Brain structural changes in late-life generalized anxiety disorder

Abstract

Late-life Generalized Anxiety Disorder (GAD) is relatively understudied and the underlying structural and functional neuroanatomy has received little attention. In this study, we compare the brain structural characteristics in white and gray matter in 31 non-anxious older adults and 28 late-life GAD participants. Gray matter indices (cortical thickness and volume) were measured using FreeSurfer parcellation and segmentation, and mean diffusivity was obtained through Diffusion Tensor Imaging (DTI). We assessed both macroscopic white matter changes [using white matter hyperintensity (WMH) burden] and microscopic white matter integrity [using fractional anisotropy (FA)]. No differences in macro- or microscopic white matter integrity were found between GAD and non-anxious controls (HC). GAD participants had lower cortical thickness in the orbitofrontal cortex (OFC), inferior frontal gyrus, and pregenual anterior cingulate cortex (ACC). Higher worry severity was associated with gray matter changes in OFC, ACC and the putamen. The results did not survive the multiple comparison correction, but the effect sizes indicate a moderate effect. The study suggests that late-life GAD is associated with gray matter changes in areas involved in emotion regulation, more so than with white matter changes. We conclude that anxiety-related chronic hypercortisolemia may have a dissociative effect on gray and white matter integrity.

Systematic review and meta-analyses of neural structural and functional differences in generalized anxiety disorder and healthy controls using magnetic resonance imaging

“…However, it should be noted that a few studies ( n = 3) showed increased FC in the dlPFC (Andreescu et al., 2015 (insula seed); Toazza et al., 2016 (basolateral amygdala seed); Wang et al., 2016a (whole-brain ALFF)). Finally, results indicated that subjects with GAD had reduced dlPFC volume ( n = 5; Andreescu et al., 2017; Moon and Jeong, 2015a, 2016, 2017a, 2017b).…”

“…1 for flow diagram). Of the included records, 35 included structural analyses (Abdallah et al., 2013; Andreescu et al., 2017; Brambilla et al., 2012; Cha et al., 2016a; Cha et al., 2014b; Cha et al., 2016b; Chen and Etkin, 2013; De Bellis et al., 2000, 2002; Etkin et al., 2009; Hettema et al., 2012; Hilbert et al., 2015; Karim et al., 2016; Liao et al., 2013, 2014a, 2014b; Makovac et al., 2016a; Mohlman et al., 2009; Molent et al., 2017; Moon and Jeong, 2015a, 2016, 2017a, 2017b; Moon et al., 2015a, 2014, 2015b; Mueller et al., 2013; Schienle et al., 2011; Strawn et al., 2014, 2013; Terlevic et al., 2013; Tromp et al., 2012; Wang et al., 2016b; Zhang et al., 2011; Zhang et al., 2013), 32 included FC analyses (Andreescu et al., 2015; Andreescu et al., 2014; Buff et al., 2016; Cha et al., 2014a; Cha et al., 2016b; Chen and Etkin, 2013; Cui et al., 2016; Etkin et al., 2010; Etkin et al., 2009; Etkin and Schatzberg, 2011; Fonzo et al., 2014; Greenberg et al., 2013; Hölzel et al., 2013; Laufer et al., 2016; Li et al., 2018; Li et al., 2016; Liu et al., 2015; Makovac et al., 2016b; Makovac et al., 2018; McClure et al., 2007; Mohlman et al., 2017; Monk et al., 2008; Oathes et al., 2015; Pace-Schott et al., 2017; Qiao et al., 2017; Rabany et al., 2017; Roy et al., 2013; Strawn et al., 2012; Toazza et al., 2016; Tromp et al., 2012; Wang et al., 2016a;…”

Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction

“…Additionally, some structural and functional deficits in this area have been found in fMRI studies in neuropsychiatric disorders, such as generalized anxiety disorder (Andreescu et al 2017) and PTSD (Shvil et al 2014), which both affect severely the extinction of fear memories. In the case of PTSD, interestingly, the activation of ACC, together with the vmPFC and hippocampus, is sexually dimorphic: men with PTSD exhibited increased activation in the left rostral dACC during extinction recall compared to women with PTSD (Shvil et al 2014;Yoon et al 2017).…”

Dorsal Anterior Cingulate Cortical Thickness Is Associated with Improvement in Worry Severity Following Treatment in Late-Life Generalized Anxiety Disorder

“…Cortical thickness measurements were obtained from Freesurfer segmentations. Six regions were selected based on a previous study [2]: left dorsal and rostral ACC, left and right medial orbitofrontal, right pars triangularis and right pars opercularis. We normalized the cortical thickness measurements from each region using the average cortical thickness of the brain.…”

“…Previously in a whole brain analysis we explored the differences between gray matter indices (cortical thickness and volume) in late-life GAD and non-anxious elderly participants. GAD participants had lower cortical thickness in the orbitofrontal cortex (OFC) and dorsal anterior cingulate cortex, and lower cortical volume in inferior frontal gyrus (ACC) [2]. Higher worry severity was associated with lower gray matter thickness in BA24 region (left dorsal and rostral ACC).…”