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

George S. Alexopoulos, Matthew J. Hoptman, Genevieve Yuen, Dora Kanellopoulos, Joanna K. Seirup, Kelvin O. Lim, Faith M. Gunning

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)398-405
Number of pages8
JournalJournal of Affective Disorders
Issue number1-3
StatePublished - Jul 2013

Bibliographical note

Funding Information:
Personnel and imaging cost of this work was supported by NIMH grants R01 MH65653, R01 MH079414, P030 MH085943, T32 MH019132 (GSA), K23 MH74818 (FGD) and the Sanchez Foundation. Escitalopram and placebo were provided free of cost by Forest Pharmaceuticals, Inc.

Funding Information:
Dr. Alexopoulos has received grant support from Forest Pharmaceuticals; has consulted to Hoffman-LaRoche, Lilly, Pfizer, and Otsuka; and has served at the speakers’ bureaus of Astra Zeneca, Avanir, Forest, Merck, Novartis, and Sunovion. No other authors report conflicts of interest.


  • Apathy
  • Functional connectivity
  • Late life depression


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