For example, the amygdala facilitates stress-related corticotropin-releasing hormone

(CRH) release154 and electrical stimulation of the amygdala, in humans increases Cortisol secretion,155 suggesting a mechanism via which excessive amygdala activity may participate in inducing the CRH and Cortisol hypersecretion that, is evident in MDD. In Inhibitors,research,lifescience,medical PET studies of MDD and BD, CBF and metabolism in the left amygdala correlates positively with stressed plasma Cortisol secretion, which may reflect the effect of either amygdala activity on CRH secretion or Cortisol or CRH on amygdala, function.136 If the reduction in amygdala volume is associated with reductions in synaptic contacts formed by afferent projections from regions known to modulate amygdala function, then amygdala neuronal activity may become disinhibited. The above reports that amygdala blood flow and metabolism arc abnormally elevated and hemodynamic responses to emotional stimuli are abnormally persistent, in MDD Inhibitors,research,lifescience,medical support this hypothesis. Notably, Siegle et al44 reported that the abnormally prolonged hemodynamic responses of the amygdala to sad

words occurred particularly in the Inhibitors,research,lifescience,medical MDD subjects who had reduced amygdala volumes. If the neurotrophic effects of mood-stabilizing drugs restore and protect modulatory connections formed between the amygdala and cortex,1 then the volumetric changes observed during treatment may contribute to their therapeutic effects in mood disorders. Abnormalities in anatomically related limbic and subcortical structures In the medial thalamus and ventral striatum, CBF and metabolism are abnormally elevated in the depressed phase of MDD and BD, and decrease during antidepressant pharmacotherapy.8,95,134,136,154,156,157 Inhibitors,research,lifescience,medical Several groups also reported abnormally increased CBF in the posterior cingulate cortex in the unmedicated, depressed

phase of MDD.8,112,158 Bench et al158 specifically reported that the find protocol elevation Inhibitors,research,lifescience,medical of posterior cingulate flow in depressives relative to controls correlated positively with anxiety ratings. Exposure to aversive stimuli of various types results in increased physiological secondly activity in the posterior cingulate cortex.159 The posterior cingulate cortex sends major anatomical projections to the pregenual ACC.160 Neuroreceptor imaging abnormalities in mood disorders Neuroreceptor imaging studies of mood disorders have demonstrated reductions in 5-HT1a receptor binding in mood disorders, which would appear to hold major implications for alterations in neuroplasticity in these conditions. Both presynaptic (in the raphe) and postsynaptic (insula, anterior, and posterior cingulate cortices, parietooccipital cortex, orbital/ventrolateral PFC) 5-HT1a binding is abnormally decreased in MDD and panic disorder (irrespective of the current presence of comorbid depression), and postsynaptic 5-HT1a receptor binding is also decreased in RD.