Table 2.
Correlates of clinical severity with age, and age-adjusted biochemical, neurophysiologic, and neuroimaging biomarkers
| Characteristic | Total CSS | Cognitive Domain | Communication Domain | Motor Domain | Epilepsy Domain | Psychiatric Domain |
|---|---|---|---|---|---|---|
| R | R | R | R | R | R | |
| p value | p value | p value | p value | p value | p value | |
| Age | -0.302 | -0.054 | 0.31 | 0.368 | -0.576 | -0.522 |
| 0.03 | 0.71 | 0.03 | 0.009 | < 0.001 | < 0.001 | |
| Gene expression, 2^ΔCT | ||||||
| ALDH5A1 (N = 23) | 0.154 | 0.038 | -0.173 | 0.179 | -0.113 | 0.418 |
| 0.49 | 0.86 | 0.44 | 0.42 | 0.62 | 0.05 | |
| ABAT (N = 23) | -0.232 | -0.568 | 0.272 | 0.156 | -0.3 | -0.089 |
| 0.29 | 0.006 | 0.22 | 0.48 | 0.17 | 0.69 | |
| GLS (N = 23) | -0.008 | -0.299 | 0.245 | 0.195 | 0.054 | -0.1 |
| 0.97 | 0.17 | 0.27 | 0.38 | 0.81 | 0.65 | |
| GLUL (N = 23) | -0.092 | -0.104 | -0.131 | -0.325 | -0.072 | 0.163 |
| 0.68 | 0.64 | 0.56 | 0.14 | 0.75 | 0.68 | |
| GLUD1 (N = 23) | -0.064 | -0.367 | 0.151 | 0.196 | 0.073 | -0.137 |
| 0.77 | 0.09 | 0.5 | 0.38 | 0.74 | 0.54 | |
| Biochemical | ||||||
| Plasma GABA, µM/L (N = 43) | 0.337 | 0.067 | 0.149 | -0.149 | 0.402 | 0.354 |
| 0.02 | 0.66 | 0.33 | 0.33 | 0.007 | 0.01 | |
| Plasma GHB, µM/L (N = 35) | 0.36 | 0.145 | 0.18 | -0.11 | 0.215 | 0.431 |
| 0.05 | 0.44 | 0.34 | 0.95 | 0.25 | 0.01 | |
| MRS | ||||||
| GABA/NAA, (BG, PCG, OCC)* (N = 16) | 0.031 | -0.225 | 0.201 | -0.231 | 0.211 | 0.24 |
| 0.9 | 0.37 | 0.42 | 0.35 | 0.4 | 0.33 | |
| TMS | ||||||
| rMT, %MO (N = 23) | -0.312 | -0.19 | -0.262 | -0.215 | -0.095 | -0.227 |
| 0.15 | 0.39 | 0.23 | 0.33 | 0.67 | 0.31 | |
| CSP, ms (N = 21) | -0.085 | -0.281 | 0.054 | 0.36 | 0.045 | -0.234 |
| 0.72 | 0.23 | 0.82 | 0.11 | 0.85 | 0.32 | |
| LICI, log (MEPt/MEPc) (N = 18) | -0.264 | -0.295 | -0.031 | -0.211 | -0.101 | -0.123 |
| 0.3 | 0.25 | 0.9 | 0.416 | 0.7 | 0.63 |
ABAT- 4-aminobutyrate aminotransferase; ADOS-2- Autism Diagnostic Observation Schedule-Second Edition; ALDH5A1- Aldehyde dehydrogenase 5 family member A1; ASD- Autism Spectrum Disorder; BG- basal ganglia; CSP- cortical silent period; EEG- Electroencephalogram; EEM- estimated marginal means adjusted for age; FSIQ- full-scale intellectual quotient; GABA- γ-aminobutyrate; GHB- γ-hydroxybutyrate; GLS- Glutaminase; GLUD1- Glutamate dehydrogenase 1; GLUL- Glutamate-ammonia ligase; IQR- Interquartile ratio; LICI- long interval intracortical inhibition; MEPc- motor evoked potential, condition; MEPt- motor evoked potential, test; MO- machine output; MRS- Magnetic resonance spectroscopy; ms- milliseconds; NAA- N-acetyl aspartate; OCC- occipital cortex; PCG- posterior cingulate gyrus; R- correlation coefficient; SD- Standard deviation; SE- standard error; SSADHD- succinic semialdehyde dehydrogenase deficiency; TMS- transcranial magnetic stimulation; Bold indicates significant. *Mean value of the GABA/NAA ratios measured from the basal ganglia, posterior cingulate gyrus, and occipital cortex)