Smaller orbital frontal cortex volumes associated with functional disability in depressed elders

Abstract

Background

Depression is associated with significant functional impairment. Recent evidence has linked the orbital frontal cortex (OFC) with depression. We examined the relationship between OFC volumes in older subjects and impairment in the basic (BADL) and instrumental (IADL) activities of daily living.

Methods

The sample consisted of 81 subjects aged 60 years or older; 41 were depressed subjects and 40 healthy control subjects. In a structured interview, subjects reported their medical history and ability to perform both BADL and IADL. Subjects then had a brain magnetic resonance imaging (MRI) scan; the OFC was manually traced bilaterally using neuroanatomical landmarks. Logistic regression was used to examine the effect of OFC volume on BADL and IADL while controlling for the effects of total brain volume, subject status, medical comorbidity, and demographic factors.

Results

Smaller OFC volumes, along with greater cognitive impairment as measured by the Mini-Mental State Examination, were significantly associated with BADL impairment. Smaller OFC volumes and being depressed were significantly associated with IADL impairment.

Conclusions

Smaller OFC volumes are independently associated with functional impairment, supporting its role in depression. Further studies are needed to determine how smaller OFC volumes are related to other MRI abnormalities associated with depression and functional impairment.

Introduction

It is well established that depression in the elderly is associated with significant functional impairment Armenian et al 1998, Bruce et al 1994, Lenze et al 2001, Sato et al 1999. Disability is typically categorized as either impairment in basic activities of daily living (BADL), such as using the toilet, bathing, or dressing, or impairment in instrumental activities of daily living (IADL), such as shopping, preparing meals, or managing finances. Clinical studies in older subjects usually find depression-associated impairment in both of these domains Alexopoulos et al 1996, Bruce et al 1994, Femia et al 2001, Steffens et al 1999, which may improve with antidepressant therapy Chemerinski et al 2001, Oslin et al 2000.

How are depression and functional disability related? This is a complex relationship that becomes more complicated when one considers that cognitive dysfunction may be seen in late-life depression. One common deficit is an impaired response to negative feedback Elliott et al 1996, Elliott et al 1997, Elliott et al 1998, Steffens et al 2001, a finding described as a “catastrophic response to perceived failure” (Beats et al 1996). This finding has been considered to be an important link between cognitive and emotional processes (Elliott et al 1997). Output pathways from the medial orbital frontal cortex (OFC) to the striatum are thought to be critically involved in stimulus reinforcement Bechara et al 1999, Bechara et al 2000. Impairment of this circuit may contribute to impaired response to negative feedback Elliott et al 1996, Elliott et al 1997, Elliott et al 1998. If this pathway is associated with depression and disability, difficulties with ADLs could lead to frustration, decreased effort, and increased disability.

Recent evidence has further implicated the medial OFC in late-life depression (Ebert and Ebmeier 1996). Smaller OFC volumes Bremner et al 2002, Lai et al 2000, decreased OFC neuronal density (Rajkowska et al 1999), and greater OFC lesion severity (MacFall et al 2001) are associated with depression. If impairment of OFC circuits is truly involved in impaired responses to negative feedback and depression, it should also be associated with greater functional impairment. We hypothesized that smaller OFC volumes would be associated with greater BADL and IADL impairment.