130 These data suggest that the right subgenual PFC facilitates expression of visceral responses during emotional processing, while the left subgenual PFC inhibits or modulates such responses.130 It is thus noteworthy that

the gray matter reduction in this region in MDD and BD was lateralized to the left side, suggesting that it may contribute to disinhibition of neuroendocrine and autonomic function in depression.127,131,132 The ventral ACC also appears to participate in processing of behavioral incentive and motivated behavior. These areas send efferent projections to the VTA and substantia nigra, and receive dense dopaminergic innervation Inhibitors,research,lifescience,medical from VTA.124 In rats, electrical or glutamatergic stimulation of medial PFC areas that include prelimbic cortex elicits burst firing patterns from dopamine (DA) cells in the VTA and increases DA release in the accumbens.113 These phasic, burst firing patterns of DA neurons appear to encode information

regarding stimuli that Inhibitors,research,lifescience,medical predict, reward and deviations between such predictions and actual occurrence of reward.133 Ventral ACC dysfunction may thus conceivably contribute to disturbances of motivated behavior and hedonic perception in mood disorders. Inhibitors,research,lifescience,medical Dorsomedial/dorsal anterolateral PFC Metabolism and CBF arc abnormally GSK1349572 decreased in the dorsolateral and dorsomedial Inhibitors,research,lifescience,medical PFC in MDD.1 The dorsomedial PFC region includes the dorsal ACC92 and an area rostral to the dorsal ACC involving cortex on the medial and lateral surface of the superior frontal gyrus (approximately corresponding to BA9 and BA32).8,19,91 Postmortem studies

of MDD and BD found abnormal reductions in the size of neurons and/or the density of glia in this portion of BA9,18,20,134 which may account Inhibitors,research,lifescience,medical for the reduction in metabolism in this region in MDD, and for the failure of antidepressant drug treatment, to correct metabolism in these areas.8,19 Nevertheless, currently remitted MDD subjects who experience depressive relapse during tryptophan depletion show increased metabolic activity within these areas in the depressed versus the remitted conditions,93 similar to other structures where histopathological and gray matter volume changes exist, in MDD. Flow normally increases in the vicinity of this GPX6 dorsomedial/dorsal anterolateral PFC in healthy humans as they perform tasks that elicit emotional responses or require emotional evaluations.1 In healthy humans, CBF increases in this region during anxious anticipation of an electrical shock to an extent that correlates inversely with changes in anxiety ratings and heart rate, suggesting that this region functions to attenuate emotional expression.