Differences in mGluR5 Availability Depending on the Level of Social Avoidance in Drug-Naïve Young Patients with Major Depressive Disorder

Figures & data

Table 1 Demographic/Clinical Characteristics and PET Scan Information

Variables	Patients (n=20)	Controls (n=18)	p value
Demographic and clinical characteristics
Age (years)	23.2 ± 2.6	25.1 ± 3.9	0.094^a
Gender (male/female)	7/13	9/9	0.350^b
Duration of current episode (months)	9.8 ± 12.5	NA	NA
Age of onset (years)	16.6 ± 1.1	NA	NA
HAMD-17	18.3 ± 9.3	NA	NA
Range of HAMD-17	8–41	NA	NA
BDI	24.2 ± 6.7	1.0 ± 1.2	<0.0001^a
SADS	99.4 ± 19.8	74.1 ± 17.6	0.0002^a
PET scan information
Injected dose (MBq)	643.9 ± 44.9	633.9 ± 65.4	0.583^a
Specific activity (GBq/μmol)	16.0 ± 7.8	16.9 ± 6.9	0.729^a

Notes: Values are presented as mean ± standard deviation. ^aComputed using independent samples t-test. ^bComputed using chi-square test.

Abbreviations: PET, positron emission tomography; NA, not applicable; HAMD-17, Hamilton Rating Scale for Depression with 17 items; BDI, Beck Depression Inventory; SADS, Social Avoidance and Distress Scale.

Table 2 Demographic/Clinical Characteristics and PET Scan Information for L-SADS Patients, H-SADS Patients, and Healthy Controls

Variables	(a) L-SADS Patients (n=11)	(b) H-SADS Patients (n=9)	(c) Healthy Controls (n=18)	Between-Group Comparison (p value)	Post-Hoc Test^d (p value)
					a vs b	b vs c	a vs c
Demographic and clinical characteristics
Age (years)	23.2 ± 3.0	23.2 ± 2.1	24.9 ± 4.0	0.250^a	NA	NA	NA
Gender (male/female)	4/7	3/6	9/7	0.640^b	NA	NA	NA
Duration of current episode (months)	9.7 ± 13.3	9.9 ± 12.3	NA	0.962^c	NA	NA	NA
Age of onset (years)	16.3 ± 1.0	16.9 ± 1.2	NA	0.200^c	NA	NA	NA
HAMD-17	16.6 ± 9.0	20.3 ± 9.7	NA	0.389^c	NA	NA	NA
BDI	21.5 ± 5.2	27.6 ± 7.0	0.8 ± 1.2	<0.0001^a	0.109	<0.0001	<0.0001
SADS	84.6 ± 13.5	117.3 ± 6.1	71.2 ± 16.4	<0.0001^a	<0.0001	<0.0001	0.200
PET scan information
Injected dose (MBq)	626.7 ± 36.0	664.9 ± 47.6	636.7 ± 68.9	0.265^a	NA	NA	NA
Specific activity (GBq/μmol)	17.1 ± 7.0	14.6 ± 9.0	17.2 ± 7.3	0.726^a	NA	NA	NA

Notes: Values are presented as mean ± standard deviation. ^aCalculated using one-way ANOVA or Welch’s ANOVA where appropriate. ^bCalculated using chi-square test. ^cCalculated using independent samples t-test. ^dCalculated using Bonferroni or Games-Howell post-hoc test where appropriate.

Abbreviations: PET, positron emission tomography; L-SADS, depressed patients with low levels of social avoidance; H-SADS, depressed patients with high levels of social avoidance; NA, not applicable; HAMD-17, Hamilton Rating Scale for Depression with 17 items; BDI, Beck Depression Inventory; SADS, Social Avoidance and Distress Scale; ANOVA, analysis of variance.

Figure 1 Representative mean images of [¹¹C]ABP688 BP_ND, PET, and 3-Tesla MRI for 18 healthy controls. The [¹¹C]ABP688 PET image is generated by averaging the reconstructed 21 frames of dynamic image.

Abbreviations: BP_ND, non-displaceable binding potential; PET, positron emission tomography; MRI, magnetic resonance imaging.

