Stratification of MDD and GAD patients by resting state brain connectivity predicts cognitive bias

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.

Locus coeruleus connectivity alterations in late-life major depressive disorder during a visual oddball task

“…Moreover, it is also important to highlight that disrupted connectivity between the LC and the ACC was associated with MDD severity (GDS scores and number of recurrences), indicating that benefit-cost attentional processes may be increasingly impaired with both current symptom severity and disease burden. Structural ACC abnormalities have indeed been previously related to disease severity in MDD ( Bijsterbosch et al, 2018 , Satterthwaite et al, 2016 ). Notably, the correlation with GDS scores was indeed the result of a qualitative difference between asymptomatic patients and those in an active depressive episode, which suggests that LC-ACC connectivity may be a state marker in late-life MDD.…”

Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

“…The hippocampus is known to be affected in depression and is connected to emotion-related brain regions such as the PFC and amygdala [9]. Interestingly, greater connectivity between fronto-limbic regions has been associated with greater depressive severity [82]. It is widely accepted that patients with MDD have smaller hippocampal volumes and decreased hippocampal activity [83,84].…”

A Generalizable Multivariate Brain Pattern for Interpersonal Guilt

“…Characterizing how specific emotions are generated and represented in the brain is a central question in affective neuroscience and important for understanding emotions and their regulation in healthy and clinical individuals (Hamann 2012;Bijsterbosch et al 2018).…”