Demographic Data
Demographic and clinical data of subjects are shown in Table 1. As reported previously, the DUP (mean) was 29 weeks (SD=26 weeks) and the duration of antipsychotic use was <3 days prior to the first scan session. SOFAS scores were significantly different between the 2 groups (t(29)=12.466, P<0.001). The time in between baseline and follow-up (FUP) scan was 5.9 months (SD=1.3 months) for patients and 7.3 months (SD=1.9 months) for healthy controls (HC).
Table 1. Demographic and clinical characteristics.
Characteristic
|
Patient group
(N = 21)
|
Healthy controls
(N = 10)
|
t/χ2
|
p
|
Gender (male/female)
|
16/5
|
5/5
|
2.13
|
0.145
|
Marital status (Mar/S)
|
1/20
|
1/9
|
0.31
|
0.58
|
Inpatient at baseline (Y/N)
|
11/10
|
|
|
|
Family Hx (Y/N/DN)
|
10/6/5
|
|
|
|
AP exposure at baseline (M/SD; days)
|
2.95/3.11
|
|
|
|
Total DDD-days at baseline scan (M/SD)
|
2.25/4.74
|
|
|
|
Total DDD-days at FUP scan (M/SD)
|
145.68/97.56
|
|
|
|
DUP (M/SD/median; weeks)
|
29.38/26.65/18
|
|
|
|
Ethnicity (Black/White/Other)
|
2/18/1
|
0/5/5
|
4.51
|
0.034a
|
Age (M/SD)
|
22.33/5.29
|
21.60/3.37
|
-0.47
|
0.645
|
SOFAS at baseline scan (M/SD)
SOFAS at FUP scan (M/SD)
|
42.33/12.84
61.25/9.85
|
83.70/5.62
85.10/3.21
|
12.47
9.83
|
0.000
0.000
|
PANSS-8 total at baseline scan (M/SD)
PANSS-8 total at FUP scan (M/SD)
|
24.67/5.30
14.35/4.77
|
|
|
|
Smoker (yes/no)
|
6/15
|
0/10
|
3.54
|
0.060
|
Cannabis user (yes/no)
|
13/8
|
0/10
|
10.66
|
0.001
|
Time between scans (M/SD; months)
|
5.93/1.25
|
7.67/1.90
|
2.63
|
0.021
|
P values for differences between groups were calculated using chi-square analyses for categorical variables and independent t tests for continuous variables.
Mar married, S single, Y yes, N no, Hx history, DN don’t know, AP antipsychotic, M mean, SD standard deviation, DDD defined daily dose, FUP follow-up, DUP duration untreated psychosis.
a White vs non-White comparison.
|
Cramer-Rao lower bounds (CRLB) values indicating the quality of myo-inositol measurement was quantified for both groups. Myo-inositol CRLB values for HC and FES were 4% (SD=1%) for both baseline and FUP. Thus the 2 groups had acceptable qualitative metrics for myo-inositol estimation at both time points. A sample of fitted spectrum is presented in Figure 1. We present the concentrations and CRLBs of metabolites other than myo-inositol in the Supplementary Material.
Myo-inositol Levels
Repeated measures ANOVA revealed a significant group × time interaction (F(1,27)=6.40, P=0.018, partial eta-squared pη2=0.19) as well as a group effect (F(1,27)=8.08, P=0.008, pη2=0.23), between FES (M=4.72 mM, SD=0.64 mM) and HC (M=5.44 mM, SD=0.65 mM) but no effect on time (F(1,27)=0.05, P=0.83). Parameter estimates revealed that at baseline, FES had lower myo-inositol than healthy controls (t(29)=4.88, P<0.001), but this difference was not present at follow-up (t(29)=0.78, P=0.44). A simple contrast of time in each group revealed no significant effect in both the healthy control group (F(1,7)=0.34, P=0.58; 8.2% decrease) and in patients (F(1,18)=0.28, P=0.60; 8.9% increase) (Figure 2). Younger age and female gender were associated with lower levels at both time points (F(1,27)=8.1-11.2, pη2=0.14-0.36, P=0.06-0.001).
Lastly, the time interval between scans in months was not related to myo-inositol concentration differences (FUP-baseline) in either group (HC: r=0.005, P=0.90; FES: r=-0.096, P=0.68). Nevertheless, to address spurious differences in change scores that may arise due to time differences in between scans, we generated time-adjusted, i.e. annualized myo-inositol concentration values. Annualized change scores in myo-inositol change were significantly different between the two groups (t(29)=-2.50, P=0.018) and indicated a 0.19 mM/year (SD=0.37 mM) increase in patients and a 0.12 mM/year (SD=0.15 mM) reduction in healthy controls.
Myo-inositol and Clinical Measures
As myo-inositol concentration increased in patients, PANSS-8 scores reduced significantly (Spearman’s rho=-0.61, P=0.004) and SOFAS increased marginally (rho=0.44, P=0.05), but changes in myo-inositol did not track changes in depressive burden measured using CDSS (rho=0.001, P=0.90) (Figure 3). There was no significant correlation between annualized myo-inositol concentration changes and DUP (rho=0.05, P=0.83). We also did not see any correlation between baseline (unadjusted) myo-inositol concentration and DUP (rho=0.30, P=0.22), SOFAS (rho=-0.27, P=0.23), CDSS (rho=-0.10, P=0.65), or PANSS-8 total (rho=0.18, P=0.43).
Lastly, there was no significant relationship between baseline antipsychotic exposure defined daily dose (DDD) myo-inositol levels (rho=-0.15, P=0.51) and DDD at follow-up and myo-inositol (r=-0.06, P=0.81) as well as between DDD at follow-up and annualized myo-inositol change (r=-0.14, P=0.56).