Abstract
Patients with Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) show between-group comorbidity and symptom overlap, and within-group heterogeneity. Resting state functional connectivity might provide an alternate, biologically informed means by which to stratify patients with GAD or MDD. Resting state functional magnetic resonance imaging data were acquired from 23 adults with GAD, 21 adults with MDD, and 27 healthy adult control participants. We investigated whether within- or between-network connectivity indices from five resting state networks predicted scores on continuous measures of depression and anxiety. Successful predictors were used to stratify participants into two new groups. We examined whether this stratification predicted attentional bias towards threat and whether this varied between patients and controls. Depression scores were linked to elevated connectivity within a limbic network including the amygdala, hippocampus, VMPFC and subgenual ACC. Patients with GAD or MDD with high limbic connectivity showed poorer performance on an attention-to-threat task than patients with low limbic connectivity. No parallel effect was observed for control participants, resulting in an interaction of clinical status by resting state group. Our findings provide initial evidence for the external validity of stratification of MDD and GAD patients by functional connectivity markers. This stratification cuts across diagnostic boundaries and might valuably inform future intervention studies. Our findings also highlight that biomarkers of interest can have different cognitive correlates in individuals with versus without clinically significant symptomatology. This might reflect protective influences leading to resilience in some individuals but not others.
Highlights
A quarter of the adult US population meet criteria for an anxiety or depressive disorder within a 12-month period, creating a substantial health burden for society (Kessler et al, 2005)
The group level functional connectivity matrix constructed from participants' ROI time-series data is shown in Fig. 2, together with the five networks identified by hierarchical clustering performed on the matrix
These five networks were as follows: a limbic network comprising amygdala, hippocampus, subgenual ACC and VMPFC; a posterior cortical - midline network comprising IPC, posterior midcingulate cortex (pMCC), posterior cingulate cortex (PCC) and precuneus; a frontal-striatal network comprising regions implicated in cognitive and emotional control including DLPFC, OFC, caudate, putamen, and thalamus; an insula-cingulate network comprising regions implicated in processing stimulus saliency (Seeley et al, 2007), including posterior insula, anterior insula, anterior midcingulate cortex (aMCC), posterior paracingulate cortex, and SMA; and a cingulate-paracingulate network comprising anterior and middle paracingulate cortex and pregenual ACC
Summary
A quarter of the adult US population meet criteria for an anxiety or depressive disorder within a 12-month period, creating a substantial health burden for society (Kessler et al, 2005). Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) show extensive comorbidity and symptom overlap (Brown et al, 2001; Kessler et al, 2008). Findings indicate significant shared genetic influences (Kendler et al, 2007), and overlapping neural substrates (Diener et al, 2012; Etkin and Schatzberg, 2011; Mochcovitch et al, 2014; van Tol et al, 2010). These findings have led to the suggestion that both disorders may share common etiological processes. It has been argued that biomarker driven definition of patient groups might enable patient stratification to be more closely aligned to the mechanisms that are disrupted, potentially improving both outcome prediction and treatment choice (Cuthbert and Insel, 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
