Subcortical biophysical abnormalities in patients with mood disorders

Abstract

Cortical–subcortical circuits have been implicated in the pathophysiology of mood disorders. Structural and biochemical abnormalities have been identified in patients diagnosed with mood disorders using magnetic resonance imaging-related approaches. In this study, we used magnetization transfer (MT), an innovative magnetic resonance approach, to study biophysical changes in both gray and white matter regions in cortical–subcortical circuits implicated in emotional regulation and behavior. Our study samples comprised 28 patients clinically diagnosed with major depressive disorder (MDD) and 31 non-depressed subjects of comparable age and gender. MT ratio (MTR), representing the biophysical integrity of macromolecular proteins within key components of cortical–subcortical circuits—the caudate, thalamic, striatal, orbitofrontal, anterior cingulate and dorsolateral regions—was the primary outcome measure. In our study, the MTR in the head of the right caudate nucleus was significantly lower in the MDD group when compared with the comparison group. MTR values showed an inverse relationship with age in both groups, with more widespread relationships observed in the MDD group. These data indicate that focal biophysical abnormalities in the caudate nucleus may be central to the pathophysiology of depression and critical to the cortical–subcortical abnormalities that underlie mood disorders. Depression may also accentuate age-related changes in the biophysical properties of cortical and subcortical regions. These observations have broad implications for the neuronal circuitry underlying mood disorders across the lifespan.

Biophysical changes in subcortical nuclei: the impact of diabetes and major depression

“…11,28 Three of the five circuits-the anterior cingulate, lateral orbitofrontal and the dorsolateral prefrontal circuits-have an established role in the regulation of behavior and cognition and our findings underscore the importance of subcortical structures in the pathophysiology of MDD. 11,12,28 In our earlier reports, we emphasized biophysical impairments in the caudate in both patients with type 2 diabetes and MDD and in patients diagnosed with unipolar depression without diabetes when compared with appropriate comparison groups.…”

“…11,28 Three of the five circuits-the anterior cingulate, lateral orbitofrontal and the dorsolateral prefrontal circuits-have an established role in the regulation of behavior and cognition and our findings underscore the importance of subcortical structures in the pathophysiology of MDD. 11,12,28 In our earlier reports, we emphasized biophysical impairments in the caudate in both patients with type 2 diabetes and MDD and in patients diagnosed with unipolar depression without diabetes when compared with appropriate comparison groups. 11,12 In those studies, whereas MTR differences between MDD and control groups in the caudate were striking and statistically significant, lower MTR was also detected in other subcortical regions, though the patient-control differences did not reach statistical significance.…”

“…HC subjects were free of diabetes and had hemoglobin A1c levels within normal limits. All clinical methods, including inclusion and exclusion criteria, have been previously reported 11,23 and are available online (see Supplementary eMethods).…”

“…23 Further, in a study of patients with unipolar MDD without diabetes and comparison subjects without depression, we identified significantly lower MTR in the right caudate nucleus in the MDD group. 11 A limitation of our earlier MT study was the lack of a control group with MDD without diabetes. 12 This limitation precluded us from commenting on the biological underpinnings of depression associated with diabetes when compared with patients diagnosed with unipolar depression without diabetes.…”

“…[10][11][12][13] Multiple neuroimaging modalities including structural, functional and microstructural approaches have been used to characterize the integrity of specific circuits in psychiatric disorders. [11][12][13] The neural substrates underlying mood disorders are widely distributed in the brain 14 and connectomicsbased approaches, using diffusion tensor imaging, have identified the default mode network and the cortical-subcortical network as being particularly impaired in a sample of patients with unipolar depression when compared with controls. [15][16][17][18] Magnetization transfer (MT) is a noninvasive magnetic resonance-related approach that permits us to examine the biophysical status of macromolecular proteins in cortical and subcortical regions.…”