Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: a voxel-based morphometric analysis

Abstract

Background Studies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research. Method To examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants. Results The severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression. Conclusions Reduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations.

Cortical abnormalities and association with symptom dimensions across the depressive spectrum

“…Therefore, CV reduction in the MDD group, particularly in frontal, medial temporal, and limbic areas, may reflect stress-related neurotoxic effects (Treadway et al 2015) that precede manifestation of illness. This is supported by a recent study that demonstrated an association between ACC and orbitofrontal cortical volumetric reduction and subclinical depressive symptoms in a cohort of non-depressed subjects (Webb et al 2014). Our study extends upon this finding as CV reduction in the VLPFC associated with depressive symptoms along a spectrum from healthy subjects to patients diagnosed with depression.…”

“…Consistent with several structural and functional studies in MDD showing fronto-limbic abnormalities (Etkin, Egner, and Kalisch 2011; Pizzagalli 2011; Heller et al 2013), our study showed that reductions of cortical thickness in the rACC (a limbic area), was associated with symptoms related to emotion dysregulation. This adds to previous work showing that reductions in ACC gray matter is an important neural substrate for affective instability and a potential endophenotype for depression (Boes et al 2008; van Eijndhoven et al 2013; Webb et al 2014). …”

Rostral Anterior Cingulate Cortex Morphology Predicts Treatment Response to Internet-Based Cognitive Behavioral Therapy for Depression

“…Smaller rACC volumes have been repeatedly linked with elevated depressive symptoms in cross-sectional studies (57, 58). Indeed, within our data, smaller rACC volumes were correlated with higher depression severity at baseline (for HRSD, right rACC r = −.…”

Vertex-wise examination of depressive symptom dimensions and brain volumes in older adults

“…The primary finding was a relationship between higher severity of depressed mood symptoms and increased left inferior temporal volume. Temporal regions, including the inferior temporal gyrus, have consistently been implicated in structural imaging studies of both major depression and subthreshold depression (Andreescu et al, 2007; Dotson et al, 2009b; Son et al, 2013; Webb et al, 2014). In contrast to reports of reduced temporal volumes related to depression in many studies, there has been a report of increased grey matter volumes in parts of the left temporal lobe associated with depression (Ballmaier et al, 2004).…”