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

Abstract

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 nonresponders 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 10mg daily for 12 weeks. The Apathy Evaluation Scale (AES) and 24-item Hamilton Depression Rating Scale (HDRS) were administered at baseline and 12 weeks. MRI scans were acquired at baseline for concurrent structural and diffusion tensor imaging of anterior cingulate grey matter and associated white 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 to 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.

The course of apathy in late‐life depression treated with electroconvulsive therapy; a prospective cohort study

“…Our findings are in line with Yuen et al, who demonstrated a clinically significant decrease in apathy symptoms following treatment with escitalopram. In their sample of older persons with depression, 43.8% had post‐treatment apathy according to the Apathy Evaluation Scale.…”

“…To our knowledge, 2 randomized clinical trials and 1 prospective cohort study have investigated the course of apathy in older patients with depression. The first 2 studies investigated the course of apathy during treatment with selective serotonin reuptake inhibitors, both demonstrating an improvement in depression severity and a partial response of apathy symptoms, independent from each other . The longitudinal, naturalistic study of Groeneweg‐Koolhoven et al demonstrated 80% persistence of apathy and 41% persistence of depression in a group of 199 older persons with depression during 2‐year follow‐up.…”

Apathy in Late-Life Depression: Common, Persistent, and Disabling

“…In a previous analysis, we found that escitalopram only modestly improved apathy in a small sample of older depressed individuals (11). Defining the clinical significance of apathy and of its improvement after treatment with escitalopram may contribute further to the identification of apathy as a clinically meaningful dimension of the late-life depressive disorder.…”

A specific role for serotonin in overcoming effort cost

“…However, other studies also reported that SSRI treatments increase motivation or at least the sensitivity to reward (Tang et al, 2009; Stoy et al, 2012; Yuen et al, 2014). The related animal literature is also contradictory: some studies on cost/benefit trade-off showed reduced effort expenditure with SSRIs (Yohn et al, 2016) or no effect with serotonin blockers (Denk et al, 2005), while other studies reported increased motor activity induced by SSRI (Weber et al, 2009) or optogenetic stimulation of the dorsal raphe nucleus (Warden et al, 2012).…”

“…One issue with clinical studies is that SSRI effects may be confounded by an interaction with the pathological state: an SSRI treatment was reported to decrease apathy in late-life depression (Yuen et al, 2014) and to increase it in Parkinson’s disease (Zahodne et al, 2012). Another issue is that apathy may not be a simple construct.…”