Clinical application of brain imaging for the diagnosis of mood disorders: the current state of play

Abstract

In response to queries about whether brain imaging technology has reached the point where it is useful for making a clinical diagnosis and for helping to guide treatment selection, the American Psychiatric Association (APA) has recently written a position paper on the Clinical Application of Brain Imaging in Psychiatry. The following perspective piece is based on our contribution to this APA position paper, which specifically emphasized the application of neuroimaging in mood disorders. We present an introductory overview of the challenges faced by researchers in developing valid and reliable biomarkers for psychiatric disorders, followed by a synopsis of the extant neuroimaging findings in mood disorders, and an evidence-based review of the current research on brain imaging biomarkers in adult mood disorders. Although there are a number of promising results, by the standards proposed below, we argue that there are currently no brain imaging biomarkers that are clinically useful for establishing diagnosis or predicting treatment outcome in mood disorders.

Figures

Figure 1

(a) Statistical parametric mapping images consisting of voxel-wise values of the t-statistic in the bilateral amygdala indicate differences in the hemodynamic response to masked sad versus masked happy faces (SN-HN) between currently depressed people with major depressive disorder (dMDD) and healthy controls (HCs), shown on a coronal slice located 1 mm posterior to the anterior commissure. (b) Coordinates of peak voxel t-value signifying the difference in the amygdala response to SN-HN for dMDD participants versus HCs that correspond to the stereotaxic array of Talairach and Tournoux as the distance in millimeters from the origin (anterior commissure), with positive x-value indicating right, positive y-value indicating anterior and positive z-value indicating dorsal. Cluster size indicates contiguous voxels (P<0.05). Contrast β-weights are shown for specified contrasts in dMDD versus HCs for loci identified in the left (c, d) and right amygdala (e) (reproduced with permission from Victor et al.).

Figure 2

Coronal slices showing consummatory reward activity (monetary gains) in basal ganglia regions are displayed for both comparison subjects and participants with major depression. Relative to the comparison group, the major depression group showed significantly reduced activation in response to gain feedback in the left nucleus accumbens (a) and the caudate bilaterally (b). All contrasts are thresholded at P<0.005. Left hemisphere is displayed on the viewer's right (reproduced with permission from Pizzagalli et al.).

Figure 3

Coronal magnetic resonance imaging (MRI) sections showing the habenula and the local anatomical landmarks that enabled its segmentation. The upper and lower panels show the identical image. The tracing of the habenula is shown in yellow in the lower panel. The small size of the habenula (∼30 mm3) poses significant challenges for the accurate measurement of its volume and functional activity (adapted from Savitz et al., ).

Figure 4

Scatterplots of raw data of anterior cingulate cortex gamma-aminobutyric acid (GABA) relative to unsuppressed voxel tissue water concentrations (GABA/w) in healthy controls and adolescents with major depressive disorder (MDD) (a) and healthy controls, non-anhedonic adolescents with MDD, and anhedonic adolescents with MDD (b). Open circles represent subjects with melancholic MDD. Note the overlap in the statistical distributions between the mood disorder patients and the healthy controls which is common to all current imaging modalities, and poses challenges for the development of diagnostic tests for mood disorders (reproduced with permission from Gabbay et al.).

Figure 5

Increased default-mode network functional connectivity in subjects with major depression. Axial images of group default-mode functional connectivity in depressed subjects (a) and in healthy controls (b). The contrast map in (c) demonstrates clusters in the subgenual cingulate, thalamus and precuneus where resting-state functional connectivity was greater in depressed subjects versus controls. The t-score bars are shown at right. Note that while the color scale range begins at 1, the minimum t-values for the analyses were 3.42 for the depressed group map (a), 3.58 for the control group map (b) and 2.41 for the depressed versus control contrast map (c). Numbers at the bottom left of the images refer to the z-coordinates (and for the sagittal image the x-coordinates) in the standard space of the Montreal Neurological Institute (MNI) template. The left side of the image corresponds to the left side of the brain (reproduced with permission from Greicius et al.).

Figure 6

Fractional anisotropy (FA) maps showing (from left to right) coronal, axial and sagittal views. Colored voxels represent regions in which FA differs significantly in subjects with bipolar disorder (BD) versus control subjects. Red-yellow indicates greater FA in subjects with BD versus controls; light blue, decreased FA in subjects with BD versus controls (t>3.0 and P<0.05 corrected for both (scale ranging from red and/or blue to yellow and/or light blue)). (a) Three-dimensional views highlighting in red-yellow the central cluster in the left uncinate fasciculus in which FA was significantly increased in subjects with BD versus controls (t=3.0, P<0.05 corrected). (b) Three-dimensional views highlighting in red-yellow an orbitomedial prefrontal cortex cluster in the left uncinate fasciculus in which FA was significantly increased in subjects with BD versus controls (t=4.5, P<0.05 corrected). (c) Three-dimensional views highlighting in light blue a cluster in the right uncinate fasciculus in which FA was significantly reduced in subjects with BD versus controls (t=3.3, P<0.05 corrected). MNI, Montreal Neurological Institute (reproduced with permission from Versace et al.).