Reduction of neuronal activity in frontocortical and limbic circuits is considered a characteristic of depression. We aimed to test this hypothesis by pooling all available data from experimental literature. All investigations were included comparing regional cerebral blood flow (rCBF) or glucose metabolism (rCMRGlc) between acutely depressed unipolar major depressive patients and healthy controls. For cortical and subcortical regions we computed the percentage difference between depressives (n = 337) and controls (n = 321). In patients with unipolar major depression rCBF and rCMRGlc were lowered in left (-4.4%, P = 0.022) and right frontal (-3.2%, P = 0.053), left (-1.7%, P = 0.061) and right temporal (-3.0%, P=0.003), left (-6.5%, P = 0.002), and right parietal (-8.8%, P=0.001), and left (-6.6%, P = 0.083) and right occipital cortex (-4.2%, P = 0.02). Moreover, there were reductions in left (-6.3%, P = 0.029) and right basal ganglia (-4.8%, P = 0.002), left (-3.4%, P = 0.114) and right thalamus (-3.1%, P = 0.036), and left limbic system (-2.2%, P = 0.127). Parameters were increased by 1.0% (P = 0.714) only in the right limbic system. There were no hemispheric asymmetries (P > 0.05). Moreover, there was no indication for an anterior-posterior gradient (P > 0.05), and thus no 'hypofrontality'. In contrast to the current view, the data indicate a diffuse cortical rather than regionalized reduction of neuronal activity in unipolar major depression.
Anxiety disorder (AD), major depressive disorder (MDD) and schizophrenia (SZ) share the characteristic of imbalanced γ-amino butyric acid (GABA), dopamine (DA) and serotonin (5-HT) function. The individual disorders, however, greatly differ as to the affected brain regions, the affected synaptic constituents and the direction of dysfunction in terms of either sensitization or desensitization of receptor and transporter binding sites [1][2][3]. While, in AD, GABA A receptor (R) desensitization involves the whole nigrostriatal and mesolimbocortical system, in SZ, GABA A R dysfunction is confined to frontal and temporal cortex and, in MDD, even appears to be normal. In contrast, in AD, inhibitory D 2 Rs are merely desensitized in the dorsal striatum, while, in SZ, they are additionally dysfunctional in thalamus, temporal cortex and midbrain. In MDD, no D 2 R desensitization is evident -rather, D 2 Rs are sensitized in the cingulate. Excitatory D 1 R binding sites in both AD and MDD are desensitized in the dorsal striatum, whereas in, in SZ, their sensitization, besides the ventral striatum, involves the entire neocortex. Dopamine transporter (DAT) function is most widely inpaired in MDD with reductions in substantia nigra, cingulate, amygdala and prefrontal cortex, whereas, in SZ, DAT desensitization is confined to the dorsal striatum and, in AD, no DAT dysfunction is evident at all. The most extensive impairment of inhibitory 5-HT 1 R binding is observed in AD with 5-HT 1 R desensitization in the midbrain and throughout limbic system as well as neocortex, whereas, in SZ, 5-HT 1 R desensitization is confined to midbrain, amygdala and occipitotemporal regions. In MDD, 5-HT 1 R are also desensitized in the midbrain, but sensitized in the limbic parahippocampal gyrus. The most widely spread dysfunction of excitatory 5-HT 2 Rs is observed in MDD, with a sensitization of 5-HT 2 Rs in the thalamus and a desensitization throughout both limbic system and neocortex. In contrast, in AD, 5-HT 2 Rs are sensitized in the temporal cortex and desensitized in the ventral striatum, while, in SZ, 5-HT 2 R desensitization involves the entire neocortex. In AD, the serotonin transporter (SERT) is desensitized in thalamus, hippocampus and amygdala, while, in MDD, SERT desensitization is even more extensive, involving -apart from thalamus and amygdala -also midbrain, dorsal striatum and prefrontal cortex. In addition, in MDD, SERT is sensitized in the insula. Interestingly, no alterations of SERT are evident in SZ.
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