Subgenual prefrontal cortex abnormalities in mood disorders

Abstract

Pathological disturbances of mood may follow a 'bipolar' course, in which normal moods alternate with both depression and mania, or a 'unipolar' course, in which only depression occurs. Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical, neuroendocrine and autonomic abnormalities. The neurobiological basis for these abnormalities has not been established. Using positron emission tomographic (PET) images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the prefrontal cortex ventral to the genu of the corpus callosum in both familial bipolar depressives and familial unipolar depressives. This decrement in activity was at least partly explained by a corresponding reduction in cortical volume, as magnetic resonance imaging (MRI) demonstrated reductions in the mean grey matter volume in the same area of 39 and 48% in the bipolar and unipolar samples, respectively. This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs.

Gray Matter Changes in Late Life Depression—a Structural MRI Analysis

“…In this case, lower volumes would be interpreted as a marker of neuronal loss related to an as yet undeclared neurodegenerative or vascular process (Alexopoulos et al, 1993; Greenwald et al, 1997). Most findings supporting this theory have been described in left medial temporal lobe (Greenwald et al, 1997), left caudate (Greenwald et al, 1997; Krishnan et al, 1992), anterior cingulate (Drevets et al, 1997), and putamen (Husain et al, 1991).…”

Subgenual Cingulate Theta Activity Predicts Treatment Response of Repetitive Transcranial Magnetic Stimulation in Participants With Vascular Depression

“…9, 30–32 The subgenual ACC is considered a more archaic region than the rostral ACC; has extensive connections with other parts of the brain such as the amygdala, raphe nuclei, and brain stem autonomic nuclei; and is involved in emotional processing, monoaminergic neurotransmitter release, and autonomic regulation. 33 While abnormal function has been found in both the rostral and the subgenual ACC in major depression, only the subgenual ACC has been associated with a reduction in volume, 31,34 and this may represent the core abnormality of treatment resistant depression. 35 Although elevated activity in the rostral ACC has been shown to predict response to pharmacological treatment, 9,10 response to antidepressant treatment has been shown to be primarily mediated by the subgenual ACC.…”

The phenotypes of bipolar disorder: relevance for genetic investigations

“…Two groups found significant reductions in grey matter volume in the subgenual prefrontal cortex in family history-positive subjects, suggesting that studying more homogenous patient groups may result in more consistent findings as further studies emerge. 203,204 Some of the changes may constitute primary biological traits associated with the risk of developing mood disorder, while others may represent sequelae of the illness and its burden 205 or treatment effects. 195 Primary changes that could be used as endophenotypes should be detectable in a proportion of unaffected relatives, but such studies are less common.…”