Neuroimaging Studies

Neuroimaging Studies

Neuroimaging technology provides opportunities for elucidating the anatomic correlates of mood disorders (Thase and Howland, 1995; Kegeles and Mann, 1997; Soares and Mann, 1997a, 1997b; Dougherty and Rauch, 1997; Drevets et al., 1999, 2000, 2001). Neuroimaging studies of major depression have identified struc-tural and functional abnormalities in multiple areas of the orbital and medial prefrontal cortex, the amygdala, and related parts of the striatum and thalamus (Thase and Howland, 1995; Soares and Mann, 1997a, b; Dougherty and Rauch, 1997; Drevets et al., 1999; Dubovsky and Buzan, 1999, Drevets, 2000, 2001).

The most consistently indentified functional neuroimag-ing finding has been prefrontal lobe dysfunction, as indicated by reduced blood flow and glucose metabolism (Soares and Mann, 1997b; Drevets, 2000, 2001). There is evidence of abnormalities in basal ganglia, temporal lobe and related limbic structures. Unipolar depression is associated with dysfunction primarily in the prefrontal cortex and basal ganglia, while bipolar depression may be associated with dysfunction in the temporal lobe, in addi-tion to these other areas. Some of these functional abnormalities appear mood-state-dependent and are located in regions where cerebral blood flow increases during normal and some pathologic emotional states. These neurophysiologic differences between depressives and control subjects may thus implicate areas where physiologic activity changes to mediate or respond to the emo-tional, behavioral and cognitive manifestations of major depres-sive episodes. Other abnormalities persist following symptom remission, and are found in orbital and medial prefrontal cortex areas where postmortem studies demonstrate reductions in cor-tex volume and histopathologic changes in primary mood disor-ders (Mann and Arango, 1999). These areas appear to modulate emotional behavior and stress responses, based upon evidence from brain mapping, lesion analysis and electrophysiologic stud-ies of humans and experimental animals. Dysfunction involving these regions is thus hypothesized to play a role in the patho-genesis of depressive symptoms. Taken together, these findings implicate interconnected neural circuits in which pathologic pat-terns of neurotransmission may result in the emotional, motiva-tional, cognitive and behavioral manifestations of primary and secondary affective disorders.

The development of selective ligands for neuroreceptor imaging is providing rapidly expanding capabilities for noninva-sive quantitation of in vivo receptor binding and neurotransmitter function. PET and SPECT studies provided important informa-tion regarding the role of serotonergic receptors in the pathogen-esis of mood disorders. Such studies will permit more complete characterization of the neurotransmitter abnormalities suggested by studies of body fluids, postmortem tissue and neuroendo-crine function. This area is becoming one of the most important applications for PET and SPECT technologies.