Table 3 The ROI-Based Between-Group Comparisons of [¹¹C]ABP688 BP_ND

Regions		[^11C]ABP688 BPND			Between-Group Comparison		Post-Hoc Test (Uncorrected p value)
		(a) L-SADS Patients (n=11)	(b) H-SADS Patients (n=9)	(c) Healthy Controls (n=18)	F value (Uncorrected p value)	Cohen’s f value	a vs b	b vs c	a vs c
Lateral surface	Rt. SFC	0.42 ± 0.07	0.50 ± 0.10	0.50 ± 0.06	4.30 (0.031*)	0.49	0.159	1.000	0.024*
	Lt. SFC	0.42 ± 0.08	0.51 ± 0.11	0.51 ± 0.06	4.32 (0.021*)	0.50	0.074	1.000	0.029*
	Rt. MFC	0.52 ± 0.08	0.60 ± 0.11	0.60 ± 0.08	3.51 (0.041*)	0.45	0.114	1.000	0.059
	Lt. MFC	0.50 ± 0.08	0.59 ± 0.11	0.59 ± 0.07	4.16 (0.024*)	0.49	0.083	1.000	0.032*
	Rt. IFCoperc	0.54 ± 0.10	0.64 ± 0.14	0.64 ± 0.11	3.45 (0.043*)	0.44	0.132	1.000	0.057
	Lt. IFCoperc	0.52 ± 0.08	0.58 ± 0.12	0.58 ± 0.09	1.63 (0.210)	0.31	NA	NA	NA
	Rt. IFCtriang	0.48 ± 0.07	0.55 ± 0.10	0.54 ± 0.07	2.75 (0.078)	0.40	NA	NA	NA
	Lt. IFCtriang	0.48 ± 0.07	0.56 ± 0.12	0.54 ± 0.07	2.41 (0.105)	0.37	NA	NA	NA
Medial surface	Rt. SFCmedial	0.48 ± 0.08	0.58 ± 0.11	0.57 ± 0.07	4.79 (0.014*)	0.52	0.042*	1.000	0.024*
	Lt. SFCmedial	0.52 ± 0.07	0.61 ± 0.12	0.59 ± 0.08	3.40 (0.045*)	0.44	0.075	1.000	0.101
	Rt. SMA	0.37 ± 0.06	0.44 ± 0.09	0.43 ± 0.06	2.73 (0.079)	0.40	NA	NA	NA
	Lt. SMA	0.42 ± 0.06	0.49 ± 0.10	0.48 ± 0.07	3.38 (0.045*)	0.44	0.081	1.000	0.095
	Rt. PCL	0.28 ± 0.06	0.34 ± 0.06	0.33 ± 0.08	1.84 (0.174)	0.32	NA	NA	NA
	Lt. PCL	0.25 ± 0.05	0.30 ± 0.06	0.29 ± 0.06	2.43 (0.102)	0.37	NA	NA	NA
Orbital surface	Rt. SFCorb	0.56 ± 0.09	0.68 ± 0.12	0.65 ± 0.09	3.91 (0.029*)	0.47	0.040*	1.000	0.094
	Lt. SFCorb	0.56 ± 0.09	0.68 ± 0.13	0.64 ± 0.10	3.59 (0.038*)	0.45	0.048*	1.000	0.133
	Rt. SFCventmed	0.67 ± 0.08	0.78 ± 0.13	0.75 ± 0.10	3.29 (0.049*)	0.43	0.066	1.000	0.144
	Lt. SFCventmed	0.75 ± 0.10	0.89 ± 0.18	0.85 ± 0.12	3.40 (0.045*)	0.44	0.055	1.000	0.156
	Rt. MFCorb	0.53 ± 0.08	0.67 ± 0.13	0.61 ± 0.09	5.38 (0.009**)	0.55	0.008**	0.362	0.124
	Lt. MFCorb	0.55 ± 0.10	0.68 ± 0.15	0.65 ± 0.09	4.21 (0.023*)	0.49	0.037*	1.000	0.062
	Rt. IFCorb	0.54 ± 0.08	0.65 ± 0.13	0.61 ± 0.07	3.81 (0.032*)	0.47	0.034*	0.868	0.162
	Lt. IFCorb	0.52 ± 0.08	0.64 ± 0.13	0.60 ± 0.09	4.02 (0.027*)	0.48	0.032*	1.000	0.109
	Rt. REC	0.72 ± 0.09	0.84 ± 0.17	0.80 ± 0.12	2.40 (0.105)	0.37	NA	NA	NA
	Lt. REC	0.73 ± 0.09	0.87 ± 0.17	0.83 ± 0.12	3.11 (0.057)	0.42	NA	NA	NA
	Rt. OLF	0.68 ± 0.11	0.80 ± 0.17	0.79 ± 0.14	2.45 (0.101)	0.37	NA	NA	NA
	Lt. OLF	0.74 ± 0.13	0.86 ± 0.15	0.86 ± 0.15	2.69 (0.082)	0.39	NA	NA	NA

