The impact of age of onset on amygdala intrinsic connectivity in major depression

Figures & data

Table 1 Demographics

Characteristics	Group			Significance
	MDD onset over 18 years (n=34)	MDD onset 18 years and below (n=21)	Healthy controls (n=19)
Sex (F/M)	17/17	16/5	11/8	χ^2=3.72 df=2 p=0.16
Age** (years)	41.05±9.41	29.1±7.7	32.68±9.99	F (2, 71) =12.23 p<0.001
Age of onset** (years)	31.55±8.08	14.3±2.5	–	t53=9.48 p<0.001
Illness duration (months)	114.4±92.6	161.9±99.9	–	t53=1.80 p=0.079
Duration of current episode	43.1±55.3	60.0±72.4	–	t53=0.98 p=0.33
Number of episodes*	1.68±1.65	4.43±5.66	–	t53=2.67 p=0.01
HDRS	21.6±4.3	21.5±3.5	–	t53=0.09 p=0.93

Notes: Except for sex and scanner, all values are mean ± SD.

* p<0.05,

** p<0.01.

Abbreviations: df, degrees of freedom; HDRS, Hamilton Depression Rating Scale; MDD, major depression disorder.

Figure 1 Significant clusters arising from group analysis. In this analysis, age, sex, and scanner were used as covariates of non-interest.

Notes: Brain regions show group differences in resting-state functional connectivity with the amygdala, as revealed by ANCOVA. Colored areas indicate significant z-scores. Shown are significant clusters indicating difference in left amygdala connectivity with (A) DLPFC, (B) inferior parietal cortex, and (C) MPFC. Mean z-scores (± SEM) extracted from significant clusters for each group are displayed on the right of each cluster (*p<0.05, **p<0.01).
Abbreviations: ANCOVA, analysis of covariance; AO-MDD, adult-onset major depressive disorder; DLPFC, dorsolateral prefrontal cortex; EO-MDD, early-onset major depressive disorder; HC, healthy control; MPFC, medial prefrontal cortex; SEM, standard error of the mean.

Table 2 Differences in amygdala intrinsic connectivity between early-onset MDD, adult-onset MDD, and healthy controls

	Region (hemisphere)	BA	Cluster size	MNI coordinates			z-score
				x	y	z
	ANCOVA (effects of group)
Left	DLPFC (L)	9/45	168	−30	52	38	4.15
	Inferior parietal (L)	7	159	−42	−68	50	4.61
	MPFC (R)	32	98	20	56	6	3.40
Right	Inferior parietal (L)	7	134	−42	−68	52	3.92

Notes: Group analysis was performed considering age, sex and scanner as covariates of non-interest. Brain regions exhibiting a significant group difference between groups (EO-MDD, AO-MDD and HC), as revealed by ANCOVA, in the resting-state functional connectivity with the left and right amygdala (corrected voxel-wise at p<0.01, corrected for multiple comparisons at p<0.05).

Abbreviations: BA, Brodmann’s area; DLPFC, dorsolateral prefrontal; HC, healthy controls; MPFC, medial prefrontal; MNI, Montreal Neurological Institute.

Figure 2 Significant clusters arising from group analysis considering illness burden as covariate of non-interest.

Notes: In this analysis, the number of episodes and duration of illness, in addition to age, sex, and scanner were used as covariates of non-interest. Brain regions show group differences in resting-state functional connectivity with the amygdala, as revealed by ANCOVA. Colored areas indicate significant z-scores. Shown are significant clusters indicating difference in left amygdala connectivity with (A) DLPFC and (C) inferior temporal. (B) Differences in right amygdala–left inferior parietal cortex connectivity. Mean z-scores (± SEM) extracted from significant clusters for each group are displayed on the right of each cluster (*p<0.05, **p<0.01).
Abbreviations: ANCOVA, analysis of covariance; AO-MDD, adult-onset major depressive disorder; DLPFC, dorsolateral prefrontal cortex; EO-MDD, early-onset major depressive disorder; HC, healthy control; MPFC, medial prefrontal cortex; SEM, standard error of the mean.

Table 3 Group differences in amygdala intrinsic connectivity after controlling for illness burden

	Region (hemisphere)	BA	Cluster size	MNI coordinates			z-score
				x	y	z
	ANCOVA (effects of group, controlling for illness burden)
Left	DLPFC (L)	9/45	202	−30	52	38	4.03
	Inferior temporal (R)	21	92	54	−2	−38	3.24
Right	Inferior parietal (L)	7	79	−58	−58	40	3.41

Notes: Group analysis was performed considering age, sex, scanner, number of episodes, and duration of illness as covariates of non-interest. Brain regions exhibiting a significant group difference between groups (EO-MDD, AO-MDD, and HC), as revealed by ANCOVA, in the resting-state functional connectivity with the left and right amygdala (corrected voxel-wise at p<0.01, corrected for multiple comparisons at p<0.05).

Abbreviations: ANCOVA, analysis of covariance; BA, Brodmann’s area; DLPFC, dorsolateral prefrontal cortex; HC, healthy control; MNI, Montreal Neurological Institute.