Functional connectivity in apathy of late-life depression: A preliminary study

Background: Apathy is common in late-life depression and is associated with disability and poor antidepressant response. This study examined whether resting functional connectivity (FC) of the nucleus accumbens (NAcc) and the dorsal anterior cingulate (dACC) with other structures can distinguish apathetic depressed older patients from non-apathetic depressed patients and normal subjects. Methods: Twenty-six non-demented, non-MCI older adults were studied. Of these, 16 had major depression (7 also had apathy) and 10 had no psychopathology. Resting state fMRI was performed prior to treatment in subjects who were psychotropic-free for at least two weeks. FC was determined by placing seeds in the NAcc and the dACC bilaterally. Results: Apathetic depressed patients had lower FC of the NAcc with the amygdala, caudate, putamen, globus pallidus, and thalamus and increased FC with the dorsomedial prefrontal cortex, the superior frontal cortex, and the insula than non-apathetic patients. Further, apathetic patients had lower FC of the dACC with dorsolateral and ventrolateral prefrontal cortices and higher FC with the insula and the orbitofrontal cortex than non-apathetic patients. Limitations: Small number of subjects, lack of random sampling, use of a 1.5T MRI scanner. Conclusions: This preliminary study suggests that FC between the NAcc and the dACC and structures related to reward and related behavioral responses constitute the functional topography of abnormalities characterizing apathy of late life depression. However, replication is needed.