In fact, alterations in neuronal density and size have been found in the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortex, the neurons of which give rise to the frontal circuits critical for higher cognitive and limbic functioning.55 Subtle neuronal alterations are also reported in the hypothalamus and hippocampus, further evidence of dysfunction in limbic circuits in depression. Some of the cellular abnormalities detected postmortem in cortical and subcortical structures in MDD and BPD

may be related to disruption of monoaminergic transmission in depression. Inhibitors,research,lifescience,medical Studies in postmortem brain tissue identify alterations in serotonin and norepinephrine receptors and transporters Inhibitors,research,lifescience,medical in the dorsolateral prefrontal cortex and ventrolateral/orbitofrontal cortex in brains from suicide victims

with or without clinical depression.56 These cortical regions also exhibit, abnormal cell density and size in cell-counting studies of postmortem tissue. For example, cellular changes found in superficial layers of the prefrontal cortex in depressed subjects may be related to alterations in serotonin-1A receptors in superficial layers of cortex in suicide victims.57 In a neuroimaging study, the authors find that radioligand binding to scrotonin-1A receptors Inhibitors,research,lifescience,medical is decreased in medication-free subjects with MDD in several cortical regions, including medial temporal cortex,

the temporal pole, orbitofrontal Inhibitors,research,lifescience,medical cortex, anterior cingulate cortex, insula and dorsolateral prefrontal cortex.58 Expression of another component of serotonin neurotransmission, the serotonin transporter, is also decreased in the dorsolateral prefrontal and ventral/orbitofrontal cortex in postmortem brains from depressed suicide victims.59,60 Inhibitors,research,lifescience,medical Detailed laminar analysis of the density of serotonin transporter-immunoreactive axons reveals that this deficit in depression is localized in cortical layer VI of the dorsolateral prefrontal cortex.59 The serotonin-transporter deficit, may be related to the no pathology of layer VI neurons reported in the same cortical layer by postmortem cell-counting studies in depression. Moreover, subtle neuronal abnormalities reported by some studies in the monoaminergic brain stem nuclei Selleckchem Wnt inhibitor suggest dysfunction of monoaminergic projections originating from the brain stem neurons and terminating in frontolimbic cortical regions. It is likely that the functions and morphology of cortical neurons are affected by alterations in the functional state of noradrenergic, serotonergic, and dopaminergic neurons that project axons to prefrontal and anterior cingulate cortex.