Hypogyrification in Generalized Anxiety Disorder and Associated with Insomnia Symptoms

Figures & data

Table 1 Demographic and Clinical Characteristics of Participants

	Patients	Controls	p
Sample size (n)	73	74
Age (y)^†	36.86 (12.65)	35.05(12.38)	0.382
Gender (m/f)	26/47	17/57	0.741
Education level (y)^†	11.45(3.38)	12.41(3.74)	0.107
HAMA^‡	18(7)	2(3)	<0.001
ISI score^†	12.41(6.92)	1.41(1.34)	<0.001
Age of onset (years)^†	33.38(12.61)	N/A
Duration (months)^‡	6(21)	N/A
SSRIs	14	N/A
SNRIs	17	N/A
TCAs	1	N/A
Antianxietics	3	N/A
Benzodiazepines	4	N/A
Non-benzodiazepines	3	N/A
Anticonvulsant	1
NaSSA	1	N/A
Antipsychotics	5	N/A
TIV(mm^3)^†	1507178(137257.85)	1502252(138291.61)	0.829

Notes: Age, educational level, HAMA score, ISI score, and TIV were compared between groups using an independent sample t-test or Wilcoxon test, and gender ratios were compared using chi-square test. ^†Data presented as mean (standard deviation). ^‡Data presented as median (interquartile range).

Abbreviations: HAMA, Hamilton Anxiety Scale; ISI, Insomnia Severity Index; NaSSA, norepinephrine and specific serotonergic antidepressants; SNRIs, serotonin–norepinephrine reuptake inhibitors; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants; TIV, total intracranial volume.

Table 2 Comparison of Local Gyrification Index Between Patients with Generalized Anxiety Disorder and Healthy Controls

Clusters	Max T Value	VtxMax	Size (mm^2)	TalX	TalY	TalZ	CWP	NVtxs	Effect Size (Cohen’s d)
Left LGI GAD<HC
FFA	−5.690	44,003	2678.68	−41.2	−49.7	−15.3	0.0001	4562	−0.945
Insula	−3.967	56,365	1687.7	−61.7	−10.8	11.4	0.0001	4061	−0.659
OFC	−6.542	89,332	1337.1	−15.5	21.7	−19.5	0.0001	2741	−1.087
Temporal pole	−5.365	54,281	483.31	−27.3	8.7	−35.9	0.0068	927	−0.891
rMFG	−3.991	82,490	364.51	−18.9	43.9	33.7	0.0239	588	−0.663
Right LGI GAD<HC
OFC	−4.473	51,311	1119.52	7.5	35.2	−23	0.0001	2123	−0.743
Insula	−3.566	115,361	693.17	36.5	−12.5	−0.4	0.0009	1705	−0.592

Abbreviations: CWP, Cluster-wise probability and nominal p value; FFA, fusiform area; GAD, generalized anxiety disorder; HC, healthy control; LGI, local gyrification index; NVtxs, number of vertices in cluster; OFC, orbitofrontal cortex; rMFG, rostral middle frontal gyrus; TalX/Y/Z, the Talairach coordinate of peak vertex; VtxMax, number of peak vertex of the significant cluster.

Figure 1 Local gyrification index (LGI) comparison in the left hemisphere. (A) Patients with GAD displayed hypogyrification in the insula, orbitofrontal cortex (OFC), middle frontal gyrus (MFG), temporal pole, and fusiform area. (B) A negative relationship between the LGI of the OFC, insula, MFG, and insomnia was found.

Figure 2 Local gyrification index (LGI) comparison in the right hemisphere. Patients with GAD displayed hypogyrification in the insula and orbitofrontal cortex (OFC). A negative relationship was found between the LGI of the OFC and insomnia.

Figure 3 Cortical thickness (CT) and surface area (SA) in GAD patients compared with controls in the region with LGI reduction in GAD. CT in the right orbitofrontal cortex (OFC) was increased whereas SA was reduced in the left OFC.

Table 3 Regions Showing Significant Differences in Seed-Based Functional Connectivity Analysis

Brain Regions (GAD>HC)	Voxel Size	MNI Coordinate (x, y, z)	Statistic (t value)	Effect Size (Cohen’s d)
R.SFG	44	24, 51, 12	4.609	0.766
R.IPL	42	51, -45, 36	4.288	0.712

Note: Statistical maps were corrected using the Gaussian random field method with significance for voxel p <0.001 and cluster p <0.05 (two-tailed).

Abbreviations: GAD, Generalized anxiety disorder; MNI, Montreal Neurological Institute; R.IPL, right inferior parietal lobe; R.SFG, right superior frontal gyrus.

Figure 4 Patients with GAD displayed stronger functional connectivity between the left insula and the right superior frontal cortex and inferior parietal lobe than healthy controls.