The anatomy of melancholia: does frontal-subcortical pathophysiology underpin its psychomotor and cognitive manifestations?

The last few years have witnessed a major paradigm shift in the understanding of basal ganglia function. In line with this has been an increasing appreciation of both the centrality of psychomotor deficits in melancholia and the striking clinical parallels between melancholia and certain basal ganglia disorders such as Parkinson's disease. It is in view of these developments that a more considered appraisal of the role of the basal ganglia and their frontal connections in the pathogenesis of melancholia has become possible. ' Endogenous' or 'melancholic' depression has been regarded by many as a categorical entity with its own pathophysiological underpinnings (Carney et al. 1965), though classification of the depressive disorders remains contentious (Kendell, 1968). Among a number of statistical attempts to separate melancholic and non-melancholic depression, some factor analytical studies have demonstrated that psychomotor retardation may be one of the best discriminators of these two syndromes (Nelson & Charney, 1981). Within this context the last decade has seen a re-evaluation of the clinical features of melancholia, with increased interest in the objective or behavioural aspects both motor and cognitive of this disorder. In particular, motor disturbance is gaining increasing attention as a potential core behavioural manifestation of melancholia (Widlocher, 1983; Parker et al. 1990, 1994). Cognitive deficits are also a prominent feature, especially in elderly and/or severely depressed patients, where the impairment is sometimes of such magnitude that these patients have been described as suffering from a 'depressive pseudodementia' (Kiloh, 1961) or 'depressive dementia' (Stoudemire et al. 1989). Concurrent with this focus upon behavioural aspects of depression has been the development of the concept of'sub-cortical dementia'. This term was introduced by Albert et al. (1974) to describe the clinical presentation of disorders with predominant subcortical pathology such as progressive supranuclear palsy, Parkinson's disease, Huntington's Chorea and Wilson's disease which are characterized by slowed mentation and movement, apathy, depression and reduced ability to manipulate acquired knowledge. In view of the significant 'frontal' executive deficits also noted in these disorders, the term was subsequently revised by Albert (1978) to 'frontal-subcortical dementia'. Although the clinical validity of both 'sub-cortical dementia' and 'depressive dementia' has since been questioned (Mahendra, 1985), the use of these terms has led to another important conceptual shift: from defining functional psychiatric disorders, including depression, in purely phenomenological terms to viewing them in terms of regional cerebral dysfunction and disruption of neuronal networks. Traditionally, the basal ganglia were considered to be involved only in the modulation of movement. More recently, however, Alexander et al. (1986) have proposed the existence of a number of functional neural networks passing through the basal ganglia that may impact not only on motor function but also cognitive processes and mood. For example, motor disturbance could result from dysfunction of Alexander et a/. 's (1986) 'motor loop'. Mood and motivational disturbances seen in these disorders could be related to dysfunction in the 'limbic loop' linking medial prefrontal structures with the ventral striatum, and cognitive deficits to disturbances in the 'prefrontal loop' linking lateral prefrontal structures to the caudate nucleus.