 = 0.180 S = 5853.7 p = 0.3004 padj = 0.4440 | |
bz |
9B
| Latency and interoceptive network functional connectivity (not normal; Spearman’s rank correlationrho; n = 35) | R = 0.312 S = 4909.9 p = 0.0678 padj = 0.3627 | |
ca |
9C
| Salience and interoceptive network functional connectivity (not normal; Spearman’s rank correlationrho; n = 37) | R = 0.595 S = 3414 p = 0.0001 padj = 0.0017 | |
cb |
9D
| Latency and cingulate cortex functional connectivity (not normal; Spearman’s rank correlationrho; n = 35) | R = –0.484 S = 10597 p = 0.0032 padj = 0.0320 | |
cc |
9E
| Cingulate cortex and salience network functional connectivity (not normal; Spearman’s rankcorrelation rho; n = 37) | R = –0.560 S = 13158 p = 0.0004 padj = 0.0044 | |
cd |
9F
| Cingulate cortex and interoceptive network functional connectivity (not normal; Spearman’srank correlation rho; n = 37) | R = –0.402 S = 11828 p = 0.0142 padj = 0.1137 | |
ce |
9G
| Latency and Glx/tCr (latency not normal; Spearman’s rank correlation rho; n = 51) | R = 0.180 S = 18116 p = 0.2055 padj = 0.4440 | |
cf |
9H
| Latency and hippocampal volume (latency not normal; Spearman’s rank correlation rho; n = 52) | R = 0.262 S = 17285 p = 0.0605 padj = 0.3627 | |
cg |
9I
| Postrestraint latency and baseline hippocampal volume of CRS group (normal; Pearson’s product-moment correlation; n = 23) | R = 0.311 t(21) = 1.50 p = 0.1480 padj = 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 = 0.341 S = 5124 p = 0.0427 padj = 0.2990 | |
ci |
9K
| Hippocampal volume and interoceptive network functional connectivity (interoceptive networkfunctional connectivity not normal; Spearman’s rank correlation rho; n = 36) | R = 0.299 S = 5444 p = 0.0764 padj = 0.3627 | |
cj |
9L
| Hippocampal volume and cingulate cortex functional connectivity (cingulate cortex functionalconnectivity not normal; Spearman’s rank correlation rho; n = 36) | R = –0.431 S = 11122 p = 0.0091 padj = 0.0822 | |