Ventral striatal subregional dysfunction in late-life grief: Relationships with yearning and depressive symptoms

Bereaved older adults experiencing high grief in the first year after an attachment loss is at increased risk for prolonged grief disorder (PGD) via unknown mechanisms. Yearning, a core grief symptom, is linked to the ventral striatal (VS) brain function, but the role of this neuronal system in late-life grief is poorly understood. As a first step, we examined the VS subregional abnormalities associated with multidimensional symptoms in bereaved elders during the first year post-loss. Sixty-five bereaved elders completed clinical assessments within 13 months post-loss. Ventral caudate (VCau) and nucleus accumbens (NAcc) functional connectivity (FC) was assessed using seed-based resting-state functional MRI. VCau and NAcc FC differences between high (inventory of complicated grief [ICG] score≥30; n = 35) and low (ICG score<30; n = 30) grief, and the relationships between ventral striatal subregional FC and clinical measures (yearning and depressive symptoms) were assessed after covariate adjustments (α < 0.05; 3dClustSim corrected). Relative to low grief participants, those with high grief showed higher FC between VCau and the medial prefrontal, orbitofrontal, and subgenual cingulate cortices. VCau FC abnormalities positively correlated with yearning (r² = 0.24, p < 0.001). In contrast, FC between VCau and temporoparietal junction negatively correlated with depressive symptoms, a commonly co-occurring symptom (r² = 0.37, p < 0.001). The FC between NAcc and insula/striatum positively correlated with yearning (r² = 0.35, p < 0.001); no other NAcc FC findings were seen in the full sample. In women, higher FC between the NAcc and bilateral posterior cingulate, precuneus, and visual areas were found in those with high, relative to low grief symptoms. Distinct VS subregional abnormalities associate with yearning and depressive symptoms in bereaved elders. Whether ventral striatal dysfunction correlates with PGD development and/or worsening depression remains to be elucidated.