Biological markers of depression.

The recent advances in molecular genetics (Gershon et al. 1987) have given a new impetus to the search for biological markers of depression. It is now feasible to use molecular techniques to study the functional expression of specific genes associated with clearly defined marker abnormalities in patients with depression. Such studies could yield valuable information regarding the classification and aetiology of depressive disorder and would be a valuable approach to complement linkage study. While linkage study alone has the potential to demonstrate an association between a small area of the genome and a clinical diagnosis, it offers no information about disease mechanisms at the molecular level. Our present ability to conduct innovative functional molecular investigations is limited principally by the difficulty of demonstrating reliable biological abnormalities in groups of depressed patients. More recent studies of biological markers in depression have used notably improved methodology incorporating large groups of carefully diagnosed, drug-free patients. This has resulted in the more convincing validation of some putative markers, and the undoing of others. A number of other important issues have emerged. First, is an identified biological abnormality a state marker, present only when the patient is depressed or (possibly more relevant for genetic studies) does it persist into clinical recovery and thus represent a trait abnormality, an indicator, perhaps, of vulnerability to the disorder? Secondly, what is the specificity of the proposed marker to depressive disorders? Does it occur in other conditions such as obsessional neurosis or panic disorder? Thirdly, can the biological abnormality be accounted for in terms of the epiphenomena of the depressed state such as weight loss or sleep disturbance? Some recent biological marker studies are considered below with these points in mind.