Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response

Background: Apathy is a prominent feature of geriatric depression that predicts poor clinical outcomes and hinders depression treatment. Yet little is known about the neurobiology and treatment of apathy in late-life depression. This study examined apathy prevalence in a clinical sample of depressed elderly, response of apathy to selective serotonin reuptake inhibitor (SSRI) treatment, and neuroanatomical correlates that distinguished responders from non responders and healthy controls. Methods: Participants included 45 non demented, elderly with major depression and 43 elderly comparison individuals. After a 2-week single-blind placebo period, depressed participants received escitalopram 10 mg daily for 12 weeks. The Apathy Evaluation Scale (AES) and 24-item Hamilton Depression Raring Scale (HDRS) were administered at baseline and 12 weeks. MR1 scans were acquired at baseline for concurrent structural and diffusion tensor imaging of anterior cingulate gray matter and associated while matter tracts. Results: 35.5% of depressed patients suffered from apathy. This declined to 15.6% (p < 0.1) following treatment, but 43% of initial sufferers continued W report significant apathy. Improvement of apathy with SSRI was independent of change in depression but correlated with larger left posterior subgenual cingulate volumes and greater fractional anisotropy of left uncinate fasciculi. Limitations: Modest sample size, no placebo control, post-hoc secondary analysis, use of 1.5T MRI scanner Conclusions: While prevalent in geriatric depression, apathy is separable from depression with regards to medication response. Structural abnormalities of the posterior subgenual cingulate and uncinate fasciculus may perpetuate apathetic states by interfering with prefrontal cortical recruitment of limbic activity essential to motivated behavior. (C) 2014 Elsevier B.V. All rights reserved