Notes: [¹¹C]ABP688 BP_ND values are indicated as mean ± standard deviation. The results of one-way ANOVA with Bonferroni post-hoc test or Welch’s ANOVA with Games-Howell post-hoc test are presented in this table. The statistical significance is indicated as *Uncorrected p < 0.05 and **Uncorrected p < 0.01. Cohen’s f value represents the effect size for one-way ANOVA or Welch’s ANOVA.

Abbreviations: ROI, region of interest; BP_ND, non-displaceable binding potential; L-SADS, depressed patients with low levels of social avoidance; H-SADS, depressed patients with high levels of social avoidance; Rt, right; SFC, superior frontal cortex; Lt, left; MFC, middle frontal cortex; IFCoperc, inferior frontal cortex (opercular part); NA, not applicable; IFCtriang, inferior frontal cortex (triangular part); SFCmedial, superior frontal cortex (medial part); SMA, supplementary motor area; PCL, paracentral lobule; SFCorb, superior frontal cortex (orbital part); SFCventmed, superior frontal cortex (medial orbital part); MFCorb, middle frontal cortex (orbital part); IFCorb, inferior frontal cortex (orbital part); REC, gyrus rectus; OLF, olfactory cortex; ANOVA, analysis of variance.

Figure 2 Box plots of the ROI-based between-group comparisons in [¹¹C]ABP688 BP_ND values. (A–C) The L-SADS patient group had significantly lower [¹¹C]ABP688 BP_ND in the bilateral SFC (right: uncorrected p = 0.024, left: uncorrected p = 0.029) and left MFC (uncorrected p = 0.032) compared to control group. (D) In addition, the L-SADS patient group showed significantly lower [¹¹C]ABP688 BP_ND in the right SFCmedial relative to both the H-SADS patient group (uncorrected p = 0.042) and control group (uncorrected p = 0.024). (E–J) Moreover, the L-SADS patient group had significantly lower [¹¹C]ABP688 BP_ND in the bilateral SFCorb (right: uncorrected p = 0.040, left: uncorrected p = 0.048), bilateral MFCorb (right: uncorrected p = 0.008, left: uncorrected p = 0.037), and bilateral IFCorb (right: uncorrected p = 0.034, left: uncorrected p = 0.032) compared with the H-SADS patient group. In box plots, the statistical significance is indicated as *Uncorrected p < 0.05 and **Uncorrected p < 0.01.

Abbreviations: ROI, region of interest; BP_ND, non-displaceable binding potential; L-SADS, depressed patients with low levels of social avoidance; SFC, superior frontal cortex; MFC, middle frontal cortex; SFCmedial, superior frontal cortex (medial part); H-SADS, depressed patients with high levels of social avoidance; SFCorb, superior frontal cortex (orbital part); MFCorb, middle frontal cortex (orbital part); IFCorb, inferior frontal cortex (orbital part).

Figure 3 Scatter plots of the correlations between the SADS score and [¹¹C]ABP688 BP_ND in the entire MDD patient group. The SADS score had significant positive correlations with [¹¹C]ABP688 BP_ND in the (A) right SFCmedial (r = 0.450, p = 0.046), (B and C) bilateral SFCorb (right: r = 0.458, p = 0.042, left: r = 0.463, p = 0.040), (D and E) bilateral MFCorb (right: r = 0.499, p = 0.025, left: r = 0.451, p = 0.046), and (F and G) bilateral IFCorb (right: r = 0.450, p = 0.046, left: r = 0.503, p = 0.024). Yellow and blue dots indicate the L-SADS patient group and the H-SADS patient group, respectively. ^†Cross marks indicate MDD patients with comorbid social phobia. The solid and dotted lines indicate the regression lines and 95% confidence intervals, respectively.

Abbreviations: SADS, Social Avoidance and Distress Scale; BP_ND, non-displaceable binding potential; MDD, major depressive disorder; SFCmedial, superior frontal cortex (medial part); SFCorb, superior frontal cortex (orbital part); MFCorb, middle frontal cortex (orbital part); IFCorb, inferior frontal cortex (orbital part); L-SADS, depressed patients with low levels of social avoidance; H-SADS, depressed patients with high levels of social avoidance.