Ocular motor differences between melancholic and non-melancholic depression

Abstract

Background

Major depressive disorder may be a heterogeneous disorder, yet melancholic depression is the most consistently described subtype, regarded as qualitatively different to non-melancholic depression in terms of cognitive and motor impairments. Eye movement studies in depression are infrequent and findings are inconclusive.

Methods

This study employed a battery of saccadic eye movement tasks to explore reflexive saccades, as well as higher order cognitive aspects of saccades including inhibitory control and spatial working memory. Nineteen patients with major depressive disorder (9 melancholic; 10 non-melancholic) and 15 healthy controls participated.

Results

Differences were revealed between melancholic and non-melancholic patients. Melancholia was associated with longer latencies, difficulty increasing peak velocities as target amplitudes increased, and hypometric primary saccades during the predictable protocol. In contrast, the non-melancholic depression group performed similarly to controls on most tasks, but saccadic peak velocity was increased for reflexive saccades at larger amplitudes.

Limitations

Most patients were taking antidepressant medication.

Conclusions

The latency increases, reduced peak velocity and primary saccade hypometria with more severe melancholia may be explained by functional changes in the fronto–striatal–collicular networks, related to dopamine dysfunction. In contrast, the serotonergic system plays a greater role in non-melancholic symptoms and this may underpin the observed increases in saccadic peak velocity. These findings provide neurophysiological support for functional differences between depression subgroups that are consistent with previous motor and cognitive findings.

Introduction

Major depressive disorder (MDD) has been conceptualized as a heterogeneous disorder. Melancholic depression is the most consistently described subtype (Joyce et al., 2002, Leventhal and Rehm, 2005, Parker and Hadzi-Pavlovic, 1996b, Türkçapar et al., 1999), and is considered qualitatively different to non-melancholic depression in terms of cognitive and motor impairments (Austin et al., 1999, Pier et al., 2004, Rogers et al., 2002, Rogers et al., 2004, Rogers et al., 2000a), as well as underlying neuropathology (Austin and Mitchell, 1995, Austin and Mitchell, 1996).

Psychomotor disturbances have been proposed as one of the strongest indicators of the melancholic subtype (Parker et al., 1989, Pier et al., 2004, Rush and Weissenburger, 1994, Sobin and Sackeim, 1997). However, current definitions of psychomotor disturbances remain nebulous and the term encompasses both motor slowing and motor agitation that occurs during a depressed state (Sobin and Sackeim, 1997). Studies exploring motor disturbances in melancholic depression are relatively limited. Findings suggest that unlike non-melancholic patients, melancholic patients exhibit motor slowing (Pier et al., 2004, Rogers et al., 2000a, Rogers et al., 2000b) and particular difficulties initiating movements in the absence of external cues (Rogers et al., 2000b).

Eye movement tasks offer a useful and sensitive behavioural tool to investigate psychomotor functioning, through exploration of basic sensorimotor functions as well as higher levels of motor control including spatial working memory, prediction, and response suppression. The neural systems controlling saccades (rapid eye movements) have been extensively investigated, permitting insights into patterns of abnormality that can provide important clues about location of neuropathology.

A number of studies have explored eye movements in groups of patients with major depression. These studies have reported the presence of intact reflexive saccades (Done and Frith, 1989, Mahlberg et al., 2001, Sweeney et al., 1998); normal latencies and velocities for voluntary saccades (Sweeney et al., 1998), but increased durations (Sweeney et al., 1998); normal, or slightly increased rates of response suppression errors (Fukushima et al., 1990, Katsanis et al., 1997, Sweeney et al., 1998); and reduced accuracy for memory-guided saccades (Sweeney et al., 1998). However, no studies to date have explored differences in eye movements between melancholic and non-melancholic patients. In addition, no studies have reported the performance of depressed patients in regards to the ability to develop anticipatory behaviour and the ability to generate express saccades. These tasks allow further exploration of prominent neural pathways involved in eye movement control (encompassing the dorsolateral prefrontal cortex, frontal eye fields and superior colliculus).

The aim of this study was to comprehensively explore the control and execution of saccades in melancholic and non-melancholic patients with MDD. Reflexive saccade performance was compared to volitional, memory-guided saccade performance. Inhibitory control was explored using four tasks that increased in demand, but had the constant requirement of suppressing inappropriate reflexive saccades. The ability to generate express and anticipatory saccades was also investigated. Spatial working memory was investigated in two tasks: a standard memory-guided task and a more challenging two-step memory guided task, which involved an intervening visually guided saccade during the delay period. We hypothesized that motor disturbance would be more pronounced in melancholic than in non-melancholic patients with MDD.