Deep phenotyping of attention impairments and the ‘Inattention Biotype’ in Major Depressive Disorder

Abstract

BackgroundAttention impairment is an under-investigated feature and diagnostic criterion of Major Depressive Disorder (MDD) that is associated with poorer outcomes. Despite increasing knowledge regarding mechanisms of attention in healthy adults, we lack a detailed characterization of attention impairments and their neural signatures in MDD.MethodsHere, we focus on selective attention and advance a deep multi-modal characterization of these impairments in MDD, using data acquired from n = 1008 patients and n = 336 age- and sex-matched healthy controls. Selective attention impairments were operationalized and anchored in a behavioral performance measure, assessed within a battery of cognitive tests. We sought to establish the accompanying neural signature using independent measures of functional magnetic resonance imaging (15% of the sample) and electroencephalographic recordings of oscillatory neural activity.ResultsGreater impairment on the behavioral measure of selective attention was associated with intrinsic hypo-connectivity of the fronto-parietal attention network. Not only was this relationship specific to the fronto-parietal network unlike other large-scale networks; this hypo-connectivity was also specific to selective attention performance unlike other measures of cognition. Selective attention impairment was also associated with lower posterior alpha (8–13 Hz) power at rest and was related to more severe negative bias (frequent misidentifications of neutral faces as sad and lingering attention on sad faces), relevant to clinical features of negative attributions and brooding. Selective attention impairments were independent of overall depression severity and of worrying or sleep problems.ConclusionsThese results provide a foundation for the clinical translational development of objective markers and targeted therapeutics for attention impairment in MDD.

Characterizing transdiagnostic premorbid biotypes can help progress in selective prevention in psychiatry

“…Neurobiological entities seem to cut a­cross psychiatric diagnostic categories. Con­sistent with this view, biotypes of depression 7 and autism 8 have been identified in studies examining the heterogeneity of these syndromes. Interestingly, similar to psychotic disorders, cognitive impairments may serve as valuable stratification markers in these populations as well.…”

Stress Markers for Mental States and Biotypes of Depression and Anxiety: A Scoping Review and Preliminary Illustrative Analysis

“…The frontoparietal attention circuit is defined by core regions in the superior frontal cortex and anterior inferior parietal lobe and connecting with frontal eye fields. Relative hypo-connectivity within this circuit is thought to reflect the inattention common across mood and anxiety disorders 11 , 83 . The executive or cognitive control circuit involves the dorsal components of the lateral prefrontal (DLPFC), anterior cingulate (dACC), and parietal cortices engaged by tasks that require higher cognitive functions such as working memory and selective control of cognition (for meta-analysis 84 ).…”

Cognitive dysfunction in mice lacking proper glucocorticoid receptor dimerization

“…While mutations within the ligand binding domain of GR gene can lead to a complex endocrinological phenotype, typified as 'GC resistance syndrome' [19], polymorphic variations might account for more subtle changes in GR function and indeed have been associated with MDD [20]. Cognitive aspects of depression mostly aggregate around two main foci: cognitive biases ('negative thinking') and cognitive deficits, such as impaired attention and concentration, short-term memory, autobiographical memory specificity and executive function [21][22][23]. The hippocampus has been attributed a major role in the cognitive impairment observed in MDD, due to its general central role in learning and memory [24][25][26], and the structural changes observed in the hippocampus proper in patients with MDD.…”