Neural and cognitive response to emotional faces in dizygotic twins at familial risk of depression

groups. Means and standard deviation (SD) are displayed for normally distributed data, while medians and interquartile ranges (IR) are displayed for non-normally distributed data.
*Number of severe LEs in the lifetime before the original baseline assessment in 2003-2005.**Stressful life events in the seven years prior to the present study. Abbreviations: LE, life event; SD, standard deviation; IR, interquartile range.
Table 2 Peak cluster activation in brain regions of increased BOLD response (whole-brain analyses with Z=2.0, P=0.05, cluster-corrected, and within the amygdala in the analyses using the structural amygdala for small volume correction) during processing of fearful and happy faces vs. fixation: (i) across all participants (main effect of task) and (ii) in high-risk vs. low-risk twins, and (iii) peaks in clusters showing negative functional coupling (anticorrelations) with amygdala in high-risk vs. low-risk twins (Low-risk>High-risk) in whole-brain PPI analyses (Z=2.0, P=0.05, cluster-corrected).

Task and Region	Voxels	P-value	Z-value		Coordinates
					X	Y		Z
Emotional faces versus fixation baseline
Main effect of task
Left anterior cingulate gyrus (BA 24)	100,476	0		8.31	-6		-6		52
Left fusiform gyrus (BA 37)				8.21	-40		-56		-24
Right declive, cerebellum				8.12	4		-62		-22
Right fusiform gyrus (BA 37)				8.09	38		-44		-24
Left amygdala	297	0.00159		6.62	-20		-12		-8
Right amygdala	352	0.00090		6.81	-18		-10		-16
High-risk < Low-risk
Right fusiform gyrus (BA 19)	1,694	<0.0001		3.64	38		-74		-16
Right inferior frontal gyrus (BA 46)	1,251	0.00027		3.46	54		36		12
Right superior frontal gyrus (BA 8)	847	0.0055		3.64	8		38		54
Functional connectivity from left amygdala, High-risk < Low-risk
Right pregenual anterior cingulate cortex (BA 24)	954	0.0017		3.93	8	30		12
Right medial frontal gyrus (BA 10)	778	0.0070		3.79	6	50		-6
Fearful > Happy faces
High-risk > Low-risk twins
Left middle frontal gyrus (BA 9)	1,915	<0.0001		6.32	-30	10		32
Right superior temporal gyrus (BA 22)	1,365	<0.0001		4.62	56	0		2
Left superior temporal gyrus (BA 22)	981	0.00054		3.27	-56	-6		-2

MNI coordinates (x, y, z) refer to the point of peak activation within each cluster identified using this threshold. BA: Brodmann area.

Figure 1 Behavioral data. A. Fear vigilance in the faces-dot probe test. High-risk twins displayed reduced supraliminal vigilance to fearful vs. neutral faces, as reflected by longer response times for dots replacing unmasked fearful vs. neutral faces. B. Accuracy in the recognition of emotional facial expressions corrected for participants response tendency (d’). High-risk twins showed a specific reduction in the recognition of fearful and happy expressions compared with low-risk twins in the absence of general differences in accuracy across the other emotions. C. Recognition of fearful and happy facial expressions across the 10 emotion intensity levels. High-risk twins showed reduced recognition of moderate to high intensity fear but no differential accuracy for happiness across the different intensity levels compared with low-risk twins. Values represent the mean scores. Error bars represent the s.e.m. One star indicates p<0.05, two stars indicate p<0.01 and three stars indicate p<0.001.

Figure 2 Whole-brain analyses. A. Neural response to emotional (happy and fearful) faces vs. baseline across all participants (main effect of task; marked with green), areas showing reduced response to emotional faces vs. baseline in high-risk twins (group x task interaction; marked with blue), and regions showing greater response to fearful vs. happy faces in high-risk vs. low-risk twins (group x task interaction; marked with yellow). B. Extraction of BOLD signal change from the regions showing a group x task interaction for emotional faces vs. baseline revealed reduced activity to emotional faces vs. baseline in high-risk (N=22) compared with low-risk twins (N=20) within the inferior and superior frontal and fusiform gyri. C. Extraction of BOLD signal change from the regions showing a group x task interaction for fearful vs. happy faces revealed specifically greater fear-associated activity in high-risk vs. low-risk twins. Values represent mean percentage signal change. Error bars represent the s.e.m. One star indicates p<0.05, two stars indicate p<0.01 and three stars indicate p<0.001. Increased MFG and SFG response to fearful vs. happy faces correlated negatively with fear-specific bilateral amygdala response in the high-risk group and across the entire cohort. The solid and dotted lines denote the linear trends for the correlation in high-risk twins and across the entire cohort, respectively. Please note that the ROI was non-independent and thus the effect sizes may be exaggerated (Kriegeskorte, Simmons, Bellgowan & Baker, 2009).
Figure 3. Whole-brain PPI analysis with left amygdala functional cluster (emotional faces versus baseline across all participants) as the seed region showed different functional coupling (FC) of the left amygdala with MFG (BA 10) and pgACC (BA 24) in high-risk compared with low-risk twins (amygdala–MFG coupling: t=4.22, df=40, p≤0.001; amygdala–pgACC coupling: t=3.93, df=40, p≤0.001); Whereas low-risk twins showed positive FC of the left amygdala with MFG (BA 10) and pgACC (BA 24), high-risk twins showed negative FC (anticorrelations) between these regions. Amygdala-MFG anticorrelations correlated with reduced recognition of fear in high-risk twins and across the entire cohort. Values represent the mean standardized betas in the clusters. Error bars represent the s.e.m. One star indicates p<0.05, two stars indicate p<0.01 and three stars indicate p<0.001. The solid and dotted lines denote the linear trends for the correlation in high-risk twins and across the entire cohort, respectively.