Introduction

Melancholic depression is by nature an episodic disorder, with imputed transient and/or fluctuating abnormalities in neurotransmission (Ferrier and Perry 1992). Given the hypothesis (Austin and Mitchell 1995; Krishnan 1993b; and Chapter 15) that dysfunction in frontal-subcortical neural pathways contributes to the pathogenesis of melancholia, the use of functional imaging, which allows us to capture the physiological changes present at the time of scanning, is ideal for the study of such a recurrent clinical condition. Neuroimaging strategies can be divided into those providing information on structure (e.g., CT and magnetic resonance imaging [MRI]) or on function (e.g., positron emission tomography [PET] and single photon emission computed tomography [SPECT]). The introduction of functional imaging techniques such as PET and SPECT to quantify changes in regional cerebral blood flow (rCBF) and metabolism thus holds the potential to elucidate the neuroanatomical substrate specific to melancholic (vs. non-melancholic) depression and may even eventually aid in the diagnostic process.

PET and SPECT Techniques. PET allows assessment of regional cerebral metabolism, and therefore regional cerebral function. In contrast to PET, SPECT measures rCBF, relying on the premise that under normal conditions, rCBF is tightly yoked to regional metabolism. Whereas SPECT measures the emission of single gamma rays or photons from the radiotracer, PET measures the simultaneous emission of two gamma rays (produced by the reaction of an electron and a positron) and thus enables “absolute” quantitation of gamma ray counts to take place.